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(Posterior funiculus: posterior white-column of the spinal cord, the large wedge-shaped fiber bundle lying between the dorsal gray column and the posterior median septum, composed largely of dorsal root fibers.)

(Lateral horn: the small lateral grey column of the spinal cord as appearing in transverse section, containing the intermediolateral cell column.)

(Lateral funiculus (cord): the lateral white column of the spinal cord between the lines of exit and entrance of the posterior and anterior nerve roots)



(LF3)
(Rolando gelatinous substance: the apical part of the dorsal horn of the spinal cords gray matter, composed largely of very small nerve cells, its gelatinous appearance is due to its very low content in myelinated nerve fibers)

(LF3)
(Gracile (slender) fasciculus (bundle) of Goll: The smaller medial subdivision of the posterior funiculus (cord))

(Cuneate (wedge-shaped) fasciculus of Burdach: the larger lateral subdivision of the posterior funiculus)

(Fasciculi proprii: (fasciculus proprius anterior [TA], fasciculus proprius lateralis [TA], fasciculus proprius posterior [TA]); ascending and descending spinospinal association fiber systems of the spinal cord that lie in the anterior, lateral, and posterior funiculi at the gray matter-white matter interface

(LF3)
Arrowhead of neurologic differential diagnosis - arrangement according to how acute the condition is
Start from top and left to right

1. Trauma\Mechanical
2. Toxic\Metatbolic (DEENO), Vascular
3. Referred, Inf\Inf\Neo, Epileptic
4. Other non-neuro, Psych, Deg\Dev, CSF circulation

(Trauma\Mechan: traumatic disorder such as subdural hematoma, nontraumatic mechanical disorders such as herniated intervertebral disc.)

(Vascular: infarct, hemorrhage, migraine, vascular malformation)

(Epileptic: partial or generalized seizure)

(CSF circulation: hydrocephalus, pseudotumor cerebri, intracranial hypertension)

(Tox\Met: toxic disorders such as opiate overdose, metabolic disorders such as hepatic encephalopathy, DEENO = drugs, endocrine, electrolytes, nutrition, organ failure)

(Deg\Dev: degenerative disorders (ie. Alzheimer's disease), developmental disorders (ie. tuberous sclerosis)

(Referred: left arm parasthesias due to cardiac ischemia)

(Psych: major depression, conversion disorder)

(Other non-neuro: loss of consciousness due to cardiac arrhythmia, impaired gait due to joint deformity)

(Blumenfield)
Signs
a. Pain on straight-leg raising is a sign of
b. Kernig's sign - what, sign of
c. Brudzinski's sign - what, sign of
a. Nerve root compression.

b. Kernig's sign
When examiner straightens the patient's knees with the hip flexed, patient has pain in the hamstrings.
Sign of meningeal inflammation.

c. Brudzinski's sign
When examiner flexes the patient's neck, patient flexes legs at hip.
Sign of meningeal irritation.

(Blumenfield)
The three main divisions of the developing brain and their subdivisions
1. Prosencephalon
a. Telencephalon
(: cerebral cortex, subcortical white matter, basal ganglia, basal forebrain nuclei)
b. Diencephalon
(Thalamus, Hypothalamus, Epithalamus)

2. Mesencephalon\Midbrain
(Cerebral peduncles, mid brain tectum, midbrain tegmentum)

3. Rhombencephalon\Hindbrain
a. Metencephalon (pons, cerebellum)
b. Myelencephalon (medulla)

(Blumenfeld)
Brain
a. Divisions of telencephalon of prosencephalon\forebrain (4)
b. Division of diencephalon of prosencephalon\forebrain (2)
c. Divisions of mesencephalon\midbrain (3)
d. Divisions of metencephalon of rhombencephalon\hindbrain
a. Telencephalon of prosencephalon\forebrain
1. Cerebral cortex
2. Subcortical white matter
3. Basal ganglia
4. Basal forebrain nuclei
(Telos: end, telencephalon: anterior end or division of prosencephalon)
(Proso: forward -> prosencephalon)

b. Diencephalon of prosencephalon\forebrain
1. Thalamus
2. Hypothalamus
3. Epithalamus
(Diencephalon (di-: through): the caudal part of the prosencephalon)

c. Mesencephalon\Midbrain
1. Cerebral peduncles
2. Midbrain tectum (roof-shaped structure)
3. Midbrain tegmentum (covering structure)

d. Metencephalon of rhombencephalon\hindbrain
1. Pons
2. Cerebellum

(Blumenfeld)
Parts of the peripheral nervous system (4)
1. Cranial nerves and ganglia

2. Spinal nerves and ganglia

3. Sympathetic and parasympathetic nerves and ganglia

4. Enteric nervous system

(Blumenfeld)
Orientation of the nervous system - equate anterior, posterior, superior, and inferior to ventral, dorsal, rostral, and caudal
a. Above the midbrain-diencephalic junction
b. Below the midbrain-diencephalic junction
a.
Anterior = Rostral ('beak' - rooster's rostrum)
Posterior = Caudal (tail, as in reptil)
Superior = dorsal ('back' as in shark's fin)
Inferior = Ventral (venter: belly, toward belly in reptile)
(Equal to reptiles)

b.
Anterior = Ventral
Posterior = Dorsal
Superior = Rostral
Inferior = Caudal

(There is a 90 degree rotation somewhere between the forebrain and spinal cord, by convention in midbrain-diencephalic junction)

(Anterior, posterior, superior, inferior = remain constant with respect to the environment, the other (ventral, dorsal, rostral, caudal) changes.)

(Blumenfeld)
Types of neurons and examples (4)
1. Multipolar -
Several dendrites as well as several axons
Most, ie. pyramidal cells

2. Bipolar neurons
A single dendrite and a single axon
Many sensory neurons - ie. as involved in vision or olfaction

3. Pseudounipolar neuron
The processes are initially fused and then split to produce two long axons.
Dorsal root ganglion sensory neurons

4. Unipolar neurons
Both axons and dendrites arise from a single process coming off the cell body
Ie. in invertebrates and during embryogenesis

(Blumenfeld)
Neurotransmitters
a. Which is the most common excitatory neurotransmitter in the CNS
b. Which is the most common inhibitory neurotransmitter in the CNS
a. Glutamate

b. GABA (Gamma-aminobutyric acid)

(Blumenfeld)
Glutamate
a. Location of cell bodies
b. Main projections
c. Receptor subtypes and their main action (3)
a. Entire CNS

b. entire CNS

c.
1. AMPA\kainate -> excitatory neurotransmission
(AMPA because it also binds alpha-amino-3-hydroxy-5-methyl-4-isoaxozole propionic acid)
(Kainate because it binds kainate)
2. NMDA -> Modulation of synaptic plasticity
(Plasticity: the capability of being formed or molded.)
(Binds N-methyl D-aspartate, an excitotoxic amino acid used to identify these receptors)
3. Metabotropic -> Gq

(Blumenfeld)
GABA
a. Location of cell bodies
b. Main projections
c. Receptor subtypes and their main actions
a. Entire CNS.

b. Entire CNS.

c.
1. GABA A,B -> Inhibitory neurotransmission
2. GABA C -> inhibitory neurotransmission
(In retina)
Acetylcholine - location of cell bodies, main projections, receptor subtypes, and main actions
1. Spinal cord anterior horns -> skeletal muscles -> muscle contractio
Nicotinic

2. Autonomic preganglionic nuclei -> autonomic ganglia -> autonomic functions
Nicotinic

3. Parasympathetic ganglia -> glands, smooth muscle, cardiac muscle -> parasympathetic functions
Muscarinic

4. Basal forebrain (nucleus basalis, medial septal nucleus, nucleus of diagonal band) -> cerebral cortex -> neuromodulation
Muscarinic and nicotinic subtypes

5. Pontomesencephalic region (pedunculopontine nucleus, laterodorsal tegmental nucleus) -> thalamus, cerebellum, pons, medulla -> neuromodulation
Nicotinic and muscarinic
(Muscarine is a toxin with neurologic effects, first derived from a mushroom (amanita muscaria))

(Blumenfeld)
Norepinephrine - location of cell bodies, main projections, receptor subtypes, main actions (2)
1. Sympathetic ganglia -> smooth muscle, cardiac muscle, glands -> sympathetic functions
Alpha and beta subtypes

2. Pons: locus ceruleus and lateral tegmental area -> entire CNS -> neuromodulation
Alpha 1A-D. Alpha 2A-D, Beta1-3

(Blumenfeld)
Dopamine - location of cell bodies, main projections, receptor subtypes, main actions
Midbrain: substantia nigra, pars compacta, ventral tegmental area -> striatum, prefrontal cortex, limbic cortex, nucleus accumbens, amygdala -> neuromodulation
D1-5

(Blumenfeld)
Serotonin - location of cell bodies, main projections, receptor subtypes, main actions
Midbrain and pons: raphe nuclei -> entire CNS -> neuromodulation
5-HT 1A-F, 5-HT 2A-C, 5-HT3-7
(5-HT: 5-hydroxytryptamine\Serotonin)

(Blumenfeld)
Histamine - location of cell bodies, main projections, receptor subtypes, main actions
Hypothalamus: tuberomammilary nucleus, midbrain: reticular formation -> entire brain -> mainly excitatory neuromodulation
H1-3

(Blumenfeld)
Glycine - location of cell bodies, main projections, receptor subtypes, main actions
Spinal cord (possibly also brain stem and retina) -> spinal cord, brainstem, retina -> inhibitory neurotransmission (also have a modulatory role by binding to the NMDA receptor and increasing its response to glutamate)
Glycine receptor

(Blumenfeld)
Peptides -
a. Examples - which often coexist with norepinephrine, with acetylcholine, with serotonin
b. location of cell bodies, main projections, receptor subtypes, main actions
a.
Norepinephrine: Galanin, Enkephalin, Neuropeptide Y
Acetylcholine: VIP, Substance P
Serotonin: Substance P, TRH, Enkephalin

b. Entire CNS -> Entire CNS -> neuromodulation

(Blumenfeld, Wikipedia)
Neuromodulation
Includes a broad range of cellular mechanisms involving signaling cascades that regulate synaptic transmission, neuronal growth, and other functions.

Neuromodulation can either facilitate or inhibit the subsequent signaling properties of the neuron.

(Examples: Acetylcholine, Dopamine, Serotonin, Peptides (substance P, Enkephalins, Neuropeptide Y)

(Blumenfeld, Wikipedia)
white matter
a. Synonyms for white matter pathways in the CNS (4)
b. What is a white matte pathway called that connects structures on the right and left sides of the CNS
a.
1. Tract
2. Fascicle
(A band or bundle of fibers, fascis: bundle)
3. Lemniscus
(A bundle of nerve fibers)
4. Bundle

b. Commissure (Commisura: a joining together, com- mitto: to combine)

(Blumenfeld)
Pattern of exit of spinal nerves from the verrtebral column
C1-7 exits above the vertebra with the same number.

C8 exits above T1 since C8 vertebra don't exist.

T1-Co exit below their respective vertebra.

(Blumenfeld)
Spinal cord
a. Where does it end? why
b. What do we find below this
c. Where is the spinal cord enlargement for the brachial plexus
d. Where is the spinal cord enlargement for the lumbosacral plexus for the legs
e. Where does the thoracic spinal cord end in relation to the vertebra, the lumbar, the sacral
a. At L1-L2. The bony vertebral canal increases in length faster than the spinal cord.

b. Cauda equina (horse's tail), a collection of nerve roots.

c. C3-T2
(L. intumescentia cervicalis)

d. T10->Medullary cone
(L. intumescentia lumbosacralis)

e.
Thoracic -> T11 (beginning)
Lumbar -> L1 (beginning)
Sacral (and coccygeal) -> L2 (beginning)

(Blumenfeld)
Autonomic nervous system
a. Location of sympathetic nervous system
b. Location of parasympathetic nervous system
a. Intermediolateral and intermediomedial cell columns of T1-L3
(Thoracolumbar division)

b.
CN 3,7,9,10
S2-4
(Craniosacral division)

(Blumenfeld)
The cerebrum - borders or location of
a. The frontal lobes
b. The parietal lobes
c. The isnular cortex
a. Front of the brain
Separated from the parietal lobes by the central Sulcus of Rolando
Separated inferiorly from the temporal lobes by the Sylvian fissure (especially deep sulcus)

b. The parietal lobes
Separated anteriorly from the frontal lobes by the central sulcus of Rolando
No sharp demarcation inferiorly or posteriorly from the temporal and occipital lobes.
(When viewed from the medial aspect, the parieto-occipital sulcus can be seen more easily)

c. Buried within the depths of the Sylvian fissure. covered anteriorly by a lip of frontal cortex called the frontal operculum ('lid') and posteriorly by the parietal cortex - called parietal operculum.

(Blumenfeld)
(Supramarginal sulcus - surrounding the end of the Sylvian fissure)

(Angular gyrus - surrounding the end of the superior temporal sulcus)
Calcarine fissure\Sulcus
a. Location
b. Mark a line between ....
c. The cortex in the depth of the sulcus corresponds to...
a. A deep fissure on the medial aspect of the cerebral cortex. Extending on an arched line from the isthmus of the fornicate gyrus back to the occipital lobe.

b. The cuneus ('wedge') above and the lingula below it.

c. The horizontal meridian of the contralateral half of the visual field.

(Calcarine: spur-shaped (ie. cock's spur)

(Stedman)
Anterior commissure
a. What
b. Parts (2)
a. A round bundle of nerve fibers that crosses the midline of the brain near the anterior limit of the third ventricle.

b.
1. A smaller anterior part - its fibers pass into the olfactory bulbs.
2. A larger posterior part - its fibers interconnect the right and left temporal lobes.

(Stedman)

(Commissura: a joining together. Com- mitto: to combine)
Septum pellucidum
A thin membrane of nervous tissue that forms the medial wall of the lateral ventricles in the brain.

(Pellucidum: transparent)
Lamina terminalis
A thin layer of gray matter in the telencephalon that extends backward from the corpus callosum ('hard') above the optic and forms the median portion of the rostral wall of the third ventricle.

(Merriam-Webster)
Areas of the brain
a. Location of primary motor cortex
b. Location of primary somatosensory cortex
c. Location of the primary auditory cortex
a. Precentral gyrus of the frontal lobe.

b. Postcentral gyrus of the parietal lobe.

c. Composed of the transverse gyri of Heschl, which are two fingerike gyri that lie inside the Sylvian fissure on the superior surface of each temporal lobe.

(Blumenfeld)
The brain
a. Describe how sensory and motor pathways are topographically organized (usually
b. These somatotopic maps on the cortex are sometimes called the motor or sensory ...
c. Adjacent retinal areas are mapped in a .... fashion onto the primary visual cortex.
d. Adjacent regions of the cochlea, sensing different frequencies, have a ..... representation on the primary auditory cortex.
e. Describe the location of the feet, tongue\mouth, hand, face, pharynx, and arms on the pre- and postcentral gyri
a. This means that adjacent areas on the receptive or motor surface are mapped to adjacent fibers in white matter pathways and to adajcent regions of cortex.

b. Homunculus ('little man')

c. Retinotopic

d. Tonotopic (tono-: tone, tension, pressure)

e. From medial to lateral
Feet -> trunk -> arm (thumb most laterally) -> face (with forehead first -> eyes -> nose -> mouth -> tongue) -> pharynx
(Soler seg på ei brygge med føttene i vannet)

(Blumenfeld)
Cell layers of the cortex
a. Layer I - synonym (1), main connections
b. Layer II - synonyms (2), main connections
c. Layer III - synonyms (2), main connections
d. Layer IV - synonyms (2), main connections
e. Layer V - synonyms (2), main connections
f. Layer VI - synonym (2), main connections
a. Layer I\Molecular layer
<- dendrites and axons from other layers

b. Layer II\Small pyramidal layer\External granular layer
Cortical-cortical connections

c. Layer III\Medium pyramidal layer\External pyramidal layer
Cortical-cortical connections

d. Layer IV\Granular layer\Internal granular
<- Thalamus

e. Layer V\Large pyramidal layer\Internal pyramidal layer
-> subcortical structures (besides thalamus, ie. brainstem, spinal cord, basal ganglia)

f. Layer VI\Polymorphic layer\Multiform layer
-> Thalamus

(From surface->internal)

(Blumenfeld)
Brodmann's areas - By Korbinian Brodmann in 1909
a. Number of cytoarchitectonic areas
b. Location of primary somatosensory cortex
c. Location of primary motor cortex
d. Location of the prefrontal association cortex and frontal eye fields - for thought, cognition, and movement planning
e. Location of primary visual cortex for vision
a. 52

b. 1,2,3 (Postcentral gyrus, touch)

c. 4 (Precentral gyrus, voluntary movement control)

d. 9,10,11,12
(Superior, middle frontal gyri, median frontal lobe)

e. 17
(Banks of calcarine fissure)

(Blumenfeld)
Brodmann's area
a. Location of secondary visual field for vision and depth
b. Location of tertiary visual field for vision, color, motion, and depth
c. Location of primary auditory cortex for hearing
d. Location of secondary auditory cortex for hearing
e. Location of gustatory cortex for taste
a. 18 (Medial and lateral occipital gyri)

b. 19 (Medial and lateral occipital gyri)

c. 41 (Heschl's gyri and superior temporal gyrus)

d. 42 (Heschl's gyri and superior temporal gyrus)

e. 43 (Insular cortex, frontoparietal operculum)

(Blumenfeld)
Corticospinal tract
a. Synonym
b. Pyramidal decussation - % of axons, where
a. Pyramidal tract (<- triangular shape in the medulla)

b. 85%, in medulla\spinal cord junction
Lesions in motor systems
a. Lesions in the cerebellum leads to disorders in coordination and balance, often referred to as ....
b. Lesions in the basal ganglia cause two contrasting conditions ...
Give characteristics and example.
a. Ataxia

b.
1. Hypokinetic movement disorders, such as Parkinsonism.
Movement are infrequent, slow, and rigid.

2. Hyperkinetic movement disorders, such as Huntington's disease.
Dancelike, involuntary movements.

(Blumenfeld)
Diencephalon
a. Components (3)
b. Function
c. Parts of the epithalamus (3)
a. Thalamus, Hypothalamus, Epithalamus

b. Control of autonomic, neuroendocrine, limbic, and other circuits.

c. Epithalamus
1. Pineal body
2. Habenula
3. Parts of pretectum\pretectal area

(Blumenfeld)
What is the name for the groove between the pons and medulla? Which cranial nerves emerge from here?
Medullopontine sulcus

CN VI, VII, VIII

(Stedman)
Brain sand
a. Synonyms (3)
b. What
a.
1. Acervulus cerebri (sand of brain)
2. Corpora arenacea (arena: sand)
3. Psamammoa bodies (psammo: sand)

b. Small calcerous concretions in the stroma of the pineal and other central nervous system tissues.

(Stedman)
Anterior medullary velum\Superior medullary velum
The thin layer of white matter, stretching between the two superior cerebellar peduncles, forming the roof of the superior recess of the fourth ventricle.

(Blumenfeld)

(Velum: sail)
The limbic system
a. Role in earlier phylogenetic stages
b. Function now
a. Olfaction

b. Regulation of emotions, memory, appetite drives, and autonomic and neuroendocrine control.

(Blumenfeld)
Epileptic seizures
a. Most commonly arise from
b. Resulting in seizures that may begin with prodromal symptoms such as (3)
a. The limbic structures of the medial temporal lobe - amydala, hippocampus, and parahippocampal gyrus.

b.
1. Emotions such as fear
2. Memory distortions such as deja vu
3. Olfactory hallucinations.

(Blumenfeld)
Association cortex
a. Function
b. The two types
c. What is the name of the unimodal association cortex of the primary motor cortex
a. Carries out higher-order information processing.

b.
1. Unimodal
(Single sensory or motor modality, usually located adjacent to a primary motor or sensory area.)
2. Heteromodal
(Involved in integrating functions from multiple sensory and\or motor modalities)

c. Premotor cortex and supplementary motor area.

(Blumenfeld)
Lesions in the inferior parietal lobule (between the occipital area and angular gyrus) in the dominant hemisphere can produce a constellation of abnormalities
a. What is the name of the syndrome
b. What are the symptoms (4)
a. Gerstmann's syndrome

b.
1. Acalculia
2. Finger agnosia (inability to identify fingers by name)
3. Difficulties with written language - Agraphia
4. Right-left confusion

(Blumenfeld)
Apraxia and agnosia
a. Common characteristic
b. Apraxia
c. Cause of apraxia
d. Types of apraxia (3)
e. Agnosia
f. Cause of agnosia
g. Types (4)
a. Both are caused by dysfunction of association cortex.
(a-, pratto: to do)

b. Abnormalities in motor conceptualization, planning, and execution.
(Not caused by loss of comprehension, motor power, sensibility, and coordination in general)

c. Dysfunction of association cortex related to motor function
1. Diffuse lesions of the cortex
2. Focal lesions affecting the frontal or left parietal lobe

c. Gait apraxia, Ocular motor apraxia, limb-kinetic apraxia

d. Agnosia
Impairment of ability to recognize, or comprehend the meaning of, various sensory stimuli.
(Not attributable to disorders of the primary receptors or general intellect)
(Gnosis: knowledge)

g. Dysfunction of the association cortices associated with sensation.

h. Finger agnosia, color agnosia, Tactile agnosia, visual agnosia...
Spatial awareness
a. Which part of the cortex play an important role in spatial awareness
b. Lesion to this region result in (3)
a. The nondominant parietal lobe.

b.
1. Distortion of perceived space
2. Hemineglect of contralateral side
(Patients will often ignore objects in their contralateral field (most often left), but they may see them if their attention is strongly drawn to that side. They may draw a clock face without filling in any numbers on the left side. They may also be completely unaware of the left side of their body.)
3. Extinction
(A tactile or visual stimulus is perceived normally when it is presented to one side only, but when it is presented to the contralateral side simultaneously with an identical stimulus on the normal side, the patient neglects the stimulus on the side opposite of the lesion.)

(Blumenfeld)
Anosognosia
Unawareness of a deficit.

(a-: lack, nosos: disease, gnosis: knowledge)

(Blumenfeld)
Frontal lobe lesions cause a variety of disorders in personality and cognitive functioning
a. Symptoms (7)
a.
1. Frontal release signs
(primitive reflexes that are normal in infants: grasp, root, suck, snout reflexes)
2. Perserverate when asked to do a sequence of actions repeatedly or to change from one activity to another
(Perseverate: repeat a single action over and over without moving on to the next one)
3. Disinhibited behaviors
4. Impaired judgment
(Cheerful lack of concern about one's illness, inappropriate joking)
5. Abulic
(Reduction in speech, movement, , thought, and emotional reaction)
6. Magnetic gait
(Feet shuffle close to the floor)
7. Urinary incontinence

(Blumenfeld)
Lesions in the visual association cortex in the parieto-occipital and inferior temporal lobes can produce the following symptoms
1. Prosopagnosia
(Prosop: face, inability to recognize faces)

2. Achromatopsia
(chroma: color, opsis: vision)
(Inability to recognize colors)

3. Palinopsia
(Palin: moving backward)
(Persistence or reappearance of an objects viewed earlier)

(Blumenfeld)
The six subdivisions of the neurologic exam
1. Mental status
2. Cranial nerves
3. Motor exam
4. Reflexes
5. Coordination and gait
6. Sensory exam

(Blumenfeld)
By testing the muscles of articulation, which cranial nerves do you test (5)
CN V, VII, IX, X, XII

(Blumenfeld)
Signs
a. Agraphia
a. Graphesthesia
a. Inability to write properly in the absence of abnormalities of the limb
(Often in association with aphasia and alexia)
(Caused by lesions in various portions of the cerebrum, especially in those at or near the angular gyrus)
(grapho: to write)

b. Tactual ability to recognize writing on the skin.

(Blumenfeld)
The mental status part of the neurologic exam - slubdivisions
1. Level of alertness, attention, and cooperation

2. Orientation - A&Ox3

3. Memory - recent, remote

4. Language
(spontaneous speech (paraphasic errors: inappropriately substituted words or syllables), neologism (logos: word): nonexistent, invented words), comprehension, naming, repetition, reading, writing)

5. Calculations, right-left confusion, finger agnosia, agraphia
(-> Gerstmann's syndrome)

6. Apraxia
(Used here as inability to follow a motor command, when this inability is not due to a primary motor deficit or a language impairment.)

7. Neglect and constructions
(Hemineglect is an abnormality in attention to one side of the universe that is not due to a primary sensory or motor disturbance. Can test by extinction on double simultaneous stimulation. Anosognosia (nosos: disease) is also often exhibited with non-dominant parietal lobe lesion -> left-side is more severe and common)

8. Sequencing tasks and frontal release signs
(Perserveration - stuck on one part of an alternating sequence task, Luria manual sequencing task: the patient is asked to tap the table with a fist, open palm, and side of an open hand and then to repeat the sequence as rapidly as possible, Motor impersistence: the patient only briefly sustains a motor action in response to a command, abulia: very slow responses. -> frontal lobe lesion)

9. Logic and abstraction
(Simple problems, proverbs, comprehension of similarities, generalizations)

10. Delusions and hallucinations

11. Mood
(Depression, anxiety, mania)

(Blumenfeld)
Testing of the cranial nerves as part of the neurological exam - what are the subdivisions of the test, and which nerves do they test for (12)
(All tests must be performed on both sides)

1. Olfaction -> CN I
(Coffee, soap. Noxious odors may stimulate pain fibers from CN V)

2. Ophthalmoscopic exam -> CN II
(damage to the retina or retina vessels, optic nerve atrophic changes, papilledema..)

3. Vision -> CN II
(Visual acuity -> eye chart, color vision -> red desaturation (dullness of color of red object) (optic neuritis), visual fields -> when is a moving finger seen, visual extinction -> double simultaneous stimulation (nondominant parietal lesion))

4. Pupillary response -> CN II, III
(Size, shape)
(Direct response, consensual response, swinging flashlight test (0.3Hz), hippus (physiological brief oscillation of pupillary size in response to light)
(Pupillary response to accommodation \ near response)

5. Extraocular movements -> CN III, IV, VI
(All quadrants (experience diplopia?), smooth pursuit horizontally and vertically, convergence movements, spontaneous nystagmus, dysconjugate gaze (eyes not both fixated on the same point), saccades (test by looking back at forth between two objects, ie. fingers), optokinetic nystagmus (OKN): nystagmus with slow and rapid phase, coma: oculocephalogyric (turning the eye and head toward the source of a stimuli) or caloric testing)

6. Facial sensation and muscles of mastication -> CN V
(Sensation: cotton wisp and a sharp object, tactile extinction by using double simultaneous stimulation, corneal reflex (both CN V and VII), jaw jerk reflex (tapping on the jaw with the mouth slightly open, its presence is abnormal and is a sign of hyperreflexia)

7. Muscles of facial expression and taste -> CN VII
(Asymmetry (shape, movement, blinking), shallow furrows, smile, puff out their cheeks, clench their eyes tight, wrinkle their brown)
(Taste: sugar or salt on cotton on lateral aspect of tongue)
(The upper face (upper orbicularis oculi and frontalis) project to the facial nuclei bilaterally)

8. Hearing and vestibular sense -> CN VIII
(Tuning fork can distinguish mechanical and conductive hearing problems), vestibular test for: patients with vertigo, patients with limitations of horizontal or vertical gaze (vestibuloocular reflex (<- oculochepalogyric maneuver or calorid testing)), patients in coma)

9. Palate elevation and gag reflex -> CN IX, X
(Does the palate elevate symmetrically when the patient says 'Aah')
(Gag reflex (elicited in posterior pharynx) is necessary to test only for patients with suspected brainstem pathology, impaired consciousness, or impaired swallowing)

10. Muscles of articulation -> CN V, VII, IX, X, XII
(Hoarse, slurred (dysarthria), quiet, breathy, nasal, low or high pitched)

11. Sternocleidomastoid and trapezius muscles -> CN XI
(Shrug, turn head in both directions, flex head)
(Sternocleidomastoid has bilateral projections -> spared in unilateral upper motor neuron lesion)

12. Tongue muscles -> CN XII
(Atrophy, fasciculations (spontaneous, quivering movements), protrude, side-to-side movement), unilateral tongue weakness causes the tongue to deviate toward the weak side)

(Blumenfeld)
Pupillary response - what is being tested
a. What is the pretectal area
b. Direct response (pupil illuminated)
c. Consensual response (contralateral pupil iluminated)
d. Accommodation (response to looking at something moving toward the eye)
a. A narrow zone of the rostral mesencephalic tectum. It contains several nuclei that receives fibers from the optic tract, it has bilateral efferent connections with the Edinger-Westphal nucleus of the oculomotor nuclear complex by way of which it mediates the pupillary light reflex.

b. Impaired in lesions of the ipsilateral optic nerve, the pretectal area, the ipsilateral parasympathetics traveling in CN III, or the pupillary constrictor muscle of the iris.

c. Impaired in lesions of the contralateral optic nerve, the pretectal area, the ipsilateral parasympathetics traveling in CN III, or the pupillary constrictor muscle.

d. Impaired in lesions of the ipsilateral optic nerve, the ipsilateral parasympatehtics traveling in CN III, the pupillary constrictor muscle, or in bilateral lesions of the pathways from the optic tracts to the visual cortex.
(Spared in lesions of the pretectal area -> pupillary light-near dissociation (a stronger near\accommodation pupil response than light response <- weak pupillomotor input, Argyll-Robertson pupil, dorsal midbrain syndrome)

(Argyll-Robertsonian pupil
<- tabetic (progressive wasting) neurosyphilis
: miosis, irregular shape, loss of direct and consensual pupillary light reflex, spared near response)

(Blumenfeld)
Signs of upper motor neuron (UMN) and lower motor neuron (LMN) lesions
a. Weakness
b. Atrophy
c. Fasciculations (spontaneous, quivering movements)
d. Reflexes
e. Tone
a. Weakness
UMN: Yes
LMN: Yes

b. Atrophy
UMN: No (or mild due to disuse)
LMN: Yes

c. Fasciculations
UMN: No
LMN: Yes

d. Reflexes
UMN: Increased
LMN: Decreased

e. Tone
UMN: Increased
LMN: Decreased

(With acute UMN lesion, reflexes and tones may be absent)

(Blumenfeld)
Motor exam part of neurologic exams - steps
1. Observation
(Twitches, tremor, involuntary movements, posture)

2. Inspection
(Muscle wasting, hypertrophy, fasciculations (generalized LMN lesion -> intrinsic hand muscles, shoulder girdle, thigh are most prominent)

3. Palpation
(Myositis -> tenderness)

4. Muscle tone testing
(Feel for resistance or rigidity to movement)

5. Functional testing
(Drifting (have the patient hold up both arms or legs and close their eyes), fine movements (-> rapid finger tapping, rapid hand pronation-supination (screwing a light bulb), rapid hand tapping, rapid foot tapping)

6. Strength of individual muscle groups
(Test the strength of each muscle group and record it systematically)
(0\5: no contraction, 1\5: muscle flicker without movement, 2\5: movement possible, but not against gravity, 3\5: movement possible against gravity, but not against resistance of examiner, 4\5: possible against some resistance of the examiner, 5\5: normal)
(Proximal weakness -> muscle, distal weakness -> nerve)
Upper extremity strength testing - give muscle and innervation
a. Elbow flexion (with forearm supinated)
b. Elbow extension
c. Arm abduction at shoulder
d. Finger abduction
e. Thumb opposition
a. Elbow flexion with forearm supinated -> biceps, brachialis -> musculocutaneous nerve -> C5,C6

b. Elbow extension -> Triceps -> Radial nerve -> C6-8

c. Arm abduction at shoulder -> Deltoid -> Axillary nerve -> C5-6

d. Finger abduction -> Dorsal interossei, abductor digiti minimi -> Ulnar nerve -> C8, T1

e. Thumb opposition -> Opponens pollicis -> Median nerve -> C8, T1

(Blumenfeld)
Lower extremity strength testing - give muscle and innervation
a. Hip flexion
b. Knee extension
c. Knee flexion
d. Foot dorsiflexion
e. Foot plantar flexion
f. Leg abduction
a. Hip extension -> iliopsoas -> femoral nerve and L1-L3 nerve roots -> L1-4

b. Knee extension -> Quadriceps -> Femoral nerve -> L2-4

c. Knee flexion -> Hamstrings (Semimembranosus, semitendinosus, biceps femoris) -> Sciatic nerve -> L5-S2

d. Foot dorsiflexion -> Tibialis anterior -> Deep peroneal nerve -> L4-5

e. Foot plantar flexion -> Triceps surae (gastrocnemius, soleus) -> Tibial nerve -> S1-2

f. Leg abduction -> Gluteus medius, Gluteus minimus, Tensor fasciae latae -> Superior gluteal nerve -> L4-S1

(Blumenfeld)
Reflex testing as part of the neurologic exam - different tests (3)
1. Deep tendon reflexes
(When reflexes are very brisk, clonus can sometime be seen (repetitive vibratory contraction of the muscle that occurs in response to muscle and tendon stretch)
(0: absent, 1+ Trace\with reinforcement (contract other muscle..), 2+ normal, 3+ brisk, 4+ nonsustained clonus, 5+ sustained clonus. 1-3 is normal)
(Bad: spreading of reflexes, crossed adduction of the opposite leg when the medial aspect of the knee is tested, Hoffman's sign)

2. Plantar response, toe extension = Babinski's sign
(Scrape object from heel to little toe and arch to large toe)

3. Special circumstances
a. Spinal cord damage
(Abdominal cutaneous reflexes, cremasteric reflex, bulbocavernous reflex, anal wink)
b. Frontal lobe lesion -> frontal release signs
(grasp, snout, suck reflexes)
c. Neurodegenerative disorders
(Glabeller response -> continue blinking is + > Myerson's sign)
(Palmomental reflex: scrape hypothenar eminence -> ipsilateral mentalis contraction)

(Blumenfeld)
Cortical sensation - which phenomena can be used to test it (3)
1. Stereognosis - the appreciation of the form of an object by means of touch

2. Graphesthesia - tactual ability to recognize writing on the skin

3. Tactile extinction on double simultaneous stimulation
(<- right parietal lobe, seldomly left. Can also come from right frontal or subcortical lesions)

(Blumenfeld)
Doll's test
a. Synonym
a. Method
a. Oculocephalic maneuver\Oculocephalogyric reflex.

b. Turning of the eyes and head toward the source of an auditory, visual, or other form of stimulation.

(Stedman)
Important external steps of cranial trauma - list and explain the six most common (6)
1. Bony step-off
Palpable discontinuity in shape of skull due to displaced fracture.

2. CSF rhinorrhea (rhoia: flow)
Exudation of CSF from the nose due to base-of-skull fracture, usually involving the ethmoid bone.

3. CSF otorrhea
Exudation of CSF from the ear due to base-of-skull fracture, usually involving the temporal bone.

4. Hemotympanum
Blood (dark purple) visible behind the tympanic membrane caused by base-of-skull fracture usually involving the temporal bone.

5. Battle's sign
Ecchymoses (dark purple, > 3 mm) visible in the skin overlying the mastoid processes due to base-of-skull fracture and blood exudation into the subcutaneous tissue.

6. Racoon eyes
Ecchymoses visible in the skin around the eyes due to base-of-skull fracture and blood exudation into the subcutaneous tissue.

(Blumenfeld)
Coma
a. Definition
b. The four most common causes
c. Three conditions that can be mistaken for coma
a. Unarousable unresponsiveness in which the patient lies with eyes closed.
(Plum & Posner)

b.
1. Lesion of brainstem reticular formation
2. Bilateral lesions of cerebral hemispheres
3. Bilateral lesions of thalami
4. Metabolic or toxic conditions

c.
1. Akinetic mutism
(From large lesions of the frontal lobes or their connections, a severe abulia)
2. Catatonia (Kata: down, tonos: tone)
(Profoundly decreased responsiveness due to psychiatric illness.)
3. Locked-in syndrome
(Consciousness and sensation is intact, but the patient is unable to move. <- lesion in the brainstem motor pathways, or peripheral neuromuscular blockade.)

(Blumenfeld)
Reflexes or tests for the comatose patient
a. Blink-to-threat
b. Oculocephalic reflex
c. Caloric stimulation\Caloric reflex test
d. Flexor and extensor posturing - which is synonymous to decorticate ('no cortex') and decerebrate ('no brain') posturing
e. How can you distinguish purposeful withdrawal from flexor or extensor response (2)
a. Can be used to roughly map visual fields. Observe whether the patient blinks in response to moving your hand rapidly toward their eyes from different directions.

b. Hold the patient's eyes open and rotate the head from side to side or up and down. The eyes should move in the direction opposite to the head movement.
(Used to test whether brain stem eye movement pathways are intact)
(Also called Doll's eyes)
(Not usually present in awake patients)

c. Have the patient in supine position with head elevated (30 degrees). Infuse ice water into one ear. If the brainstem vestibulo-ocular reflex pathways are intact, this will produce nystagmus, with the fast phase directed opposite to the side of the cold water infusion.
(fast phase mnemonic: COWS: Cold Opposite, Warm Same)
(Possible mechanism is by inducing a temperature change across the semicircular canals, thus altering the density of the endolymph. This creates convection current that cause cupular deflection. <- Barany)

d. Flexor\Decorticate posturing, Extensor\Decerebrate posturing.
(Extensor posturing have slightly worse prognosis)
(Mnemonic: in decorticate posturing the lesion is higher, and flexed arms point up toward the cortex, in decerebrate posturing the lesion is lower, and extended arms point down.)
(Extensor posturing of the lower extremities often accompanies either flexor or extensor upper extremity posturing)

e. In purposeful withdrawal the limb\body part is always moved away from the painful stimulus. While in the extensor and flexor response, the body part will move toward the painful stimulus if elicited at that side of the limb. Also, in purposeful withdrawal there is often abduction as well.

(Blumenfeld)
Pupillary responses in comatose patients - what condition do the findings indicate
a. Normal-sized, reactive pupils
b. Asymmetrical, unresponsive, and or bilateral dilated ("blown") pupils
c. Small but responsive pupils
d. BIlateral pinpoint pupils
a. Toxic or metabolic conditions.

b. Transtentorial herniation or other disorders affecting the midbrain.

c. Pontine lesions.

d. Opiate overdosage.

(Blumenfeld)
Psychiatric disorders feigning neurologic disorders
a. Conversion disorder
b. Somatization disorder
c. Factitious disorder, include synonym as well
d. Malingering
a. Psychiatric illness causes the patient to have sensory or motor deficits without corresponding focal lesion in the nervous system.

b. Patients have multiple somatic complaints that change over time.
(In both these conditions, the patients are not consciously "faking" their symptoms, and they usually believe that they have a nonpsychiatric illness.)
(Synonyms for both = hypochondriasis\hysteria)

c. Factitious (artificial, self-induced)\Munchausen syndrome (refer to the most severe cases)
These patients feign illness because they gaine some form of emotional pleasure from assuming the role of patient.
(The ulterior motive is internal to the patient.)

d. Feign illness but the ulterior motive involves some external gain for the patient, such as avoiding work, obtaining disability benefits, etc.

(Blumenfeld)
Techniques used to distinguish neurologic disorders from psychogenic disorders (6)
1. Hand-dropping test
(Coma: when their hand is released directly above their face, their hand should strike their face on its way down.)

2. Saccadic eye movements
(Coma: not present, though present in locked in syndrome)

3. Variable resistance
(A patient with psychogenic weakness of alimb may vary their resistance over a wide range up to normal strength when their strength is tested by variable resistance from the examiner. Distinguish from paratonia from frontal lobe lesions.)

4. Unconscious movements
(Patients with psychogenic paralysis may be observed to move the affected limbs during sleep, while being transferred onto a stretcher, or in other situations when distracted.)

5. Midline change in vibration sense
(Loss of vibration sense on only one side of the sternum or skull is nonphysiological, since vibration is readily conducted through the bone to the contralateral side)

6. Hoover test
(In unilateral leg weakness, palpate the contralateral gastrocnemius while the patient tries to raise the affected leg off the bed. In normal indiivduals the contralateral gastrocnemius is used to exert force aginst the bed, and it should contract. Lack of gastrocnemius contraction demonstrates lack of mental effort.)

(Blumenfeld)
Why is the angle of axial slices in CT scans sometimes adjusted by a few degrees of the true axial plane?
This adjustment enables the whole brain to be covered using fewer slices and decreases radiation exposure to the eyes.
(By declining from the supraorbital frontal bone to the lower occiptal lobe.)

(Blumenfeld)
Computerized tomography (CT) scans
a. What does it measure
b. Hyperdense area - color, example of structures
c. Hypodense areas - color, examples of structures
d. Isodense areas - color, examples of structures
e. Color of white matter
f. Scale used for density
a. Density of the tissues being studied.

b. Bright color,
Bone or other calcifications

c. Darker color
Air, fat tissue (seen subcutaneously outside the skull)

d. Gray
Brain tissue, CSF fluid (dark grey)

e. Slightly darker than cellular gray matter due to its myelin (fat) content.

f. Hounsfield units (HU). 0 for water, -1000 for air, as reference values.
(Dark --> Bright
Air: -1000 to -600
Fat: -100 to -60
Water: 0
CSF: 8-18
White matter: 30-34
Gray matter 37-41
Freshly coagulated blood 50-100
Bone 600-2000)

(Blumenfeld)
Intracranial hemorrhages on CT scan
a. Appearance of fresh intracranial hemorrhage (acute)
b. Appearance of a one week old hemorrhage
c. Appearance of 2-3 week old hemorrhage (chronic)
a. Hyperdense, almost as bone, due to rapid coagulation.
(HU: freshly coagulated blood: 50-100, bone: 600-2000, brain: 30-41)

b. Isodense, due to degradation of the clot in the hemorrhage.

c. Hypodense, more progressed degradation.

(Blumenfeld)
Cerebral infarctions on CT scan
a. Appearance of infarction within 6-12 hours
b. Appearance after 6-12 hours, why
c. Appearance after weeks to months, why
a. Often cannot be seen

b. Area of hypodensity seen in the distribution of the occluded artery. From cell death and edema.

c.
1. The brain tissue may shrink -> enlarged sulci or ventricles
2. Persistent areas of hypodensity <- gliosis, brain necrosis with replacement of CSF

(Blumenfeld)
Mass effect in relation to radiology
a. What
b. How can it be seen (3)
a. Anything that distorts the brain's usual anatomy by displacement. Can be hemorrhage, neoplasm, edema, and other conditions.

b.
1. Localized compression of the ventricles
2. Effacement ('thinning') of the sulci
3. Distortion of other brain structures seen, ie. in subfalcine herniation of brain structures across the midline.

(Blumenfeld)
Neoplasms on CT scans
a. How do they appear, why
b. How can they more easily be identified, how
a.
Hypodense <- hemorrhage\fluid-filled cysts
Isodense <- hemorrhage\fluid-filled cysts
Hyperdense <- calcifications
(Bone 600-2000 HU, gray matter 37-41 HU, white matter 30-34 HU, CSF 0-18)

b. Intravenous contrast dye
Ie. iodine has higher density than the brain -> the brain will appear hyperdense in areas of increased vascularity or breakdown of the blood-brain barrier.

(Blumenfeld)
MRI vs CT
a. Advantages of MRI (2)
d. Disadvantages of MRI (4)
a. Advantages
1. High-contrast imaging in striking anatomical detail
(-> imaging method of choice for detecting low-contrast\small lesions such as MS plaques, low-grade astrocytomas, and accoustic neuromas)

2. No shadow artifacts from bones as seen on CT -> clearer images of basilar structures (brain stem, cerebellum, pituitary fossa)
(Also spinal cord)

b.
1. Time
(20-45min vs 5-10min in CT)

2. Cost

(CT costs 2\3 of an MRI)
3. Avoidance of patients with metallic devices
(pacemaker, orthopedic devices..)

4. Bad detection of hemorrhages
(Hemorrhages has high density due to fibrinogen but its proton density which the MRI detects is similar to the CSF)

(CT: first-choice for patients with hread trauma or suspected intracranial hemorrhage and as a first screening method to detect most intracranial lesions.)
(MRI: patients suspected to have low-contrast lesion, brainstem or skull-base lesion, or as secondary after CT)

(Blumenfeld)
MRI
a. Protons have two properties that contribute to MRI signals
b. Effect of excitation by radio frequency waves (2)
c. Three properties of tissues determine the intensity of MRI signals
d. Regions of neoplasm (increased uptake) or inflammation (breakdown of BBB) often increase with which contrast
a.
1. Spins
(quantum mechanical property, parallel (up) or antiparallel (down))
(The presence of a magnetic field Bo) tend to align slightly more proton spins parallel rather than antiparallel -> net magnetization M in the same direction as Bo, called z-direction)

2. Precessions
(The rotation of the spinning top in a cone-shaped trajectory)

b.
1. Flip their spins to antiparallel (-> decrease M in z-direction)
2. Brings precession into phase with each other (-> M in x-y direction)
(The longer the radio frequency pulse the longer the net magnetization vector M will rotate away from the direction of the magnetic field)

c.
1. Proton density
2. Proton relaxation time T1\Longitudinal\Spin-lattice relaxation
(Z-axis, depend on net direction of spins)
(Biological tissue: 300-2000 ms)
3. Proton relaxation time T2\Transverse\Spin-spin relaxtion
(x-y plane, perpendicular to the magnetic field, depend on net coherence of precessions)
(Especially important for fMRI)
(Biological tissue 30-150 ms)

(Different radio wave pulses are used to emphasize either T1 (T1-weighted) or T2. With spin echo (SE) pulse sequence, repetition time (TR) determines the time during T1 relaxation when the MR image is obtained, while echo time (TE) ---||-- T2..)
(T1-weighted: short TR and TE, T2-weighted: long TR and TE)

d. Gadolinium

(Blumenfeld)
MRI
a. Does T1-weighted images or T2-weighted images look like a film negative?
b. T1-weighted images - how does gray matter, white matter, and CSF\water appear
c. T2-weighted images - how does gray matter, white matter, and CSF\water appear
d. What is FLAIR
a. T2-weighted images.
(The first - T1-weighted, is normal.)

b. T1-weighted images - water appear dark (hypointense), fat appear bright (hyperintense)
Gray matter -> gray (edema and demyelination or gliosis also appears grey)
White matter -> white (hyperintense)(so does fat, Ca bound to protein, and proteinaceous fluid)
CSF\Water -> black (hypointense) (also air, bone, and calcification)
(Best for identifying anatomy)

c. T2-weighted images: water appear bright, fat appear dark
Water\CSF -> bright (hyperintense)(also fat, edema, demyelination, and gliosis)
White matter (lipid) -> dark (hypointense) (also Ca bound to protein)
Gray matter -> light dark
(Air, bone\calcification and ferritin deposits (ie basal ganglia) appear black (hyperintense)
(T2-weighted images are most useful for detecting pathologic changes.)

d. Fluid attenuation inversion recovery (FLAIR) imaging. Produce scans that appear similar to T2-weighted images but with dark CSF.
(Small areas of edema, gliosis, demyelination, or infarction adjacent to the CSF can be easily seen as bright regions.)

(Blumenfeld)
MRI appearance of intracranial hemorrhage - give appearance on T1-weighted and T2-weighted images, and reason
a. Acute (6-24 hours)
b. Early subacute (1-5 days)
c. Middle subacute (3-7 days)
d. Late subacute (3-30 days)
e. Chronic (> 14 days)
a. Acute, 6-24 hours
<- Intracellular oxyhemoglobin
T1: Gray
T2: Light gray
(Like gray matter)

b. Early subacute, 1-5 days
<- Intracellular deoxyhemoglobin
T1: Gray
T2: Dark grey

c. Middle subacute, 3-7 days
<- Intracellular methemoglobin
T1: White
T2: Dark gray

d. Late subacute, 3-30 days
<- Extracellular methemoglobin
T1: White
T2: White

e. Chronic, > 14 days
<- Hemosiderin (mainly on outer rim)
T1: Dark gray
T2: Black
(Eventually, the center of the hemorrhage may resorb, forming a fluid-filled cavity that is dark on T1-weighted images and bright on T2-weighted images)

(Blumenfeld)
Other MRI methods (4)
1. Diffusion-weighted imaging (DWI)
(Use rapid image acquisition (1 minute) with strong gradients to measure the diffusion of water protons in brain tissue. Allow detection of acute ischemic stroke within 30 minutes (At least 2 hours with T2-weighted)

2. Magnetic resonance spectroscopy (MRS)
(Can measure neurotransmitters and other biochemicals, some clinical application with evaluating brain tumors and epileptic seizures)

3. fMRI

4. Diffusion tensor imaging (DTI)
(Allow sensitive assessment of white matter pathways by tracing the direction of maximal water diffusion, constrained by white matter microarchitecture)

(Blumenfeld)
(Netter)
(Netter)
Functional neuroimaging - methods (7)
1. EEG
(Low sensitivity and spatial resolution for detecting focal lesions, useful for diagnosis of seizures)

2. Evoked potentials
(Similar to EEG, brain electrical signals are recorded in response to specific stimuli)

3. Magnetoencephalography (MEG)
(Use a superconducting quantum interference device (SQUID) to detect the very weak magnetic signals from the brain)
Methods dependent on brain metabolic activity and blood flow

4. Single photon emission computerized tomography (SPECT)
(Tc99m is the most frequent agent used)

5. perfusion MRI (Dynamic contrast functional MRI)

6. Fluoro-deoxyglucose positron emission tomography (FDG-PET)
(Used in patients with dementia or epilepsy to localized regions of abnormal glucose metabolism)
(Also for distinguishing metabolically active recurrent brain tumors from radiation-induced necrosis)

7. Blood oxygen level-dependent functional MR (BOLD fMRI)
(Can measure blood flow, blood volume, and the rate of oxygen metabolism)
(Used to help plan for neurosurgery by localizing regions of sensory-motor function and language function. Can replace the angiogram Wada test for amobarbital is selectively injected into different vessels)

(Blumenfeld)
Arachnoid trabeculae
Fine, delicate strands that traverse the subarachnoid space between the arachnoid mater and the pia mater.

(Consist of fibroblasts and extracellular collagen.)
(Between the arachnoid mater, which is attached to the dura, and the pia mater, which is adherent to the surface of the brain.)

(Stedman)
Layers of protection for the brain
SCALP

Skin - subcutaneous tissue

Connective tissue

Aponeuretica (Galea)

Loose areolar connective tissue

Pericarnium (periosteum)
Dura mater
a. What are its two components
b. How are they connected
c. How is it different in the spinal cord
a. Meningeal and periosteal layer.

b. Tightly adherent, except at points where the dura mater fold inward, which is mainly at the falx cerebri, tentorium cerebelli, and diaphragma sellae.

c. There is a layer of epidural fat in the spinal canal between the dura and periosteum.
(While in the cranium, both layers adhere tightly to bone.)

(Blumenfeld)
Cranium
a. What separates the anterior fossa from the middle fossa
b. What separates the middle fossa from the posterior fossa
c. What does the anterior fossa contain
d. What does the middle fossa contain
e. What does the posterior fossa contain
a. The lesser wing of the sphenoid bone.

b. The petrous ridge of the temporal bone and the tentorium cerebelli.

c. The frontal lobes.

d. The temporal lobes.

e. The cerebellum and brainstem.

(Blumenfeld)
Tentorium cerebelli
a. What is the name of the area above, and which structures does it house, what is the name of the area below and which structures does it contain
b. What passes through the tentorial notch\incisura
a. Supratentorial and infratentorial.
The infratentorial space contains the brainstem and cerebellum in the posterior cranial fossa.

b. The midbrain
(Cerebral peduncles and midbrain reticular formation.)

(Blumenfeld)

(Blumenfeld)
Perivascular space
a. Synonym
b. Formed by
a. Virchow-Robin space

b. The pia mater surrounding the initial portion of the blood vessels as it penetrates the brain surface.
(It then fuses with the vessel wall.)

(Blumenfeld)
The potential spaces of the meninges - location and blood vessels
a. Epidural space
b. Subdural space
c. Subarachnoid space
a. Epidural space
Between the inner surface of the skull and the periosteal layer of the dura mater.
Middle meningeal artery
(Via foramen spinosum)

(The dural venous sinuses lie enclosed within the dura mater)

c. Subarachnoid space
Arachnoid-pia
The major vessels of the brain.

b. Subdural space
Between meningeal layer of dura mater and arachnoid space.
Bridging veins
(Veins which traverse the subdural space to empty into dural venous sinuses while draining the cerebral hemispheres)
Ventricles and cerebrospinal fluid
a. What is the structure that produce the majority of the cerebrospinal fluid
b. What cell type is the inner wall of the venitrcles lined with
c. What cell type are the blood vessels of the choroid plexus lined with
a. The choroid plexus inside the ventricles.

b. Ependymal cells.
(Pyramidal shape in the central canal of the spinal cord and cuboidal shape in the ventricles of the brain)

c. Choroid epithelial cells.
(Both are cuboidal cells)

(Blumenfeld)
Cerebrospinal fluid
a. Arachnoid villus
b. Arachnoid granulation
a. Microscopic projections of the arachnoid into some of the dural venous sinuses.

b. enlarged arachnoid villi projecting into the venous sinuses and creating slight depressions on the surface of the cranium.

(The spongy tissue of the arachnoid villi contain tubules that serve as one-way valves for transfer of cerebrospinal fluid from the subarachnoid space to the venous system.)

(Stedman)
(Netter)
Brain ventricles - location of
a. Lateral ventricles
b. Frontal\Anterior horn of lateral ventricle
c. Body of lateral ventricle
d. Atrium\Trigone of lateral ventricle
e. Occipital\Posterior horn of lateral ventricle
f. Temporal\Inferior horn of lateral ventricle
a. Within the cerebral hemispheres.

b. Begins anterior to the interventricular foramen of Monro and extends into the frontal lobe.

c. Posterior to the interventricular foramen of Monro, within the frontal and parietal lobes.

d. Area of convergence of the occipital horn, the temporal horn, and the body of the lateral ventricle.

e. Extends from the atrium posteriorly into the occipital lobe.

f. Extends from the atrium inferiorly into the temporal lobe.

(Blumenfeld)
Brain ventricles
a. Synonyms for lateral ventricles
b. Location of lateral ventricles
c. Location of third ventricle
d. Location of fourth ventricle
a. 1st and 2nd ventricle.

b. Within the cerebral hemispheres.

c. Within the thalamus and hypothalamus.

d. Within the pons, medulla, and cerebellum.

(Blumenfeld)
C-shaped structures that follow the curve of the lateral ventricles - describe the position of
a. The caudate nucleus and thalamus
b. The septum pellucidum
c. The corpus callosum
d. The fornix
e. The hippocampal formation
a. The caudate ('tailed') nucleus and thalamus
Bulge inward from the lateral walls of the lateral ventricles.
(The caudate nucleus forms a C-shaped structure that lies along the wall of the C-shaped lateral ventricle in all planes of section.)

b. Hangs from the corpus callosum, thin membrane that separates the two lateral ventricles in the midline.

c. The corpus callosum forms the roof of most parts of the lateral
ventricles.

d. The fornix ('arch') hangs from the bottom of the septum pellucidum.
(Pair of archlike bundles of myelinated axons that connect structures in the temporal lobes to the hypothalamus and basal forebrain.)

e. Lies on the floor and the medial wall of the temporal horn of the lateral ventricles.
(A structure involved in memory and other limbic functions.)

(Also the stria terminalis\terminal stria ('stripe'))

(Blumenfeld)
The fourth ventricle
a. What are the borders - roof and floor
b. What are its foramina, and with what are they connected (3)
a. The roof is formed by the cerebellum, and the floor is formed by the pons and medulla.

b.
1. Third ventricle <-cerebral aqueduct of Sylvius-> Fourth ventricle
2. Fourth ventricle (lateral recess) <-the lateral foramina of Luschka-> Subarachnoid space
3. Fourth ventricle <-the midline foramen of Magendie-> Subarachnoid space

(Blumenfeld)
Cisterns of the subarachnoid space
a. What
b. List the most important cisterns (6, 3 is part of a group)
a. Local dilations of the subarachnoid space.

b.
1. Perimesencephalic cisterns
a. The ambient ('surrounding') cistern
(Located lateral to the midbrain)
b. The quadrigeminal cistern
(Posterior to the tectum of the midbrain, beneath the posterior portion of the corpus callosum
(Quadrigeminal <- four bumps on it from the superior and inferior colliculi)
c. The interpeduncular cistern\fossa
(on the ventral surface of the midbrain betweent he cerebral peduncles, CN III exits the midbrain through it)

2. Prepontine\Pontine cistern
(Ventral to pons, contains the basilar artery and the sixth nerves)

3. Cisterna magna\Cerebellomedullary cistern
(The largest, beneath the cerebellum near the foramen magnum)

4. Lumbar cistern
(Contains the cauda equina, lumbar puncture)

(Blumenfeld)
Microcirculation
a. Components of the blood-brain barrier
b. components of the blood-CSF barrier
c. Permeability of the ependymal cells for passage from brain parenchyma to cerebrospinal fluid
d. Passage from CSF to venous sinuses
e. Name some of the circumventricular organs where the blood-brain barrier is interrupted (5)
a. Mainly the tight junctions of the capillary endothelia.

(Most substances are dependent on active transport, facilitated diffusion, ion exchange, and ion channels.)

b. Mainly the choroid epithelial cells
(The capillary endothelial cells here are relatively permeable.)

c. High

d. By arachnoid villus cells via formation of giant vacuoles (large enough to engulf entire RBCs)

e.
1. Median eminence and neurohypophysis
(involved in regulation and release of pituitary hormones)
2. The area postrema\The chemotactic trigger zone
(Paired, located along the caudal wall of the fourth ventricle in the medulla, involved in detecting circulating toxins that cause vomiting)
3. The organum vasculosom of the lamina terminalis
(Senses osmolality and alters vasopressin secretion)

4. The subfornical organ
(Initiates drinking in response to ATII)

5. The pineal gland
(Involved in melatonin-related circadian rhythms.)
(Also the subcommissural organ, but its function is uncertain)

(Blumenfeld)
Headache
a. Which nerve innervates the pain receptors in the brain parenchyma
b. Which nerve innervates the supratentorial dura
c. Which nerve innervates the infratentorial dura
(Posterior cranial fossa)
d. Which structures in the brain are sensitive to pain (4)
e. What mechanisms for eliciting pain are headache caused by
a. There is no pain receptors in the brain parenchyma itself.

b. CN V

c. CN X mainly, also CN IX and C1-3

d.
1. Blood vessels
2. Meninges
3. Scalp
4. Skull

e.
1. Mechanical traction
2. Inflammation
3. Irritation of other structures in the head that are innervated

(Blumenfeld)
Differential diagnosis of headaches
a. Vascular headache
1. Migraine
2. Cluster headache

b. Tension headache

c. Other causes
1. Acute trauma
2. Intracranial hemorrhage
3. Cerebral infarct
4. Carotid or vertebral artery dissection
5. Venous sinus thrombosis
6. Post-ictal headache
7. Hydrocephalus
8. Pseudotumor cerebri\Idiopathic intracranial hypertension
(No mass lesions, obese adolescent females, acetazolamide is effective)
9. Low CSF pressure
(Worse while standing up)
10. Toixc or metabolic derangements
11. Meningitis
(Stiff neck, photophobia)
12. Epidural abscess
13. Vasculitis
(Temporal arteritis\Giant cell arteritis: elderly, temporal artery enlarged and firm, blood ESR, treated by steroids, also affect vessels supplying retina)
14. Trigeminal or occipital neuralgia
(Occipital neuralgia\Cervical tension syndrome\Posttraumatic neck syndrome)
15. Neoplasms
(-> increased ICP -> worse when lying down, such as during sleep)
16. Disorders of the eyes, ears, sinuses, teeth, joints, or scalp

(Blumenfeld)

Migraine
a. Pathophysiology of all vascular headaches (migraine and cluster headache)
b. Migraine - characteristics of prodromal symptoms\aura (4)
c. Characteristics of migraine (6)
a. Not fully understood, thought to involve inflammatory, autonomic, serotonergic, neuroendocrine, and other influences on blood vessel caliber in the head, leading to headache and the other associated symptoms.

b.
1. Visual blurring
2. Shimmering (glimmering)
3. Scintillating distortions (flashes)
4. Fortification scotoma
(A characteristic region of visual loss bordered by zigzagging lines resembling the walls of a fort)

c.
1. Genetic component (75% of patients have a positive family history)
2. Symptoms may be provoked by certain foods, stress, menstrual cycle, changes in sleep pattern..
3. The pain is often throbbing
4. Often exacerbated by light (photophobia), sound, (phonophobia), or sudden head movement
5. Duration - 30 min-24 hours
6. Frequency - several times per week to once every few years

(Blumenfeld)
Complicated migraine
Migraine accompanied by a variety of transient focal neurologic deficits, including sensory phenomena, motor deficits (ie. hemiplegia), visual loss, brainstem findings in basilar migraine, and impaired eye movements in ophthalmoplegic migraine.

(Blumenfeld)
Migraine
a. Treatment of acute migraine (5)
b. Preventive measures
a.
1. Resting in a dark, quiet room
2. NSAIDs
3. Anti-emetics
4. Triptans
(serotonin agonists: ie. sumatriptan)
5. Ergot derivatives
(<- fungus, ie. pergolide)

b.
1. Avoiding triggers
2. Beta-blockers
3. Topramiate
(Anticonvulsant)
4. Valproate
(Anticonvulsant)
5. Calcium channel blockers
(Ie. flunarizine)
6. Tricyclic antidepressants
(Ie. amitryptiline)
7. NSAIDs

(Blumenfeld)
Cluster-headache
a. Characteristics (5)
b. Associated symptoms
c. Treatment
a.
1. 1\10 as common as migraine
2. 5x more common in males
3. Clusters of headaches occurs from once to several times per day for a few weeks, and then disappears for a few months
4. Steady, burning sensation retroorbitally
5. 30-90 minutes

b.
1. Tearing
2. Eye redness
3. Horner's syndrome
4. Sweating
5. Nasal congestion

c. Similar as for migraine
(a. For acute attacks
1. Resting in a dark, quiet room
2. NSAIDs
3. Anti-emetics
4. Triptans
(serotonin agonists: ie. sumatriptan)
5. Ergot derivatives
(<- fungus, ie. pergolide)

b. Preventive means
1. Avoiding triggers
2. Beta-blockers
3. Topramiate
(Anticonvulsant)
4. Valproate
(Anticonvulsant)
5. Calcium channel blockers
(Ie. flunarizine)
6. Tricyclic antidepressants
(Ie. amitryptiline)
7. NSAIDs)

(In addition, inhaled oxygen is often effective in aborting attacks)

(Blumenfeld)
Tension-type headache
a. Characteristic
b. Cause
c. Treatment (4)
a.
1. Steady, dull ache, sometimes described as a bandlike sensation.
2. Can occur continuously for days to years
(Experienced by people without the disorder from time to time, but then lasting only up to a few hours.)
3. Associated with psychological stress

b. Not fully known, possibly related to excessive contraction of scalp and neck muscles.

c.
1. Muscle relaxation techniques
2. NSAIDs
3. Other analgesics
4. Tricyclic antidepressants

(Same type as seen in posttraumatic headaches)

(Blumenfeld)
Intracranial mass lesions
a. What
b. Can cause neurologic symptoms by .. (3)
c. How can the mass effect be seen on scans (2)
d. How can it cause focal symptoms, headache, vasogenic edema, hydrocephalus, hemorrhage, and infarction
a. Anything abnormal that occupies volume within the cranial vault
(Tumor, hemorrhage, edema, abscess, hydrocephalus..)

b.
1. Compression and destruction of adjacent regions of the brain
2. Increasing ICP
3. Herniation
(Displacement of central nervous structures into other compartments)

c. (Any distortion of nromal brain geometry due to a mass lesion)
1. Effacement of sulci and ventricles
2. Midline shift, best observed by position of the pineal calcifications
(Shift of the pineal calcification is a good indicator of how much the reticular formation is distorted at the midbrain-diencephalic junction. > 10 mm shift is usually associated with profound coma.)
(Often also cause edema which is seen as hypodense on CT, and obstruction of CSF flow in the contralateral half)
d.
Irritate meninges and vessels -> headache
Disrupt BBB -> vasogenic edema
Obstruction of CSF flow -> hydrocephalus
Erosion through blood vessels -> hemorrhage
Compression of blood vessels -> infarction

(Blumenfeld)
Dermatomes - which dermatome(s) cover
a. The clavicles
b. The lateral part of the upper limb
c. The medial sides of the upper limb
d. The thumb
e. The hand
f. The ring and little finger
a. C5

b. C5-7

c. C8-T1

d. C6

e. C6-8

f. C8

(Blumenfeld)
Dermatomes - which cover
a. The level of the nipples
b. The level of umbilicus
c. The inguinal groin regions
d. Anterior and inner surface of lower limb
e. Foot
f. medial side of great toe
g. Posterior and outer surface of lower limb
h. Lateral margin of foot and little toe
i. Perineum
Intracranial pressure (ICP)
a. Formula for cerebral perfusion pressure (CPP)
b. Signs and symptoms of elevated ICP (7)
c. Normal value
d. Why should not lumbar puncture be performed on a patient with suspected severe increased ICP
e. How can the ICP be measured (4)
a. Cerebral perfusion pressure (CPP) = Mean arterial pressure (MAP) - intracranial pressure (ICP)

b.
1. Headache
(Often worse in the morning, since brain edema increases overnight from the effects of gravity on a patient in the reclining position)

2. Altered mental status - especially irritability and depressed level of alertness and attention
(Often the most important indicator)

3. Nausea and vomiting
(Mechanism is not known)

4. Papilledema
(The elevated ICP is transmitted through the subarachnoid space to the optic nerve sheath, obstructing axonal transport and venous return in the optic nerve)
(Often not present in the acute setting, usually takes several hours to days to develop)

5. Visual loss
(Transient or permanent optic nerve injury associated with papilledema)
(Can include an increased blind spot, a concentric visual field deficit (peripheral margins, these fibers are located more superficially in the optic nerve and are therefore more susceptible to compression))

6. Diplopia
(<- Downward traction on CN VI causing uni- or bilateral abducens nerve palsies)

7. Cushing's triad - hypertension, bradycardia, irregular respirations
(Respirations are caused by impaired brainstem function)
(However, hypotension and tachycardia can also be seen in increased ICP)

c. < 15 mmHg (torr)\20 mmH2O

d. It can precipitate herniation.

e.
1. During lumbar puncture
2. Ventricular drain
3. Intraparenchymal monitor
4. Subarachnoid bold

(Blumenfeld)
Elevated intracranial pressure - treatment strategies and their mechanisms (7)
1. Elevate head of bed to 30 degrees, and maintain head straight (avoid obstructing jugular venous return) -> promote venous drainage
(Immediate effect)

2. Intubate and hyperventilate to pCO2 of 25-30 mmHg -> cerebral vasoconstriction
(Effect within 30 seconds)

3. IV mannitol or hypertonic saline -> promote removal of edema from CNS while maintaining cerebral perfusion
(IV mannitol: 1 g\kg bolus, then 0.25 g\kg every 6 hours.
Hypertonic saline: aim for serum Na > 138 mM and osmolarity 300-310 mM, while maintaining normal volume status and normal blood pressure. Furosemide may also be added.)
(Effect within 5 minutes)

4. Ventricular drainge -> removal of CSF decreases intracranial pressure
(Effect within minutes)

5. Barbiturate-induced coma -> cerebral vasoconstriction and reduced metabolic demands
(Effect within 1 hour)
(If other measures fail)

6. Craniotomy
(Use Borr holes and remove saw to remove bone flap, or simply borr holes)

7. Steroids -> reduces cerebral edema
(Possibly by strengthening the BBB, not shown to improve outcome in acute head trauma, stroke, or hemorrhage. More often used with brain tumors)
(Takes hours for the effect to take place)

(Blumenfeld)
Epiphenomenon
A symptom appearing during the course of a disease, not of usual occurrence, and not necessarily associated with the disease.

(Blumenfeld)
The three most clinically important herniation syndromes
1. Transtentorial herniation\Tentorial herniation

2. Central herniation

3. Subfalcine herniation
(Herniation under the falx cerebri)

(Blumenfeld)
Transtentorial herniation
a. Which structure herniates, through what
b. Cause
c. Clinical triad
a. The medial temporal lobe, especially the uncus (-> uncal herniation)
The tentorial notch\incisura
(-> Duret-Bernard hemorrhage: small brainstem hemorrhage resulting from brainstem distortion secondary to transtentorial herniation.)

b. Caused by supratentorial mass lesions.
(Large mass lesions in the posterior fossa can cause upward transtentorial herniation)

c. Clinical triad of
1. Blown pupil
(Compression of CN III, ipsilateral in 85% of the cases in uncal herniation, first dilated, unresponsive pupil, and later impairment of eye movements.)

2. Hemiplegia
(Compression of the cerebral peduncles)
(Can be contra- or ipsilateral, most often contralateral <- the corticospinal tract don't decussate before medulla. Ipsilateral hemiplegia is called Kernohan's phenomenon (midbrain is pushed all the way over until it is compressed by the opposite side of the tentorial notch)

3. Coma
(Distortion of midbrain reticular formation, compression of the posterior cerebral arteries)
Central herniation
a. What
b. Cause
c. Effect, signs and symptoms
a. Central downward displacement of the brainstem.

b. Can be caused by any lesion associated with elevated ICP
(Hydrocephalus, diffuse cerebral edema)

c.
1. Central herniation through the tentorial opening -> bilateral uncal herniation (plegia, blown pupil, coma)
2. Herniation of cerebellar tonsils down foramen magnum (tonsillar herniation) -> cmopression of the medulla -> respiratory arrest, blood pressure instability, death
(Controversy over whether central herniation is seen only as a postmortem phenomenon)

(Blumenfeld)
Subfalcine herniation
b. What
b. Effect, signs, and symptoms
a. Displacement of cingulate gyrus and other brain structures under the falx cerebri as a result of unilateral mass lesions.

b. One or both anterior cerebral arteries can be occluded under the falx -> infarcts in the anterior cerebral territory

(Blumenfeld)
Head trauma
a. Concussion
b. Signs and symptoms of concussion (5)
c. Postconcussive syndrom
a. Reversible impairment of neurologic function for a period of minutes to hours following a head injury.
(Unknown mechanism, may involve transient diffuse neuronal dysfunction)
(Normal CT and MRI scans)

b.
1. LOC
2. "Seeing stars"
3. Headache
3. Dizziness
4. Nausea and vomiting
5. Anterograde and retrograde amnesia
(For a period of several hours surrounding the injury)

c. Can develop even after relatively minor trauma. Symptoms include
1. Headaches
2. Lethargy
3. Mental dullness

(Blumenfeld)
Head trauma - severe trauma can cause permanent injury to the brain through the following mechanisms (6)
1. Diffuse axonal shear injury
(Cause widespread or patchy damage to the white matter and cranial nerves)

2. Petechial hemorrhages in the white matter

3. Larger intracranial hemorrhages

4. Cerebral contusion
(a bruising, usually of the surface, of the brain with extravasation of blood but without rupture of the pia-arachnoid; healing results in a superficial depressed sclerotic area, possibly with incorporated meninges)

5. Penetrating trauma

6. Cereberal edema
(With or without other injuries)

(Blumenfeld)
Intracranial classification
a. Broad classification
b. Types
a. Traumatic and atraumatic.

b.
1. Epidural hematoma (EDH)
2. Subdural hematoma (SDH)
3. Subarachnoid hematoma (SAH)
4. Intracerebral or intraparenchymal hemorrhage (ICH)

(Parenchyma: the distinguishing or specific cells of a gland or organ, contained in and supported by the connective tissue framework, the stroma)

(Blumenfeld)
Epidural hematoma
a. Location
b. Usual cause
c. Radiological appearance
d. Clinical features (3)
a. In the tight potential space between the dura and the skull.

b. Rupture of the middle meningeal artery due to fracture of the temporal bone by head trauma

c. Lens-shaped biconvex hematoma
(Often don't spread past the cranial sutures where the dura is tightly apposed to the skull. The arterial pressure peels the dura away from the inner surface of the skull.)

d.
1. Lucid interval
2. Compress brain tissue
3. Elevated ICP -> herniation
Chronic subdural hematoma
a. Location
b. Usual cause
c. Radiologic appearance
d. Signs and symptoms (4)
a. In the potential space between the dura and the loosely adherent arachnoid.

b. Rupture of the bridging veins. Often seen in elderly patients, in whom atrophy allows the brain to move more freely within the cranial vault, thus making the bridging veins more susceptible to shear injury. Can be seen with no or minimal trauma.
(Veins which drain the underlying neural tissue and puncture the dura mater and empty into the dural sinuses)
(These are particularly vulnerable to shear injury as the cross from the arachnoid into the dura)

c. Crescent-shaped appearance
(Venous blood dissects ('separates') relatively easily between the dura and the arachnoid, and thus spread out over a large area)

d.
1. Headache
2. Cognitive impairment
3. Unsteady gait
4. Focal dysfunction of the underlying cortex may result in focal neurologic deficits and seizures

(The vague symptoms are due to the slow flow of the venous blood (over weeks to months), this allows the brain to accommodate and partially compensate for the lesion)

(Blumenfeld)
Acute subdural hematoma
a. Location
b. Usual cause
c. Radiologic appearance
a. In the potential space between the dura and the loosely adherent arachnoid.

b. Rupture of the bridging vein due to high-energy trauma.
(-> Often co-occur with other serious injuries such subarachnoid hemorrhage and brain contusion)
(Worse prognosis than with epidural hematoma)

c. Crescent-shaped and spread over a large area
(The arachnoid is loosely adherent to the dura and allow the venous blood to dissect easily)
Density depends on the age of the blood
1. Hyperdense - acute blood
2. Isodense - 1-2 weeks
(Clot begin to liquefy)
3. Hypodense - 3-4 weeks, hematoma is completely liquefied
4. Mixed density due to liquefied chronic blood mixed with clotted hyperdense blood
(Sometimes you get an hematocrit effect - the denser acute blood settles to the bottom)

(Blumenfeld)
Aneurysm
a. What is a saccular\berry aneurysm
b. What is the most common locations for it (4)
c. What is a fusiform aneurysm
d. What is the most common locations for it
e. Treatment (2)
a. Balloon-like outpouchings of the vessel wall that typically have a neck connected to the parent vessel and a fragile dome that can rupture.

b.
1. Anterior communicating artery (30%)
2. Posterior communicating artery
(25%)
(-> CN III palsy by compression
3. Middle cerebral artery
(20%)
4. Different locations in the vertebrobasilar system
(15%, PICA, AICA, SCA)

c. An elongated spindle-shaped dilation of an artery. Less prone to rupture than saccular aneurysms.

d. The main vessels - internal carotid artery, basilar artery

e.
1. Hypertension and situations causing sudden elevation in blood pressure
2. Cigarette smoking
3. Alcohol consumption

e.
1. Neurosurgical placement of a clip across the neck of the aneurysm
2. Interventional neuroradioloy to place a stent
(The choice of 1 or 2 depend on size, shape, and location of the aneurysm, and the patient's overall condition)

(Blumenfeld)
Traumatic subarachnoid hemorrhage
a. Cause
b. Signs and symptoms
c. Radiological appearance
a. Bleeding into the CSF from damaged blood vessels associated with cerebral contusions and other traumatic injuries.
(More common than spontaneous subarachnoid hemorrhages)

b.
1. Severe headache
(<- meningeal irritation by the blood in the CSF)
2. Focal neurologic deficits are usually associated with other concomitant cerebral injuries.
3. Meningeal irritation - nuchal rigidity, photophobia
4. Vasospasm is not usually seen

c. Crescent-shaped hematoma
(acute -> hyperdense)
(Venous blood dissects relatively easily between the dura and the arachnoid due to their loose adherence to each other)

(Blumenfeld)
Traumatic intracerebral or intraparenchymal hemorrhage (Contusion)
a. Location
a. Within the brain parenchyma in the cerebral hemispheres, the brainstem, the cerebellum, or the spinal cord.
Occur especially where the cortical gyri abut the ridges of the bony skull -> frontal and temporal poles.
Coup and countrecoup injury.
(Rebound of the brain against the skull.)

(Severe injuries often are accompanied by a combination of contusion, subarachnoid hemorrhage, and subdural hemorrhage.)

(Blumenfeld)
Nontraumatic intracerebral or intraparenchymal hemorrhage
a. Causes (9)
b. What causes lipohyalinosis and microaneurysms of Charcot-Bouchard\Miliary aneurysms
c. What are the most common locations for hypertensive hemorrhage, in decreasing order (4)
d. What explains the clinical worsening which peaks after 3 days
a.
1. Hypertensive hemorrhage
(Most common type, tend to involve small, penetrating blood vessels - 'Lipohyalinosis'. Lacunar infarcts are a result of lipohyalinosis and atherosclerosis)
2. Brain tumors
3. Secondary hemorrhage after ischemic infarction
4. Vascular malformations
5. Blood coagulation abnormalities
6. Infections
7. Vessel fragility caused by deposition of amyloid protein in the blood vessel wall (amyloid angiopathy)
(Most common cause of lobar hemorrhage (occipital, parietal, temporal, frontal))
(Recurrent and multiple, in elderly, smaller, TIA)
8. Vasculitis
9. Mycotic (infectious) aneurysms in the setting of endocarditis

b. Hypertensive hemorrhage
(Lipohyalinosis is small vessel disease in the brain. Hypertension is a strong causative factor. So called deep perforating arteries, relatively small arteries branching off of relatively large arteries are especially prone)
(Miliary aneurysms - dilation in the diameter of small arteries and arterioles secondary to lipohyalinosis from long-standing hypertension, associated with intracerebral hematomas. (Resembling a millet seed (2mm)).

c.
1. Basal ganglia
(Usually the putamen)
2. Thalamus
3. Cerebellum
4. Pons

d.
1. Continued enlargement of the hematoma
2. Edema

(Low risk of rebleeding, unlike aneurysmal hemorrhage)
Vascular malformations
1. Arteriovenous malformations (AVMs)
(Congenital, abnormal direct connection between artery and vein, seen as flow voids on MRI (the absence of signal from blood whose activated protons leave a region before their magnetization is measured.), from cm to half the brain, seizure, migraine-like headaches, 1-4% risk of bleeding per year, usually intraparenchymal)
(Treatment by neurosurgical removal, intravascular embolization, and stereotactic radiosurgery)

2. Cavernomas\Cavernous hemangiomas\Cavernous angiomas\Cavernous malformations
(Abnormally dilated vascular cavities lined by only one layer of vascular endothelium)
(Not visible on angiography, only on MRI. Dark brim of T2-weighted sequence due to hemosiderin)
(Seizures)
(0.1-2.7% risk of hemorrhage per year)

3. Capillary telangiectasias\Capillary angiomas
(Small regions of abnormally dilated capillaries, visible on MRI as a single flow void, not known to cause any clinical symptoms themselves, but are associated with cavernomas)

4. Developmental venous anomalies\Venous angiomas\Venous malformations

(1 & 2 have high likelihood of causing intracerebral hemorrhage.)
Extracranial hemorrhage
a. Battle's sign
b. Hemotympanum
c. Subgalaeal hemorrhage\'Goose egg'
d. Cephalohematoma
a. Hemorrhage in subcutaneous retroauricular tissue.
(Racoon eyes when its located around the eyes)

b. Hemorrhage in the inner ear.

c. Hemorrhage in the loose space between the external periosteum and galea aponeurotica.

d. In newborns during delivery, between the skull and external periosteum (pericranium).

(Blumenfeld)
Hydrocephalus
a. Causes (3)
b. Communicating and noncommunicating hydrocephalus
c. Signs and symptoms (9)
d. Treatment (3)
a.
1. excess CSF production
(Rare, seen in choroid plexus papilloma)
2. Obstruction of flow
(Common, <- tumors, intraparenchymal hemorrhage, congenital malformations. Most common at narrow points such as foramen of Monroe, Cerebral aqueduct and the fourth ventricle)
(<- Adhesion from prioer hemorrhage, infection, or inflammation)

3. Decrease in reabsorption via the arachnoid granulations
(Often difficult to distinguish from obstruction of CSF flow in the subarachnoid space, can have similar causes (prior hemorrhage, infection, inflammation.)

b.
1. Communicating hydrocephalus
Impaired CSF reabsorption in the arachnoid granulations, obstruction of flow in the subarachnoid space, or by excess CSF production.

2. Noncommunicating hydrocephalus
Caused by obstruction of flow within the ventricular system.

c.
From increased ICP
1. Headache
2. Nausea and vomiting
3. Cognitive impairment
4. Decreased level of consciousness
5. Papilledema
6. Decreased vision
7. Sixth nerve palsies
(Major sign in slowly developing hydrocephalus, with severe hydrocephalus, inward deviation may be seen on both eyes)

8. Magnetic gait and incontinence
(Ventricular dilation -> compress descending white matter pathways from the frontal lobe)
9. Parinaud's syndrome
(<- dilation of the supraprineal recess of the posterior third ventricle compress the collicular plate of the midbrain)
(Bilateral deviation of the eyes, downward and inward. Limited vertical gaze, especially superiorly)

d.
1. Ventriculostomy\External ventricular drain
2. Ventriculoperitoneal shunt
(<- Lateral ventricle)
3. Endoscopic neurosurgery
(Via cranium or spine)
(Vs obstructive hydrocephalus and intraventricular mass lesions)

(Blumenfeld)
Hydrocephalus
a. Normal pressure hydrocephalus
b. Hydrocephalus ex vacuo
a. Commonly seen in elderly. Chronically dilated ventricles. Clinical triad of gait difficulties, urinary incontinence, and mental decline.
(Some studies have shown pressure elevations to occur only intermittently)
(Thought to be due to impaired reabsorption at the arachnoid villi)
(Some patients benefit after ventriculoperitoneal shunting)

b. Descriptive term for hydrocephalus (excess CSF) in a region where brain tissue was lost as a result of stroke, surgery, atrophy, trauma, or other insult.

(Blumenfeld)
Brain tumors
a. What are most common of primary and metastatic brain tumors
b. Are most supratentorial or infratentorial
c. Most common pediatric brain tumors (3)
a. Metastases are 5-10 times more common than all primary CNS tumors combined.

b.
Adults - most supratentorial
(70% supratentorial and 30% infratentorial)
Children - opposite
(30%, 70%)
(Their location make them prone to cause hydrocephalus by compressing the cerebral aqueduct of Sylvius)

c.
1. Cerebellar astrocytoma
(Astrocytoma grade I, often cured by surgical resection)
(< 10 years 90% of the time)
2. Medulloblastoma
(2-20 years)
3. Ependyoma

(Blumenfeld)

Primary brain tumors - which are most common, in descending order
1. Glioma (33%)
a. Glioblastoma multiforme\Astrocytoma grade IV (20%)
b. Astrocytoma grades I and II (5%)
c. Astrocytoma grade III (3%)
(WHO grading system according to degree of malignancy, IV is worst)
(And oligodendroglioma, ependyoma..)

2. Meningioma (33%)
(<- Arachnoid villus cells)
(Most common in 1. Lateral convexities, in the falx, along the basal regions)

3. Pituitary adenoma (12%)
(Endocrine disturbances and bitemporal visual field defect)
(Other lesions in this area: meningioma, craniopharyngioma (<- Rathke's pouch), hypothalamic glioma)
(-> Dopaminergic agonists, transshepnoidal resection)

4. Schwannoma (9%)
(Most common on CN VIII)

5. Lymphoma (3%)
(HIV, B lymphocytes, ventricles -> lumbar puncture diagnosis)

6. Embryonal\Primitive\Medulloblastoma (1%)

(Blumenfeld)
Brain tumors
a. Signs and symptoms (3)
b. Treatment (4)
a. (Size, location, rate of growth)
1. Headache and other signs of elevated ICP
2. Seizures
(The tumors most associated with seizures are low-grade gliomas and meningiomas)
3. Focal symptoms and signs

b.
1. Surgical excision
(> 90% should be removed to have a positive effect on the outcome)
2. Chemotherapy
3. Radiotherapy
4. Steroids
(To reduce edema and swelling)

(Unlike systemically, a malignant primary CNS tumor usually don't metastasize outside the CNS, and a benign primary CNS tumor can be lethal by being in a inoperable location and compressing on vital structures.)

(Blumenfeld)
Brain tumors
a. The three most common metastases in descending order
b. Tumors with high tendency to cause hemorrhage, which is the most common cause of hemorrhage
c. Which tumors most often cause pareneoplastic syndromes related to the nervous system, effects
1. Lung carcinoma
2. Breast carcinoma
3. Melanoma

b. Melanoma, renal cell carcinoma, thyroid carcinoma, and choriocarcinoma.

Lung carcinoma due to its prevalence.

c. Small cell lung carcinoma, breast cancer, and ovarian cancer.
->
1. Impaired neuromuscular transmission (Lambert-Eaton syndrome)(<- small cell lung carcincoma)
2. Opsoclonus myoclonus (irregualr jerking movements of the eyes and limbs) (Opsoclonus: opsos: eye, klonus)
3. Cerbellar Purkinje cell loss

(Blumenfeld)
Infectious meningitis
a. What
b. Signs and symptoms (5)
a. Infection of the CSF in the subarachnoid space.

b. Meningeal irritation\Meningismus
1. Headache
2. Lethargy
3. Photophobia and phonophobia
4. Fever
5. Nuchal rigidity - unable to touch chin to chest
(Kernig's sign: pain in hamstrings when knees are straightened hips flexed)
(Brudzinski's sign: flexion at neck causes hips to flex)

(Also seen in SAH, carcinomatous meningitis, and chemical meningitis)

c.
Cerebrospinal fluid profiles
a. Normal values - white blood cells\mm3, protein, glucose
b. How is these changed in acute bacterial meningitis
c. How is these changed in viral meningitis or "aspectic" meningitis
a. < 10 lymphocytes, 15-45 mg\dl protein, 50-100 mg\dl glucose
(Expect 1 additional white blood cell for every 700 red blood cells in cause of traumatic lumbar puncture)

b.
1. Massive Increase in white blood cells
(100-5000, usually polymorphonuclear leukocytes
2. Massive increase in protein
(100-1000 mg\dl)
3. decrease in glucose
(< 40 mg\dl, < 50% of serum value in patients with hyperglycemia)

c.
1. Increased white blood cells
(10-300, usually lymphocytes)
2. Increased protein
(50-100 mg\dl)
3. Normal glucose
(Occasionally reduced in herpes, mumps, and lymphocytic choriomeningitis virus)

(Blumenfeld)
Bacterial meningitis - common pathogens and treatment based on age
a. Birth to 1 month (3)
b. 1-3 months (6)
c. 3 months to 7 years (3)
d. 7 years to adult (3)
a. Birth to 1 month
1. Escherichia coli
2. Group B, D streptococcus
3. Listeria

-> Ampicillin (penicillin) and Ceftriaxone (3rd generation cephalosprorin)

b. 1-3 months
1. Escherichia coli
2. Group B, D streptococcus
3. Listeria
4. Haemophilus influenzae
5. Neisseria meningitidis
6. Streptococcus pneumoniae
-> Ampicillin and ceftriaxone
(1-3 is same as birth to one month)

c. 3 months to 7 years
1. Haemophilus influenzae
2. Neisseria meningitidis
3. Streptococcus pneumoniae
-> Ceftriaxone

d. 7 years to adult
1. Neisseria meningitidis
2. Streptococcus pneumoniae
3. Listeria
-> Ceftriaxone and ampicillin

(Blumenfeld)
Bacterial meningitis
a. Signs and symptoms (6)
a.
1. seizures
2. Cranial neuropathies
3. Cerebral edema
4. Hydrocephalus
5. Herniation
6. Cerebral infarcts

(Blumenfeld)
Brain abscess
a. What
b. Signs and symptoms (7)

c. Pathogens (5)
a. Bacterial (or parasitic) infection of the nervous system, which presents as an expanding intracranial mass lesion, much like a brain tumor, but often with a more rapid course

b.
1. Headache
2. Fever
(absent in 40% of cases)
3. Lethargy
4. Nuchal rigidity
5. Nasuea and vomiting
6. seizures
7. Focal signs

(Peripheral white blood cell count is normal in 20% of cases)

c.
Bacterial
1. Streptococci
2. Bacteroides
3. Enterobacteriaceae
4. Staphylococcus areus

Parasite
5. Toxoplasmosis gondii (HIV)

(Blumenfeld)
Differential diagnosis of lymphocyte-predminant or aseptic meningitis (18)
1. Viral infections
(Ie HIV)
2. Partially treated bacterial meningitis
3. Tuberculous meningitis
4. Fungal meningitis
(Ie. cryptococcal)
5. Parameningeal infection
(Ie. epidural abscess)
6. Postinfectious encephalomyelitis
7. Postvaccination encephalomyelitis
8. Myelitis
9. Lyme disease
10. Neurosyphilis (spirochetal,<- treponema pallidum)
11. Parasitic infections
(Eosinophils may also be present)
12. Carcinomatous (or other neoplastic) meningitis
13. Central nervous system vasculitis
14. Sarcoidosis
15. Venous sinus thrombosis
16. SAH several days previously
17. Drug reaction
18. Chemical reaction
(Ie. from contrast material injected in CSF)

(Blumenfeld)
Neurosyphilis
a. What
b. Signs and symptoms (4)
c. Diagnosis (3)
a. Tertiary syphilis (primary and secondary are primary cutaneous) from the spirochete treponema pallidum, occur 4-15 years after infection.

b.
1. Meningovascular syphilis -> general paresis, dementia, behavioral changes, delusions of grandeur, psychosis, diffuse UMN lesions
(Inflammation of medium-sized vessels -> infarction)
2. Tabes dorsalis -> sensory loss, sensory ataxia, high-stepping tabetic gait, incontinence
(Involvement of the spinal cord dorsal roots, especially in the dorsal columns)
3. Argyll Robertson pupils
4. Optic atrophy

c.
1. Blood tests for treponemes (FTA-ABS, MHA-TP)
2. Lymphocyte-predominant findings in the CSF
3. Usually positive VDRL
(a flocculation ('precipitation') test for syphilis, using cardiolipin-lecithin-cholesterol antigen as developed by the Venereal Disease Research Laboratory of the United States Public Health Service)

(Treated by IV penicillin G)

(Blumenfeld)
Lyme disease
a. <-
b. Signs and symptoms
a. Infection of the spirochete Borrelia burgdorferi carried by the Ixodes species of the deer tick
(Endemic in certain areas of US, Europe, and Australia)

b.
1. Erythema chronicum migrans
(Often heralded by this sign, it gradually shifts location and enlarges over days to weeks)
2. Lymphocyte-predomiant meningitis
3. Mild meningoencephalitis -> meningeal signs, emotional changes, impaired memory and concentration
4. Cranial neuropathies - especially Bells palsy
5. Peripheral neuropathies
(Other systemic signs include arthritis and cardiac conduction abnormalities)

(Blumenfeld)
Viral meningoencephalitis
a. Most common pathogen
b. Signs and symptoms (10)
c. Treatment
a.
1. Herpes simplex virus type 1
(Tropism for limbic cortex)

b.
1. Bizarre psychotic behavior
(Tropism for limbic cortex)
2. Confusion
3. Lethargy
4. Headache
5. Fever
6. meningeal sings
7. Seizures
8. Focal signs
(Anosmia, hemiparesis, memory loss, aphasia, aphasia)
9. Period sharp waves seen over both temporal waves on EEG
10. Elevated lymphocytic or mixed lymphocytic-polymorphonuclear predominance with elevated protein and normal glucose
(Untreated it cause necrosis of unilateral or bilateral temporal and frontal structures ->-(days)-> coma and death)

c. Acyclovir

(Identified by PCR)

(Blumenfeld)
Virus
a. Measles can cause
b. Herpes zoster can cause
c. Transverse myelitis can be caused by
d. HTLV-1 (Human T-cell lymphoma virus) can cause
a. Subacute sclerosing panencephalitis
(Slowly progressive fatal encephalitis)

b. Painful rash conforming to nerve root distributions.

c. Enteroviruses (coxsackie, poliomyelitis), varicella-zoster virus, HIV, EBV, CMV

d. HTLV-1 associated myelopathy\Tropical spastic paraparesis
(Chronic type of spinal cord disease, paraparesis is weakness affecting the lower extremities)

(Blumenfeld)
HIV-associated disorders of the nervous system (7)
1. HIV-associated neurocognitive disorder (HAND)
(Dementia..., improved by HAART)

2. Encephalitis caused by HSV and VZV and CMV (<- retinitis can be treated by ganciclovir)

3. Progressive multifocal leukoencephalopathy (PML)
(<- JC virus (papova), -> gradual demyelination (T2 bright white matter abnormalities), especially in posterior regions, JC virus is also associated with cerbellar atrophy caused by granule cell neuronopathy)

4. Bacterial infections - tuberculous meningitis, neurosyphlis

5. Fungal infections - Cryptococcal meningitis
(Very common, should be suspected in all HIV-positive patients with chronic headache, india ink, antigen, treated by IV amphotericin B followed by oral fluconazole)

6. Parasitic infections - Toxoplasmosis (toxoplasmosis gondii)
(Cysts in cat feces or undercooked meat, form brain abscesses with ring-enhancing lesions visible on MRI, mass effect by edema (most common cause of mass lesions in HIV patients), PCR of CSF, treateed with epyrimethamine and sulfadiazine)

7. Primary CNS lymphoma
(Second most common cause of intracranial mass lesions on HIV patients)

(Rarely Kaposi's sarcoma can metastasize to the CNS)

(Blumenfeld)
Prion-related illness
a. Types (4)
b. Signs and symptoms
c. Diagnosis (3)
a.
1. Creutzfeldt-Jakob disease
(Most common, 1 new case\million\year)
2. Gerstmann-Straussler-Scheinker disease
3. Kuru
4. Familial fatal insomnia
(Can be transmitted by infection or genetic)

b. Rapidly progressing
1. Dementia
2. Myoclonus
3. Visual disturbances
4. Ataxia

c.
1. Periodic sharp wave complexes in EEG
2. Increased 14-3-3 protein in CSF
3. Increased signal in the basal ganglia and cortical ribbon (on DWI) on MRI

(Death usually ensues after 6 to 12 months, incubation period from 2-25 years)

(Blumenfeld)
Lumbar puncture
a. What structure is the CSF tapped from
b. Where does the conus medullaris end
c. Where is the spina needle inserted, what serves as the landmark
d. Normal values
e. Red blood cells in the CSF indicate
a. The lumbar cistern

b. < 15 mmHg
(When the patient is lying down, hydrostatic pressure adds to it when the patient is standing)

b. L1-L2

c. Between the L4 or L5 vertebral bones. The posterior iliac crest serves as a landmark to determine the approximate level of the L4-L5 interspace.

d.
1. White blood cells: < 5-10\mm3, lymphocytes only
(If traumatic lumbar puncture, expect 1 additional white blood cell for every 700 red blood cells)

e.
1. Subarachnoid hemorrhage
2. Hemorrhagic herpes encephalitis
3. Traumatic tap
(With a traumatic tap the number of red blood cells usually decreases from the first to last tubes of CSF collected, if the CSF is centrifuged, the supernatant may have a yellowish\xanthochromic appearance as a result of hemolysis if hemorrhage occurred several hours previously, but no xanthochromia should be present in a traumatic tap if the CSF is centrifugated immediately after collection)
2. protein: 15-45 mg\dl
3. Glucose: 50-100 mg\dl

(Blumenfeld)
Craniotomy
a. Which access is used for surgery on anterior circulation and basilar tip aneurysms, the cavernous sinus, and suprasellar tumors

b. Which access is used to resect temporal lobe seizure foci and for decompression of most intracranial hematomas in head trauma
c. Which access is used to operate on frontal lobe lesions such as tumors
d. Which access is used to operate on posterior fossa structures such as the cerebellopontine angle, vertebral artery, brainstem, and lower cranial nerves
e. Which access is used to reach the pituitary gland
a. Pterional craniotomy.
(Via pterion - the region where frontal, parietal, temporal, and sphenoid bones meet. -> Inferior frontotemporal lobes)

b. Temporal craniotomy.

c. Frontal craniotomy.

d. Suboccipital craniotomy.

e. The transsphenoidal approach via the nasal passsages.

(Blumenfeld)
Contusion
Any mechanical injury (usually caused by a blow) resulting in hemorrhage beneath unbroken skin.

(Stedman)
Contusion
a. Which parts of the cortex is especially susceptible to contusion
b. Why
a. The frontal and temporal poles.

b. Due to their virtue of abutting the bony ridges of the anterior and middle cranial fossae.

(Blumenfeld)
Pineal region tumors
a. Variants (2\4)
b. Effect, signs, and symptoms
a.
1. Pinealomas
a. Pineocytoma
b. Pineoblastoma (\Primitive neuroectodermal tumor (PNET))
2. Germinoma
(Rarely
3. Teratoma
4. Glioma)

b.
1. Obstruct the cerebral aqueduct -> hydrocephalus
2. Compress the dorsal midbrain -> Parinaud's syndrome

(Blumenfeld)
The clinical triad of shuffling "magnetic" gait, incontinence and mental decline suggest
Normal pressure hydrocephalus.

(Blumenfeld)
Cerebrospinal fluid
a. Total amount
a. Amount produced per hour
a. 150 ml

b. 20 ml\hour (500 ml\day)

(Blumenfeld)
The interventricular foramen of Monro - borders
1. Medially and superiorly by fornix

2. Laterally by the thalami

3. Inferiorly by the anterior commissure

(Blumenfeld)
The third ventricle - borders
1. Laterally by the thalami and hypthalamus.

2. Superiorly by the fornix.

3. Inferiorly by the hypothalamus.

4. Anteriorly by the anterior comissure, fornix, lamina terminalis, and hypothalamus

5. Posteriorly by the posterior commissure, pineal region, and hypothalamus.

(Blumenfeld)
Somatotopic organization
a. What
b. Examples (2)
c. Mnemonic for remembering the somatotopic representation along the motor and sensory pathways
a. Adjacent regions on the cortex corresponds to adjacent areas on the body surface.

b. Motor homunculus and sensory homunculus in the primary motor cortex and primary sensory cortex, respectively.
(The somatotopic organization is not confined to the cortex, it extends along the entire motor and sensory pathways.)

c. The arms are medial to the legs with two exceptions: the sensorimotor cortices and the posterior columns.

(Blumenfeld)
Spinal cord - Rexed's laminae I-X, their synonym, and their region
Dorsal horn
1. Rexed's laminae I = Marginal zone
2. Rexed's laminae II = Substantia gelatinosa
3. Rexed's laminae III, IV = Nucleus proprius
4. Rexed's laminae V = Neck of dorsal horn
5. Rexed's laminae VI = Base of dorsal horn

Intermediate zone
6. Rexed's laminae VII = Clarke's nucleus, intermediolateral nucleus

Ventral horn
7. Rexed's laminae VIII = Commissural nucleus
8. Rexed's laminae IX = Motor nuclei
(Medial and lateral motor nuclei)

Gray matter surrounding central canal
9. Rexed's laminae X = Grisea ('gray') centralis
Spinal cord
a. Level of cervical enlargement (Intumescentia cervicalis)
b. Level of lumbosacral enlargement (Intumescentia lumbosacralis)
a. C3-T1

b. L1-S2

(Blumenfeld)
What is the two special characteristics of the spinal cord at the thoracic level
1. Lateral horn of the gray matter which contains the intermediolateral cell column with the preganglionic sympathetic neurons.
(Similar lateral motor nuclei in cervical and sacrolumbar enlargements for limb muscles)

2. Nucleus dorsalis of Clark\Posterior thoracic nucleus
A column of large neurons located in the intermediate zone\Rexed's laminae VII of the gray column. It gives rise to the spinocerebellar tract of the same side. Extends from T1 to L2.

(Stedman, Blumenfeld)
Spinal cord
a. Which artery provides the major blood supply to the lumbar and sacral cord
b. Where does this artery arise from
c. Where is the vulnerable zone, in terms of perfusion
d. What part of the spinal cord does the anterior spinal artery supply, what about the posterior spinal arteries
e. Venous return from the spinal cord occurs initially via drainage into the
a. Great radicular artery of Adamkiewicz.

b. From T5-L3, usually between T9-T12.

c. The mid-thoracic region (T4-T8), because it lies between the lumbar and vertebral arterial supply.
(Susceptible to infarction during thoracic surgery or other conditions causing decreased perfusion.)

d. Anterior spinal artery supplies the anterior 2\3 of the spinal cord - the anterior horns and the lateral white matter. The posterior spinal arteries supply the posterior columns and part of the posterior horns.

e. Batson's plexus of epidural veins
(Don't contain valves -> increased intra-abdominal pressure can cause reflux of blood carrying metastatic ie. prostatic cancer cells to the epidural space.)

(Blumenfeld)
Apraxia
A condition characterized by a deficit in higher-order motor planning and execution despite normal strength.

(Blumenfeld)
Motor systems
a. How is the basal ganglia involved in the motor pathways
b. How is the cerebellum involved in the motor pathways
a. The basal ganglia forms a feedback loop by receiving input from the motor cortex and relaying it back to it via the thalamus. It also projects to the brainstem which have connections with the spinal cord.

b. Like the basal ganglia the cerebellum receives input from the cerebral cortex via the pons, and then relays it back via the thalamus to form a feedback loop. It also projects to the brainstem which have connections with the spinal cord.

(Blumenfeld)
Motor systems
a. What is the location and projection of the lateral motor system
b. What is the members of the lateral motor system (2)
c. What is the location and projection of the medial motor system
d. What is the members of the medial motor system (4)
a. Travel in the lateral columns on the spinal cord and synapse on the more lateral group of the ventral horn motor neurons and interneurons with the anterior horn cells for distal muscles of the extremities.

b.
1. The lateral corticospinal tract
(Rapid, dextrous movements at individual digits or joints)
2. The Rubrospinal tract
(Descend contralaterally)

c. The medial motor system travel in the anteromedial spinal cord columns to synapse on medial ventral horn motor neurons and interneurons, which contain anterior horn cells mainly for proximal trunk muscles.

d.
1. The anterior corticospinal tract
2. The vestibulospinal tract
3. The reticulospinal tract
4. The tectospinal tract
(Tend to terminate on interneurons that project to both sides of the spinal cord, controlling movements that involve multiple bilateral spinal segments)
(Proximal axial and girdle muscles involved in postural tone, balance, orienting movements of the head and neck, and automatic gait-related movements.)
(Decsend ipsi- or bilaterally)

(Blumenfeld)
Lateral corticospinal tract of lateral motor system
a. Site of origin
b. Pathway
c. Levels of termination
a. Primary motor cortex (#4)(>50%) and other frontal (premotor and supplementary motor cortex, #6) and parietal areas (#3,1,2,5,7).
(Pyramidal cells in cortical layer 5 of primary motor cortex, 3% is giant pyramidal cells called Betz cells)

b.
1. a. -> Corona radiata
(Upper portion of the cerebral white matter)
2. Posterior limb of internal capsule ->
3. Basis pedunculi of midbrain ->
(The base of the midbrain consisting of the cerebral peduncles and the substantia nigra)
3. Basis pontis\Basilar part of pons ->
(The large bulbous portion of the pons seen on the ventral portion of the brainstem and ventral to the medial lemniscus in a cross section, it contains longitudinal fibers (corticospinal, corticopontine, corticoreticular...) and the transversely oriented pontocerebellar fibers)
4. Pyramid of medulla ->
(An elongated white prominence on the ventral surface of the medulla oblongata on either side along the anterior median fissure, corresponding to the position of the fibers forming the corticospinal tracts)
5. Pyramidal decussation in cervicomedullary junction ->
(85% cross, 15% remain to form the ipsilateral anterior corticospinal tract)
6. Lateral corticospinal tract ->
(Dorsal half of lateral funiculus, somatotopically arranged with arm, trunk, leg medially to laterally, and the upper extremity located medially to the lower extremity)
7. Lateral intermediate zone (interneurons) and lateral motor nuclei (distal limb muscles)

c. Entire cord
(Predominantly at the cervical and lumbosacral enlargements.)

d. Movement of contralateral limb.

(Blumenfeld)
Rubrospinal tract of lateral motor system
a. Site of origin
b. Pathway
c. Levels of termination
d. Function
a. Red nucleus, magnocellular division - of midbrain

b.
1. a. -> Ventral tegmental decussation in midbrain
(The anterior tegmental\Ford's decussation is formed by the crossing of the left and right rubrospinal and rubrobulbar tracts, both decussations are located in the mesencephalon)
2. Lateral funiculus of the spinal cord ->
3. Lateral intermediate zone and lateral motor nuclei (-> distal limb muscles)

c. Cervical cord

d. Movement of contralateral limbs
(Function in humans is uncertain).
(Small)
(May participate in taking over functions after corticospinal injury, and may also play a role in flexor (decorticate) posturing of the upper extremities, which is typically seen with a lesion above the level of the red nuclei, in which the rubrospinal tract is spared )

(Blumenfeld)
Anterior corticospinal tract of medial motor system
a. Site of origin
b. Pathway
c. Levels of termination
d. Function
a. Primary motor cortex and supplementary motor area.

b.
1. a. -> Posterior limb of internal capsule ->
2. Basis pedunculi of midbrain ->
(The base of the midbrain consisting of the cerebral peduncles and the substantia nigra)
3. Basis pontis\Basilar part of pons ->
(The large bulbous portion of the pons seen on the ventral portion of the brainstem and ventral to the medial lemniscus in a cross section, it contains longitudinal fibers (corticospinal, corticopontine, corticoreticular...) and the transversely oriented pontocerebellar fibers)
4. Pyramid of medulla ->
(An elongated white prominence on the ventral surface of the medulla oblongata on either side along the anterior median fissure, corresponding to the position of the fibers forming the corticospinal tracts)
5. Ventral column of spinal cord ->
6. Medial intermediate zone and medial motor nuclei (-> proximal axial muscles)

c. Cervical and upper thoracic cod.

d. Control of bilateral axial and girdle muscles.

(Ipsilateral descent, terminate with interneurons with projections to muscles on both sides)

(Blumenfeld)
Lentiform nucleus - components (2)
Putamen and globus pallidus.

('Lens-shaped')

(Blumenfeld)
The internal capsule
a. Parts of the anterior limb (2)
b. Parts of the genu (1)
c. Parts of the posterior limb (3)
d. What surrounds it medially
e. What surrounds it laterally
a.
1. Anterior thalamic radiation
(Radiation formed by fibers interconnecting, via the anterior limb of the internal capsule, the anterior and medial thalamic nuclei and the cerebral cortex of the frontal lobe (excluding the precentral gyrus bordering on the central sulcus)
2. Frontopontine and other corticofugal fibers
(Corticofugal fibers: fibers conveying nerve impulses away from the cortex (fugio: to flee))
(The anterior limb separates the lentiform nucleus from the head of caudate)

b. The corticobulbar tract
(term formerly used to describe projections of the motor and sensory cortices to nuclei of the rhombencephalon innervating the musculature of the face, tongue, and jaws and some fibers to rhombencephalic relay nuclei; replaced by bullar corticonuclear fibers (to medulla), pontine corticonuclear fibers (to pons), mesencephalic corticonuclear fibers (to midbrain).)

c.
1. Corticopontine and other corticofugal fibers
2. Superior thalamic radiation
(Include somatosensory radiation)
3. Corticospinal tract

d. Rostrally the head of caudate nucleus, caudally the thalamus

d. The lentiform nucleus - the globus pallidus (nearest) and the putamen.

(Blumenfeld)
Cerebral peduncles of the midbrain - parts (2)
1. Substantia nigra
(The gray matter of the cerebral peduncles)

2. Basis pedunculi
(The white matter of the cerebral peduncles)
(The middle one-third contains the corticospinal and corticobular tract, the rest contains primarily corticopontine fibers)

(Blumenfeld)
Vestibulospinal tracts (VSTs) of the medial motor system
a. Site of origin
b. Levels of termination
c. Function
a.
1. Medial VST: medial and inferior vestibular nuclei
2. Lateral VST: laterael vestibular nuclei

b.
1. Medial VST: cervical and upper thoracic
2. Lateral VST: entire cord

c.
1. Medial VST: positioning of head and neck
2. Lateral VST: balance

(-> Medial intermediate zone and medial motor nuclei for proximal axial and girdle muscles)

(Medial VST have bilateral branching in rostral medulla, lateral VST is ipsilateral)

(Blumenfeld)
Reticulopsinal tracts of the medial motor system
a. Site of origin
b. Levels of termination
c. Function
a. Pontine adn medullar reticular formation.

b. Entire cord.

c. Automatic posture and gait-related movements.

(-> Medial intermediate zone and medial motor nuclei for proximal axial and girdle muscles)

(Ipsilateral)

(Blumenfeld)
Tectospinal tract of the medial motor system
a. Site of origin
b. Site of decussation
c. Levels of termination
d. Function
a. Superior colliculus of midbrain

b. Dorsal tegmental decussation, in midbrain
(\Meynert's decussation - formed by crossing of the left and right tectospinal and tectobulbar tracts)

c. Cervical cord.

d. Coordination of head and eye movement.
(Uncertain in humans.)

(-> Medial intermediate zone and medial motor nuclei for proximal axial and girdle muscles)

(Blumenfeld)
Upper motor neuron lesions
a. Upper motor neurons
b. Signs and symptoms, compared to lower motor neuron lesion (7)
c. What is thought to be the cause of the spasticity
a. Neurons of the cerebral cortex that project to lower motor neurons via the corticospinal tract and the corticobulbar tract.

b.
1. Paresis
2. Less atrophy than LMN lesion
(Some due to disuse still)
3. No fasciculations as seen in LMN lesions
4. Hyperreflexia
5. Increased tone
(Increased tone and hyperreflexia is sometimes referred to as spasticity -> UMN lesion\Spastic paresis)
6. Babinski's sign
7. Hoffmann sign
(Flexion of the terminal phalanx of the thumb and of the second and third phalanges of one or more of the fingers when the volar surface of the terminal phalanx of the fingers is flicked.)

(With acute upper motor neuron lesions, flaccid paralysis with hypotonia and hyporeflexia may initially occur and gradually, over hours or even months, develop into spastic paresis.)

c. Damage to descending inhibitory pathways that travel closely with the corticospinal tract, rather than by damage to the corticospinal tract itself.
(Animal experiments where the corticospinal tract has been selectively lesioned has not produced spastic paralysis)
(Loss of inhibitory signas -> increased excitability of motor neurons in the anterior horn -> brisk reflexes and increased tone)

(Blumenfeld)
Terms commonly used to describe weakness - give definition, and example with its clinical symptoms

Terms denoting severity
a. Paresis
b. -Plegia
c. Paralysis
d. Palsy

Terms denoting location
e. Hemi-
f. Para-
g. Mono-
h. Di-
i. Quadri-\Tetra-
a. Paresis
Weakness or partial paralysis
Hemiparesis - weakness of one side of the body (face, arm, leg)
(L. a slackening)

b. -Plegia
No movement
Hemiplegia - no movement of one side of the body (face, arm, leg)
(plege: stroke)

c. Paralysis
No movement
Leg paralysis - no movement of the leg
(In UMN lesion, reflexes may be present in paralysis and -plegia)

d. Palsy
Imprecise term for weakness or no movement.
Facial palsy - weakness or paralysis of face muscles.

e. Hemi-
One side of body (face, arm, leg)
Hemiplegia - no movement of one side of the body

f. Para-
Both legs
Paraparesis - weakness of both legs

g. Mono-
One limb
Monoparesis - weakness of one limb (arm or leg)

h. Di- both sides of the body equally affected
Facial diplegia - symmetrical facial weakness

i. Quadri-\Tetra-
All four limbs
Quadriplegia\Tetraplegia - paralysis of all four limbs

(Blumenfeld)
Weakness can be caused by lesions or dysfunctions at ... (6)
1. The association and limbic cortices involved in volitional or motivational control of movement.
(Volo: to wish. Volition: the conscious impulse to perform any act or to abstain from its performance; voluntary action.)

2. The upper motor neurons of the corticospinal tract anywhere from the cortex to the spinal cord

3. The lower motor neurons anywhere from anterior horn to peripheral nerve.

4. The neuromuscular junction

5. The muscles

6. The mechanical function of joints and tendons.

(Blumenfeld)
Weakness pattern and localization - hemiparesis or hemiplegia (face, arm, leg) with no associated sensory deficits
a. Location
b. Side of lesion
c. Common causes (4)
d. Associated features (2)
a. Corticospinal and corticobulbar tract fibers below the cortex and above the medulla: corona radiata, posterior limb and genu of the internal capsule, basis pontis, or middle third of the basis pedunculi of the cerebral peduncle.
(Unlikely to be cortical because the lesion would have to involve the entire motor strip, in which case sensory involvement is hard to avoid. Unlikely to be muscle or peripheral nerve because in that case conicidental involvement of the face, arm and leg, all one side of the body, would be required. Not the spinal cord or medulla because in that case the face would be spared.)

b. Contralateral to weakness
(Above the pyramidal decussation.)

c.
1. Lacunar infarct of the internal capsule
a. Lenticulostriate branches of the middle cerebral artery
(Lenticulostriate: relating to the lenticulate nucleus and the caudate nucleus)
b. Anterior choroidal artery
(Of internal carotid or middle cerebral artery (rarely).
(Lacunar infarcts are small (0.2 to 15 mm in diameter) noncortical infarcts caused by occlusion of a single penetrating branch of a large cerebral artery)

2. Lacunar infarct of the pons - of the median perforating branches of the basilar artery

3. Infarct of the cerebral peduncle

4. Other: demyelination, tumor, or abscess in these locations or in the corona radiata can also cause pure motor hemiparesis.

d.
1. Dysarthria
(-> Dysarthria-pure motor hemiparesis)
2. Ataxia of the affected side
(-> Ataxia-hemiparesis)
(From involvement of the cerebellar pathways (corticopontine fibers)

(Blumenfeld)

(Blumenfeld)
Unilateral face, arm, and leg weakness or paralysis (hemiparesis or hemiplegia) with associated somatosensory, oculomotor, visual, or higher cortical deficits
a. Location
b. Side of lesion
c. Common causes (6)
a.
1. Entire primary motor cortex
2. Corticospinal and corticobulbar tract fibers above the medulla (ie. tha thalamocapsular lacune)
(Unlikely to be below medulla. Unlikely to be muscle or peripheral nerve because in that case conicidental involvement of the face, arm and leg, all one side of the body, would be required. Not the spinal cord or medulla because in that case the face would be spared.)

b. Contralateral to weakness.
(Above the pyramidal decussation.)

c. Numerous - infarct, hemorrhage, tumor, trauma, herniation, post-ictal state..

d. Dysarthria or ataxia.

(Blumenfeld)
Unilateral arm and leg weakness or paralysis
a. Other names (2)
b. Possible locations (2)
c. Side of lesion (2)
d. Common causes (5)
a.
1. Hemiplegia (paralysis) or hemiparesis (weakness) sparing the face
2. Brachiocrural plegia or paresis

b.
1. Arm and leg area of the motor cortex
2. Corticospinal tract from the lower medulla to the C5 level of the cervical spinal cord
(Unlikely to be the corticospinal tract below the motor cortex above the medulla, because the corticobulbar tract fibers are located very close nearby and the face would thus usually be involved. Unlikely to be muscle or peripheral nerve because in that case coincidental involvement of both the arm and the leg on one side of the body would be required. Not below C5 in the cervical spinal cord because in that case some arm muscles would be spared)

c.
1. Motor cortex or medulla above the pyramidal decussation contralateral to the weakness.
2. Cervical spinal cord ipsilateral to the weakness.

d.
1. Watershed infarct - anterior cerebral-middle cerebral watershed
2. Medial or combined medial and lateral medullary infarcts
3. Multiple sclerosis
4. Trauma or compression of the cervical spinal cord.
5. Occasionally, infarcts of the posterior limb of the internal capsule that are removed from the genu may cause contralateral hemiparesis sparing the face.

(Associated features allowing further localization
1. Affecting the cortex
a. "Man in the barrel" syndrome
(Cortical lesions sparing the face are often in a watershed distribution, and they affect proximal more than distal muscles)
b. Aphasia or hemineglect

2. Affecting the medial medulla
a. Loss of vibration and joint position on the same side as the weakness
b. Tongue weakness on the opposite side

3. Affecting the lateral medulla
a. The lateral medullary syndrome\PICA syndrome
(Dysarthria, dysphagia, staggering gait and vertigo, hypotonia, ataxia, nystagmus, Horner's syndrome on ipsilateral side, loss of pain and temperature on contralateral side)

4. Lesions affecting the spinal cord
a. Brow-Sequard syndrome
(Proprioception loss and weakness occur ipsilateral to the lesion, pain and temperature sensation loss contralateral to the lesion)
b. High cervical lesions can involve the spinal trigeminal nucleus and tarct -> decreased facial sensation)

(Blumenfeld)
Unilateral face and arm weakness and paralysis
a. Synonym
b. Location (2)
a. Faciobrachial paresis or plegia

b. Face and arm areas of the primary motor cortex
(Unlikely to be muscle or peripheral nerve because in that case coincidental involvement of the face and arm would be required. Uncommon in lesions at the internal capsule or below because the corticobulbar and corticospinal tracts are fairly compact, resulting leg involvement with most lesions.)

c. Contralateral to weakness.
(Above the pyramidal decussation.)

d.
1. Infarct of superior division of the middle cerebral artery
2. Tumor, abscess, or other lesions in this location

(Associated features allowing further localization
1. Dysarthria and UMN signs
2. Dominant hemisphere lesions (left 90-95%) -> Broca's aphasia
3. Nondominant hemisphere lesions -> hemineglect
4. sensory loss can occur if the lesion extends into the parietal lobe)

(Blumenfeld)
Unilateral arm weakness or paralysis
a. Synonym (1)
b. Probable locations (2)
c. Common causes (2)
a. Brachial monoparesis or monoplegia
(There are different names for different weakness patterns associated with peripheral nerve injuries)

b.
1. Arm area of primary motor cortex
2. Peripheral nerves supplying the arm
(Unlikely anywhere along the corticospinal tract (internal capsule, brainstem, spinal cord), because in that case the face and \ or lower extremity would also likely be involved. Rare cases of foramen magnum tumors may initially affect one arm.)

c.
1. Motor cortex lesion
a. Infarct of a small cortical branch of the MCA
b. A small tumor, abscess, or the like
2. Peripheral nerve lesion
a. Compression injury
b. Diabetic neuropathy

(Associated features allowing further localization
1. Motor cortex lesion
a. UMN lesion signs
b. Cortical sensory loss
c. Aphasia
d. Subtle involvement of face or leg
e. The weakness pattern may be incompatible with a lesion of peripheral nerves
(Marked weakness of all finger, hand, and wrist muscles with no sensory loss and normal proximal strength does not occur with peripheral nerve lesions)
2. Peripheral nerve lesions
a. LMN lesion signs
b. Weakness and sensory loss may be compatible with a known pattern for a peripheral nerve lesion)

(Blumenfeld)
Unilateral facial weakness or paralysis
a. Other names (2)
b. Probable locations (3)
c. Common causes (2)
a.
1. Bell's palsy (peripheral nerve lesion)
2. Isolated facial weakness

b.
1. Peripheral facial nerve dysfunction
(Common)
2. Dysfunction of facial nucleus or exiting nerve fascicles in the pons or rostral lateral medulla
3. Lesions in the face area of the primary motor cortex or in the genu of the internal capsule
(Uncommon, usually associated with arm and leg involvement as well)

c.
1. Facial nerve
a. Bell's palsy
(Probably due to viral infection which cause demyelination)
b. Trauma or surgery
2. Infarct of motor cortex, capsular genu, pons, or medulla

(Associated features allowing further localization
1. Facial nerve lesions
a. LMN lesion signs
b. The forehead and orbicularis oculi are not spared
c. Hyperacusis (m. stapedius)
d. Hypogeusia (decreased taste)
e. Decreased lacrimation
f. Retroauricular ipsilateral pain

2. Facial nucleus lesion
a. LMN lesion signs
b. Usually deficits associated with damage to nearby nuclei and pathways such as CN VI, CN V, or the corticospinal tract.
c. In rostral lateral medullary lesions, a lateral medullary syndrome\PICA syndrome will be present
(due usually to thrombosis, characterized by dysarthria, dysphagia, staggering gait, and vertigo, and marked by hypotonia, incoordination of voluntary movement, nystagmus, Horner syndrome on the ipsilateral side, and loss of pain and temperature senses on the side of the body opposite to the lesion.)

3. Motor cortex or capsular genu lesions
a. UMN lesion signs
b. The forehead is relatively spared
(Both hemispheres contribute to movement, not spared on LMN lesion because both hemispheres synapse on the same nerves)
c. Dysarthria and unilateral tongue weakness
d. Subtle arm involvement
e. Sensory loss or aphasia)

(Facial diplegia is very hard to detect since the weakness is symmetrical. It can be caused by motor neuron disease, bilateral peripheral nerve lesions (Guillain-Barre syndrome, sarcoidosis, Lyme disease, Bilateral Bell's palsy, or bilateral white matter abnormalities caused by ischemia or demyelination (pseudobulbar palsy).)

(Blumenfeld)
Bilateral arm weakness or paralysis
a. Other names (1)
b. Probable locations (3)
c. Probable causes
a. Brachial diplegia

b.c.
1. Medial fibers of both lateral corticospinal tracts
2. Bilateral cervical spine ventral horn cells
3. Peripheral nerve or muscle disorders affecting both arms

c.
1. Medial fibers of both lateral corticospinal tracts can be affected by central cord syndrome
a. Syringomyelia
(The presence in the spinal cord of longitudinal cavities lined by dense, gliogenous tissue, which are not caused by vascular insufficiency. Syringomyelia is marked clinically by pain and paresthesia, followed by muscular atrophy of the hands and analgesia with thermoanesthesia of the hands and arms, but with the tactile sense preserved; later marked by painless whitlows, spastic paralysis in the lower extremities, and scoliosis of the lumbar spine. Some cases are associated with low grade astrocytomas or vascular malformations of the spinal cord. Syn: Morvan disease, hydrosyringomyelia, syringomyelus.)
b. Intrinsic spinal cord tumor
c. Myelitis

2. Anterior cord syndrome can affect the cervical ventral horn cells
a. Anterior spinal artery infarct
b. Trauma
c. Myelitis

3. Peripheral nerve
a. Bilateral carpal tunnel syndrome
b. Disc herniation

(Blumenfeld)
Bilateral leg weakness or paralysis
a. Other names
b. Probable locations (4)
c. Common causes
a. Paraparesis or paraplegia

b.
1. Bilateral leg areas of the primary motor cortex along the medial surface of the frontal lobes
2. Lateral corticospinal tract below T1
3. Cauda equina syndrome
4. Other peripheral nerve or muscle disorders affecting both legs

c.
1. Bilateral medial frontal lesions
a. Parasagittal meningioma
b. Bilateral ACA infarcts
c. Cerebral palsy (bilateral periventricular leukomalacia)

2. Spinal cord lesions
a. Tumor
b. Trauma
c. Myelitis
d. Epidural abscess

3. Bilateral peripheral nerve or muscle disorders
a. Cauda equina syndrome
(involvement, often asymmetric, of multiple roots making up the cauda equina (i.e., L2–S3 roots), manifested by pain, paresthesia, and weakness; often bladder and bowel sphincter function is unaffected because of sacral sparing (lack of compromise of the S2, S3, and S4 roots).)
b. Tumor
c. Trauma
d. Disc herniation
e. Guillain-Barre syndrome, Lambert-Eaton syndrome, numerous muscle disorders, and distal symmetrical polyneuropathies (<- diabetes, toxic, metabolic, congenital, or inflammatory conditions) <- All tend to affect the lower extremities first

(Associated features allowing further localization
1. Bilateral medial frontal lesions
a. UMN lesion signs
b. Frontal lobe dysfunction - confusion, apathy, grasp reflexes, incontinence

2. Spinal cord lesion
a. UMN lesion signs
b. Sphincter dysfunction and autonomic dysfunction
c. Dermatomal sensory level loss or loss of specific reflexes can help to determine the segmental level of the lesion

3. Bilateral peripheral nerve or muscle disorders
a. Cauda equina syndrome -> sphincter and erectile dysfunction, sensory loss in lumbar or sacral dermatomes, LMN lesion signs
b. Symmetrical polyneuropathies -> preferentially affect distal muscles, distal glove-stocking sensory loss, LMN lesion sign
c. Neuromuscular disorders and myopathies often affect proximal muscles more than distal muscles)

(Blumenfeld)
Bilateral arm and leg weakness or paralysis
a. Other names
b. Probable locations (3)
c. Common causes
a. Quadriparesis\Tetraparesis or Quadriplegia\Tetraplegia

b.
1. Bilateral arm and leg areas of the motor cortex
2. Bilateral lesions of the corticospinal tracts from the lower medulla to C5
3. Severe peripheral nerve, motor neuron, or muscle disorders
(Usually also affect the face, but in some cases face involvement may be relatively mild)

c.
1. Bilateral watershed infarct (ACA-MCA) affecting the motor cortex
(Watershed: the area of marginal blood flow at the extreme periphery of a vascular bed)
2. Upper cervical and lower medulla region
a. Tumor
b. Infarct
c. Trauma
d. Multiple sclerosis

3. Numerous peripheral nerve, motor neuron, and muscle disorders.

(Associated features allowing further localization
1. Bilateral motor cortex lesion
a. Cortical lesions sparing the face are often in a watershed distribution and affect proximal more than distal muscles ("man in the barrel" syndrome
b. UMN lesion signs
c. Aphasia, neglect, other cognitive disturbances

2. Bilateral upper cervical cord lesions
a. UMN lesion signs
b. Sensory level dysfunction
c. Sphincter dysfunction
d. Autonomic dysfunction
(Gastric paresis, bladder atony, loss of erectile function, orthostatic hypotension)
e. Respiratory weakness
f. Involve the trigeminal nucleus -> loss of facial sensation

3. Lower medullary lesions
a. UMN lesion signs
b. Occpital headache
c. Tongue weakness
d. Sensory loss
e. Hiccups
f. Respiratory weakness
g. Autonomic dysfunction
h. Sphincter dysfunction
i. Abnormal eye movements

4. Peripheral nerve or muscle disorders
a. LMN lesion signs in nerve disorders)

(Blumenfeld)
Generalized weakness or paralysis
a. Probable location (4)
b. Causes
a.
1. Bilateral lesion of the entire motor cortex.

2. Bilateral lesions of the corticospinal and corticobulbar tracts anywhere from the corona radiata to pons

3. Diffuse disorders involving all lower motor neurons, peripheral axons, neuromuscular junctions, or muscles

4. Bilateral ventral pontine ischemia due to basilar artery stenosis

b.
1. Global cerebral anoxia
2. Pontine infarct or hemorrhage (locked-in-syndrome)
3. Advanced ALS, Guillain-Barre syndrome, myasthenia gravis, botulism..
4. Diffuse neoplastic, inflammatory, infectious, traumatic, toxic, or metabolic conditions

(Associated features allowing further localization
1. UMN vs LMN lesion signs
2. Respiratory depression is common with severe generalized weakness)

(Blumenfeld)
Tests to detect subtle hemiparesis and mild corticospinal damage (8)
1. Pronator drift
(Patient holds arms extended, palms up, and closes eyes. Slight pronation of one forearm, or even a slight curling of the fingertips on one side.)

2. Finger extensors
(Patient holds fingers extended and resists while examiner tries to flex them. This is an excellent test because corticospinal damage generally spares flexors relative to extensors, and finger extensors are relatively weak muscles with large cortical representation.)

3. Fine movements
(a. Have the patient rapidly tap index finger and thumb together
b. Tap each finger to the thumb in sequence
c. Rapidly pronate and supinate the hand (screw a lightbulb, slap palm and dorsum on leg)
d. Tap the foot rapidly on the floor or bed)

4. Isolated finger movements
(Patient holds fingers abducted and extended and then moves one finger at a time.)

5. Spastic catch
(Feel for a subtle "catch" on one side compared to the other when holding the patient's hand in a handshake position and then rapidly supinate the patient's forearm)

6. Subtle decreased nasolabial fold
(Observe the patient's face carefully in several different settings, including rest, spontaneous smiling, and grimacing during exam, not just during voluntary smile)

7. Careful gait testing
(Look for slight circumduction of one leg (the leg swings out in a circular arch with each step) or decreased arm swing. Also have the patient hop on each foot and walk on the toes.)

8. Silent plantar
(If a normal flexor plantar response on one side, then a silent plantar response on the other side may represent a subtle Babinski's sign.)

(Damage to the cerebellum, basal ganglia, or peripheral nerves can also produce abnormalities in some of these tests.)

(Blumenfeld)
Ataxic and vertiginous gait
a. Description of gait abnormalities
b. Localization of possible lesion
c. Common causes of ataxic (3) and vertiginous (4) gait
a. Wide based, unsteady, staggering side to side, and falling toward side of worse pathology. Positive Romberg sign.
(Patients sway and fall when attempting to stand with feet together and eyes closed)
(Subtle deficits can be detected with tandem (heel-to-toe\"drunk walk") gait testing)

b.
Cerebellar -> Cerebellar vermis or other midline cerebellar structures.
Vestibular system ->
1. Vestibular nuclei or its nerve
2. Semicircular canals

c.
Cerebellar
1. Toxins such as alcohol and medications
2. Lesions of vermis or its pathways: tumor, ischemia\infarcts
3. Cerebellar degeneration

Vestibular
1. Toxins such as alcohol
2. Infarct\ischemia of vestibular nuclei
3. Benign positional vertigo (of Barany)
(Brief attacks of paroxysmal vertigo and nystagmus that occur solely with certain head movements or positions, e.g., with neck extension; due to labyrinthine dysfunction.)
4. Meniere's disease
(An affectio
n characterized clinically by vertigo, nausea, vomiting, tinnitus, and progressive hearing loss due to hydrops of the endolymphatic duct.)
(Hydrops: an excessive accumulation of fluid)

(Barany: Austrian-Hungarian otologist and Nobel laureate. in cases of ear disease, in which the vestibule is healthy, injection into the external auditory canal of water below the body temperature will cause rotatory nystagmus toward the opposite side; when the injected fluid is above the body temperature the nystagmus will be toward the injected side; if the labyrinth is diseased or nonfunctional there may be diminished or absent nystagmus.)

(Blumenfeld)
Frontal gait
a. Description of gait abnormalities
b. Localization of possible lesion (2)
c. Common causes (4)
a.
1. Slow
2. Unsteady
3. "Magnetic" and shuffling
(Magnetic: Barely raising the feet of the floor.
Shuffling: sliding along or back and forth without lifting)
(Can be narrow or wide)
(Sometimes resembles Parkinsonian gait.)
(Gait apraxia: some patients can perform cycling movements on their back, much better than they can walk, giving rise to the term gait apraxia in this condition)

b.
1. Frontal lobes
2. Frontal subcortical white matter

c.
1. Hydrocephalus
2. Frontal tumors
(Glioblastoma, meningioma)
3. Bilateral ACA infarcts
4. Diffuse subcortical white matter disease

(Blumenfeld)
Parkinsonian gait
a. Description of gait abnormalities
b. Localization of lesion
c. Causes (2)
a.
1. Slow
2. Shuffling
(Shuffling: sliding along or back and forth without lifting)
3. Narrow
4. Difficulty initiating movement
(Often stooped forward, with decreased arm swing. Unsteady, with "retropulsion"," taking several rapid steps to regain balance when pushed backward)

b. Substantia nigra or other regions of basal ganglia.

c.
1. Parkinson's disease
2. Other Parkinsonian syndromes
(Progressive supranuclear palsy (lesions above the primary motor neurons), use of neuroleptic drugs)

(Blumenfeld)
Spastic gait
a. Description of gait abnormalities
b. Localization of lesion
c. Common causes (5)
a.
1. Uni- or bilateral
2. Stiff-legged
3. Circumduction
4. Scissoring of legs (involuntary crossing of legs) and toe walking (from increased muscle tone in calf muscles)
5. Unsteady, falling toward side of greater spasticity
(Decreased arm swing)

b. Unilataral or bilateral corticospinal tracts

c.
1. Cortical, subcortical, or brainstem infarcts affecting UMN pathways
2. Cerebral palsy
3. Degenerative conditions
4. Multiple sclerosis
5. spinal cord lesion

(Blumenfeld

(Blumenfeld)
Dyskinetic gait
a. Description of gait abnormalities
b. Localization
c. Common cause (3)
a. Uni- or bilateral
1. Dancelike\choreic movements during walking
2. Flinging\ballistic movements during walking
3. Writhing\athetoid movements during walk
4. Some unsteadiness

b. Subthalamic nucleus or other regions of basal ganglia.

c.
1. Huntington's disease
2. Infarct of subthalamic nucleus or striatum
3. Side effect of levodopa
4. Familial or drug-induced dyskinesia
(Dyskinesia: Difficulty in performing voluntary movements. Term usually used in relation to various extrapyramidal disorders.)

(Blumenfeld)
Tabetic gait
a. Description of gait abnormalities
b. Localization
c. Common cause (3)
a.
1. High-stepping
2. Foot-flapping
3. Particular difficulty when walking in the dark or on uneven surfaces
4. +Romberg sign
(Patient sway and fall in attempts to stand with feet together and eyes closed.)

b. Posterior columns or sensory nerve fibers.

c.
1. Posterior cord syndrome
2. Severe sensory neuropathy
3. Tabes dorsalis\Syphilitic myelopathy

(Blumenfeld)

(Blumenfeld)
Paretic (paresis) gait
a. Description of gait abnormalities (ie with hip weakness, thigh weakness, fibular nerve weakness)
b. Localization
a. Exact appearance depend on location of lesion
1. Proximal hip weakness -> waddling, Trendelenburg gait
2. Severe thigh weakness -> Knee buckling
3. Foot-drop -> High-stepping, slapping gait

b. Nerve roots, peripheral nerves, neuromuscular junction, or muscles.

(Blumenfeld)
Painful\Antalgic gait
a. Description of gait abnormalities
b. Localization
c. Common causes (5)
a.
1. Pain may be obvious based on patient's report or facial expression
2. Tend to avoid putting pressure on affected limb

b. Peripheral nerve or orthopedic injury.

c.
1. Herniated disc
2. Peripheral neuropathy
3. Muscle strain
4. Contusion
(Any mechanical injury (usually caused by a blow) resulting in hemorrhage beneath unbroken skin.)
5. fractures

(Blumenfeld)
Multiple sclerosis
a. Clinical definition
b. Hypothesized cause
c. Pathological findings
a. Two or more neurologic deficits separated in neuroanatomical space and time.

b. T lymphocytes may be triggered by a combination of genetic and environmental factors to react against oligodendroglial myelin.
(Peripheral myelin is unaffected.)

c. Discrete plaques of demyelination and inflammatory response which appear and disappear in multiple locations in the CNS over time, eventually form sclerotic glial scars.
(Some axons may be destroyed as well in multiple slerotic plaques.)

(Blumenfeld)
Multiple sclerosis
a. Effect of demyelination on function of the nervous system (3)
b. Prevalence
c. Practical diagnosis of MS (4)
d. Treatment options
a.
1. Slowed conduction velocity
2. Dispersion\Loss of coherence of action potential volleys
(Dispersion is worse with warm temperature)
3. Ultimately conduction block

b. 0.1% in the United States.
(2:1 in females, peak age of onset is 20-40 years, 3-5% chance if first-degree relative has the disease)

c.
1. Typical clinical features
(Motor, sensory, cerebellar, CNs\brainstem, autonomic..)
(> 50% of patients with optic neuritis or transverse myelitis develop MS)
(The clinical course starts with a relapse-remitting pattern which progress to a refractory chronic progressive phase)
(Motor: paresis, spasticity, hyperreflexia, Babinski's, Sensory: impairment of vibration\position sense, impairment off pain\temperature, or touch sense, pain, Lhermitte's sign, Cerebellar: ataxia (limb, gait, truncal), tremor, nystagmus, dysarthria, Autonomic: bladder, bowel, sexual, Psychiatric: depression, euphoria, cognitive abnormalities, fatigue)

2. MRI evidence of white matter lesions
(T2-bright areas -> demyelinating plaques in the white matter. Tend to extend into the white matter from periventricular locations -> Dawson's fingers)

3. Slowed conduction velocities on evoked potentials

4. Oligoclonal bands in CSF
(Abnormal discrete bands seen on CSF gel electrophoresis, which result from the synthesis of large amounts of relatively homogenous antibodies, 85% of patients.)

d.
1. Acute exacerbation -> high-dose corticosteroids
2. Relapse-remitting ->
a. First-line: beta-interferon, glatiramer acetate (copolymer)
(It is a random polymer of four amino acids found in myelin basic protein, namely glutamic acid, lysine, alanine, and tyrosine, and may work as a decoy for the immune system.)
b. Second-line: monoclonal antibodies (natalizumab, rituximab, alamtuzamab), chemotherapeutic agents (cyclophosphamide, mitoxantrone)

(Natalizumab: Antibody against the cellular adhesion molecule α4-integrin. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood-brain barrier.)

(Alemtuzumab targets CD52, a protein present on the surface of mature lymphocytes)

(Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells)

(Lhermitte's sign: sudden electric-like shocks extending down the spine on flexion of the head.)

(Blumenfeld)
Amyotrophic lateral sclerosis (ALS)\Lou Gehrig's disease
a. What
b. Initial symptoms
c. Important diagnostic test, what does it show in ALT
d. Other disorders that rarely can cause similar findings (6)
a. Disease characterized by gradually progressive degeneration of both UMN and LMN, leading eventually to respiratory failure and death. Usually normal sensory and mental status.
(1-3\100 000, peak age of onset 50-60 years)
(Present with both UMN and LMN lesion signs: hypertonia, hyperreflexia, atrophy, and fasciculation.)
(Median survival once diagnosed is 23-52 months)

b.
1. Weakness and clumsiness, which often begins focally and then spreads.
2. Painful muscle-cramping and fasciculations (tongue)
(Later: head droop, UMN and LMN lesion signs, pseudobulbar affect (crying and laughing without the emotion)

c. EMG, shows evidence of denervation and reinnervation.

d.
1. Lead toxicity
2. Dysproteinemia
3. Thyroid dysfunction
4. Vitamin B deficiency
5. Hexosaminidase A deficiency
6. Cervical spine compression
(LMN and UMN in upper extremities)

(The extraocular muscles tend to be relatively spared -> communication via eye movements.)
(Riluzole, a blocker of glutamate release extend survival by several months.)

(Blumenfeld)
Motor neuron diseases
a. Example of upper and lower motor neuron disease
b. Example of upper motor neuron disease
c. Example of lower motor neuron disease
a. Amyotrophic lateral sclerosis (ALS)

b. Primary lateral sclerosis

c. Spinal muscular atrophy
(When it occurs in infancy it is known as Werdnig-Hoffmann disease and usually leads to death by the second year of life.)

(Blumenfeld)
The somatosensory system
a. What does the term somatosensory refer to
b. What are the two main pathways, and what do they transmit
c. Which sensation is carried in both and are thus not completely eliminated in isolated lesions of any of the pathways
a. Bodily sensations of touch, pain, temperature, vibration, and proprioception (limb or point position).

b.
1. The posterior-column-medial lemniscal pathway
Proprioception, vibration sense, and fine, discriminative touch.

2. The anterolateral pathways: the spinothalamic tractand others.
Pain, temperature sense, and crude touch.

c. Touch.

(Blumenfeld)
Posterior column-medial lemniscal pathway
a. Transmitted modalities (3)
b. Pathway from dorsal root
c. Name and area of decussation
a.
1. Vibration
(Type A-beta\II neurons)
2. Joint position
(Type A-alpha\I and A-beta\II neurons)
3. Fine touch
(Type A-beta\II neurons)

b.
1. The medial portion of the dorsal root entry zone ->
2. Ipsilateral posterior columns - cuneate and gracile fasciculi ->
(Some axons collaterals enter the spinal cord central gray matter to synapse onto interneurons and motor neurons.)
(Fibers add on laterally from higher levels as the posterior column ascend. Thus, the medial portion, called the gracile ('thin') fasciculus carries information from the legs and lower trunk, while the more lateral cuneate fasciculus ('wedge-shaped') carries information from the upper trunk above T6, and from the arms and nec.)
3. Posterior column nuclei - cuneate and gracile nuclei in the caudal medulla ->
4. Decussate as internal arcuate fibers in caudal medulla ->
5. Medial lemniscus ('bundle') ->
(The somatotopic organization of the medial lemniscus assumes a "vertical" position in the medulla such that the feet are represented more ventrally ("the little person stands up") and then inclines again in the pons and midbrain such that the arms are represented more medially and legs more laterally ("the little person lies down")
6. Ascend in brainstem ->
7. Ventral posterior lateral nucleus (VPL) of the thalamus
8. Posterior limb of the internal capsule in the thalamic somatosensory radiations ->
9. The primary somatosensory cortex in the postcentral gyrus.
(Mostly cortical layer IV and deep portions of III. Some input reach layer VI)
(An analogous pathway called the trigeminal lemniscus conveys touch sensation for the face via the ventral posterior medial nucleus (VPM) of the thalamus to the somatosensory cortex.)

(Blumenfeld)
Anterolateral pathways
a. Transmitted modalities (3)
b. Members (3)
c. Pathway from dorsal root
d. What is the Lissauer's tract
a.
1. Pain
(Type A-delta\III and C\IV)
2. Temperature
(Type A-delta\III for cold and C\IV for warmth)
3. Crude touch

b.
1. The spinothalamic tract
(Mediate location and intensity of pain)
(<- Rexed's laminae VII (Intermediate zone) and VI-VIII (VI: base of dorsal horn, VIII: Commissural nucleus)
2. The spinoreticular tract
(Convey emotional and arousal aspects of pain)
(<- Rexed's laminae I (Marginal zone) and V (Neck of dorsal horn))
3. The spinomesencephalic tract
(Participates in central modulation of pain)
(<- Rexed's laminae I (Marginal zone) and V (Neck of dorsal horn))

c.
1. Dorsal root entry zone
2. Synapse immediately in the dorsal horn marginal zone\Rexed's lamina I and lamina V (Neck of dorsal horn)
3. Cross over in the spinal cord anterior commissure
(Over 2-3 spinal segments)
4. Anterolateral white matter
5. Ascend laterally in the medulla between the inferior olives and the inferior cerebellar peduncles
6. Ascend via pons and midbrain through pontine tegmentum lateral to the medial lemniscus
7.
a. Spinothalamic tract - 2 projections -> ventral posterior lateral (VPL) nucleus of thalamus -> thalamic somatosensory radiations -> the primary somatosensory cortex
(Parallel to equivalent trigeminothalamic tract),
Or intralaminar thalamic nuclei (central lateral nucleus) and medial thalamic nuclei (ie. mediodorsal nuclei) -> emotional and arousal aspect of pain with the spinoreticular tract
b. The spinoreticular -> same as second option of the spinothalamic tract
c. The spinomesencephalic -> periaqueductal gray matter and the superior colliculi of the midbrain

d. The Lissauer's tract\Dorsolateral fasciculus is made up of axon collaterals from the anterolateral tracts that descend or ascend a few spinal segments before they synapse, in the Rexed's lamina I\Marginal zone.

(Blumenfeld)
Sensory neuron fiber types - give the two names, state whether they are myelinated, their associated receptors and their sensory modalities
1. A-alpha\I
Myelinated
Muscle spindle, Golgi tendon organ -> Proprioception
(13-20 um)

2. A-beta\II
Myelinated

Muscle spindle -> Proprioception
Meissner's\tactile corpuscle -> Superficial touch
(In dermal papillae of thick skin, especially of fingers and toes. Capsulated)
Merkel's receptor\Tactile meniscus -> Superficial touch
(Epidermis, terminal cuplike expansion of an axon in contact with a single keratinocyte.)
Pacinian corpuscle\Lamellated corpuscles -> Deep touch, vibration
(In skin of fingers, mesenterery, tendons...Concentric layers of connective tissue with a core in which the axon runs.)
Ruffini ending -> deep touch, vibration
(Subcutaneous tissue of fingers, ovoid capsule)
Hair receptor -> touch, vibration
(6-12 um)

3. A-delta\III
Myelinated
Free nerve ending -> pain, cold temperature, itch
(1-5 um)

4. C\IV
Myelinated
Free nerve ending -> pain, itch, hot temperature
(0.2-1.5 um)

(Blumenfeld)
Somatosensory cortex
a. What Brodmann's areas are the primary somatosensory cortex
b. Where are the information from the primary somatosensory cortex conveyed, where is this structure located

c. Where does further processing of the somatosensory information take place

d. What are the deficits called which result from lesions of the somatosensory cortex and adjacent regions.
a. 3,1,2.

b. The secondary somatosensory association cortex.
In the parietal operculum which is located on the superior margin of the Sylvian fissure. Brodmann's area.

c. In the superior parietal lobule.
(Include Brodmann's area 5 and 7.)

d. Cortical sensory loss.

(Blumenfeld)
Central modulation of pain
a. Explain the gate control theory
b. How is the periaqueductal gray matter involved in pain modulation - where does it receive input from, where is the relay stations, and what type of neurotransmitter do they produce
c. Name the 3 endogenous opiates and where they are found in particularly high concentrations in relation to pain modulation
a. Sensory inputs from large-diameter, nonpain A-beta\II fibers (Proprioception, superficial touch, deep touch, and vibration) reduce pain transmission through the dorsal horn.
(Explains mechanism behind transcutaneous electrical nerve stimulation (TENS) devices that work to reduce chronic pain by activating A-beta fibers.)

b. The periaqueductal gray matter
<- Hypothalamus (use Beta-endorphin), pons, amygdala, and cortex.
Mediate pain via rostral ventral medulla (RVM)\Nucleus Raphe-Magnus region in the pontomedullary junction. This modulate pain
1. Directly via its serotonergic neurons (nuclei raphe) to the spinal cord dorsal horn to modulate pain
2. Substance P -> Locus ceruleus -> Noradrenergic projections to dorsal horn of spinal cord to modulate pain

c.
1. Enkephalin and dynorphin are found in high concenrtations in the periaqueductal gray matter, RVM and spinal cord dorsal horn.
2. Beta-endorphin are found in neurons in regions of the hypothalamus that project to the periaqueductal gray matter.

(Blumenfeld)
Most important causes of hypoglycemia, related to
a. Drugs (3)
b. Major organ failure
c. Hormonal deficiencies (2)
d. Tumors (3)
e. Others
a. Drugs
1. Insulin and other antidiabetic drugs
2. Beta-adrenergic antagonists

b. Major organ failure
1. Liver, kidney, and heart failure
2. Shock and sepsis

c. Hormonal deficiencies
1. Adrenal failure
2. Hypopituitarism

d. Tumors
1. Insulin producing tumors - insulinoma of pancreas
2. IGF producing tumors - ie. leiomyosarcoma
(Malignant neoplasm derived from smooth muscle. (Leio-: smooth)
3. Glucose-storing and -consuming tumors - ie. hepatocellular carcinoma

e. Others - Malnutrition (ie by anorexia nervosa)

(Damjanov)
The thalamus
a. Relay station for the cortex for (4)
b. Parts of the diencephalon (3)
c. Location and structure of the thalami
d. Divisions of the thalamus (6)
a.
1. Most sensory input
2. Motor inputs from the cerebellum and basal ganglia
3. Limbic inputs
4. Modulatory inputs involved in behavioral arousal and sleep-wake cycles

b.
1. Thalamus
2. Hypothalamus
3. Epithalamus
(Several small nuclei - habenula, parts of the pretectum, and the pineal body.)

c. Located just rostral to the midbrain, shaped like egss, with their posterior ends angled outward, forming and inverted V.

d.
1. A medial nuclear group
(Mediodorsal nucleus)
2. A lateral nuclear group
3. An anterior nuclear group
(By a Y-shaped white matter structure called the internal medullary lamina)
4. Intralaminar nuclei
(In internal medullary lamina)
5. The midline thalamic nuclei
(Thin collection of nuclei lying adjacent to the third ventricle, several of which are continuous with and functionally very similar to the intralaminar nuclei.)
6. The thalamic reticular nucleus
(Not same as the reticular nuclei of the brainstem. Forms a thin sheet enveloping the lateral aspect of the thalamus.)

(Blumenfeld)

(''Inner chamber\Bedroom'')
Thalamus
a. The three main categories of thalamic nuclei (3)
b. Function of the relay nuclei
Give main input, outputs, and proposed function of the following relay nuclei
c. Ventral posterior lateral nucleus (VPL) of lateral nuclear group
d. Ventral posteromedial nucleus (VPM) of lateral nuclear group
a.
1. Relay nuclei
2. Intralaminar nuclei
3. Reticular nucleus

b. Receive inputs from numerous pathways and then project to the cortex, it also receives massive reciprocal connections back from the cortex.
(Most of the thalamus)
(Projections to the cortex can be quite localized or more diffuse)

c. Ventral posterior lateral (VPL) nucleus of lateral nuclear group
<- Medial lemniscus, spinothalamic tract
-> Somatosensory cortex
(Localized projection)
Relay somatosensory spinal inputs to cortex.

d. Ventral posteromedial (VPM) nucleus of lateral nuclear group
<- Trigeminal lemniscus, trigeminothalamic tract, taste inputs
-> Somatosensory and taste cortex
Relay somatosensory cranial nerve inputs and taste to cortex.
(Localized projection)

(Blumenfeld)
Thalamic nuclei - main inputs, outputs, and proposed functions
a. Lateral geniculate nucleus (LGN) of lateral nuclear group
b. Medial geniculate nucleus (MGN) of lateral nuclear group
c. Ventral lateral nucleus (VL) of lateral nuclear group
d. Ventral anterior nucleus (VA) of lateral nuclear group
a. Lateral geniculate nucleus (LGN) of lateral nuclear group
<- Retina
-> Primary visual cortex
Relay visual inputs to cortex

b. Medial geniculate nucleus (MGN) of lateral nuclear group
<- Inferior colliculus
-> Primary auditory cortex
Relay auditory inputs to cortex
(Medial = music = auditory, Lateral = light = visual)

c. Ventral lateral nucleus (VL) of lateral nuclear group
<-
1. Internal globus pallidus
2. Deep cerebellar nuclei
(Into pars caudalis, rest input to pars oralis who have the same connections as VA nucleus)
3. Substantia nigra pars reticulata
-> Motor, premotor, and supplementary motor cortex
Relays basal ganglia and cerebellar inputs to cortex.

d. Ventral anterior nucleus (VA) of lateral nuclear group
<-
1. Internal globus pallidus
2. Deep cerebellar nuclei
3. Substantia nigra pars reticulata
-> Widespread to frontal lobe
(Prefrontal, premotor, motor, supplementary motor cortex)
Relays basal ganglia and cerebellar inputs to cortex.

(In addition, all thalamic nuclei receive reciprocal inputs from the cortex and from the thalamic reticular nucleus. Modulatory cholinergic, noradrenergic, serotonergic, and histaminergic inputs also reach most thalamic nuclei.)

(Blumenfeld)
Thalamic nuclei - main inputs, outputs, and proposed functions
a. Pulvinar and lateral posterior nucleus of lateral nuclear group
b. Lateral dorsal nucleus of lateral nuclear group and anterior nucleus of anterior nuclear group (only of anterior nuclear group)
c. Ventral medial nucleus of lateral nuclear group
d. Mediodorsal (MD) nucleus of medial nuclear group
a. Pulvinar and lateral posterior nucleus of lateral nuclear group
<- Tectum (extrageniculate visual pathway, especially superior colliculi), other sensory inputs
-> Parieto-temporo-occipital association
(Moderately diffuse projections)
Behaviraol orientation toward relevant visual and other stimuli

b. Lateral dorsal nucleus of lateral nuclear group and anterior nucleus of anterior nuclear group (the only nucleus of the anterior nuclear group)
<-
1. Mammillary body
2. Hippocampal formation
-> Cingulate gyrus
Limbic pathways

c. Ventral medial nucleus of lateral nuclear group
<- Midbrain reticular formation
--> Widespread to cortex
May help maintain alert, conscious state

d. Mediodorsal (MD) nucleus of medial nuclear group
<-
1. Amygdala
2. Olfactory cortex
3. Limbic basal ganglia
-> Frontal cortex
Limbic pathways
(Major relay to frontal cortex)

(In addition, all thalamic nuclei receive reciprocal inputs from the cortex and from the thalamic reticular nucleus. Modulatory cholinergic, noradrenergic, serotonergic, and histaminergic inputs also reach most thalamic nuclei.)

(Blumenfeld)
Thalamus - members of
a. Lateral nuclear group
b. Medial nuclear group
c. Anterior nuclear group
d. Intralaminar nuclei
e. Other nuclei
a. Lateral nuclear group
b. Medial nuclear group
1. Ventral medial nucleus
2. Ventral anterior nucleus
3. Lateral dorsal nucleus
4. Ventral lateral nucleus
5. Lateral posterior nucleus
6. Ventral posterior lateral nucleus
7. Ventral posterior medial nucleus
8. Pulvinar nucleus
9. Lateral geniculate body
10. Medial geniculate body

c. Anterior nuclear group
1. Anterior nucleus

d. Intralaminar nuclei
1. Rostral intralaminar nuclei
(Central medial nucleus, paracentral nucleus, and central lateral nucleus)
2. Caudal intralaminar nucleus
(Centromedian nucleus, parafascicular nucleus)

e. Other nuclei
1. Thalamic reticular nuclei
(Not the same as the reticular nuclei of the brainstem. It forms an extensive but thin sheet enveloping the lateral aspect of the thalamus, just medial to the internal capsule)
2. The midline thalamic nuclei
(Thin collection of nuclei lying adjacent to the third ventricle, several of which are continuous with and functionally very similar to the intralaminar nuclei.)

(Blumenfeld)
Thalamic nuclei - main inputs, outputs, and proposed functions
a. Midline thalamic nuclei (paraventricular, parataenial, interanteromedial, intermediodorsal, rhomboid, reuniens\medial ventral)
b. Rostral intralaminar nuclei (central medial nucleus, paracentral nucleus, central lateral nucleus) of intralaminar nuclei
c. Caudal intralaminar nuclei (centromedian and parafascicular nuclei) of intralaminar nuclei
d. Thalamic reticular nucleus
a. Midline thalamic nuclei (paraventricular, parataenial, interanteromedial, intermediodorsal, rhomboid, reuniens\medial ventral)
<-
1. Hypothalamus
2. Basal forebrain
3. Amygdala
4. Hippocampus
->
1. Amygdala
2. Hippocampus
3. Limbic cortex
(Moderately diffuse projections)
Limbic pathways


b. Rostral intralaminar nuclei (central medial nucleus, paracentral nucleus, central lateral nucleus) of intralaminar nuclei
<-
1. Deep cerebellar nuclei
2. Globus pallidus
3. ARAS (ascending..) of brainstem
4. Sensory pathways

->
1. Cerebral cortex
2. Striatum (Caudate nucleus and putamen)
(Very diffuse projections)
Maintain alert consciousness and function as motor relay for basal ganglia and cerebellum.

c. Caudal intralaminar nuclei (centromedian and parafascicular nuclei) of intralaminar nuclei
<-
1. Globus pallidus
2. ARAS of brainstem
3. Sensory pathways
->
1. Cerebral cortex
2. Striatum
(Very diffuse projections)
Motor relay for basal ganglia

d. Thalamic reticular nucleus
<-
1. Cerebral cortex
2. Thalamic relay and intralaminar nuclei
3. ARAS of brainstem
->
1. Thalamic relay and intralaminar nuclei
2. ARAS
Regulate state of other thalamic nuclei
(Only nucleus of the thalamus that don't project to the cortex.)
(Almost only inhibitory GABAergic neurons -> well suited to regulate thalamic activity.)

(In addition, all thalamic nuclei receive reciprocal inputs from the cortex and from the thalamic reticular nucleus. Modulatory cholinergic, noradrenergic, serotonergic, and histaminergic inputs also reach most thalamic nuclei.)

(Blumenfeld)
Name the thalamic nuclei that are most important in relaying the following information to the cortex
a. Somatosensory input (1)
b. somatosensory facial input (1)
c. Visual input (1)
d. Auditory input (1)
e. Basal ganglia and cerebellar input (4)
f. Limbic input (3)
a. Somatosensory input
Ventral posterior lateral (VPL) nucleus of lateral nuclear group.
(Medial lemniscus, spinothalamic tracts.)

b. somatosensory facial input
Ventral posteromedial (VPM) nucleus of lateral nuclear group.
(Trigeminal lemniscus, trigeminothalamic tract, gustatory inputs)

c. Visual input
Lateral geniculate nucleus (LGN)
(Optic tract)

d. Auditory input
Medial geniculate nucleus (MGN)
(Via inferior colliculus of mesencephalic tectum.)

e. Basal ganglia and cerebellar input
1. Ventral anterior nucleus (VA) of lateral nuclear group
2. Ventral lateral nucleus (VL) of lateral nuclear group
3. Rostral intralaminar nuclei
(Central medial, paracentral, and central lateral nuclei)
4. Caudal intralaminar nuclei
(Centromedian and parafascicular nuclei)
(Only basal ganglia)
f. Limbic input
1. Mediodorsal nucleus (MD) of medial nuclear group
2. Anterior nucleus of anterior nuclear group
3. Midline thalamic nuclei
(Paraventricular, parataenial, interanteromedial, intermediodorsal, rhomboid, reuniens\medial ventral)

(Blumenfeld)
Sensory system - terms
a. Paresthesia
b. Dysesthesia
c. Allodynia
d. Hyperpathia\Hyperalgesia
e. Hypesthesia
a. Paresthesia
Abnormal positive sensory phenomenoa.

b. Dysesthesia
Unpleasant, abnormal sensation.

c. Allodynia (allo-: other, -dynia: pain)
Painful sensations provoked by normally non-painful stimuli such as light touch.


d. Hyperpathia\Hyperalgesia
(Pathos-: suffering, algesia: a sense of pain)
Enhanced pain to normally painful stimuli.

e. Hypesthesia
Decreased sensation. = Hypoesthesia

(Blumenfeld)
Paresthesias - characteristics of lesions of different structures
a. Posterior column-medial lemniscal pathways (3)
b. Anterolateral pathways
c. Thalamus - characteristics, name of syndrome
d. Cervical spine - accompanied by which sign
e. Nerve roots
f. Peripheral nerves
g. Parietal lobe or primary sensory cortex
a. Posterior column-medial lemniscal pathways ->
1. Tingling, numb sensation
2. Feeling of a tight, bandlike sensation around the trunks or limbs
3. Sensation similar to a gauze on the fingers when trying to palpate objects

b. Anterolateral pathways ->
1. Sharp burning\searing pain

c. Thalamus - characteristics, name of syndrome
Dejerine-Roussy syndrome - severe contralateral pain.

d. Cervical spine - accompanied by which sign
Rhermitte's sign - an electricity-like sensation running down the back and into the extremities upon neck flexion.

e. Nerve roots
Radicular pain that radiates in a dermatomal distribution and is accompanied by numbness and tingling.
(Provoked by movements that stretch the nerve root.)

f. Peripheral nerves
Pain, numbness, and tingling in their sensory distribution.

g. Parietal lobe or primary sensory cortex ->
Contralateral numbness, tingling and pain.

(Blumenfeld)
Spinal cord lesion - causes (8)
1. Trauma or mechanical
(Contusion, compression, disc herniation, degenerative disorders of vertebral bones, disc embolus (intervertebral disc material that enters local circulation, most often due to trauma))

2. Vascular
(Anterior spinal artery infarct, watershed infarct, spinal dural AVM, epidural hematoma)
(ASA infarct -> anterior cord syndrome. <- trauma, aortic dissection, thromboemboli, disc emboli)
(Watershed infarcts is usually at the mid-thoracic vulnerable zone)
3. Nutritional deficiency
(Vitamin B12, Vitamin E)

4. Epidural abscess

5. Infectious myelitis
(Viral (ie. HIV), Lyme disease, Tertiary syphilis, Tropical spastic paraparesis, Schistosomiasis)

6. Inflammatory myelitis
(MS, SLE, Postinfectious myelitis)
(Myelitis usually develop quick over hours to days, T2 bright areas)

7. Neoplasms
(Epidural metastasis, meningioma, schwannoma, carcinomatous meningitis, astrocytoma, ependyoma, hemangioblastoma)

8. Degenerative\Developmental
(Spina bifida, Chiari malformation (Displacement of the medulla and cerebellar tonsils into the upper spinal canal), Syringomyelia)

(The most common causes of spinal cord dysfunction are extrinsic compression due to degenerative disease of the spine, trauma, and metastatic cancer.)

(Blumenfeld)
Spinal shock
a. What
b. Signs and symptoms
c. Duration
a. A transient phase following acute, severe spinal cord lesions with spinal cord dysfunction.

b.
1. Flaccid paralysis below the lesion
2. Loss of tendon reflexes
3. Decreased sympathetic outflow to vascular smooth muscle -> moderately decreased blood pressure
4. Absent sphincteric reflexes and tone

c. Weeks to months.
(After this period, spasticity and other signs of UMN lesions appear. Some sphincteric and erectile reflexes may return, although often without voluntary control.)

(Blumenfeld)
Sensory loss
a. Sensory loss (except in the face) can be caused by lesions in ... (6)
Characteristics of sensory loss due to
b. Thalamic VPL and VPM nuclei or thalamic somatosensory radiations (2)
c. Lateral pons or lateral medulla (2)
d. Medial medulla (2)
a.
1. Peripheral nerves
2. Nerve roots
3. Posterior column-medial lemniscal and anterolateral pathways
4. The thalamus
5. The thalamocortical white matter pathways
6. The primary somatosensory cortex

b. Thalamic VPL and VPM nuclei or thalamic somatosensory radiations
1. Deficit may be more noticeable in body parts that are highly innervated - distal extremity and lips.
2. Small lesions can be without paresis. Larger lesions can be accompanied by hemiparesis (internal capsule) or hemianopia (LGN or optic radiations).

c. Lateral pons or lateral medulla
1. Involve anterolateral pathways and the ipsilateral spinal trigeminal nucleus -> contralateral loss of pain and temperature sensation and ipsilateral loss of sensation in the face
2. Lateral pontine and lateral medullary syndromes

c. Medial medulla
1. Involves the medial lemniscus -> contralateral loss of vibration and joint position sense
2. Medial medullary syndrome

(Blumenfeld)
Lesion of primary somatosensory cortex
a. Which sensory modalities are often most affected
b. Sometimes all primary modalities are relatively spared, but a pattern called cortical sensory loss is present. What are the clinical triad of this
c. Associated deficits (3)
a. Discriminative touch and joint position sense.

b. Impaired
1. Tactile extinction on double simultaneous stimulation
2. Stereognosia
(Ability to identify various objects by touch)
3. Graphesthesia
(Ability to identify letters or numbers that are being traced onto their palm or the tip of their fingers)

c.
1. UMN lesion signs
2. Aphasia
3. Visual field deficits

(Blumenfeld)
Brown-Sequard syndrome
a. Effect, signs, and symptoms (3)
b. Common causes
a.
1. Ipsilateral UMN-type weakness from damage to the lateral corticospinal tract
2. Ipsilateral loss of vibration and joint position due to damage to the posterior column
3. Contralateral loss of pain and temperature sensation - 2-3 segments lower than the lesion.
(It decussates over 2-3 spinal segments.)
(Can be some ipsilateral temperature and pain sensation loss of one or two segments around the lesion due to damage of the posterior horn cells before their axons have crossed over.)

b.
1. Penetrating injuries
2. MS
3. Lateral compression from tumors

(Blumenfeld)
Central cord syndrome
a. Effects, signs, and symptoms of small lesions (1)
b. Effects, signs, and symptoms of larger lesions (4)
c. Common causes (3)
a.
1. Bilateral regions of suspended sensory loss to pain and temperature
(<- Damage to decussating spinothalamic fibers in the ventral commissure.)
(Lesions of the cervical cord produces the classic cape distribution)

b. In addition to findings in small lesions
1. Damage to anterior horn cells -> LMN-type signs in the area of the lesion
2. Damage to corticospinal tracts -> UMN lesion signs in the area below the lesion
3. Posterior column involvement below
4. Anterolateral pathways are compressed from the center -> can have sacral sparing (feet are somatotopically lateral to upper extremities)

c.
1. Spinal cord contusion
2. Nontraumatic or posttraumatic syringomyelia
(The presence in the spinal cord of longitudinal cavities lined by dense, gliogenous tissue.)
3. Intrinsic spinal cord tumors - hemangioblastoma, ependyoma, astrocytoma

(Blumenfeld)
Posterior cord syndrome
a. Effects, signs, and symptoms (2)
b. Common causes (5)
a.
1. Lesion of the posterior columns -> loss of vibration and position sense below the lesion
2. Larger lesions can encroach upon the lateral corticospinal tract -> UMN lesion signs below

b.
1. Trauma
2. Extrinsic compression from posteriorly located tumors
3. MS
4. Vitamin B12 deficiency
5. Tabes dorsalis (tertiary syphilis)
(4 and 5 preferentially affect the posterior cord.)

(Blumenfeld)
Anatomy of bowel, bladder, and sexual function
a. Onuf nucleus
b. Nuclei and nerve roots for sympathetic innervation of bladder function (bladder neck, urethra, and bladder dome (both alpha and beta) and sexual function (innervation of vaginal wall, erectile and anti-erectile pathways, and sympathetic ejaculatory pathway)
c. Does the afferents ascend in the posterior or anterolateral columns?
a. Onuf nucleus
Nuclei in ventral horn of the spinal cord at S2 (nerve roots S3-4) that innervate the external anal and urethral sphincters.

b. Intermediolateral cell column of the spinal cord. T11-L1.

c. Both
(Urethral afferents in posterior columns and bladder wall afferents in anterolateral columns.)

(Blumenfeld)
Bladder function
a. Which CNS areas is involved (8)
b. Voiding\Detrusor reflex - mediated by, regulated by, mechanism
c. Urethral reflex - mechanism, what is it triggered by
Effect of lesions
d. Bilateral frontal micturition
centers
e. Between pontine micturition center and S2 (UMN)
f. Peripheral nerves or of the spinal cord at S2-S4 (LMN)
a.
1. The primary somatosensory cortex
2. Medial frontal micturition centers
(frontal lobes)
(Activate or inhibit the voiding\detrusor reflex via the pons micturition center)
3. Pontine micturition area
(Regulate the intrinsic spinal cord detrusor\voiding reflex)
4. Cerebellar and basal ganglia pathways
(Possibly involved)
5. Sympathetic intermediolateral cell column
(T11-L1)
(Alpha and beta, bladder neck contraction, bladder detrusor relaxation)
6. Onuf's nucleus
(S2-4, control urethral and external anal sphincters)
7. Sacral parasympathetic nuclei
(S2-4)
(Detrusor contraction)
8. Sacral anterior horn cells
(Pelvic floor muscle contraction)

b. Voiding\Detrusor reflex
Mediated by intrinsic spinal cord circuits, and regulated by the pontine micturition center.

Normally initiated by voluntary relaxation of the external urethral sphincter -> inhibition of sympathetics to the bladder neck to cause it to relax and activation of parasympathetic to cause detrusor contraction.
(The sensation of urine flow through the urethra activates continued sphincter relaxation and detrusor contraction. When flow stops, the urethral sphincters contract, thereby triggering detrusor relaxation through the urethral reflex.)

c. Urethral reflex
Urethral sphincter contract due to stop of flow or voluntary contraction -> detrusor relaxation.

d. Bilateral frontal micturition centers
Loss of voluntary control of the voiding\detrusor reflex.
(Reflex activation of the pontine and spinal micturition centers when the bladder is full.)
(<- Hydrocephalus, parasagittal meningioma, bifrontal glioblastoma, trumatic brain injury, neurodegenerative disorders)

e. Between pontine micturition center and S2
Initially
1.Flaccid, atonic (acontractile) bladder accompanied by persistent reflex contractions of the sphincters -> urinary retention, bladder distention
(Catheterization is usually necessary)
After weeks or months
2. Hyperreflexic\spastic bladder after weeks or months
3. Detrusor-sphincter dyssynergia
(Both detrusor and urethral sphincter tone are increased) -> Urinary urgency or urge incontinence
(When the involuntary detrusor reflex occurs. Accompanied by increased residual volume)
(<- Trauma, tumors, transverse myelitis, MS)

f. Peripheral nerves or of the spinal cord at S2-S4 (LMN)
1. Flaccid areflexic bladder
(Or significantly impaired bladder contractility resembling an atonic bladder)
(<- Loss of parasympathetic outflow to the detrusor and \ or loss of afferent sensory information from the bladder and urethra.)
2. Overflow incontinence
(<- Diabetic neuropathy, compression of the conus medullaris or cauda equina by trauma, tumor, or disc herniation)

(Neruogenic bladder = nonspecific term for both flaccid and hyperreflexive bladder disorders)

(Urinary retention and incontinence can also be caused many non-neurologic conditions such as prostatic hypertrophy, urethral strictures, and intrinsic sphincter deficiency.)

(Blumenfeld)
Bowel function
a. Fecal continence is controlled by
b. Anal sphincter closure is maintained by ... (3), innervated by (3)
c. Fecal incontinence can be caused by
a. Descending pathways originating mainly in the medial frontal lobes.
(Close to frontal micturition centers).

b.
1. Internal smooth muscle sphincter <- sacral parasympathetics
2. External striated muscle sphincter <- pelvic nerves <- Onuf's nucleus
3. Pelvic floor muscles <- sacral anterior horn cells
(All three from S2-S4)

c.
1. Diffuse cerebral or medial frontal lesions
2. Spinal cord lesions
3. Lesions of the sacral nerve roots, pelvic, or pudendal nerves.

(Blumenfeld)
Gerstmann's syndrome
a. Signs and symptoms (4)
b. Associated lesion
a.
1. Finger agnosia
2. Right-left confusion
(Confusion of laterality of body
3. Agraphia
(Inability to write properly in the absence of abnormalities of the limb. <- Angular gyrus lesions)
4. Acalculia
(Inability to perform simple mathematical problems)

b. Dominant inferior parietal lobule, in the region of the angular gyrus.

(Blumenfeld)
Deep tendon reflexes -
a. Explain the 0-5+ staging
b. What is normal
c. Other signs of hyperreflexia (4)
a.
1. 0 - Absent reflex
2. 1+ - Trace\Seen only with reinforcement
(-> gently contract the specific muscle, distract)
3. 2+ - Normal
4. 3+ - Brisk
4. 4+ Nonsustained clonus
(Repetitive vibratory movements)
5. 5+ - Sustained clonus

b. 1+ to 3+, unless they are asymmetrical or there is a dramatic difference between upper and lower extremities.

c.
1. Babinski's sing (+plantar response)
2. Spreading of reflexes
(Spreading of reflexes to other muscles not directly being tested)
3. Crossed adduction of the opposite leg when the medial aspect of the knee is tapped
4. Hoffmann's sign
(Heightened reflexes involving the finger flexor muscles. Elicited by holding the patient's middle finger loosely and flicking the fingernail downward, causing the finger to rebound slightly into extension. If the thumb flexes and adducts in response, Hoffmann's sign is present.)

(Blumenfeld)
Syringomyelia
a. What
b. Causes (3)
c. Patients presents with
a. Fluid-filled cavity in the spinal cord.

b. Can occur with
1. Spinal cord tumors
2. Congenital abnormalities of the craniocervical junction
3. Trauma
(Posttraumatic syringomyelia is a delayed sequela of about 1% of spinal cord injuries, with symptoms beginning 9 years after the injury on average (months-30 years).

c. A central cord syndrome
(First crossing of spinothalamic tract at ventral commissure, lateral corticospinal tract and anterior horn cells, finally posterior columns.)

(Blumenfeld)
Myopathies
a. Typical presentation
b. Examples of immune-mediated myopathies
c. Examples of dystrophic myopathy
d. Other myopathies (4)
e. General diagnosis
a. Weakness that is more severe proximally than distally.
(No sensory or reflex involvement.)

b. Dermatomyositis
(Characteristic violet-colored skin rash, typically involving the extensor surfaces of the knuckles and other joints.

c. Duchenne muscular dystrophy
(Muscular dystrophy: a general term for a number of hereditary, degenerative progressive disorders affecting the skeletal muscles, and often other organ systems as well.)
(Dystrophin is the involved protein, X-linked inheritance)

d.
1. Thyroid disease
2. Malnutrition
3. Toxins
4. Viral infections

e.
1. Elevated blood creatine kinase (CK)
2. EMG studies

(Blumenfeld)
Back pain
a. Trauma\Mechanical causes (6)
b. Vascular causes (4)
c. I I N - Infectious, Inflammatory, Neoplastic causes (8)
d. D D - Degenerative, Developmental causes (3)
e. Non-neurologic causes (8)
a. Trauma\Mechanical causes
1. Disc herniation
2. Spondylolysis
(Fractures that appear in the interarticular portion of the vertebral bone, between the facet joints)
3. Vertebral fracture
4. Arthritis
5. Muscle or ligament strain
6. Soft tissue injury

b. Vascular causes
1. Spinal AVM
2. Spinal cord infarct
3. SAB
4. Spinal epidural hematoma

c. I I N - Infectious, Inflammatory, Neoplastic causes
1. Osteomyelitis
2. Arachnoiditis
3. Spinal epidural abscess
4. Myositis
5. CMV radiculitis
6. Muscle aches in viral illness
7. Guillain-Barre syndrome
8. Primary or metastatic neoplasms
(Extradural, extramedullary, intramedullary)

d. D D - Degenerative, Developmental causes
1. Scoliosis
2. Degenerative joint disease
3. ALS

e. Non-neurologic causes
1. Pregnancy - normal, ectopic
2. Urogenital - menses, UTI, pyelonephritis, renal stone
3. Retroperitoneal abscess, hematoma, or tumor
4. Pancreatitis
5. Aortic aneurysm or dissection
6. Angina
7. MI
8. Pulmonary embolus

(Musculoskeletal causes are most common in all age groups. Usually worsens with exertion and improves with rest. > 50 years -> neoplasm should be suspected.)

(Blumenfeld)
Definitions related to degenerative disorders of the spine
a. Spondylolysis (2)
b. Spondylolisthesis
c. Osteophytes
a.
1. General term for degenerative disorders of the spine.
(Spondylos: spine)
2. Fractures that appear in the interarticular portion of the vertebral bone, between the facet joints.

b. Displacement of a vertebral body relative to the vertebral body beneath it.
Anterolisthesis and posterolisthesis refers to anterior and posterior dispalcement of the upper vertebral bone.
(Often coexist with spondylolysis)
(Listhesis - 'slipping and falling')

c. Bony spurs that form on regions of apposition between adjacent vertebrae because of chronic degeneration.
(Phyton: plant or outgrowth)
(Apposition: the placing in contact of two substances)

(Blumenfeld)
Radiculopathy
a. Radiculopathy
b. Effect, signs, and symptoms (3)
c. Causes (9)
d. T1 radiculopathy can cause, Below L1 radiculopathy can cause
e. Diagnostic tests (3)
a. Sensory or motor dysfunction caused by pathology of a nerve root.

b.
1. Burning, tingling pain radiating in a dermatomal distribution
2. LMN-lesion signs
3. Sensory loss is best determined by pin prick sensation due to a large degree of overlapping of touch nerve endings.

c.
1. Disc herniation
(Most common, most common at C6, C7, L5, S1. Lumbosacral are 2-3x as common as cervical)
2. Osteophytes
3. Spinal stenosis
(Congenitally or as a result of vertebral degenerative disease)
(Lumbar stenosis -> neurogenic claudication (bilateral pain and weakness in legs when ambulant) ("limping"))
4. Trauma
(<- compression, traction, avulsion)
5. Diabetes
(Particularly at thoracic region)
6. Epidural abscess or metastases
(Metastases most often in vertebral bodies)
7. Nerve sheath tumors - schwannomas and neurofibromas
8. Meningeal carcinomatosis
(Infiltration of carcinoma cells in subarachnoid and subdural space)
(Adenocarcinoma, lymphoma, medulloblastoma, glioblastoma)
9. Guillain-Barre syndrome
(Predilection for nerve roots)
10. Infectious -
Herpes zoster\Shingles (Chicken pox, in dorsal root ganglia, critical when in CN V1, treated by oral valacyclovir, famciclovir and acyclovir, also postherpetic neuralgia)
Lyme disease
(Tick-borne, spirocehete Borrelia Burgdorfer)
CMV polyradiculopathy
(in patients with HIV, lumbosacral)

d.
T1 -> Horner's syndrome
Below L1 -> Cauda equina syndrome

e.
1. Straight-leg raising test
(For mechanical nerve root compression, patients lies supine, positive if it reproduce radicular pain, negative if the pain is elicited < 10 degrees and > 60 degrees)
2. Crossed straight-leg raising test
(Elevate the asymptomatic leg cause typical symptoms in the symptomatic leg, specificity > 90%)
3. Pain on percussion of spine
(-> infectious, metastatic, epidural abscess..)
The three most important nerve roots in the arm - give main weakness, reflex decreased, region of sensory abnormality, and usual disc involved for each
a. C5
b. C6
c. C7
a. C5
Main weakness - Deltoid (infraspinatus, biceps)
Reflex decreased - biceps
Region of sensory abnormality - shoulder, upper lateral arm
Usual disc involved - C4-C5
(7% of cervical radiculopathies)

b. C6
Reflex decreased - biceps, brachioradialis
Region of sensory abnormality - First and second fingers, lateral forearm
Usual disc involved - C5-C6
(18% of cervical radiculopathies)

c. C7
Main weakness - Triceps
(Finger extensors)
Reflex decreased - Triceps
Region of sensory abnormality - Third finger
Usual disc involved - C6-C7
(46% of cervical radiculopathies)

(C8 - 6%, weakness of intrinsic hand muscles, decreased sensation in 4th and 5th digits)
(20% of cervical radiculopathies involve > 1 nerve root)

(Blumenfeld)
The three clinically most important nerve roots in the leg - give main weakness, reflex decreased, region of sensory abnormality, and usual disc involved for
a. L4
b. L5
c. S1
a. L4
Main weakness - Iliopsoas, Quadriceps
Reflex decreased - Patellar tendon (Knee jerk)
Region of sensory abnormality - Knee, medial lower leg
Usual disc involved - L3-L4
(3-10% of lumbosacral radiculopathies)

b. L5
Main weakness - Foot dorsiflexion
(Big toe extension, foot eversion and inversion)
Reflex decreased - none
Region of sensory abnormality - Dorsum of foot, big toe
Usual disc involved - L4-L5
(40-45% of lumbosacral radiculopathies)

c. S1
Main weakness - Foot plantar flexion
Reflex decreased - Achilles tendon (ankle jerk)
Region of sensory abnormality - Lateral foot, small toe, sole
Usual disc involved - L5-S1
(45-50% of lumbosacral radiculopathies)

(Blumenfeld)
The brachial plexus
a. The nerve branches of the posterior cord (4)
b. The muscles innervated by the musculocutaneous nerve (3)
c. Branches of the upper trunk (2)
d. Branches of the medial cord (3)
e. Other branches - which and origin
a. STAR
Subscapularis
Thoracodorsal
Axillary
Radial

b. BBC
Brachialis
Biceps
Coracobrachialis

c.
1. Suprascaular
2. Nerve to subclavian
(-> lateral & posterior cord)

d.
1. Medial pectoral nerve
2. Medial cutaneous nerve of arm
3. Medial cutaneous nerve of forearm

e.
1. Dorsal scapular nerve from C5 root
2. Lateral pectoral nerve from lateral cord
3. Bell's long thoracic nerve from the roots of C5-C7

(Robert (roots) Taylor (Trunks) Drinks (Divisions) Coffee (Cords) Black (Branches)

(Blumenfeld)
The brachial plexus
a. The nerve branches of the posterior cord (4)
b. The muscles innervated by the musculocutaneous nerve (3)
c. Branches of the upper trunk (2)
d. Branches of the medial cord (3)
e. Other branches - which and origin
a. STAR
Subscapularis
Thoracodorsal
Axillary
Radial

b. BBC
Brachialis
Biceps
Coracobrachialis

c.
1. Suprascaular
2. Nerve to subclavian
(-> lateral & posterior cord)

d.
1. Medial pectoral nerve
2. Medial cutaneous nerve of arm
3. Medial cutaneous nerve of forearm

e.
1. Dorsal scapular nerve from C5 root
2. Lateral pectoral nerve from lateral cord
3. Bell's long thoracic nerve from the roots of C5-C7

(Robert (roots) Taylor (Trunks) Drinks (Divisions) Coffee (Cords) Black (Branches)

(Blumenfeld)
The brachial plexus
a. The nerve branches of the posterior cord (4)
b. The muscles innervated by the musculocutaneous nerve (3)
c. Branches of the upper trunk (2)
d. Branches of the medial cord (3)
e. Other branches - which and origin
a. STAR
Subscapularis
Thoracodorsal
Axillary
Radial

b. BBC
Brachialis
Biceps
Coracobrachialis

c.
1. Suprascaular
2. Nerve to subclavian
(-> lateral & posterior cord)

d.
1. Medial pectoral nerve
2. Medial cutaneous nerve of arm
3. Medial cutaneous nerve of forearm

e.
1. Dorsal scapular nerve from C5 root
2. Lateral pectoral nerve from lateral cord
3. Bell's long thoracic nerve from the roots of C5-C7

(Robert (roots) Taylor (Trunks) Drinks (Divisions) Coffee (Cords) Black (Branches)

(Blumenfeld)
Draw the simplified scheme for the lumbosacral plexus.
Il hyp - iliohypgastric nerve
ILIng - ilioinguinal nerve
GF - genitofemoral nerve
LFC - lateral femoral cutaneous nerve
F - femoral nerve
Obt - obturator nerve
Saph - saphenous nerve
SG - superior gluteal nerve
IG - inferior gluteal nerve
SC - sciatic nerve
SP - superficial peroneal nerve
DP - deep peroneal nerve
T - tibial nerve
Sur - sural nerve
PFC - posterior femoral cutaneous nerve
Pud - pudendal nerve

(Blumenfeld)
Draw the simplified scheme for the lumbosacral plexus.
Il hyp - iliohypgastric nerve
ILIng - ilioinguinal nerve
GF - genitofemoral nerve
LFC - lateral femoral cutaneous nerve
F - femoral nerve
Obt - obturator nerve
Saph - saphenous nerve
SG - superior gluteal nerve
IG - inferior gluteal nerve
SC - sciatic nerve
SP - superficial peroneal nerve
DP - deep peroneal nerve
T - tibial nerve
Sur - sural nerve
PFC - posterior femoral cutaneous nerve
Pud - pudendal nerve

(Blumenfeld)
Draw the simplified scheme for the lumbosacral plexus.
Il hyp - iliohypgastric nerve
ILIng - ilioinguinal nerve
GF - genitofemoral nerve
LFC - lateral femoral cutaneous nerve
F - femoral nerve
Obt - obturator nerve
Saph - saphenous nerve
SG - superior gluteal nerve
IG - inferior gluteal nerve
SC - sciatic nerve
SP - superficial peroneal nerve
DP - deep peroneal nerve
T - tibial nerve
Sur - sural nerve
PFC - posterior femoral cutaneous nerve
Pud - pudendal nerve

(Blumenfeld)
Draw the simplified scheme for the lumbosacral plexus.
Il hyp - iliohypgastric nerve
ILIng - ilioinguinal nerve
GF - genitofemoral nerve
LFC - lateral femoral cutaneous nerve
F - femoral nerve
Obt - obturator nerve
Saph - saphenous nerve
SG - superior gluteal nerve
IG - inferior gluteal nerve
SC - sciatic nerve
SP - superficial peroneal nerve
DP - deep peroneal nerve
T - tibial nerve
Sur - sural nerve
PFC - posterior femoral cutaneous nerve
Pud - pudendal nerve

(Blumenfeld)
Draw the simplified scheme for the lumbosacral plexus.
Il hyp - iliohypgastric nerve
ILIng - ilioinguinal nerve
GF - genitofemoral nerve
LFC - lateral femoral cutaneous nerve
F - femoral nerve
Obt - obturator nerve
Saph - saphenous nerve
SG - superior gluteal nerve
IG - inferior gluteal nerve
SC - sciatic nerve
SP - superficial peroneal nerve
DP - deep peroneal nerve
T - tibial nerve
Sur - sural nerve
PFC - posterior femoral cutaneous nerve
Pud - pudendal nerve

(Blumenfeld)
Hand muscles (Digit 2-5)
a. How are the lumbrical muscles innervated, and which joints do they flex and extend
b. Palmar and dorsal interossei, innervation, which joints do they flex and extend
a.
Median nerve -> Digit 2-3 -> Flex MCP, Extend MCP and PIP
Ulnar nerve -> Digit 4-5 -> --||--

b. Ulnar nerve
Flex the MCP, extend the MCP and PIP.
(Palmar adduct, Dorsal abduct)

c.
The thumb - what are the three nerves innervating the thumb, and which muscles do they innervate
RUM

Radial nerve -> abductor pollicis longus
(in the plane of the pam)

Ulnar nerve -> adductor pollicis
(And deep head of flexor pollicis brevis)

Median nerve ->
1. Flexion via flexor pollicis longus and superficial head of flexor pollicis brevis (deep branch by ulnar nerve)
2. Opposition via opponens pollicis
3. Abduction perpendicular to the palm via abductor pollicis brevis

(Blumenfeld)
Hand muscles
a. List the intrinsic hand muscles (9)
b. Which of the intrinsic hand muscles are not innervated by the ulnar, but by the median nerve after it passes through the carpal tunnel
c. Which spinal cord level are all the intrinsic hand muscles supplied by
d. In which joint of the fingers is the median and ulnar nerves best tested
e. In which joint of the fingers is the radial nerve best tested
a.
Thenar eminence
1. Opponens pollicis
2. Abductor pollicis brevis
3. Flexor pollicis brevis
4. Adductor pollicis

Hypothenar eminence
5. Opponens digiti minimi
6. Abductor digiti minimi
7. Flexor digiti minimi

Other
8. Lumbricals
9.Dorsal and palmar interossei

b. LOAF
Lumbricals I, II
Opponens pollicis
Abudctor pollicis brevis
Flexor pollicis brevis - superficial head.

c. C8-T1

d. DIP
(Flexor digitorum profundus is innervated by median nerve in 2-3 and ulnar nerve in 4-5. It is the only muscle that innervates the DIP joints, while the uni-innervated flexor digitorum superficialis also flexes the PIP)

e. The MCP
(Other muscles such as the lumbricals also play a big role in extending the PIP and DIP)

(Blumenfeld)
Upper extremity strength testing - give the muscles, nerves, and nerve roots for the following actions
a. Finger extension at the MCP joints
b. Thumb abduction in plane of palm
c. Thumb opposition
d. Finger and thumb adduction in the plane of palm
e. Thumb abduction perpendicular to plane of palm
a. Finger extension at the MCP joints
Extensor digitorum, Extensor digiti minimi, Extensor indicis
Radial nerve (posterior interosseous nerve)
C7, C8

b. Thumb abduction in plane of palm
Abductor pollicis longus
Radial nerve (posterior interosseous nerve)
C7, C8

c. Thumb opposition
Opponens pollicis
Median nerve
C8-T1

d. Finger and thumb adduction in the plane of palm
Adductor pollicis, palmar interossei
C8, T1

e. Thumb abduction perpendicular to plane of the palm
Abductor pollicis brevis
Median nerve
C8,T1

(Blumenfeld)
Upper extremity strength testing - give the muscles, nerves, and nerve roots for the following actions
a. Flexion at DIP 2-3
b. Flexion at DIP 4-5
c. Wrist flexion and hand abduction
d. Wrist flexion and hand adduction
a. Flexion at DIP 2-3
Flexor digitorum profondus to 2-3 digit
Median nerve
C7-8

b. Flexion at DIP 4-5
Flexor digitorum profondus to digits 4-5
Ulnar nerve
C7-C8

c. Wrist flexion and hand abduction
Flexor carpi radialis
Median nerve
C6-7

d. Wrist flexion and hand adduction
Flexor carpi ulnaris
C7-T1

(Blumenfeld)
Lower extremity strength testing - give the muscles, nerves, and nerve roots for the following actions
a. Hip flexion
b. Knee extension
c. Leg abduction
d. leg adduction
a. Hip flexion
Iliopsoas
Femoral nerve, L1-L3 nerve roots
L1-L4

b. Knee extension
Quadriceps
Femoral nerve
L2-L4

c. Leg abduction
Gluteus medius & minimus, Tensor fasciae latae
Superior gluteal nerve
L4-S1

d. leg adduction
Obturator externus, adductor longus, magnus, and brevis, gracilis
Obturator nerve
L2-L4

(Blumenfeld)
Lower extremity strength testing - give the muscles, nerves, and nerve roots for the following actions
a. Foot dorsiflexion
b. Foot plantar flexion
c. Foot eversion
d. Foot inversion
a. Foot dorsiflexion
Tibialis anterior
Deep peroneal nerve
L4-L5

b. Foot plantar flexion
Triceps surae (gastrocnemius, soleus)
Tibial nerve
S1-2

c. Foot eversion
Peroneus longus & brevis
Superficial peroneal nerve
L5-S1

d. Foot inversion
Tibialis posterior
Tibial nerve
L4-L5

(Blumenfeld)
Nerves of the foot - give motor and sensory function
a. Tibial nerve
b. Superficial peroneal nerve
c. Deep peroneal nerve
a. Tibial nerve
M: Foot plantar flexion and toe flexion and inversion
S: Sole of foot

b. Superficial peroneal nerve
M: foot eversion
S: Lateral leg and lateral dorsum of foot

c. Deep peroneal nerve
M: Foot dorsiflexion and toe extension
S: Small area between toe 1-2

(Blumenfeld)
Upper-extremity nerve injuries, brachial plexus, upper trunk injury (C5-C6)
a. Synonym
b. Common causes (2)
c. Affected functions (4)
d. Common pose
a. Erb-Duchenne palsy

b.
1. Traction on an infant's shoulder during a difficult delivery
2. Motorcycle accidents

c. C5-C6, weakness in ->
1. Deltoid
2. Biceps
3. Infraspinatus
4. Wrist extensors

d. Bellmann\Waiter tip
(Arm adducted (deltoid), wrist flexed (wrist extensors), arm extended (biceps) and internally rotated (infraspinatus))

(Blumenfeld)
Brachial plexus, lower trunk injury (C8,T1)
a. Synonym
b. Common causes (3)
c. Affected functions (3)
a. Klumpke's palsy

b.
1. Upward traction produced by grabbing a branch during a fall from a tree
2. Thoracic outlet syndrome
(Symptoms increased by raising and externally rotating the arm. This can also decrease brachial artery pulses)
(Cervical rib)
3. Pancoast's syndrome
(Apical lung tumor (non-small cell carcinoma) -> lower plexus signs, Horner's syndrome, hoarseness from recurrent laryngeal nerve involvement)

c.
1. Hand and finger weakness
2. Atrophy of the hypothenar muscles
3. Sensory los on the ulnar aspect of the hand and forearm
(Horner's syndrome if T1 is damaged proximal to the sympathetic trunk)

(Blumenfeld)
Radial neuropathy
a. Common causes (3)
b. Affected functions (3)
c. How can it be differentiated from damage to the posterior interosseous nerve
a.
1. Sleeping with the arm slung over a park bench - Saturday night palsy
2. Compression in the axilla by improper crutch use - Crutch palsy
3. Fracture of the humerus damaging the radial nerve as it travels in the spiral groove

b.
1. Weakness of all extensors below the shoulder -> wrist drop
2. Loss of the triceps reflex
3. Sensory loss in the radial nerve distribution

d. The posterior interosseous nerve is a purely motor branch -> damage to this nerve spares the sensation.

(Tight wrist bands or hand cuffs -> compress the superficial branch -> isolated sensory loss in dorsolateral hand. "Cheiralgia paresthetica\Handcuff neuropathy)

(Blumenfeld)
Median neuropathy
a. Common causes (4)
b. Affected functions (5)
c. Common pose
a.
1. Sleeping with a lover's head resting on the upper arm - Honeymooner's palsy
2. Fractures of the humerus or distal radius
3. Entrapment as the nerve passes through the pronator teres
4. Entrapment as the nerve passes through the carpal tunnel - carpal tunnel syndrome
(Women > 30 years, typing and house painting. Pregnancy, oral contraceptives, hypothyroidism, wrist fracture, acromegaly, uremia, diabetes. After the median nerve passes through the carpal tunnel it innervates the LOAF)
(Patient often report shaking the hand to try and relieve symptoms - flick sign)
(Wrist flexion, flexion of 2-3 digit and sensation over the thenar eminence are usually spared)
(-> steroid injection, surgical decompression, removable wrist splint)

b. Weakness of
1. Wrist flexion
2. Wrist abduction
3. Opposition of the thumb
4. Flexion of the 2-3 digits
5. Median nerve sensory loss (1-4.5 palmar)

c. Preacher's\Orator's hand when trying to make a fist
(Loss of flexion of 2-3 digit, loss of opposition and flexion of the thumb)

(Blumenfeld)
Ulnar neuropathy
a. Common causes (3)
b. Affeected functions (4)
c. Common pose
a.
1. Entrapment at the elbow in the cubital canal (in the region of the ulnar groove ('adjacent to medial epicondyle\'funny bone')
(Tardy ulnar palsy <- delayed result of posttraumatic, degenerative, or congenital increased carrying angle at the elbow)
(-> surgical translocation to the flexor side of the elbow)
2. Fractures of the medial epicondyle
3. Compressed by a habit of resting the elbows on a hard table

(4. Compression of the nerve in the Guyot's canal can occur during cycling if leaning over excessively. Purely motor affection because the sensory innervation is given off more proximally)

b.
1. Weakness of wrist flexion
2. Weakness of wrist adduction
3. Weakness of flexion of 4-5 digits
4. Sensory loss and paresthesia in an ulnar distribution (palmar 4.5-5 digit)
(5. Fasciculations and atrophy of the hypothenar eminence in severe cases)
(Tinel's sign - median nerve is percussed in the carpal tunnel to provoke paresthesias in the median nerve. Phalen's sign - the dorsal surfaces of the hands are pressed together, flexing the wrist for about 1 minute to provoke paresthesia in the median nerve distribution. Both have relatively low sensitivity and specificity)

c. Ulnar claw\Benediction posture when the patient is asked to extend the fingers
(From weakness in lumbricals 4-5)
(DIP and PIP extended, MCP flexed)
(Combination of chronic median and ulnar nerve lesions leads to thenar and hypothenar atrophy with lack of thumb opposition, -> simian hand\monkey's paw (claw in 2-5, loss of flexion and opposition in 1)

(C8,T1)

(Blumenfeld)
Sciatic neuropathy
a. Common causes (3)
b. Affected functions (4)
c. Differential diagnosis (2)
a.
1. Posterior hip dislocation
2. Acetabular fracture
3. intramuscular injection to inferomedially in the buttocks

b. Weakness\Sensory loss\impairment in
1. All foot and ankle muscles
2. Knee flexion
3. Loss of tendon reflex
4. Sensory loss in the foot and lateral leg below the knee

d.
1. Lesions in the foot area of the motor cortex
2. Compression of nerve roots by disc material and osteophytes

(Sciatica is a vague term referring to all disorders causing painful paresthesias in a sciatic distribution)

(Blumenfeld)
Peroneal nerve palsy
a. Common causes
b. Affected functions
a. (The common peroneal nerve passes around the fibular head near the skin surface)
1. Laceration
2. Stretch injury
3. Forcible foot inversion
4. Compression by tight stockings, a cast, or trauma

b.
1. Foot droop
2. Weakness of eversion
3. Sensory loss over the dorsolateral foot and shin

(L5 radiculopathy is ruled out in the differential diagnosis by affected dorsiflexion, eversion, and INVERSION (Inversion is spared in peroneal nerve palsy because it can be carried out by tibialis posterior)

(Blumenfeld
Other neuropathies
a. Meralgia paresthetica
b. Morton's metatarsalgia
a. Entrapment of the lateral femoral cutaneous nerve (L2-3) as it passes under the inguinal ligament or fascia latae, causing sensory loss and paresthesias.
(<- obesity, pregnancy, weight loss, heavy equipment belts)

b. Morton's metatarsalgia
Patches of numbness and paresthesias in the toes, especially 4-5 due to tight-fitting shoes

(Blumenfeld)
Nerve conduction studies
a. What is a CMAP
b. What is a SNAP
c. How is demyelination observed
d. How is axonal damage (interruption of some axons) determined
e. How can myasthenia gravis and Lambert-Eaton syndrome or botulism (decreased presynaptic release) be distinguished on nerve conduction studies
a. CNAP
Compound motor action potential (CMAP) is the record on a muscle belly innervated by a stimulated nerve.

b. SNAP
(Compound) sensory neuron action potential (SNAP) is the recording obtained by placing an electrode on the skin overlying a sensory neuron proximal to the stimulated site.

(Both result from summated (compound) electrical activity)
(There are standard values for SNAp and CMAP latencies for each major nerve when stimulated at various points along its course. There are also standard SNAP amplitude values.)

c. By increased latency.

d. By decreased SNAP amplitude.

e. Myasthenia gravis shows gradual decrement in CMAP amplitude when given low-frequency (2-5Hz) repetitive stimuli. (Loss of normal safety factor)
Lambert-eaton myasthenic syndrome and botulism show CMAP increment when given fast repetitive stimulation from their baseline low starting level.

(Blumenfeld)
Electromyography (EMG)
a. What is the principle, and what is an MUP
b. How can a neuropathic (nerve or motor disease) be distinguished from a myopathic disorder
a. An electrode is inserted directly into a muscle and motor unit action potentials (MUP) are recorded from muscle cells.

b.
Neuropathic ->
1. Increased spontaneous activity - Fibrillation potentials and positive sharp waves
(Visible on clinical exam as fasciculations)
2. MUP of abnormally large amplitude and duration
(Deinnervation -> compensatory reinnervation of adjacent neurons -> abnormally large motor units)
3. Decreased\Reduced\Incomplete recruitment pattern - normal amplitude but interrupted firing
(When a muscle is voluntarily contracted, the EMG normally shows a pattern of continuous firing of motor units referred to as a normal recruitment pattern.)
(Interrupted since some motor units are not successfully activated)

Myopathic ->
1. Reduced MUP amplitude and duration
2. Normal or increased recruitment pattern but often decreased amplitude
(Increased because more motor units need to be activated for a given force)

(Blumenfeld)
Guillain-Barre syndrome
a. Synonym
b. Cause\Pathogenesis
c. Presentation
d. Diagnosis (3)
e. Treatment (2)
a. Acute inflammatory demyelinating polyneuropathy (AIDP).

b. Immune-mediated demyelination of peripheral nerves, typically 1-2 weeks following a viral illness.
(Campylobacter jejuni enteritis, HIV..)

c.
1. Progressive weakness
2. Areflexia
3. Tingling paresthesias of the hands and feet
(Motor involvement more severe than sensory)
(Symptoms peak 1-3 weeks after onset and recovery occur gradually over months. 20% have some residual weakness 1 year after onset.)

d.
1. Typical clinical presentation
2. CSF demonstrating elevated protein without a significantly elevated WBC count - Albuminocytologic dissociation
3. EMG\Nerve conduction studies compatible with demyelination.

e.
1. Plasmapheresis
2. Intravenous immunoglobulin therapy

(Differential diagnosis for generalized rapidly progressive predominantly motor weakness: myasthenia gravis, heavy metal or organophosphate toxicity, diphtheria, botulism, Lyme polyradiculitis, porphyria, poliomyelitis, tick paralysis)

(Blumenfeld)
Cerebral blood supply
a. What are the two parts of the vertebral artery called (2)
b. What are the four parts of the internal carotid artery called (5)
c. In how many percent is a complete full-caliber circle of Willis present
d. The most important branches of the supraclinoid\intracranial segment of the internal carotid artery (5)
e. Explain the A1, M1 system
a. Extra- and intracranial vertebral artery.

b.
1. Cervical segment
(Relatively vertical)
2. Petrous segment
(Sharp horizontal bend)
3. Cavernous segment
(As the artery begins an S-shaped turn, also known as the carotid siphon, within the cavernous sinus)
4. Supraclinoid segment
(Pass the anterior clinoid process to pierce the dura and bends posteriorly to enter the subarachnoid space)
5. Surpaclinoid\Intraranial segment

c. 1\3 (34%)

d.
OPAAM
Ophthalmic
(Comes off early just after the ICA enter the dura)
Posterior communiating
Anterior choroidal
Anterior cerebral
Middle cerebral

e.
A1,M1,P1 refer to the first segment of the anterior, middle, and posterior cerebral arteries. Second- and third-order branches are referred to as A2,A3, and so on.

(Blumenfeld)
Anterior cerebral artery
a. Path
b. Vascular territory
a.
1. Pass forward to travel in the interhemispheric fissure
2. Sweep back over the corpus callosum
3. Branch into callosomarginal artery which run in the sulcus between the corpus callosum and the cingulate gyrus and the pericallosal artery which pass along the corpus callosum.

b. Most of the cortex on the anterior medial surface of the brain, from the frontal to the anterior parietal lobes, usually inluding the medial sensorimotor cortex.

(Blumenfeld)
Middle cerebral artery
a. Path
b. Vascular territory
a.
1. Turn laterally to enter the Sylvian fissure
2. In the Sylvian fissure it bifurcates into the superior and the inferior division
(Somewhat variable, can be 3-4 main branches)
3. The branches form loops as they pass over the insula and then around and over the operculum to exit the Sylvian fissure onto the lateral convexity.

b.
1. Superior division - cortex above the Sylvian fissure, this includes the lateral frontal lobe and peri-Rolandic cortex.
2. Inferior division - cortex below the Sylvian fissure, including the lateral temporal lobe and a variable portion of the parietal lobe.

(Blumenfeld)
Lentiulostriate arteries
a. Origin
b. What structure do they penetrate
c. Vascular territory
d. What are infarcts of these arteries called, and why are they so common
a. The initial portions of the MCA before it enters the Sylvian fissure.

b. The anterior perforated substance.
(Bordered medially by the optic chiasm and the anterior part of the optic tract, rostrally and laterally by the olfactory stria)

c. Large regions of the basal ganglia and the internal capsule
(Lenticular nuclei: putamen and globus pallidus, striatum: putamen and caudate nucleus)

d. Lacunar infarcts.
(Look like a lake of blood on imaging studies)
They are particularly prone to narrowing in hypertension.

(Blumenfeld)
Penetrating vessels - give the name of the penetrating vessels arising from
a. ACA
b. MCA
c. PCA
d. ICA
e. What are infarcts caused by these penetrating vessels called
a. ACA
The recurrent artery of Heubner
(Portions of globus pallidus, putamen, thalamus (sometimes part of LGN), and the posterior limb of the internal capsule)

b. MCA
The lenticulostriate arteries
(-> lenticular nuclei (putamen, globus pallidus) and striatum (caudate nucleus, putamen))

c. PCA
The thalamoperforator arteries
(Thalamus, part of posterior limb of the internal capsule)
The posterior choroidal arteries
(Choroid plexus of 3rd and part of the lateral)
The thalamogeniculate arteries

d. ICA
Anterior choroidal arteries
(Portions of the head of the caudate, anterior putamen, globus pallidus, and internal capsule)
(Also choroidal plexi of lateral and third ventricles)

e. Lacunar infarcts

(Blumenfeld)
The anterior choroidal artery
a. Origin
b. Vascular territory (4)
a. The ICA

b. Portions of
1. The globus pallidus
2. The putamen
3. The thalamus (sometimes involve part of the LGN)
4. The posterior limb of the internal capsule
(Corticospinal tract and superior thalamic radiations (include somatosensory)

(Blumenfeld)
Blood supply to the internal capsule and globus pallidus, also list the function of a-c
a. The anterior limb of the internal capsule
b. The genu of the internal capsule
c. The posterior limb of the internal capsule
d. The optic radiation
e. The corona radiata (mainly)
a. The anterior limb of the internal capsule
Anterior cerebral artery via recurrent artery of Heubner and other penetrating branches
1. Anterior thalamic radiation
(Radiation formed by fibers interconnecting, via the anterior limb of the internal capsule, the anterior and medial thalamic nuclei and the cerebral cortex of the frontal lobe (excluding the precentral gyrus bordering on the central sulcus)
2. Frontopontine and other corticofugal fibers

b. The genu of the internal capsule
The lenticulostriate arteries of the MCA

The corticobulbar tract
(term formerly used to describe projections of the motor and sensory cortices to nuclei of the rhombencephalon innervating the musculature of the face, tongue, and jaws and some fibers to rhombencephalic relay nuclei; replaced by bullar corticonuclear fibers (to medulla), pontine corticonuclear fibers (to pons), mesencephalic corticonuclear fibers (to midbrain).)

c. The posterior limb of the internal capsule
The anterior choroidal artery of the ICA

1. Corticopontine and other corticofugal fibers
2. Superior thalamic radiation
(Include somatosensory radiation)
3. Corticospinal tract

d. The optic radiation
The PCA mainly and partially by the MCA


e. The corona radiata (mainly)
MCA

(Blumenfeld)
The middle cerebral artery
a. Why is strokes most common here
b. Which types of strokes do we differentiate between (4)
a. At least partially due to its large vascular territory.

b.
1. Superior division
2. Inferior division
3. Deep territory
4. MCA stem infarcts
(Large MCA territory infarcts often have a gaze preference toward the side of the lesion, especially in the acute period.)

(Blumenfeld)
MCA superior division
a. Common characteristics for left and right infarcts (2)
b. Only right (1)
c. Only left (1)
a.
1. Face and arm weakness of the UMN type
2. Rarely face and arm cortical-type sensory loss

b. Right
1. Left hemineglect (to a variable extent)

c. Left
1. Broca's\Non-fluent aphasia

(Blumenfeld)
MCA inferior division
a. Common characteristics for left and right infarcts (3)
b. Only right (3)
c. Only left (2)
a.
1. Contralateral visual field deficit
2. Right face and arm cortical-type sensory loss
3. Mild contralateral paresis

b. Right
1. Profound left hemineglect
2. Right gaze preference, especially at onset
3. Left motor neglect
(With decreased voluntary or spontaneous initiation of movements on the left side)

c. Left
1. Wernicke's\Fluent aphasia
2. Patients can initially seem confused or crazy

(Blumenfeld)
MCA deep territory infarct
a. Characteristics common for left and right side (1)
b. Only right (1)
c. Only left (1)
a.
1. Pure contralateral motor hemiparesis

b. Large infarcts -> cortical deficits: hemineglect

c. Large infarcts -> cortical deficits: aphasia

(Blumenfeld)
MCA stem infarct
a. Common characteristics for both sides
b. Only right
c. Only left
a.
1. Contralateral hemiplegia
2. Contralateral hemianesthesia
3. Contralateral homonymous hemianopia
4. Ipsilateral gaze preference, especially at the onset.
(Caused by damage to the cortical areas important for driving the eyes to the left)

b. Profound left hemineglet

c. Global aphasia

(Blumenfeld)
ACA infarct - characteristics (7)
1. Contralateral leg weakness of UMN type
(Large infarct can cause contralateral hemiplegia)
2. Contralateral leg cortical-type sensory loss
3. Grasp reflex
4. Frontal lobe behavioral abnormalities - abulia
(Very slow responses), changes in personality and judgment, flat affect
5. Contralateral hemineglect
6. Apraxia
(Impairment in the performance of skilled or purposeful movements)
7. Incontinence

(Dominant hemisphere infarct can cause transcortical motor aphasia and non-dominant hemisphere infarct can cause transcortical hemi-neglect)
(Alien-hand syndrome - semiautomatic movements of the contralateral arm that are not under voluntary control can be caused by damage to the supplementary motor area)

(Blumenfeld)
PCA infarct
a. Characteristics common for both sides (2)
b. Only left (2)
a.
1. Contralateral hemianopia
2. Larger infarcts involving the thalamus and internal capsule -> contralateral hemisensory loss and hemiparesis

b.
1. Larger infarcts involving the thalamus and internal capsule -> thalamic aphasia
(Mimicking MCA infarct)
2. Involving the splenium of the corpus callosum -> alexia without agraphia

(Also symptoms from the small perforating vessels that supply the midbrain)

(Blumenfeld)
Watershed infarcts
a. Watershed zone
b. Affected structures and functions of the ACA-MCA watershed infarct
c. Affected structures and functions of the MCA-PCA watershed infarct
a. A region between two arteries which is most susceptible to ischemia when their overall blood supply is reduced.
(ICA thrombosis, hypotension)

b. Proximal arm and leg weakness - "man in barrel" syndrome because the regions of the homunculus involved often include the trunk and the proximal limbs.
Can also cause transcortical aphasia syndromes (aphasias caused by the cortex outside the Broca's and Wernicke's areas) in the dominant hemisphere.

c. Visual association cortex -> disturbance of higher-order visual processing.

(Blumenfeld)
Differential diagnosis of transient neurologic episodes
1. Structural\Mechanical
I. Intermittent compression of spinal cord or peripheral nerves
II. Chiari malformation
(displacement of the medulla and cerebellar tonsils and vermis through the foramen magnum into the upper spinal canal; often associated with other cerebral anomalies.)
III. Platybasia
(Platy- width, flatness)
(A developmental anomaly of the skull or an acquired softening of the skull bones so that the floor of the posterior cranial fossa bulges upward in the region about the foramen magnum.)

2. Vascular
I. TIA
II. Migraine
III. AVM
IV. Amyloid angiopathy

3. Epileptic seizures

4. CSF-flow related - Colloid cyst of the 3rd ventricle

5. Genetic
I. Hypokalemic or hyperkalemic periodic paralysis
II. Episodic ataxias

6. Toxic\Metabolic
I. Medication-related
II. Toxin exposure
III. Hypoglycemia
IV. Pheochromocytoma

7. Infectious\Inflammatory
I. Encephalitis
II. MS

8. Movement disorders
I. Chorea
II. Dystonia
III. Tic disorders

9. Psychogenic
I: Panic attacks
II. Dissociative disorders
III. Somatization
(The process by which psychological needs are expressed in physical symptoms)

9. Other
I. Benign paroxysmal positional vertigo (BPPV)
II. Trigeminal neuralgia
III. Narolepsy

10. Other non-neurologic
I. Retinal detachment
II. Shoulder dislocation
III. Angina
IV. Cardiac arrhythmias
V. Hypotension
VI. Hypoglycemia
VII. Peripheral vascular disease

(Symptoms and signs can be motor, somatosensory, visual, auditory, olfactory, kinesthetic, emotional, or cognitive in nature.)

(The most common causes are TIA, migraine, seizures, and other non-neurologic conditions such as cardiac arrhythmia, and hypoglycemia)

(Blumenfeld)
Transient ischemic attack (TIA)
a. Definition
b. Prognosis following a TIA
c. Mechanism (3)
a. A neurologic deficit lasting less than 24 hours, caused by temporal brain ischemia.
(However, the typical duration is 10 minutes, and lasting longer than one hour produce at least some degree of necrosis and are such small infarcts)

b. 15% will have a stroke causing persistent deficits within 3 months, and half of these will have it within 48 hours.
(TIA is similar to unstable angina)

c.
1. Embolus
2. Thrombosis
3. Vasospasm

(Especially focal seizures and migraine can mimic TIAs. Also hypoglycemic episodes in elderly.)
Stroke
a. Definition
b. Hemorrhagic conversion
c. Large- and small-vessel infarct, characteristics, most commonly caused, by, synonym for small-vessel infarct
a. Hemorrhagic (SAH, intracerebral hemorrhage) and ischemic infarction.

b. Ischemic infarction -> increased fragility of blood vessels -> rupture -> hemorrhage - hemorrhagic conversion

c.
Large-vessel infarct
<- emboli (most often)
Involve the major blood vessels on the surface of the brain - MCA, ACA, PCA, ICA

Small-vessel infarct\Lacunar infarct (resemble small lakes\cavities when the brain is examined on pathologic section)

Involve small penetrating vessels that supply deep structures.
(Deep structures:
In the cerebral hemispheres - basal ganglia, thalamus, internal capsule
In brain stem - the medial portions)

(Blumenfeld)
Embolic infarcts
a. Sources (8)
b. Other emboli beside thrombotic emboli (7)
a.
Cardioembolic infarcts
1. Atrial fibrillation
(Thrombi form in fibrillating left atrial appendage)
2. Myocardial infarction
(Thrombi form on hypokinetic or akineti regions of infarcted myoardium)
3. Valvular disease\Mechanical (Prosthesis - thrombi form on the valve leaflets or prosthetic parts)

Artery-to-artery emboli
4. Stenosed ICA or vertebral artery
5. Ectatic (stretched\dilated) dilated basilar artery
6. Dissection of the arotid or vertebral arteries
7. Atherosclerotic disease of the aortic arch

8. Patent foramen ovale allow a thromboembolus formed in the venous system to bypass the lungs

b.
1. Air emboli
(Deep-sea divers, iatrogenic)
2. Septic emboli
(Bacterial endocarditis -> mycotic aneurysm and hemorrhage)
(Mycotic aneurysm - aneurysm caused by the growth of fungi or bacteria within the vascular wall, usually following impaction of a septic embolus).
3. Fat or cholesterol emboli
(<- Trauma to long bones or to arterial walls)
4. Proteinaceous emboli in marantic endocarditis
(Marantic - wasting)
5. Disc emboli
(Cervical trauma)
6. Amniotic fluid emboli
(child birth)
7. Foreign materials introduced into the circulation
Lacunar infarcts - associated with small-vessel disease caused by hypertension
a. How an the small vessels become occluded during hypertension (4)
a.
1. In situ thrombosis
2. Emboli
3. Hyper-tension related changes in the vessel wall known as lipohyalinosis can lead to occlusion
4. Abnormalities of the parent vessel wall (thrombosis, atheroma formation, dissection) can occlude the openings to the small vessel

(Blumenfeld)
Common launar syndromes - pure motor hemiparesis, or motor hemiparesis with dysarthria or ataxia
a. Clinical features
b. Possible locations for infarcts and possible vessels involved (4)
a.
1. Unilateral face, arm, and leg UMN-type weakness
(Dysarthria)
(Ataxia on same side as weakness. Caused by damage to proprioceptive or cerebellar circuitry)

b.
1. Posterior limb of internal capsule (common) <-
I. Lenticulostriate arteries (common)
II. Anterior choroidal artery
III. Perforating branches of PCA

2. Ventral pons (common) <- ventral penetrating branches of basilar artery

3. Corona radiata <- small MCA branches

4. Cerebral peduncle <- small proximal PCA branches

(Blumenfeld)
Common lacunar syndromes - pure sensory stroke
a. Synonym
b. Clinical features
c. Possible locations for infarct and possible vessels involved
a. Thalamic lacune.

b. Sensory loss to all primary modalities in the contralateral face and body.
(Sometimes followed by thalami pain syndrome\Dejerine-Roussy syndrome. Damage to the posteroinferior thalamus. severe loss of superficial and deep sensation with preservation of crude pain in the hypalgic limbs.)

c. VPL <- thalamoperforator branches of PCA

(Blumenfeld)
Common lacunar syndromes - Sensorimotor stroke
a. Synonym
b. Clinical features
c. Possible locations for infarct and possible vessels involved
a. Thalamocapsular lacune

b. Combination of thalamic lacune (sensory loss to all primary modalities in the contralateral face and body) and pure motor hemiparesis

c, Posterior limb of the internal capsule and thalamic VPL or thalamic somatosensory radiation <-
I. Thalamoperforator branches of the PCA
II. Lenticulostriate arteries

(Blumenfeld)
Common lacunar syndromes - Basal ganglia lacune
a. Clinical features
b. Possible locations for infarct and possible vessels involved
a. Usually asymptomatic, but can cause hemiballismus.

b. Caudate, putamen, globus pallidus, or subthalamic nucleus <-
I. Lenticulostriate arteries
II. Anterior choroidal artery
III. Heubner's arteries

(Blumenfeld)
Stroke
a. Stroke - general symptoms (3)
b. Risk factors (7)
c. Patients benefit of receiving tPA within ... hours of onset of symptoms
d. Why is intravenous heparin no longer used
a.
1. Focal neurologic deficits
2. Headache (25-30%, unilateral headache -> ipsilateral mostly to the lesion, more common in posterior strokes)
3. seizures (3-10%)
(3-4 days -> hemorrhagic conversion, delayed swelling -> edema)

b.
1. Hypertension
2. Diabetes
3. Hypercholesterolemia
4. Cigarette smoking
5. Positive family history
6. Cardiac disease - valvular, AF, patent foramen ovale, low ejection fraction)
7. Prior history CVD
8. Hypercoaguable states
(I. Deficiency of fibrinolytic proteins - protein S, protein C, ATIII
II. Dehydration
III. Adenocarcinoma
IV. Surgery, trauma, childbirth
V. DIC
VI. Antiphospholipid antibody syndromes
VII. Vasculitis (effects on vessel wall in addition to hypercoagulability)(temporal arteritis, primary CNS vasculitis (granulomatous angiits, SLE, polyarteritis nodosa, infections, neoplasms)
VIII. Sickle cell disease
IX. Polycythemia
X. Leukemia
XI. Cryoglobulinemia
XII. Homocystinuria -> increased risk of atherosclerosis)

c. 4.5 hours
(Don't give to patients with a history of intracranial hemorrhage, AVM, aneurysm, active internal bleeding, abnormal coagulation or platelet studies, or uncontrolled hypertension.)

d. The increased risk of hemorrhagic conversion outweighs any benefits.

(Blumenfeld)
Stroke - treatment options
1. tPA
(Within 4.5 hours of onset)

2. Aspirin
(Patients not eligible for tPA)

3. Intra-arterial thrombolysis and mechanical clot extraction
(May allow extension of the therapeutic window for up to 8 hours)

4. Neuroprotectant compounds - trial phase
(May preserve brain tissue before irreversible cell damage occurs.)
(Antioxidants, Ca channel blockers, glutamate receptor antagonists, antagonists against cellular receptors that modulate inflammation)

(General supportive care - avoid dehydration, maintain CPP, keep normoglycemia (hypo- or hyper- worsen infarctions, possibly by increasing local tissue acidosis and BBB permeability)

(Blumenfeld)
Carotid stenosis
a. Location
b. Where is it best heard with a stethoscope, what is the sound called
c. Diagnosis
d. How can it cause occlusion (3)
e. Treatment
a. Just distal to the carotid bifurcation is the most common site.

b. Just inferior to the mandibular angle. Bruit - a whooshing sound.

c. Doppler ultrasound or MRA\CTA is usually sufficient.
(Conventional angiography is the gold standard, but is more invasive)

d.
1. Embolization
2. Thrombosis (MCA, ACA, ophthalmic artery infarct)
3. Sudden drop in blood pressure combined with carotid stenosis -> distal hypotension -> watershed infarct

e. Carotid endartectomy
(Exposed surgically, clamped, opened longitudinally, atheromatous tissue is then removed)
(Indicated in >50% stenosis, not in 100% occlusion)
2. Angioplasty and stenting
(Under investigation)

(Blumenfeld)
Venous drainage of the cerebral hemispheres
a. The superficial veins drain mainly into
b. The deep veins drain into
c. What is the point where the sinuses converge called
d. Name the six fairly constant cortical veins, and where they drain into
a. The superior sagittal sinus and the cavernous sinus (superior petrosal sinus -> transverse sinus, inferior petrosal sinus -> internal jugular vein)

b. The great cerebral vein of Galen
(via the internal cerebral veins, the basal veins of Rosenthal, and others).

c. Torcular\Confluence of sinuses\Torcular Herophili

d.
1. The inferior anastomotic vein of Labbe -> transverse sinus
2. The superior anastomotic vein of Trolard -> superior sagittal sinus
(Superficial middle cerebral vein -> 1,2)
3. The superficial middle cerebral vein -> cavernous sinus
4. The anterior cerebral veins and deep middle cerebral veins -> The basal veins of Rosenthal
(Basal veins of Rosenthal + internal cerebral veins -> Great vein of Galen)

(Blumenfeld)

b. The great vein of Galen.
Sagittal sinus thrombosis
a. Risk factors\Associations
b. Effects,Signs, and symptoms (3)
c. Radiological diagnosis (2)
a.
1. Hypercoaguable states
2. Pregnancy and the first few weeks postpartum

b.
1. Elevated ICP
2. Parasagittal hemorrhages
3. Infarcts
(-> increased ICP -> decreased CPP)

c.
1. Empty delta sign - Central, darker filling defect of the superior sagittal sinus with CT or MRI with IV contrast
2. Increased density on CT or increased T1 signal on MRI due to coagulated blood
(3. MRV (MR venography) or conventional angiography is the gold standard)

(Can also occur less commonly in other venous sinuses, in the deep cerebral veins, or in a major cortical vein.)

(Blumenfeld)
Subarachnoid hemorrhage
a. What is the most common cause for this disorder
b. What vessels are most commonly affected (4)
c. Diagnosis and treatment
a. Rupture of an arterial aneurysm in the subarachnoid space.
(80% of the cases.)

b.
1. Anterior communicating artery (30%)
2. Posterior communicating artery
(25%)
(-> CN III palsy by compression
3. Middle cerebral artery
(20%)
4. Different locations in the vertebrobasilar system
(15%, PICA, AICA, SCA)

c. Emergency CT -> confirm with angiogram -> treat by surgical clipping or endovascular occlusion

(Blumenfeld)
The retina
a. Macula - what, how many degrees does it cover
b. Fovea - what, how many degrees does it cover, how many % of the fibers in the optic nerve and the cells in the primary visual cortex is devoted to it

c. Optic disk - what, where is the blind spot
a. Oval region (3x5 mm) in the central fixation point for each eye. Occupies the central 5 degrees of the visual field. Relatively high visual acuity.

b. Area within the macula with the highest visual acuity. Corresponds to the central 1-2 degrees of visual space. 50% of fibers in the optic nerve and cells in the primary visual cortex is devoted to it.
(This is the only area of the retina not covered by the other layers of cells - the photons have less distortions)

c. The region where the axons leave the retina, 15 degrees medial to the fovea.
The blind spot is 15 degrees temporally to the central fixation point (and slightly inferior)

(Blumenfeld)
The retina
a. What are the ratio of rods to cones
b. What are the function of the rods
c. What are the function of the cones
d. How are photoreceptors and bipolar cells different from other neurons (2)
a. 20:1

b. High-sensitivity light detection in low-level light conditions.

c. Higher spatial and temporal resolution, color vision.

d.
1. Don't fire action potentials, information is conveyed along the length of the cells by ionic diffusion.
2. Communicate through nontraditional synapses that release neurotransmitters in a graded fashion that depends on membrane potentials

(Blumenfeld)
The retina
a. What does the center-surround (concentric) configuration refer to
b. Explain the two classes of center-surround cells
c. Parasol\Palpha\A subdivison of retinal ganglion cells - characteristics, project to
d. Midget cells\Pbeta\B subdivision of retinal ganglion cells - characteristics, project to
a. The configuration of the receptive field of bipolar and ganglion cells (and LGN neurons and input neurons of the primary visual cortex) with a center-surround structure caused by lateral inhibition or excitation by interneurons (horizontal and amacrine cells)

b.
On-center cells
Excited by light in the center of their receptive field and inhibited by light in the surrounding area.

Off-center cells
Opposite.

c. Parasol\Palpha\A cells
Large cell bodies, large receptive (dendritic) field, respond best to gross stimulus features and movement
-> magnocellular layers of the LGN

d. Midget\Pbeta\B ells
Small cell bodies, small receptive\dendritic field, most sensitive to fine visual detail and color.
-> parvocellular layers of the LGN

(Blumenfeld)
The visual pathway
a. Bitemporal visual field defects can be caused by
b. Monocular visual field defects can be caused by
c. Homonymous visual field defects can be caused by
a. Optic chiasm lesions.

b. The eye, the retina, or the optic nerve.

c. Lesions proximal to the chiasm
1. Optic tracts
2. LGN
3. Optic radiations
4. Visual cortex
(The defect occurs in the same portion of the visual field for each eye.)
The optic pathway
a. The axons of the retinal ganglion cells synapse on
b. Where does the extrageniculate visual pathways project to
a.
1. Neurons in the LGN -> the primary visual cortex
Extrageniculate pathways
-> Brachium of the superior colliculus ->
(A band of fibers of the optic tract bypassing the lateral geniculate body)
2. The Pretectal area
(Pupillary light reflex, -> parasympathetic nuclei controlling the pupils)
3. The superior colliculus
(2&3 - important for directing visual attention and eye movement toward visual stimuli.)

b.
1. Numerous brain stem areas involved in directing visual attention and eye movement toward visual stimuli and for the pupillary light reflex
2. -> Pulvinar and lateral posterior nucleus of the thalamus -> association cortex (lateral parietal cortex and frontal eye fields of the prefrontal cortex)
(The retino-tecto-pulvinar-extrastriate cortex pathwayfunctions in visual attention and orientation while the retino-geniculo-striate pathway functions in visual discrimination and perception)
The lateral geniculate nucleus
a. Where does the parasol retinal ganglion cells project to, what is the function of this pathway
b. Where does the midget retinal ganglion cells project to, what is the function of this pathway
c. What are koniocellular neurons, and what are their function
d. How is information from the left and right eye segregated in the LGN
a. Parasol cells -> magnocellular layers of LGN, cortical layers 1-2
(-> Primary visual cortex, layer 4Calpha)
(1 = ventral, 6 = dorsal)
Motion and spatial analysis
(M pathway)
(Some magnocellular cells are on\off cells - firing in response to certain patterns)

b. Midget cells -> parvocellular layers of LGN - 3-6
(-> primary visual cortex layer 4Cbeta)
Detailed form and color
(P (parvocellular) pathway)

c. Interlaminar\koniocellular neurons are located between the layers of the LGN. Thought to assist parvocellular neurons in color vision.

d. Every other layer receives ipsi- and contralateral input.
(After this its intermingled)

(Blumenfeld)
The optic radiations
a. General path
b. Inferior optic radiation, specific path, synonym, defect caused by lesion, where does it project to
c. Superior optic radiation, specific path, defect caused by lesion, where does it project to
a. LGN -> enter white matter and sweep over and lateral to the atrium and temporal horn of the lateral ventricle -> primary visual cortex in the occipital lobe.
(Here axons of contra- and ipsilateral LGN neurons synapse on alternate ocular dominance columns)

b. Inferior optic radiation\Meyer's loop
Via temporal lobe
Contralateral homonymous superior quadrantanopia ("Pie in the sky" visual defect)
The inferior bank of the calcarine fissure\Lingula
(Fovea -> peripherally = posterior (occipital pole) -> anterior)

c. Superior optic radiation
Under the parietal lobe
Contralateral homonymous inferior quadrantanopia ("pie on the floor")
-> The superior bank of the calcarine fissure\Cuneus
(Fovea -> peripheral = posterior (occipital pole) -> anterior)

(Blumenfeld)
The primary visual cortex (17)
a. Why is it sometimes referred to as the striate cortex
b. Outline the pathway responsible for motion and spatial analysis from the retinal ganglion cells to the higher-order visual association cortex
c. Outline the pathway responsible for form analysis from the retinal ganglion cells to the higher-order visual association cortex
d. Outline the pathway responsible for color analysis from the retinal ganglion cells to the higher-order visual association cortex
a. Its well developed fourth cortical layer is further subdivided into 4A,4B,4Calpha, and 4Cbeta. 4B contains numerous myelinated axon collaterals -> pale-appearing Stria of Gennari (visible to the naked eye)
(It ends sharply at the junction of area 17 and 18)

b.
1. Parasol retinal ganglion cells -> magnocellular layers of LGN -> Layer 4Calpha of area 17 -> Layer 4B -> Thick stripe of area 18 (visual association cortex) and dorsolateral parieto-occipital cortex (higher-order visual association cortex)
(can also go from thick stripe of area 18 -> dorsolateral parieto-occipital cortex)
(Dorsal pathway)
(Where?)
(UP!)

c.
Midget retinal ganglion cells -> parvocellular layers of LGN -> Layer 4Cbeta and then to interblobs (specialized areas in layer 2,3) of area 17 -> pale stripe of area 18 (visual association cortex) -> inferior occipitotemporal cortex (higher-order visual association cortex)

d. Midget retinal ganglion cells -> parvocellular and interlaminar regions of LGN -> layer 4Cbeta and then blobs (specialized areas of layer 2,3) of area 17 -> thin stripe of area 18 -> inferior occipitotemporal cortex
(c & d -> DOWN!)
(Ventral pathway)
(What?)

(Blobs, and thick, thin, and pale strips are differentiated by staining with cytochrome oxidase)

(Blumenfeld)
Snellen notation
A method for measuring visual acuity.

20\X -> X is the distance at which a normal individual can see the smallest line of the eye chart seen by the subject at 20 feet.

(Blumenfeld
Terms for describing visual disturbances
a. Scotoma
b. Homonymous defect
c. Refractive error
d. Photopsias
a. Scotoma
A circumscribed region of visual loss
(Skotos - darkness)

b. Homonymous defect
A visual field defect in the same region for both eyes.

c. Refractive error
Indistinct vision improved by correcting lenses.

d. Photopsias
Bright, unformed flashes, streaks, or balls of light.
(Photo: light, opsia: vision)

e. Phosphenes
Photopsias produced by retinal shear or optic nerve disease.
(Phos: light, phaino: to show)

(Blumenfeld)
Some terms to describe visual disturbances
a. Entopic phenomena
b. Illusions
c. Hallucination
a. Entopic phenomena
Seeing structures in one's own eye.

b. Illusions
Misinterpretation of visual perception.

c. Hallucination
Perception of something that is not present.

(Blumenfeld)
Primary visual cortex
a. What are the functional units
b. Give two examples
a. Vertical columns

b. Ocular dominance columns for differentiating ipsi- and contralateral input. Orientation columns for determining different orientation\angles of lines.

(Blumenfeld)
Positive visual phenomena - simple visual phenomena
a. What is simple visual phenomena
b. Light flashes often indicate
c. Ranbow-colored halos often indicate
d. Visual blurring and fortification scotomas often indicate
e. Pulsating, colored lights or moving geometric shapes often indicate
a. Lights, colors, or geometric shapes caused by disturbances located anywhere from the eye to the primary visual cortex.

b. Retinal detachment.

c. Acute glaucoma.

d. Migraine
(Fortification <- resemblance to medieval forts due to its zigzag lines <- activation of orientation columns in primary visual cortex?)

e. Occipital seizures.

(Blumenfeld)
Formed visual hallucinations
a. What
b. Arise from which structure
c. Common causes
d. Release phenomenon
a. Perception of something that is not present, such as people, animals, or complex scenes.

b. The inferior temporo-occipital visual association cortex.

c.
1. Toxic or metabolic disturbances - hallucinogens, anticholinergics, cyclosporin
2. Withdrawal from alcohol or sedatives
3. Focal seizures
4. Complex migraine
5. Neurodegenerative conditions - Creutzfeldt-Jakob disease, Lewy-Body disease
6. Narcolepsy
7. Midbrain ischemia - peduncular hallucinosis
8. Psychiatric disorders
(Auditory hallucinations are more common)

d. Visual hallucinations in patients with visual deprivation part or all of their visual fields caused by ocular or CNS lesion.
(Especially in the early stage. Called Bonnet syndrome when it occurs as a result of impaired vision in the elderly.)

(Blumenfeld)
Methods for visual field testing
1. Confrontation testing
(Hold one finger midway between patient and examiner to use the examiner as a reference, test all the quadrants. Test one eye at the time. Use both hands for testing for extinction)

2. Blink to threat
(For testing crude visual fields in an uncooperative or lethargic patient.)

3. Goldmann perimetry
(Small lights of different sizes and intensities displayed on a screen in front of the patient)

(The normal visual field is about 60 degrees nasally and superiorly, and slightly more temporally and inferiorly)

(Blumenfeld)
Visual field defects
a. Monocular scotoma or visual loss is usually caused by
b. Bitemporal hemianopia is usually caused by
c. Homonymous visual field defects is usually caused by
d. Macular sparing
a.
1. Retina lesion (infarct, hemorrhage, infection, degeneration)
2. Optic nerve lesion (glaucoma, optic neuritis, elevated ICP, anterior ischemic optic neuropathy, optic glioma, optic schwannoma, meningioma, trauma)

(Visual loss if the lesion is severe enough.)

b. Optic chiasm lesion
(pituitary adenoma, meningioma, craniopharyngioma, hypothalamic glioma..)

c. Retrochiasmal lesions
1. Optic tracts
(Tumors, infarcts, demyelination)
2. LGN
(Tumors, infart, hemorrhage, toxoplasmosis, other infections)
(Can give keyhole-shaped sectoranopia)
3. Optic radiations
(Infarcts, tumors, demyelination, trauma, hemorrhage)
(Meyer loop\Inferior division <- MCA inferior division. Contralateral superior quadrantanopia)
Superior loop <- MCA superior division. Contralateral inferior quadrantanopia)
4. Visual cortex

(Usually more congruent for more posterior lesions)

d. Partial lesions of the optic pathway from the optic nerve -> primary visual cortex can cause sparing of the macula since the fovea has such a large projection.
(In the primary visual cortex it receives collateral flow from both MCA and PCA)
(External compression of the optic nerve from increased ICP can cause concentric visual loss\macular sparing)

(Blumenfeld)
Blood supply to the visual pathways
a. What are the three main causes of impaired blood flow in the ophthalmic artery and its branches
b. How can monocular visual loss arise via these mechanisms
c. How can monocular scotoma occur via these mechanisms
d. TIA of the central retinal artery is called
a.
1. Emboli
(Often atheromatous material arising from ipsilateral ICA9
2. Stenosis
(Diabetes, hypertension, elevated ICP)
3. Vasculitis
(Temporal arteritis)

b. Occlusion of the central retinal artery.

c. Branch retinal artery occlusion.
(-> Altitudinal (upper\lower half) scotoma)
(2 - superior and inferior)

d. Amaurosis fugax.

(Blumenfeld)
Blood supply to the visual pathways
a. What is impaired blood supply to the anterior optic nerve called, which arteries are affected, and
what is the common causes
b. Blood supply to the LGN
c. Most common cause of bilateral altitudinal scotoma
d. The "where" component of the pathways from the primary visual cortex can be affected by
e. The "what" component of the pathways from the primary visual cortex can be affected by
a. Anterior ischemic optic neuropathy (AION)
The short posterior ciliary arteries
(Branches of ophthalmic artery)
1. Arteritic AION from temporal arteritis
2. Non-arteritis AION from diabetes, hypertension, and elevated cholesterl
(Atherosclerotic mechanism)

b. LGN <-
1. Anterior choroidal artery <- ICA
2. Thalamogeniculate artery, posterior choroidal artery <- PCA
(LGN infarct can often produce unusual visual field losses.)
(Affect nearby posterior limb of the internal capsule -> thalamic somatosensory radiations, corticospinal tract)

c. Vertebrobasilar insufficiency.

d. What = ventral pathway -> inferior occipitotemporal visual association cortex
PCA

e. Where = dorsal pathway to lateral parieto-occipital visual association cortex
MCA-PCA watershed territory

(Blumenfeld)
Optic neuritis
a. What
b. 50% of patients with an episode of optic neuritis will develop
c. Effects, signs, and symptoms (4)
d. Diagnostic methods (3)
e. Differential diagnosis
a. Inflammatory demyelinating disorder of the optic nerve.
(Epidemiologically and pathophysiologically related to MS. Mean age of onset - 30s, rarely > 45 years, 2:1 female-to-male ratio)

b. MS

c.
1. Eye pain
(Worsened by eye movement)
2. Monocular visual problems - central scotoma, decreased visual acuity, impaired color vision, visual loss
3. Papillitis
(swollen optic disc if the inflammation extends to the fundus)
(Not present if the inflammation is completely retrobulbar)
4. Optic disc pallor
(Suggest earlier episodes of optic neuritis)

d.
1. Red desaturation
(Show red object to one eye at the time, less intense color in the affected eye. both to present and prior)
2. Afferent pupillary defect <- swinging flashlight test
3. Visual evoked potentials
(-> decreased conduction velocity)
(shown a shifting checkerboard pattern -> detect voltage over occipital pole)

e.
1. Retinal artery occlusion
2. Anterior ischemic optic neuropathy (AION)
3. Acute glaucoma
4. Compressive or infiltrative lesions
(MRI with gadolinium)

(Treatment with high-dose IV steroids shorten the episode, but don't have any effects on long-term prognosis)

(Onset can be acute or progressive, recovery begin within 2 weeks and is normally nearly complete within 6-8 weeks. Often some residual visual loss.)

(Blumenfeld)
The brainstem
a. What is the name of the rostral limit, where is it
b. What is the name of the junction of the midbrain and the pons
c. What is the name of the junction of the pons and the medulla
d. Where is the cervicomedullary junction
a. The midbrain-diencephalic junction.
At the level of the tentorium cerebelli.

b. The pontomesencephalic junction.

c. The pontomedullary junction.

d. The cervicomedullary junction is at the level of the foramen magnum and the pyramidal decussation.

(Blumenfeld)
The midbrain
a. What is the components of the tectum, where are they located
b. Which structure forms the ventral surface
c. Which structure limits the midbrain dorsally
d. Which structures limit the midbrain dorsolaterally
a. The inferior and superior colliculi. At the dorsal surface.

b. The cerebral peduncles
(The interpeduncular fossa lies between it.)

c. The fourth ventricle.

d. The cerebellum, via the superior, middle, and inferior cerebellar peduncles.

(Blumenfeld)
The fourth ventricle
a. Rostral limit - what, where
b. Caudal limit - what, where
c. Name the three paired structures protruding into the fourth ventricle from the ventral aspect
a. The cerebral aqueduct of Sylvius in the midbrain.
(3rd ventricle -> Cerebral aqueduct -> 4th ventricle)

b. The obex ('barrier') in the rostral medulla, which marks the embryological opening of the central canal of the spinal cord.

c. (Rostral->Caudal)
1. Facial colliculus
(Abducens nuclei and facial nerve)
2. Hypoglossal trigone
(The hypoglossal nucleus)
3. Vagal trigone
(Dorsal motor nucleus of CN X)

(Blumenfeld)
The medulla oblongata
a. Structural features of the rostral medulla
b. Structural features of the caudal medulla
a. Rostral medulla
The inferior olivary nuclei is seen ventrolaterally.
(Just lateral to the pyramids.)

b. The rostral medulla
The inferior olivary nuclei are no longer seen.
The dorsal column and its nuclei are seen. (Cuneatus & gracilis)

(Blumenfeld)
The cranial nerves
a. Which cranial nerve is unique in crossing over as it emerges from the brain stem
b. Which cranial nerve pass between the PCA and the superior cerebellar artery
c. What is the only cranial nerve that emerge dorsally from the brain stem
d. Which three cranial nerves exits from the cerebellopontine angle
a. CN IV

b. CN III

c. CN IV
(Dorsally from the midbrain)

d. CN VII, VIII, and IX

(Blumenfeld)
Cranial nerve nuclei
a. Give the relative location of the three different motor and the three different sensory columns of the cranial nerves
Give the nuclei, CNs, and functions for
b. Somatic motor\General somatic efferent
c. Branchial motor\Special visceral efferent
d. Parasympathetic\General visceral efferent (
a.
Motor - medial->lateral
I. Somatic motor\General somatic efferent column
II. Parasympathetic\General visceral efferent column
III. Branchial motor\Special visceral efferent column

Sensory - medial->lateral
I. Visceral sensory\Special and general visceral afferent column
II. General somatic sensory\General somatic afferent column
III. Special somatic sensory\Special somatic afferent column

b. Somatic motor\General somatic efferent (striated muscles from occipital somites)
I. Oculomotor nuclei -> CN III -> extraocular muscles
II. Trochlear nuclei -> CN IV -> superior oblique
III. Abducens nuclei -> CN VI -> lateral rectus
IV. Hypoglossal nuclei -> CN XII intrinsic tongue muscles

c. Branchial motor\Special visceral efferent (striated muscles from branchial arches)
I. Motor nucleus of CN V -> motor root of CN V -> Muscles of mastication, mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini
(1st branchial arch)
II. Facial nucleus -> CN VII -> Muscles of facial expression, stapedius, stylohyoid, posterior belly of digastric
(2nd branchial arch)
III. Nucleus ambiguus -> CN IX -> stylopharyngeus (3rd arch), some of the pharyngeal muscles, X -> Muscles of pharynx and larynx (4th and 6th arch)
(Accessory spinal nucleus -> CN XI -> Sternocleidomastoid, upper part of trapezius. May be from occipital. Controversy. Some call it mixed somitic\branchial)

d. Parasympathetic\General visceral efferent
I. Edinger-Westphal nuclei -> CN III -> sphincter muscle of the pupil and the ciliary musle
II. Superior salivatory nucleus (pons) -> CN VII -> sphenopalatine ganglion (lacrimal gland), and submandibular ganglion (sublingual and submandibular glands)
III. Inferior salivatory nucleus (reticular formation of medulla) -> CN IX -> otic ganglion (parotid gland)
IV. Dorsal motor nuclei of CN X (in vagal trigone in rostral medulla) -> heart, lungs, GI -> Cannon point

(SAT -> solitarius (VII, IX, X), ambiguus (IX, X), and trigeminal (V, VII, IX, X) are the three exceptions involved in > CN)

(Blumenfeld)
Cranial nerve nuclei
a. Give the relative location of the three different motor and the three different sensory columns of the cranial nerves
Give the nuclei, CNs, and functions for
b. Visceral sensory - special and general visceral afferent
c. General somatic sensory\General somatic afferent
d. Special somatic sensory\Special somatic afferent
a.
Motor - medial->lateral
I. Somatic motor\General somatic efferent column
II. Parasympathetic\General visceral efferent column
III. Branchial motor\Special visceral efferent column

Sensory - medial->lateral
I. Visceral sensory\Special and general visceral afferent column
II. General somatic sensory\General somatic afferent column
III. Special somatic sensory\Special somatic afferent column

b. Visceral sensory - special and general visceral afferent
Special visceral afferent: rhombencephalic gustatory nucleus (the rostral 1\3 of the nucleus solitarius <- CN VII, IX, X <- taste

General visceral afferent
Cardiorespiratory nucleus of nucleus solitarius (caudal portion) <- CN IX, X <- various receptors

c. General somatic sensor\General somatic afferent
Trigeminal nuclei <- CN V, VII, IX, X <- touch, pain, temperature, position and vibration sense for face, sinuses, and meninges

d. Special somatic sensory\Special somatic afferent
I. Cochlear nuclei (2, in inferior cerebellar peduncle) <- CN VIII <- hearing)
II. Vestibular nuclei (4, pons) <- CN VIII <- vestibular sensation

(Blumenfeld, Stedman)
Peripheral sensory and parasympathetic ganglia and their funtions
a. CN III (1)
b. CN V (1)
c. CN VII (3)
d. CN VIII (2)
e. CN IX (3)
f. CN X (3)
a. CN III
Ciliary ganglion -> parasympathetics to sphincter pupillae and ciliary musles

b. CN V
Trigeminal\Semilunar\Gasserian ganglion -> primary sensory neuron cell bodies for sensation in the face, mouth, sinuses, and supratentorial meninges

c. CN VII
I. Sphenopalatine\Pterygopalatine ganglion -> parasympathetics to larimal glands and nasal mucosa
II. Submandibular ganglion -> parasympathetics to submandibular and sublingual salivary glands
III. Geniculate ganglion -> primary sensory neuron in anterior 2\3 of tongue, and for sensation near outer ear

d. CN VIII
I. Spiral ganglion -> primary sensory neuron cell bodies for hearing
II. Scarpa's vestibular ganglion -> primary sensory neuron cell bodies for vestibular sensation

e. CN IX
I. Otic ganglion -> parasympathetics to parotid gland
II. Jugular\Superior glossopharyngeal ganglion -> primary sensory neuron cell bodies for sensation from middle ear, external auditory meatus, pharynx, and posterior 1\3 of the tongue
III. Inferior\petrosal glossopharyngeal ganglion -> primary sensory neuron cell bodies for same + carotid body inputs

f. CN X
I. Parasympathetic ganglia in end organs -> parasympathetics to the heart, lungs, and GI tract -> Cannon point
II. Superior\Jugular vagal ganglion -> primary sensory neuron cell bodies for sensation from pharynx, outer ear, and infratentorial meninges
III. Inferior\Nodose vagal ganglion -> primary sensory neuron cell bodies for laryngeal sensation, for taste from epiglottis, and for reflex inputs from aortic arch receptors and other thoracoabdominal viscera

(Blumenfeld)
Anosmia
a. Causes of bilateral anosmia
b. What is Foster Kennedy syndrome
a.
1. Head trauma
(Damage the olfactory nerves as they penetrate the cribriform plate)
2. Viral infections can damage the olfactory neuroepithelium
3. Certain neurodegenerative disorders - Alzheimer's, Parkinson's
4. Intracranial lesions at the base of the frontal lobes near the olfactory sulci
(Meningioma, basal meningitis, sarcoidosis)
(Small lesions in this area are often difficult to detect clinically beside anosmia, and can grow very large before they get detected)

b. Foster Kennedy syndrome
Large lesions of the olfactory sulcus region (most often meningioma) ->
1. Ipsilateral anosmia and optic atrophy from tumor compression
2. Contralateral papilledema from elevated ICP

(Blumenfeld)
Nerves for extraocular movement - point of exit
a. CN III
b. CN IV
c. CN VI
d. Which two structures do all three nerves plus V1 pass through
a. CN III
Ventrally in the interpeduncular fossa.

b. CN IV
Dorsally from the inferior tectum.

c. CN VI
Ventrally at the pontomedullary junction.

d. Cavernous sinus -> Superior orbital fissure

(Blumenfeld)
Somatic afferent innervation
a. Which three nerves innervates the external auditory meatus
b. Which nerves innervates the dura
a. CN VII, IX, X.
(Synapse on the trigeminal nuclei)

b. Supratentorial by CN V, infratentorial by CN X and upper cervical nerve roots.

(Blumenfeld)
Trigeminal somatic sensory system
a. Input to the trigeminal nuclei (4)
b. Location of the trigeminal nuclear complex
c. Components and their functions, pathway to thalamus, and the thalamic relay station of the trigeminal nuclear complex
a.
1. CN V <- Supratentorial dura, nasal sinuses, nasal cavity, face, mouth, anterior 2\3 of the tongue
2. CN VII, IX, X <- external auditory meatus
3. CN IX <- also middle ear, posterior 1\3 of the tongue, pharynx
4. CN X <- also infratentorial dura and pharynx

b. From the midbrain to the upper cervical spinal cord.

c.
1. The mesenephalic trigeminal nucleus - proprioception
2. The chief trigeminal sensory nucleus
Fine touch, dental pressure

-> Trigeminal lemniscus -> VPM
(The posterior column-medial lemniscal system is equivalent (fine touch, proprioception) and goes via medial lemniscal to VPL)

3. The spinal trigeminal nucleus
Crude touch, pain, temperature

Trigeminothalamic tract -> VPM
(Equivalent to the anterolateral systems (crude touch, pain, temperature. Spinothalamic tract -> VPL)
(Like the anterolateral system there are also pathways to intralaminar thalamic nuclei, the reticular formation, and other areas, to mediate the affective and arousal aspects of facial pain.)

(Also exist small dorsal trigeminothalamic tract. Trigeminal sensory nucleus -> ipsilateral (!!!) VPM without crossing. Appear to convey touch and pressure sensation from the oral cavity, including the teeth.)

(Blumenfeld)
The trigeminal nuclear complex
a. Location of the spinal trigeminal nucleus
b. What is the spinal tract analogous to
c. Explain the somatotopic organization of the spinal trigeminal tract and nucleus
a. In the lateral pons and medulla, extending down to the upper cervical spine.
(Where it forms a continuation of the dorsal horn.)

b. Lissauer's tract.

c.
1. Dorsal -> ventral:
Dorsal to ventral areas: external auditory meatus (CN VII, IX, X), V3, V2, V1)

2. Rostral to caudal
Perioral -> more peripheral

(Blumenfeld)
The mesencephalic trigeminal nucleus and tract
a. Location
b. Transmitted sensory modality
c. Explain the jaw jerk reflex
a. Along the lateral edge of the periaqueductal gray matter of the midbrain.
(The only case in which primary sensory neurons lie within the CNS instead of in peripheral ganglia)

b. Proprioception.
(Masticatory musles, tongue muscles, and extraocular muscles.)

c. Monosynaptic reflex. The sensory mesencephalic trigeminal neruons synapse in the motor trigeminal nucleus.

(A spasmodic contraction of the temporal muscles following a downward tap on the loosely hanging mandible.)

(Blumenfeld)
Trigeminal neuralgia\Tic Douloureux
a. What
b. Cause (3)
c. Treatments
a. Condition where patients experience recurrent episodes of brief (seconds-minutes) severe pain, most often in V2 or V3. Brought on by chewing, shawing, or touching certain trigger points in the face.
(Sensation is normal)

b. Uncertain.
Some cases have been linked to
1. Compression by aberrant vessels.
2. Compression by tumors
3. Demyelination from MS
(In the entry zone of the brainstem)

c.
1. Pharmaologically
Carbamazepine
(Drug of choice, also anticonvulsant and used for other neurogenic pain syndromes)
(Oxcarbazepine (similar), baclofen (GABAb agonist, muscle relaxant, -> MS, spinal cord injuries), lamotrigine (new class anticonvulsant, resemble phenytoin), pimozide (tranquilizing antipsychotic)

2. Surgical
I. Radiofrequency ablation of the Gasserian ganglion
II. Gamma knife
III. CyberKnife
IV. Surgical microvascular decompression

(Blumenfeld)
Trigeminal sensory loss
a. Causes affecting the ganglion and the peripheral nerves
b. Lesion of the trigeminal nucleus cause ipsi- or contralateral sensory loss
c. Describe the presentations of the typical lesion affecting the spinal trigeminal nucleus in the pons or medulla
a.
1. Trauma
2. Metastatic disease
(Especially in isolated jaw numbness)
3. Herpes zoster
4. Aneurysms of the petrous part of the ICA
5. Cavernous sinus or orbital apex disorders
6. Trigeminal or vestibular schwannoma
7. Sphenoid wing meningioma

b. Ipsilateral sensory loss.

c. Lateral pontine or medullary lesion
1. Ipsilateral loss of pain and temperature sensation in the face
2. Contralateral loss of pain and temperature sensation in the body from damage to the nearby spinothalamic tract

(Blumenfeld)
Facial nerve
a. Functions (4 groups)
b. What is the name of its two branches, and what do they carry
c. What is the facial colliculus
d. Which of the branchial muscles are affected in lesions of the cortex, the corticobulbar tracts, the facial nucleus, nerve fascicles in the pons, or peripheral nerves
d. The five main branchial motor branches
e. Parasympathetic part - nucleus, nerves, innervate
f. Where does the three terminal parts of the facial nerve exit - the main, chorda tympani, the greater petrosal nerve
a.
1. Branchial motor - facial expression, stapedius, posterior belly of digastric
2. Parasympathetic - all salivary glands except parotid gland.
I. Submandibular ganglion -> sublingual and submandibular glands
II. Sphenopalatine\Hay fever ganglion -> lacrimal glands, nasal mucosa
3. Special visceral sensory - taste from anterior 2\3 of the tongue
4. General somatic sensory - area of external auditory meatus

a.
1. The main nerve trunk - branchial motor fibers
2. Nervus intermedius - the rest

c. A projection\'bump' on the floor of the fourth ventricle formed by the facial nerve fascicles looping around the abducens nucleus.
(It then exits pons ventrolaterally via the pontomedullary junction.)

d.
UMN (cortex, corticobulbar tracts) - contralateral, but forehead is spared
(Both sides have bilateral projections to the forehead)
LMN (facial nucleus, fascicles, and peripheral nerve): complete ipsilateral plegia

d. Two Zebras Borrowed My Car
Temporal
Zygomatic
Buccal
Mandibular
Cervical
(+ smaller branch to stapedius, occipitalis, posterior belly of digastric, and stylohoid)

(Trigeminal for Tensor Tympani, Seventh for Stapedius)

e. Superior salivatory nucleus.
The greater petrosal nerve (from genu of the facial nerve) -> sphenopalatine ganglion
The chorda tympani (leave VII just before the stylomastoid foramen) -> submandibular ganglion

f.
1. The main part -> stylomastoid foramen
2. The greater petrosal nerve -> hiatus of the facial canal -> groove next to foramen lacerum, join deep petrosal nerve (sympathetic from ICA) = nerve of pterygoid canal -> pterygoid canal
3. Chorda tympani -> petrotympanic fissure

(Blumenfeld)
Muscles of the middle ear
a. Which
b. Function
c. Innervation
a. Stapedius and Tensor tympani.

b. Dampen movements of the middle ear ossicles to provide feedback modulation of acoustic signal intensity.

c. Trigeminal for Tensor tympani, Seventh (CN VII) for stapedius.

(Blumenfeld)
Taste pathway from receptors to cortical area
1. Anterior 2\3 of tongue via chorda tympani of CN VII, posterior 1\3 by CN IX, epiglottis and pharynx by CN X -> own sensory neurons ->

2. Secondary sensory neurons in the gustatory nucleus in the rostral nucleus solitarius ->

3. Tertiary sensory neurons at VPM of thalamus (both side project bilaterally) ->

4. Cortical taste area - inferior margin of the postcentral gyrus adjacent to the tongue somatosensory area and extends into the fronto-parietal operculum and insula

(Blumenfeld)
Facial nerve lesion
a. How can a UMN and LMN type lesion be differentiated
b. Bell's palsy
c. What is synkinesis
d. Bell's palsy - when is a different diagnosis likely, what is the differential diagnosis (7)
a.
UMN cortex project bilaterally to neurons in the facial nucleus controlling frontalis and part of orbicularis oculi -> UMN lesion: frontalis is spared, orbicularis oculis is partly spared (widened palpebral fissure), the rest of the contralateral face is affected.
Additional clues - neighborhood effects
1. Hand or arm paresis
2. Sensory loss
3. Aphasia
4. Dysarthria
(The UMN corticobulbar fibers controlling the facial nucleus project mainly to pontine interneurons that project to LMN in the facial nucleus)

LMN-type lesion - the whole ipsilateral face is affected.

b. Bell's palsy
The most common facial nerve disorder.
All divisons are affected within a few hours or days and then gradually recover. The cause is thought to be viral or inflammatory.
(Hyperacusis can occur because of stapedius paresis. Dry mouth. LMN-type lesion signs.)
(Treatment is controversial. Some evidence suggest that a 10-day intensive regimen of oral steroids is beneficial.)
(80% recover fully within 3 weeks)

c. The phenomenon that occurs when aberrant regeneration of different motor branches result abnormal innervation.
(Ie. if the patient is asked to close one eye, the ipsilateral platysma muscle may contract slightly, along with the orbicularis oculi.)

d. Recurrent episodes and bilateral paresis.
Differential diagnosis
1. Tumor
2. Infilitrative disorders
(1,2 by MRI)
3. Lyme disease
4. Sarcoidosis
5. HIV
(3-5 by lumbar puncture)
6. Trauma
7. Brain stem lesions


(Blumenfeld)
Reflexes involving CN VII - give the pathways, mono- or polysynaptic
a. The corneal reflex
b. The jaw jerk reflex
a. The corneal reflex
Both mono- and polysynaptic
V1 -> chief sensory and spinal trigeminal nuclei -> facial nerve nucleus -> facial nerve -> orbicularis oculi
(It is also modulated by cortical areas. -> Lesions of the sensorimotor cortex can cause a decreased response)
(Make sure to avoid eliciting the blink-to-threat reflex)

b. The jaw jerk reflex
Monosynaptic
Tap the chin with the mouth slightly open -> CN V3 -> mesencephalic trigeminal nucleus -> motor trigeminal nucleus -> jaw jerks forward

(Blumenfeld)
(Blumenfeld)
The inner ear
a. What are the structure that detect sound in the cochlea called,
and what are the receptor, which cells do they activate and what is its ganglion called
b. What are the structure that detect angular acceleration in the inner ear called, and what are the receptor, which cells do they activate and what is its ganglion called
c. What are the structure that detects linear acceleration and head tilt in the inner ear called, and what are the receptor, which cells do they activate and what is its ganglion called
a. The organ of Corti, the cilia of the hair cells are mechanoreeptors.
(Positioned in the tectorial membrane where they are relatively static compared to the movement of the basilar membrane.)
(Hair cells (mechanoreceptors in the cilia) and their supporting cells.)
Cochlear nerves, spiral ganglion (in the cochlea).

b. The ampullae of the semicircular canals.
Mechanoreceptors in the cilia of the hair cells.
Bipolar sensory neurons, vestibular ganglia of Scarpa

(Located within the gelatinous cupula that is deformed by flow)
(The hair cells are located in a ride within each ampulla - the crista ampullaris.)

c. The maculae of the utricle and saccule.
Mechanoreceptors on cilia of hair cells.
(The cilia is located within a gelatinous layer with otoliths - calcified crystals)
Inferior and superior vestibular ganglion.

(Blumenfeld)
Hearing
a. Central pathway from the hair cells
b. Does a lesion to the ventral and dorsal cochlear nuclei and distally cause a ipsi-, contra- or bilateral hearing loss
c. Does a lesion proximally to the ventral and dorsal cochlear nuclei cause a ipsi-, contra- or bilateral hearing loss
a.
1. Cochlear nerve with spiral\cochlear ganglion (in the spiral canal of the modiolus)
(Bipolar sensory neurons) ->

2. Dorsal and ventral cochlear nuclei (lateral aspect of the inferior cerebellar peduncle) ->
I. Dorsal cochlear nucleus (fibers pass dorsal to the inferior cerebellar peduncle) -> cross the pontine tegmentum -> ascend in the contralateral lateral lemniscus -> inferior colliculus
II. Ventral cochlear nucleus (many fibers pass ventral to the inferior cerebellar peduncle) -> bilateral superior olivary nuclear complex (pons)(localizing sounds horizontally in space)(fibers cross in a white matter structure called the trapezoid body (also nuclei of the trapezoid body) -> lateral lemniscus -> inferior colliculi
(Also nuclei of the lateral lemniscus)

3. Combined again. Some fibers decussate ventral and dorsal to the cerebral aquduct. The rest ascend via the brachium of the inferior colliculi ->

4. MGN of thalamus (just lateral to the superior colliculus) ->

5. Auditory radiations ->

6. The primary auditory cortex\Brodmann's area 41 on Heschl's transverse gyri
(Medial to the superior temporal gyrus in the Sylvian fissure)

b. Ipsilateral.

c. Bilateral
(But most contralateral)
(In auditory seizures (in auditory cortex), patients often perceive a tone or roaring sound (like a jetplane) approaching from the contralateral side)

(Blumenfeld)
Vestibular pathways
a. The vestibular nuclei are important for
b. Connections (3)
c. Vestibular nuclei and their functions/connections
a. Adjustment of posture, muscle tone, and eye position in response to movements of the head in space.

b.
1. The cerebellum
(Vestibulo-cerebellar connections -> flocculonodular lobes and cerebellar vermis. Some fibers bypass the vestibular nuclei entirely.)
2. The brainstem motor and extraocular systems
3. Ascending pathway through the ventral posterior part of thalamus to the cortex
(Heschl's transvere gyri, 41)
(Provide an awareness of head position that is integrated with visual and tactile spatial information in the parietal asociation cortex, Brodmann's area 5\Lateral temperoparietal junction and posterior insula.)

c. 4 - Superior, medial, lateral, and inferior
I. The lateral vestibular/Deiter's nucleus - The lateral vestibulospinal tract
(Part of medial descending motor system, balance and extensor tone)
II. The medial vestibular - the medial vestibulospinal tract
(--||--, medial vestibulospinal tract (some contribution from inferior vestibular nuclei), -> cervical spine, head and neck position)
III. Superior and medial vestibular nuclei -> Medial longitudinal fasciculus (MLF)
(Connect the nuclei involved in eye movement to each other and to vestibular nuclei, responsible for vestibulo-ocular reflex)

(Sometimes MLF is called ascending MLF and medial vestibulospinal tract is called descending MLF)

(Blumenfeld)
Vestibular system
a. What movement do the semicircular canals detect
b. What movements do the utricle and saccula detect
c. What is the input to the inferior and superior vestibular ganglia
a. Angular accelertion around three orthogonal axes.
(Cause endolymph flow through the ampullae which deforms the cupula and thus stimulate mechanoreceptors in cilia of hir cells)

b. Linear acceleration and head tilt.

c.
Superior vestibular ganglion: utricle, anterior and lateral semicircular canals.
Inferior vestibular ganglion:
saccule and posterior semicircular canal.

(Blumenfeld)
Hearing loss
a. Unilateral hearing loss can be caused by dysfunction of - differentiate between conductive hearing loss and sensorineural hearing loss causes(5)
b. Explain Rinne test
c. Explain the Weber test
a.
Conductive hearing loss causes
1. The external auditory meatus
2. The middle ear

Sensorineural hearing loss
3. The cochlea
4. CN VIII
5. The cochlear nuclei
(Proximally the cochlear nuclei give bilateral projections)

b. Rinne test
Distinguish sensorineural and conductive hearing loss.
Air conduction - hold a 512 Hz tuning fork outside the ear is compared to bone conduction - achieved by placing the tuning fork on the mastoid process.
Normal people and people with sensorineural hearing loss hear better with air conduction, people with conductive hearing loss hear better with bone conduction due to it 'bypassing' the external auditory meatus and middle ear.
(In sensorineural hearign loss, air conduction is greater than bone conduction in both ears, but hearing is decreased on the affected ear.)

c. The Weber test
Place the tuning fork on the vertex of the skull in the midline and ask the patient to report if the tone sounds equal on both sides ->
I. Sensorineural hearing loss - the tone is quieter on the affected side
II. Conductive hearing loss - the tone is louder on the affected side
(Compensatory neural or mechanical factors increase the perceived volume on the side of the conduction problem.)

(Also auditory evoked potentials can be used)

(Blumenfeld)
Hearing loss
a. List causes of conductive hearing loss (4)
b. List causes of sensorineural hearing loss (7)
a. Conductive hearing loss
1. Cerumen in the external auditory canal
2. Otitis
3. Tympanic membrane perforation
4. Sclerosis of the middle ear ossicles

b. Sensorineural hearing loss
1. Exposure to loud sounds
2. Meningitis
3. Ototoxic drugs
4. Head trauma
5. Viral infections
6. Aging
7. Meniere's disease
8. Internal auditory artery infarct
9. Cerebellopontine angle tumors
(Acoustic neuroma\vestibular schwannoma (most common, 9% of overall intracranial neoplasms, meningioma, cerebellar astrocytoma, epidermoid, glomus jugulare, metastases)

(Blumenfeld)
Acoustic neuroma\Vestibular schwannoma
a. What
b. Signs and symptoms
c. What are the second most common Schwannoma affecting cranial nerves
a. Slow-growing tumor that arise at the transitional zone between Schwann cells and oligodendrocytes as the nerve enters the internal auditory meatus.
(Acoustic neuroma is a misnomer)
(9% of intracranial neoplasms)

b.
1. Unilateral hearing loss
2. Tinnitus (ringing in the ear)
3. Unsteadiness
(Vertigo (a sensation of spinning or whirling) is a late sign)

4. Trigeminal nerve involvement - facial pain, sensory loss, decrease of corneal reflex

5. Facial nerve involvement - weakness, hypogeusia

(Later signs from large tumors include compression of the cerebellar and corticospinal tracts -> ipsilateral ataxia and contralateral hemiparesis, CN IX and X involvement -> impairment of swallowing and gag reflex, CN III and IV, compression of the fourth ventricle -> hydrocephalus -> herniation -> death)

(Treated by surgical excision or by radiosurgery)

c. Trigeminal neuroma.

(Blumenfeld)
Vertigo
a. Define true vertigo
b. What other sensations due patients often call vertigo
c. Causes of vertigo - central and peripheral
d. How can central and peripheral causes be differentiated, why is this important
a. A spinning sensation of movement.
(Most suggestive of vestibular disease)

b. Dizziness - light-headedness, faintness, nausea, and unsteadiness on one's feet.

c.
Central - brainstem or cerebellum
1. Vertebrobasilar ischemia or infarct
2. Posterior fossa hemorrhage
(Vertigo is an early sign)
3. Encephalitis
4. Tumors
5. Demyelination
6. Drugs and toxins - alcohol, anticonvulsants (cerebellum, vestibular nuclei)
7. Syphilis
8. Lyme disease
9. Epileptic seizures (parietal region)

Peripheral (Most common) - inner ear
1. Benign paroxysmal vertigo
(Most common cause, brief episodes of vertigo following change of position, <- otolithic debris (otoconia) in the posterior semicircual canal especially)
(Can be treated by habituating procedures such as Brandt-Daroff and canalith repositioning maneuvers such as Epley maneuver)
2. Vestibular neuritis
(<- viral or idiopathic, vestibular ganglia, intense vertigo for several days, feeling of unsteadiness can last for months)
3. Meniere's disease
(<- Excess fluid\pressure in the endolymphatic system, vertigo with fluctuating or progressive hearing loss and tinnitus)
4. Autoimmune inner ear disease
(Symptoms resembling Meniere's disease)
5. Vestibular schwannoma\Accoustic neuroma
(+ Hearing loss and tinnitus, often unsteadiness rather than true vertigo)
6. Ototoxic drugs - gentamicin
(Bilateral vestibular dysfunction -> unsteadiness of gait, oscillopsia (perception of oscillating vision))

d. Important because central causes often are of an acute nature
1. Central disorders are often associated with diplopia, other visual changes, somatosensory changes, weakness, dysarthria, ataxia, impaired consciousness etc..
2. Dix-Hallpike\Nylen-Barany positional testing
Patient sit, examiner guides head with one ear down down until the head is extended over the table.
I. Onset of nystagmus is immediate\delayed in central and delayed in peripheral
II. Habituation\Adaptation only occur in peripheral causes
III. Vertical vertigo is unique for central, both can have the other types.
IV. Prominent nystagmus can occur without vertigo in central while it follows nystagmus in peripheral

(The general physical exam should include orthostatic measurements to rule out hypovolemic causes of nausea\dizziness)
Meniere's disease
a. Cause
b. Signs and symptoms (2)
c. Treatment strategies (3)
a. Increased fluid and pressure in the endolymphatic system.

b.
1. Recurrent vertigo accompanied by fluctuating or progressive hearing loss and tinnitus
2. Feeling of fullness in the ear

c.
1. Salt restriction or diuretics
(No controlled studies)
2. Transtympanic gentamycin -> cause permanent peripheral loss of vestibular function
3. Surgical procedures - vestibular nerve section, labyrinthectomy, endolympathic saculotomy (decompression)

(Blumenfeld)
The glossopharyngeal nerve
a. Branchial motor function and its associated nuclei
b. Parasympathetic function and its associated nuclei
c. General somatic sensory function and its associated nuclei
d. Special visceral sensory function and its associated nuclei
e. General visceral sensory function and its associated nuclei
a. Branchial motor function and its associated nuclei
Stylopharyngeus m
Nucleus ambiguus (ambigous to discern on conventional stains)

b. Parasympathetic function and its associated nuclei
Parotid gland
Inferior salivatory nucleus
(Inferior salivatory nucleus -> CN IX -> tympanic nerve, join lesser petrosal nerve -> otic ganglion -> parotid gland)

c. General somatic sensory function and its associated nuclei
Middle ear, region near external auditory meatus, posterior one-third of tongue, part of pharynx.
Spinal trigeminal nucleus.
(Inferior\petrosal and superior\jugular glossopharyngeal ganglia)

d. Special visceral sensory function and its associated nuclei
Taste in posterior 1\3 of the tongue
Rostral nucleus solitarius

e. General visceral sensory function and its associated nuclei
Carotid body & sinus
Caudal nucleus solitarius

(Blumenfeld)
Trapezius muscle - innervation
Upper part by spinal accessory nerve\CN XI.

Lower part by cervical nerve roots C3 and C4.

(Blumenfeld)
Hypoglossal nerve
a. Which tongue muscles is not innervated by the hypoglossal nerve
b. Unilateral tongue weakness cause the tongue to deviate to which side
c. Upper motor neuron - ipsi- or contralateral
d. Lower motor - ipsi- or contralateral
a. Palatoglossus (CN X)

b. Deviate toward the weak side.

c. Contralateral
(Cross in corticobulbar pathways)

d. Ipsilateral

(Blumenfeld)
All nerves can be affected by (7)
1. Diabetic neuropathy
2. Demyelination
3. Traumatic injury
4. Inflammatory disorders
5. Neoplastic disorders
6. Toxic disorders
7. Infectious conditions
(Motor nerves can also be affected by motor neuron disease)

(Blumenfeld)
Recurrent laryngeal nerve
a. Unilateral lesions cause
b. Causes of lesion (2)
a. Unilateral vocal cord paralysis and hoarseness.

b.
1. Sugery - carotid endarterectomy, cervical disc surgery, thyroid surgery, cardiac surgery
(Endarterectomy - excision of atheromatous deposits)
2. Infiltration by apical lung tumors (Pancoast's syndrome: this, Horner's syndrome, lower trunk brachial plexopathy)

(Blumenfeld)
Glomus jugulare
a. Synonym
b. From which structure
c. Effect
a. Glomus tumors

b. Glomus bodies
(Normal, small epithelioid structures that resemble the carotid bodies histologically, but whose function is unknown. Richly innervated by CN IX, located next to the jugular foramen and along branches of CN IX leading to the middle ear cavity)

c.
1. Impairments of CN IX-XI due to compression of these nerves in the jugular foramen
2. Extends to nearby CN XII
3. Can grow upward and affect CN VII and VIII in the temporal bone.

(Blumenfeld)
Dysarthria
a. What
b. Which structures can be involved (6)
c. Common causes (8)
a. Dysfunction of articulation.
(Dysarthria is a motor articulatory disorder as opposed to aphasia which is a disorder of higher order functioning)

b.
1. The muscles of articulation - jaw, lips, palate, pharynx, tongue
2. The neuromuscular junction
3. Peripheral or central portions of CN V, VII, IX, X, and XII
4. Motor cortex face area
5. Extrapyramidal - cerebellum and basal ganglia
6. Corticobulbar tracts

c.
1. Infarcts, hemorrhages and other lesions affecting #3-6
2. MS
3. Toxins
4. Toxins - alcohol
(And other diffuse encephalopathies)
5. Myasthenia gravis and other neuromuscular junction diseases
6. Amyotrophic lateral sclerosis (ALS)
(Corticobulbar, corticospinal, and spinal motor neurons)
7. Botulism
8. Wilson's disease\Hepatolenticular degeneration
(Basal ganglia)

(Blumenfeld)
Dysphagia
a. What
b. General causes (3)
c. Describe the four phases of swallowing
d. What is the dangerous complication
e. Which reflexes can give an indication of the pharyngeal reflexes
a. Impaired swallowing.

b.
1. Local obstructions - esophageal strictures, neoplasms
2. Neuromuscular disorders - muscles of the tongue, palate, pharynx, epiglottis, larynx, or esophagus
3. Neural disorders
I. CN IX, X, XII & their nuclei
II. Descending corticobulbar pathways
(Often occurs along with dysarthria)

b.
1. The oral preparatory phase
(Preparation of the food bolus for swallowing by mastication)
2. The oral phase
(Movement of the bolus in an anterior-posterior direction by the oral tongue)
3. The pharyngeal phase
(Propulsion of the bolus through the pharynx by base-of-tongue driving force, aided by anterior-superior movement of the larynx)
4. The esophageal phase
(Opening of the upper esophageal sphincter -> esophageal peristalsis -> emptying into the stomach)

d. Aspiration
(esophageal reflux -> aspiration pneumonia -> dead)

e.
1. The gag reflex
(Afferent is IX & X, most IX, efferent is IX-X, most X. Stroke the posterior pharynx with a cotton swab)
2. Palate function by palate elevation\Say Aaah
(Unilateral lesions of CN X\Nucleus ambiguus -> uvula deviate toward the normal side)
Pseudobulbar affect
a. Which CNs are involved in crying and laughing
b. What is pseudobulbar affect
c. Which other disorders can cause this
a. CN VII, IX, X, and XII

b. A syndrome that can be caused by lesions of corticobulbar pathways in the subcortical white matter or brainstem.
Emotional incontinence - unelicited and uncontrollable bouts of laughter and crying
(Probably UMN disorder in which there is abnormal reflex activation of laughter and crying circuits in the brainstem)

c.
1. Gelastic ('inclined to laughter') epilepsy
(<- hypothalamic hamartoma, rarely with temporal lobe seizures)
(Hamartoma (hamartion: a bodily defect) - a mass resembling a tumor that represents anomalous development of tissue natural to a part or organ rather than a true tumor)

(Blumenfeld)
Eye movement disorders and pathways are separated into
1. Nuclear and infranuclear pathways
(Brainstem nuclei of III, IV, and VI, the peripheral nerves, and the muscles)

2. Supranuclear pathways
(Brainstem and forebrain circuits that control eye movements through connections with the nuclei of CN III, IV, and VI.)

(Blumenfeld)
Somatic motor column
a. which CNs
b. Location of nuclei
c. Location of point of emergence
a. Extraocular muscles (CN III, IV, VI) and tongue muscles (CN XII).

b. Near the midline, adjacent to the ventricular system.

c. exit the brainstem ventrally near the midline, with the exception of CN IV, which exits dorsally.

(Blumenfeld)
The oculomotor nerve
a. Location of nuclei
b. Point of emergence from the brainstem
c. Which structures are topologically related to CN III as it exist the brainstem
d. Where does the parasympathetic fibers of CN III run, what does this topography make it susceptible for
e. Location of the Edinger-Westphal nuclei relative to the somatic motor nuclei
f. What are the three important points about function of the oculomotor nuclei
a. In the upper midbrain at the level of the superior colliculi and red nuclei, just ventral to the periaqueductal gray matter.

b. The interpeduncular fossa.

c. It runs between the PCA and SCA.

d. Superficial and medial portion. Compression from aneurysm of Pcomm.
(Which run parallel and medial to it as it travels in the subarachnoid space)

e. Form a V shape as they curve over the dorsorostral aspect of the oculomotor nuclei.

f.
1. Unilateral paresis of the levator palpebrae superior cannot arise from unilateral lesions of the oculomotor nucleus.
2. Unilateral mydriasis cannot arise from unilateral lesions of the oculomotor nucleus.
3. Lesions of the oculomotor nucleus affect both superior rectus
(The crossing fibers traverse the oculomotor nucleus before exiting in the third nerve fascicles.)
(The rest are innervated ipsilateral)

(Blumenfeld)
The trochlear nerve
a. Location of the trochlear nuclei
b. Point of emergence from the brain stem, what does this topographical arrangement make the susceptible to
c. Why are they prone to damage of shear injury from trauma
a. In the lower midbrain at the level of the inferior colliculi and the decussation of the superior cerebellar peduncle. Just ventral to the periaqueductal gray matter.
(Bounded ventrally by the fibers of the medial longitudinal fasciculus)

b. Exit dorsally at the level of the anterior medullary velum\superior medullary velum. Compression from cerebellar tumors.
(Only CN that exit the brainstem in a completely crossed fashion)
(The superior medullary velum is the thin layer of white matter stretching between the two superior cerebellar peduncles and form the roof of the superior recess of the fourth ventricle)

c. Because they are very thin and run for a long distance in the subarachnoid space along the underside of the tentorium cerebelli.

(Blumenfeld)
Abducens nerve
a. Location of the nuclei
b. where do they exit from the brainstem
c. Course further
d. What type of injury is it prone to, why
a. On the floor of the fourth ventricle under the facial colliculi in mid-to-lower pons.

b. At the pontomedullary junction.

c.
1. Pontomedullary junction -> ascend between pons and clivus in the subarachnoid space
2. Enter Dorello's canal between the dura and skull
3. Makes a sharp bend as it enters the cavernous sinus and superior orbital fissure.

d. Its long vertical course makes it highly susceptible to downward traction injury produced by increased ICP

(Blumenfeld)
Diplopia
a. Causes (5)
b. Methods for differentiating the different causes
1. Mechanical problems - orbital fracture with muscle entrapment
2. Disorders of the extraocular muscles - thyroid disease, orbital myositis (orbital pseudotumor)
3. Disorders of the neuromuscular junction - myasthenia gravis
4. Disorders of CN III, IV, VI and their central pathways
5. Disorders of the supranuclear oculomotor pathways - internuclear ophthalmoplegia (INO), skew deviation, toxins (alcohol, anticonvulsants)

b.
1. Cover one eye - if it goes away its probably caused by an eye movement abnormality. Monocular diplopia or polyopia can be caused by ophthalmological disease, disorders of the visual cortex, or psychiatric conditions.

2. Worse when looking at objects at different distances, right, left, up, down -> pinpoint involved muscles

3. The red glass test
cover the right eye with a transparent red glass, then ask the patient to follow a white light as it is moved to nine different positions of gaze and report the locations of the white and red images.

4. Cover-uncover test
cover one eye and observe if the suspected affected eye drift slightly back toward its 'neutral position'.
(Visual input normally helps maintain the eyes yoked in the same direction. This mild latent weakness present only with an eye covered is called a phoria (exophoria, esophoria..))

(Blumenfeld)
Diplopia
a. Exotropia
b. Esotropa
c. Hypertropia
d. What is the milder symptom of dysconjugate gaze with similar casue called
e. Synonym of dysconjugate gaze
a. Exotropia
Abnormal lateral deviation of one eye.

b. Esotropa
Abnormal medial deviation of one eye.

c. Hypertropia
Vertical deviation of one eye, described with respect to the eye that is higher, by convention.
(-tropia - abnormal deviation of one eye)

d. Blurring.
(However, blurring also have other causes.)

e. Strabismus
(Strabismus in children can cause amblyopia (decreased vision in one eye)

(Blumenfeld)
Oculomotor palsy
a. Effect on position of the eye in the case of complete paralysis, how
b. Which other three findings is there, why
c. With a paresis, when is the diplopia most pronounced
d. Common causes (7)
e. Common presentation when an aneursym is the cause
f. Common presentation with diabetic or other microvascular neuropathic cause
a. Down, out and complete ptosis
Out from lateral rectus, down from superior oblique.

b.
1. Complete ptosis <- levator palpebrae superior plegia
2. Mydriasis <- sphincter pupillae plegia
3. Unresponsive <-- --||--

c. When looking at close objects (convergence is impaired) and diagonal diplopia (when looking medially and up)

d.
1. Diabetic neuropathy
(Or other microvascular neuropathy associated with hypertension or hyperlipidemia)
2. Head trauma where shearing forces damage the nerve
3. Compression by aneurysms, most commonly Pcomm
(#1 Pcomm-ICA junction, #2 Pcomm-PCA junction, #3 basilar artery-PCA junction, #4 basilar artery-SCA junction)
4. Compression from uncal herniation
(+ coma and hemiplegia)
5. Ophthalmoplegic migraine
(Children)
6. Midbrain lesions affecting the oculomotor nucleus or exiting fascicles - lacunar infarct
7. Damage of the oculomotor nerve in the subarachnoid space, cavernous sinus, or orbit by various lesions - infection, tumor, venous thrombosis
(Muscle and neuromuscular junction disorders can mimic CN III palsy)

e. Painful CN III palsy that involves the pupil, the oculomotor palsy may be subtle or complete.
(-> emergency CT angiogram\MRA, can be followed by four vessel angiogram)
(The parasympathetic fibers are superficial and medial, Pcomm is medial to CN III)

f. Painless and complete oculomotor palsy that spares the pupil.
(Very low chance of aneurysm with this presentation)

(The superior division of CN III only innervate superior rectus and levator palpebrae superior, and isolated palsy of these is most often caused by a mass in or near the orbit)

(Blumenfeld)
Trochlear palsy
a. Function of trochlear nerve
b. Effects, signs, and symptoms of trochlear paresis
c. List Bielschowsky's three step diagnostic test plus the 'missing step
d. Common causes (4)
a. Depression and intorsion.
(Intorsion is strongest when the eye is abducted, depression is strongest when it is adducted)

b.
1. Vertical diplopia, most pronounced when the eye is adducted
2. Hypertropia of the affected eye, patient compensate by chin tuck
3. Extorsion - not usually visible, but it cause the patient to tilt the head away from the affected eye to correct it
(Mnemonic: the head movement is always in the direction of action normally served by the affected muscle (down and intorsion..))

c.
1. The affected eye has hypertropia
2. Vertical diplopia worsens when the affected eye looks nasally
3. Vertical diplopia improves with head tilt away from the affected eye
4. Vertical diplopia worsens with downgaze
(Another useful diagnostic test is to have the patient look at a horizontal line (ie pen). With a palsy the patient will see two lines and the lower line will be tilted (toward the affected eye).)
(<- weakness in infraduction)

d.
1. Shear injury from head trauma
(The most commonly injured CN in head trauma, <- long course, thin)
2. Pathology (Infection, neoplasm,aneurysm) in the subarachnoid space, cavernous sinus, orbit
3. AICA disorders or pineal gland tumors can affect the trochlear nuclei or its nerve fascicles
4. Congenital fourth nerve palsy
(Quite common, often latent for years except minor head tilt, can later decompensate and produce diplopia)

(Differential diagnosis for vertical diplopia - disorders of extraocular muscles, neuromuscular junction disorders, lesions of the superior division of CN III, skew deviation (vertical disparity in the position of the eyes of supranuclear origin, <- cerebellum, brainstem, inner ear))

(Differential diagnosis of head tilt - cerebellar lesions, meningitis, incipient tonsillar herniation, torticollis)

(Torticollis (tortus - twisted, collum - neck) - A contraction, or shortening, of the muscles of the neck, chiefly those supplied by the spinal accessory nerve; the head is drawn to one side and usually rotated so that the chin points to the other side.)

(Blumenfeld)
Abducens palsy
a. Effects, signs, and symptoms (1)
b. Common causes (5)
a.
1. Horizontal diplopia that is worse when viewing far objects and when viewing laterally toward the affected eye
(Better when viewing far objects because CN III controls accommodation)

b.
1. Injury from downward traction caused by increased ICP
(<- Long course along the clivus and over the sharp ridge of the petrous temporal bone)
(Can be uni- or bilateral)
(<- Important early sign of supra- or infratentorial tumors, pseudotumor cerebri, hydrocephalus ++)
2. Head trauma
3. Various lesions in the subarachnoid space, cavernous sinus or orbit - neoplasms, infections, aneurysms, cavernous sinus thrombosis
4. Microvascular neuropathies - diabetes
5. Pontine infarcts (or other disorders) affecting the exiting abducens fascicles in the pons
(Many are idiopathic)

(Lesions of the abducens nucleus produce a horizontal gaze palsy, that is, movemvents of both eyes in one direction are decreased, facial nerve nucleus is also often affected)

(Blumenfeld)
Explain the pathway causing consensual response in the pupillary light reflex
Several points of crossing over

1. Optic nerve -> optic chiasm -> both optic tracts
2. Optic tract -> brachium of superior colliculus -> pretectal nuclei -> some fibers cross in posterior commissure as they bilaterally project to Edinger-Westphal nuclei
3. Edinger-Westphal nuclei project bilaterally

(Blumenfeld)
The accommodation response
a. What are the three components
b. Outline of the pathway
a. Pupillary constriction, accommodation of the lens ciliary muscle, and convergence of the eyes.

b. Via visual cortex and then pretectal nuclei.

(Blumenfeld)
Sympathetic nervous system in the head
a. Outline the sympathetic pathway responsible for pupil dilation (3)
a.
1. Autonomic regulatory nuclei of hypothalamus ->

2. Descending sympathetic pathway - lateral brainstem and cervical spinal cord
(Next to spinothalamic tract -> spinothalamic tract lesions are associated with Horner's syndrome)

3. Synapse on preganglionic sympathetic neurons in the intermediolateral cell column of T1-2

4. White rami communicantes -> paravertebral sympathetic chain
(Skirt the apex of the lung on the way)

5. Synapse with postganglionic parasympathetic neurons in the superior cervical ganglion

6. Ascend through the carotid plexus along the walls of the ICA to the cavernous sinus

7. Reach the pupillary dilator muscle

b.
1. Superior tarsal muscle of Muller's
(Elevate the upper lid, smooth muscle)
2. Orbitalis muscle of Muller's
(Prevent the eye from sinking back in the orbit, smooth muscle)
3. Cutaneous arteries and sweat glands in the face and the neck

(Blumenfeld)
Pupillary abnormalities
a. Anisocoria
b. Oculomotor nerve lesion - pupillary effect (4)
c. Horner's syndrome
d. Pontine pupils
e. Afferent pupillary defect\Marcus Gunn pupil
f. Argyll Robertson pupil
g. Adie's myotonic pupil
a. Anisocoria (kore: pupil)
Pupillary asymmetry.

b.
1. Unilateral dilated pupil (complete lesion -> "blown pupil") and impaired pupillary constriction)
2. Decreased direct and consensual response
3. Complete ptosis
4. Oculomotor disorders

c.
1. Partial ptosis
(<- Muller's smooth muscle palsy in the upper eye lid)
2. Miosis
(Dilation lag relative to the normal pupil when the light is removed)
(<- Pupillary dilator muscle palsy)
3. Anhidrosis
(Compare sides)
(Ciliospinal reflex - painful pinch to the neck -> sympathetic outflow -> pupillary dilation on the normal side)

d. Bilateral small pupils which are reactive to light
(<- large bilateral lesions of the pons, probably caused by disruption of the descending sympathetic pathways)

e. Afferent pupillary defect\Marcus Gunn pupil
1. Decreased direct response, normal consensual response
(Use swinging flashlight test)
(Hippus is a normal brief oscillation of the pupil size that sometimes occur in response to light)
2. No anisocoria
(Kept the same size by consensual response)

f. Argyll Robertson pupil
1. Light-near dissociation
(Pupils constrict much less in response to light than to accommodation)
2. Small and irregular pupils
(<- Neurosyphilis)
(Many other examples of light-near dissociation)

(20% of the population have a benign anisocoria up to 0.6 mm)

g. Adie's myotonic pupil
1. Mid-dilated pupil
2. React poorly to light and slightly better to accommodation, and then remain constricted and dilate very slowly - tonic\myotonic pupil
(<- degeneration of the ciliary ganglion or the postganglionic parasympathetic neurons)

(Blumenfeld)
Horner's syndrome
a. Signs and symptoms (3)
b. Causes - divide into preganglionic and postganglionic lesions (7)
a.
1. Partial ptosis
(<- Muller's smooth muscle palsy in the upper eye lid)
2. Miosis
(Dilation lag relative to the normal pupil when the light is removed)
(<- Pupillary dilator muscle palsy)
3. Anhidrosis
(Compare sides)
(Ciliospinal reflex - painful pinch to the neck -> sympathetic outflow -> pupillary dilation on the normal side)

b.
Preganglionic lesions
1. Lateral hypothalamus or brainstem - infarct, hemorrhage..
2. Spinal cord - trauma
3. T1 and T2 - Pancoast syndrome, trauma
4. sympathetic chain - tumor, trauma

Postganglionic
5. Carotid plexus - carotid dissection
6. Cavernous sinus - thrombosis, infection, aneurysm, neoplasm
7. Orbit - infection, neoplasm

(Hydroxyamphetamine eye drops can dilate miosis caused by preganglionic lesions, postganglionic lesions don't usually have anhidrosis because these pathways split more proximally)

(Blumenfeld)
Pharmacological pupillary effects
a. Opiates
b. Barbiturate overdose
c. Anticholinergic agents
a. Pinpoint pupils

b. Small pupils

c. Mydriasis
(Atropine, scopolamine. Topical in one eye mimic uncal herniation)
(1% pilocarpine (parasympathomimetic), cocaine, hydroxyamphetamine in eyedrop-form is used diagnostically)

(Blumenfeld)
Cavernous sinus syndrome and orbital apex syndrome
a. Cavernous sinus syndrome - which structures are affected (5\6)
b. Orbital apex syndrome - which structures are affected (6)
c. Causes of cavernous sinus syndrome (9)
d. Causes of orbital apex syndrome (3)
a. Cavernous sinus syndrome
1. CN III
2. CN IV
3. CN VI
4. CN V1
5. Ocular sympathetics
(6. CN V2 - variable)

b. Orbital apex syndrome
1. CN II
2. CN III
3. CN IV
4. CN VI
5. V1
6. Ocular sympathetics

c. Causes of cavernous sinus syndrome
1. Metastatic tumors
2. Extension of nasopharyngeal tumors
3. Meningioma
4. Pituitary tumors or pituitary apoplexy (spreading of hemorrhage)
5. Aneurysms of intracavernous ICA
(CN VI which lie next to it is affected first)
6. Cavernous ICA arteriovenous fistula
7. Cavernous sinus thrombosis
(<- bacterial infection)
8. Tolosa-Hunt syndrome
(Idiopathic granulomatous disease)
9. Fungal infections - aspergillosis, mucormycosis

d.
1. Metastatic tumors
2. Orbital cellulitis
(<- bacterial infection)
(Cellulitis - inflammation of subcutaneous, loose connective tissue)
2. Idiopathic granulomatous disease - orbital myositis, pseudotumor
3. fungal infections - aspergillosis

(Blumenfeld)
Eye movements
a. Saccades
b. Smooth pursuit
c. Vergence
d. Nystagmus
a. Saccades
The most rapid eye movements. Function to bring targets of interest into the field of view.
(Can be performed voluntarily or by reflexes, velocity up to 700 degrees\s)

b. Smooth pursuit
Allow stable viewing of moving objects
(Not under voluntary control, velocity up to 100 degrees\s)

c. Vergence
Maintain fused fixation by both eyes as targets move toward or away from the viewer
(Velocity about 20 degrees\s)

d. Nystagmus
Rhythmic form of relfex eye movements composed of slow eye movements in one direction interrupted by fast, saccade-like eye movements in the opposite direction
(Seen in optokinetic nystagmus, vestibulo-ocular reflex..)

(Blumenfeld)
Supranuclear control of eye movements
a. Which structure interconnect the three pairs of oculomotor nuclei so they can have a conjugate gaze in all directions
b. Which structure can be considered a horizontal gaze center
a. The medial longitudinal fasciculus (MLF)

b.
1. The abducens nucleus
(Project to its ipsilateral lateral rectus and to the contralateral medial rectus via MLF)
(the vestibular nuclei also connect to the extraocular nuclei via the MLF)

2. The paramedian pontine reticular formation
(Input from cortex and other pathways to the abducens nucleus)

(Blumenfeld)
Internuclear ophthtalmoplegia (INO)
a. Caused by lesion to which structure
a. What
c. How is the side of the INO defined
d. Causes of INO (3)
a. Lesions of the MLF.

b. Lesion of the MLF interrupt the input to the medial rectus ->
1. The eye ipsilateral to the lesion fails to adduct fully on attempted horizontal gaze
2. Nystagmus in the contralateral eye
(The abducens nuclei is the horizontal gaze center along with the paramedian pontine reticular formation (PPRF). If the abducens nucleus initates horizontal gaze, it sends ipsilateral projections to the lateral rectus and contralateral projections via MLF to the medial rectus. Thus, the site with the control center abducens nuclei have exhibit nystagmus.)
(Eye adduction on the affected side is often spared during convergence because the inputs to the oculomotor nucleus mediating convergence arise from the pretectal region and hence don't travel in the caudal MLF)

c. The same side as the LMF lesion.
(since the ascending MLF crosses almost immediately after leaving the abducens nucleus, the side of the INO is also the side on which eye adduction is weak)

c.
1. MS plaques
2. Pontine infarcts
3. Neoplasms involving the MLF

(Damage of ipsilateral MLF and abducens nuclei produce one-and-a-half syndrome, only the contralateral lateral rectus can contract, but it exhibits nystagmus due to the lesion of the contralateral LMF)

(Blumenfeld)
Vertical eye movements
a. Location of brainstem centers controlling vertical eye movements - which part is involved in downgaze and which part is involved in upgaze
b. Parinaud's syndrome - location of lesion
c. The four components of Parinaud's syndrome
d. Common causes of Parinaud's syndrome
a. In the rostral midbrain reticular formation and pretectal area - The ventral portion mediate downgaze while the dorsal region mediate upgaze
(Downgaze - rostral interstitial nucleus of the MLF, nucleus of Darkscewitsch, interstitial nucleus of Cajal)
(Lesions to dorsal part -> impaired upgaze, vice versa)

b. Dorsal midbrain and pretectal area.

c.
1. Impairment of vertical gaze, especially upgaze
(Dysfunction of the upgaze portion of the vertical gaze center located in the dorsal part of the rostral midbrain reticular formation)
2. Large, irregular pupils with light-near dissociation
(<- disruption of optic tract fibers traveling to Edinger-Westphal nucleus via the (dorsal) posterior commissure, while the fibers for accommodation from the visual cortex are spared)
3. Eyelid abnormalities - Collier's sign (bilateral lid retraction), ptosis
4. Impaired convergence
(sometimes convergence-retraction nystagmus - the eyes rhythmically converge and retract in the orbits, especially in response to attempted upgaze)

d.
1. Pineal region tumors
2. Hydrocephalus
(-> dilation of the suprapineal recess of the 3rd ventricle -> push downward on the tectum of the midbrain. Especially in children, this can produce the setting-sun sign - the eyes are adducted due to bilateral CN VI palsies and infraducted due to Parinaud's syndrome. Similar syndrome can also be seen in thalamic hemorrhage (unknown mechanism))
(In children whose fontanelles haven't closed yet, the pressure required when the fontanelles are closed cause impaired consciousness)
3. MS or vascular disease of the midbrain or pretectal area

(Blumenfeld)
Control of eye movements by the forebrain - name the two best known areas and their function
1. The frontal eye fields - contralateral saccades
(Adjacent to premotor and prefrontal cortices)
(Connections to the contralateral PPRF)

2. Parieto-occipito-temporal area - ipsilateral pursuit
(Maybe contralateral eye movements)
(Via connections with the ipsilateral vestibular nuclei, cerebellum and PPRF)

(Both receive massive input from the visual cortex)

(Blumenfeld)
Right-way eyes and wrong-way eyes
a. Right-way eyes
b. Wrong-way eyes
c. Causes of wrong-way eyes
a. Lesions of the cerebral hemispheres causing hemiplegia normally impair eye movements in the contralateral direction -> gaze preference toward the side of the lesion
(Typically accompanied by contralateral hemiplegia)

b. Refer to the conditions which cause the eyes to look toward the side of the hemiplegia after a lesion to the brain.

c.
1. Seizure activity in the cortex
(Can drive the eyes in the contralateral direction due to activation of the frontal eye fields and cause abnormal\decreased contralateral body movement due to involvement of motor association cortices)
2. Thalamic hemorrhages
(Uknown mechanism, usually in the setting of profound coma, contralateral hemiplegia from disruption of the corticospinal pathways of the internal capsule)
3. Lesions of the pontine basis and tegmentum
(Abducens nucleus or PPRF + contralateral corticospinal tract)
Optokinetic nystagmus (OKN) testing
a. Procedure
b. The slow\smooth pursuit phase is mediated by, pathway\connections
c. The fast\saccadic phase is mediated by, pathway\connections
a. Move a band with vertical stripes horizontally in front of the eyes. The eyes alternate between smooth pursuit and corrective saccade.

b. The ipsilateral posterior cortex
-> vestibular nuclei and flocculonodular lobe of the cerebellum -> PPRF and abducens nuclei

c. The frontal eye fields -> contralateral PPRF

(Blumenfeld)
Name the four functional groupings of the brainstem
1. Cranial nerve nuclei and related structures
(Lesion -> cranial nerve abnormalities)
(Ventrally)

2. Long tracts
(Lesion -> long-tract findings)
(Dorsal to cranial nerve nuclei and related structures)
(Motor pathways - corticospinal & corticobulbar, other descending somatomotor pathways, descending autonomic pathways. Somatosensory pathways - posterior column-medial lemniscal system, anterolateral system)

3. Reticular formation
(Lesion -> impaired consciousness, autonomic dysregulation)
(Dorsal to long tracts)

4. Cerebellar circuitry
(Lesion -> ataxia)
(Superior, middle, and inferior cerebellar peduncles. Pontine nuclei, red nucleus (parvocellular portion), central tegmental tract, inferior olivary nucleus)

(Blumenfeld)
Brainstem
a. What is the sulcus limitans - 'function' in the adult
b. The tectum
c. The tegmentum
d. The basis
a. The medial longitudinal groove on the inner surface of the neural tube. In the adult it is visible along the lateral wall of the fourth ventricle as it separates the motor nuclei ventromedially from sensory nuclei dorsolaterally.

b. Tectum ('roof')
In the midbrain, most posterior, consists of the superior and inferior colliculi, which lie dorsal to the cerebral aqueduct.

c. The tegmentum ('covering')
Ventral to the cerebral aqueduct in the midbrain and ventral to the fourth ventricle in the pons and medulla. Main bulk of the brainstem.

d. The basis\Basis pedunculi
The most ventral portion. Location of the corticospinal, corticobulbar, corticopontine fibers

(Blumenfeld)
Midbrain
a. Brachium conjunctivum
b. The cerebral peduncles
c. How can the rostral be differentiated from the caudal on a transverse sections
a. Brachium conjunctivum
Decussation of the superior cerebellar peduncles.

b. Cerebral peduncles
I. Substantia nigra
II. Basis pedunculi\Basis
(Corticospinal, corticobulbar, and corticopontine fibers)

c.
Rostral - superior colliculi, oculomotor nuclei, red nuclei
Caudal - inferior colliculi, trochlear nuclei, brachium conjunctivum

(Blumenfeld)
Pons
a. How to recognize on transverse sections
a. The large middle cerebellar peduncles are visible laterally.
Retroflex fasciculus\Habenointerpeduncular tract
Habenula --ventralward--> interpeduncular nucleus (base of the midbrain), raphe nuclei (caudal mesencephalic tegmentum)

(Stedman)
Medulla
a. How can the rostral and caudal medulla be differentiated on transverse sections
b. Which structure marks the cervicomedullary junction
a.
Rostral medulla - The inferior olivary nuclei, fourth ventricle
Caudal medulla - The posterior columns, The posterior columns nuclei

b. the pyramidal decussation.
Medial longitudinal fasciculus (MLF)
a. Which nuclei does it interconnect
b. Location in the midbrain
a. Extraocular (CN III, IV, VI) and vestibular nuclei.

b. Just ventral to the trochlear and oculomotor nuclei.

(Blumenfeld)
Locked-in syndrome
a. What
b. What motor function is often spared, why
c. Common causes (5)
a. Patients who have absent motor function but maintain intact sensation and cognition.

b. Vertical eye movements and eyelid elevations.
These are controlled by a region in the tegmentum of the rostral midbrain.
(Horizontal eye movements, however, depend on pontine circuits)

c.
1. Bilateral ventral pontine infarcts
2. Other lesions in the ventral pons - hemorrhage, tumor, encephalitis, MS, central pontine myelinolysis
3. Lesions in the bilateral cerebral peduncles of the midbrain
4. Lesions in the internal capsule
5. Severe peripheral disorders affecting nerves, neuromuscular junction or muscles
(3-5 are less common

(60% eventually die due to respiratory infection or other paralysis complications)

(Blumenfeld)
The reticular formation
a. What does it merge with superiorly and inferiorly
b. Location of division of the rostral and caudal reticular formations
c. In which general part of the brainstem is the RF located
a. Superiorly -> the subthalamic region and lateral hypothalamus.
Inferiorly -> the intermediate zone of the spinal cord

b.
Rostral reticular formation - midbrain and rostral pons
Caudal reticular formation - caudal pons and medulla
(Simplification the rostral RF function with diencephalic nuclei to maintain an alert conscious state in the forebrain. The caudal RF work with the CN nuclei and the spinal cord to carry out a variety of important motor, reflex, and autonomic functions)

c. In the brainstem tegmentum.
(Ventral to posterior: basis -> tegmentum -> tectum)

(Blumenfeld)
The 'consciousness system'
a. Function
b. Structures (10)
a. 3As - Alertness, Attention, and Awareness.
(Alertness depend on functioning of the brainstem and diencephalic arousal circuits and the cortex. Attention --||-- plus additional processing in frontoparietal association cortices)
(Awareness is the most vague - the subjective and personal experience. Depend on our ability to combine various higher-order forms of sensory, motor, and emotional information from various regions into a unified and efficient summary of mental activity)

b.
1. Pontomesencephalic reticular formation
2. Thalamus
3. Hypothalamus
Cortical
4. Anterior cingulate cortex
5. Medial frontal cortex
6. Lateral association cortex
7. Lateral parietal association cortex
8. Precuneus
9. Posterior cingulate cortex
10. Retrosplenial cortex

(Blumenfeld)
The reticular formation
a. What is the ascending reticular activating system (ARAS), flaws with this concept
b. Where in the brain can a lesion cause coma (3)
a. ARAS
Rostral brainstem reticular formation and medial diencephalon.
Lesion -> coma, stimulation -> awake from deep anesthesia
(Moruzzi and Magoun)
Not all are descending, some are also descending cortical. All don't originate in the reticular formation.
(There appear to be multiple interconnected arousal systems acting in parallel to maintain normal brain consciousness).

b. Where in the brain can a lesion cause coma
1. Upper brainstem reticular formation and related structures
2. Extensive bilateral regions of the cerebral cortex
3. Bilateral lesions of the thalamus - especially involving the medial and intralaminar regions

(Blumenfeld)
Subcortical arousal systems
- location, neurotransmitter, projection (5)
1. Upper brainstem neurons
Norepinephrine, serotonin, dopamine
-> Cortical and subcortical forebrain structures

2. Upper brainstem neurons containing acetylcholine and pontomesencephalic reticular formation neurons containing glutamate (possibly)
-> Thalamus, hypothalamus, basal forebrain

3. Posterior hypothalamic neurons
Histamine, Orexin
-> Cortical and subcortical targets

4. Basal forebrain neurons
Acetylcholine
-> Cerebral cortex

5. Neurons in the rostral thalamic intralaminar nuclei (and other medial thalamic nculei)
Glutamate
-> Cerebral cortex

(All which project to subcortical structures have secondary projections to cortical structures)

(Blumenfeld)
Subcortical arousal systems - input
Inputs
1. Sensory input
(Especially the spinoreticular pathway of the anterolateral system involved in pain transmission)

2. Inputs from frontoparietal association cortex

3. Inputs from limbic and cingulate cortex

4. Inputs from thalamic reticular nucleus

(The superior colliculi, cerebellum, and basal ganglia are also probably involved)

(Blumenfeld)
Widespread projection systems
a. Properties of most of the neurotransmitters
b. The reticular formation - give the locations of the cell bodies, main targets, neurotransmitter receptors, and functions
a. Neuromodulatory
(Involve signaling cascades that regulate synaptic transmission, neuronal growth, and other functions.)
(Many of the neurons also release a variety of peptides which are likely to play a neuromodulatory role as well)

b. The reticular formation
<-
1. Midbrain
2. Rostral pons

->
1. Thalamic intralaminar nuclei
2. Hypothalamus
3. Basal forebrain

Unknown, glutamate?

Alertness

(Blumenfeld)
Widespread projection systems - the intralaminar nuclei
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
Thalamic intralaminar nuclei

b. Main targets
1. Cortex
2. Striatum (caudate nucleus, putamen)

c. Neurotransmitter receptors
Unknown (Glutamate?)

d. Functions
Alertness

(Blumenfeld)
widespread projection systems in the nervous system - the norepinephrine system
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
Pons:
1. Locus ceruleus
2. Lateral tegmental area

b. Main targets
Entire CNS
(Inhibitory or excitatory on the cortex, excitatory on the thalamus)

c. Neurotransmitter receptors
1. Alpha 1A-D
2. Alpha 2A-D
3. Beta 1-3

d. Functions
1. Alertness
2. Mood elevation

(NE in the lateral tegmental area of the caudal pons and medulla are involved in sympathetic functions such as blood pressure control)

(Blumenfeld)
widespread projection systems in the nervous system - the dopamine system
a. Describe the 3 projection systems
c. Neurotransmitter receptors
d. Functions
a. The projection systems (all from ventral mesencephalon)

1. The mesostriatal\Nigrostriatal pathway
Substantia nigra pars compacta -> striatum
(Dysfunction -> Parkinson's disease)

2. The mesolimbic pathway
Ventral tegmental area -> Limbic structures - medial temporal cortex, amygdala, cingulate gyrus, nucleus accumbens
(Involved in reward circuitry and addiction)
(Overactivity -> positive symptoms of schizophrenia)

3. The mesocortical pathway
The ventral tegmental area -> The prefrontal cortex
(Also from scattered neurons in the vicinity of the substantia nigra)
(Dysfunction -> working memory dysfunction and attentional aspects of motor initiation - part of the cognitive symptoms of Parkinson's and the negative symptoms of schizophrenia)

c. Neurotransmitter receptors
D1-5

d. Functions
1. Movements
2. Initiative
3. Working memory

(Dopamine are also found in hypothalamus where it inhibits PRL release, in olfactory bulbs and in the retina)

(Blumenfeld)
widespread projection systems in the nervous system - the serotonin system
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
Midbrain, pons, and medulla: raphe nuclei
(Raphe - suture, the nuclei is in the middle, dorsal and medial raphe nuclei)
(Midbrain - nucleus linearis, dorsal and median raphe nuclei. Pons - nucleus raphe pontis & magnus. Medulla - nuclei raphe pallidus and obscuris)

b. Main targets
Entire CNS
(Rostral part -> cortex, thalamus, basal ganglia
Caudal part -> cerebellum, medulla, spinal cord)
(Projections to medulla and spinal cord are involved in pain modulation, breathing, temperature regulation, and motor control)

c. Neurotransmitter receptors
1. 5-HT 1A-F
2. 5-HT 2A-C
3. 5-HT 3-7

d. Functions
1. Alertness
2. Mood elevation
3. Breathing control

(Involved in psychiatric syndromes - depression, anxiety, OCD, aggressive behavior, and eating disorders. Associated with sudden infant death syndrome (SIDS), impaired arousal in response to hypoventilation?)

(Some serotonergic neurons are also found in the area postrema, in the spinal cord, and around the interpeduncular nucleus)

(Blumenfeld)
widespread projection systems in the nervous system - the histamine system
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
1. Hypothalamus - tuberomammillary nucleus
2. Midbrain - reticular formation

b. Main targets
Entire brain

c. Neurotransmitter receptors
H 1-3

d. Functions
Alertness

(Blumenfeld)
widespread projection systems in the nervous system - the orexin\hypocretin system
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
Posterior lateral hypothalamus

b. Main targets
Entire brain

c. Neurotransmitter receptors
OX 1-2

d. Functions
1. Alertness
2. Food intake

(Blumenfeld)
Widespread projection systems in the nervous system - the cholinergic system
a. Location of cell bodies
b. Main targets
c. Neurotransmitter receptors
d. Functions
a. Location of cell bodies
1. Basal forebrain - nucleus basalis of Meynert (-> almost entire cortex), medial septal nucleus, nucleus of diagonal band
(Medial septal nucleus and nucleus of diagonal band of Broca -> hippocampal formation)
2. Pontomesencephalic region - pedunculopontine nucleus, laterodorsal tegemental nculeus

b. Main targets
Basal forebrain -> cerebral cortex (including hippocampus)
(Produce hippocampal theta rhythm that has been postulated to be involved in hippocampus memory function(
Pontomesencephalic region ->
1. Thalamus
2. Cerebellum
3. Pons
4. Medulla

c. Neurotransmitter receptors
M 1-5, Nicotinic subtypes
(Muscarinic is most numerous)

d. Functions
1. Alertness
2. Memory

(Generally facilitatory effects)
(Degeneration of cholinergic neurons in the basal forebrain may be one of the mechanisms for memory decline in Alzheimer's disease)

(Blumenfeld)
Norepinephrine - related disorders (3)
1. Attention-deficit disorders is often treated with medication that increase noradrenergic transmission.

2. Narcolepsy --||--
(Sleep disorder characterized by excessive daytime sleepiness)
(NE is increased during the awake state and decreased during sleep, but lesion to its neurons don't cause somnolence)

3. Involved in central modulation of pain, mood disorders - depression, manic-depressive disorder, anxiety disorders - OCD

(Blumenfeld)
Adenosine
a. How is adenosine thought to be related to alertness
b. Real-life application
a.
1. Inhibitory receptors in thalamus and cortex
2. Circadian variation - highest before sleep

b. One of caffeine's stimulating effects is by inhibiting adenosine.

(Blumenfeld)
Sleep
a. Stages
b. How is the stages measured (4)
c. Where is the sleep-promoting region
a.
Stage 1-4\nonREM where 4 is deepest.
REM
(REM - general muscle tone and brainstem monoaminergic neuotransmission is lowest, EEG are more active - low-voltage mixture of relatively fast activity like awake state, most easily woken from this stage)
(nonREM - EEG resembling coma - high-voltage, slow activity)

b.
1. EEG
2. Extraocular movements
3. Body movements and muscle tone
4. Respirations

c. In the medulla
(Postulated to be in medullary reticular formation and nucleus solitarius)
(Lesion to anterior hypothalamus (ventrolateral preoptic (VLPO) area, GABAergic) and basal forebrain can also reduce sleep, esp. nonREM sleep)

(Blumenfeld)
Brainstem circuits important for sleep regulation
a. For nonREM sleep
b. For REM sleep
a.
1. Ventral lateral preoptic (VLPO) area of anterior hypothalamus have GABAergic (and galanin) projections that inhibit neurons in the ascending activating systems - including
I. Posterior hypothalamic orexin neurons
(These excite the brainstem and hypothalamic arousal systems)
(There is surrounding melanin-rich neurons which are most active in REM sleep and least active in the waking state)
II. Monoamines - histamine (tuberomammillary nucleus), serotonin (raphe nuclei), noradrenalin (locus ceruleus & lateral tegmental area), dopamine
III. Brainstem cholinergics

2. Certain regions of the pons may also play a role, probably medullary reticular formation and solitary nucleus
(damage to posterior hypothalamus cause encephalitis lethargica, where patients sleep for long periods)

b.
1. Mechanism for nonREM +
2. GABAergic REM-on cells in the pontine reticular formation inhibit norepinephrine and serotonin further (Almost to zero activity) -> removal of inhibition of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei -> increased cholierngic transmission to the thalamus -> EEG pattern resembling awake state
3. The pontomesencephalic cholinergic neurons also activate another class of glutamatergic REM-on cells in the pontine reticular formation that markedly reduce muscle tone during REM sleep by activating inhibitory glycine circuits in the medulla and spinal cord -> decreased muscle tone
4. Brainstem cholinergics -> intermittent PGO (pons-to-thalamus-to-cortex - ponto-geniculo-occipital) waves -> visual imagery of dreams and rapid eye movements

(Degeneration of the glutamatergic REM-on cells cause REM sleep behavioral disorders, as seen as a precursor to parkinsonism)

(Even though the muscles are inhibited, there are brief periods (the PGO waves are only intermittent) of extraocular and limb movements)

(Blumenfeld)
Narcolepsy
a. What
b. Clinical characteristics
c. Postulated mechanism
a. Disorder characterized by an abnormal tendency to enter REM sleep directly from the waking state.

b. Clinical characteristics
1. Excessive daytime sleepiness

2. Cataplexy
(Sudden loss of muscle tone from the awake state, often in response to an emotional stimulus)
(Cata- down, -Plexy: blow, stroke)

3. Hypnagogic (while falling asleep) or hypnopompic (while awaking) dreamlike hallucinations
(Gogic - leading into, Pompic - leading out of)

4. Sleep paralysis - awake, but remain unable to move for several minutes

c. Deficiency in orexin\hypocretin cells in the posterior lateral hypothlamaus (found in humans and mice with narcolepsy) -> loss of orexins stabilizing effect on the awake state -> unstable "flip-flow switch" provoking repeated transitions into and out of REM

(Blumenfeld)
Decreased consciousness - yes\no for 1. Purposeful response to stimuli by cerebral cortex, 2. Behavioral arousal and sleep-wake cycles by diencephalon-upper brainstem arousal systems, 3. Brainstem reflexes by byrainstem reflex and motor systems, 4. Spinal cord reflexes by spinal cord circuits
a. Brain death
b. Coma
c. Vegatative state
d. Minimally conscious state (Stupor obtundation, lethargy)
Decreased consciousness - yes\no for 1. Purposeful response to stimuli by cerebral cortex, 2. Behavioral arousal and sleep-wake cycles by diencephalon-upper brainstem arousal systems, 3. Brainstem reflexes by byrainstem reflex and motor systems, 4. Spinal cord reflexes by spinal cord circuits
a. Brain death
1. No
2. No
3. No
4. Yes

b. Coma
1. No
2. No
3. Yes
4. Yes

c. Vegatative state
1. No
2. Yes
3. Yes
4. Yes

d. Minimally conscious state (Stupor obtundation, lethargy)
1. Yes, at times
2. Yes
3. Yes
4. Yes

(Blumenfeld)
Akinetic mutism, abulia, and catatonia
a. Common feature
b. Akinetic mutism and abulia - usual cause
c. Catatonia - normally seen in
a. Dysfunction of circuits involving the frontal lobes, diencephalon, and ascending dopaminergic projections important to the initiation of motor and cognitive activity.

b. Frontal lobe lesions.
(Can sometimes be reversed by dopaminergic agonists, primary deficit is motor initiation.)

c. Advanced cases of schizophrenia.

(Blumenfeld)
Coma
a. Common causes (16)
b. Which substances are given immediately to a comatose patient (3)
c. Tests
a. Common causes
1. Head trauma
2. Brainstem ischemia
3. Diffuse anoxia
4. Cardiopulmonary arrest
5. Intracranial hemorrhage
6. Status epilepticus or its post-ictal state
7. Hydrocephalus
8. Diffuse cerebral edema
9. Drug or ethanol toxicity
10. Electrolyte abnormality
I. Elevated Na
II. Elevated Ca
III. Elevated Mg
11. Hypoglycemia
12. Hypothyroidism
13. Hyoadrenalism
14. Thiamine deficiency
15. Meningitis or encephalitis
16. Renal or hepatic failure

b. IV
1. Thiamine
2. Dextrose
(Not for infants since it can be due to a inborn error of metabolism that can get worse)
3. Naloxone
(4. Flumazenil if suspected benzodiazepine overdose)

c. Tests
1. Blood tests
2. Head CT
3. Lumbar puncture
(If not increased ICF)
4. EEG

(Blumenfeld)
Pupil findings in response to coma, what are the following pupil characteristics indicative of
a. Normal-sized, reactive pupils
b. Asymmetrical or bilaterally dilated, unresponsive ("blown") pupils
c. Bilateral pinpoint pupils
d. Bilateral small pupils, still responsive to light
a. Toxic and metabolic causes.

b. Midbrain compression and transtentorial herniation.

c. Opiate overdose.

d. Pontine lesion.

(Blumenfeld)
Respiration
a. Associated medullary nuclei
b. Lesions in medulla cause
c. Lesions of the rostral pons cause
d. Lesions of the midbrain (and other regions) cause
e. Bilateral lesions at or above the level of the upper pons cause
a.
1. Active during inspiration
I. Pre-Botzinger complex - primary pacemaker for respiration
II. Rostral ventral respiratory group
III. Dorsal respiratory group

2. Active during expiration
I. Botzinger complex
II. Caudal ventral respiratory group

3. Medial parabrachial Kolliker-Fuse area\Pneumotaxic area - modulate respiratory pattern

(Only #3 is in pons, the rest is in the medulla)
(Caudal nucleus solitarius = cardiorespiratory nucleus (Visceral sensory))

b.
I. Respiratory arrest
II. Ataxic respiration - very irregular breathing pattern, may progress to respiratory arrest

c. Apneustic respiration - has 2-3 second respiratory pauses at full inspirations
(Rarely, involve medial parabrachial Kolliker-Fuse area dorsal to the motor nucleus of CN V)

d. Central neurogenic hyperventilation

e. Cheyne-Stokes
(Crescendo-Decrescendo, also seen in high-altitude sickness and medical conditions such as cardiac failure)

(Blumenfeld)
Brain stem blood supply
a. Medial medulla
b. Lateral medulla
Brain stem blood supply
a. Medial medulla
I. Paramedian branches of the anterior spinal artery caudally and vertebral arteries rostrally.

b. Lateral medulla
I. Penetrating branches from the vertebral artery and the PICA

(Blumenfeld)
Brain stem blood supply
a. Pons - Medial, lateral
b. Midbrain - Medial, lateral
a. Pons
I. Medial - Paramedian branches of the basilar artery
II. Lateral -
1. Circumferential branches of the basilar artery
2. AICA in caudal region
3. Pontine arteries in rostral region
(A small dorsolateral part receive blood supply from SCA)

b. Midbrain
I. Medial
Penetrating paramedian branches from basilar artery, sometimes these bifurcate after their origin and give rise to arteries of Percheron

II. Lateral
Proximal PCAs
(These also supply thalamus)
Common warning signs of vertebrobasilar ischemia - give ischemic structures
a. Dizziness\vertigo and nausea
b. Incoordination (ataxia)
c. Unsteady gait
d. Dysarthria, dysphagia
a. Dizziness\vertigo and nausea
I. Vestibular nuclei
II. Cerebellum
III. Inner ear

b. Incoordination\Ataxia
I. Cerebellum
II. Cerebellar pathways

c. Unsteady gait
I. Cerebellar pathways
II. Long sensory or motor tracts

d. Dysarthria, dysphagia
I. Corticobulbar pathways
II. brainstem cranial nerve nuclei

(Blumenfeld)
Common warning signs of vertebrobasilar ischemia - give ischemic structures
a. Numbness and tingling, particularly bilateral or perioral
b. Hemiparesis, quadriparesis
c. Somnolence
d. Occipital headache
e. Frontal headache
a. Numbness and tingling, particularly bilateral or perioral
I. Long somatosensory pathawys
II. Trigeminal system

b. Hemiparesis, quadriparesis
I. Corticospinal tract

c. Somnolence
I. Pontomesencephalic reticular formation
II. Bilateral thalami

d. Occipital headache
I. Posterior fossa meninges and vessels innervated by CN X and cervical roots (C2-3 by greater occipital nerve)

e. Frontal headache
Supratentorial meninges and vessels innervated by CN V
(PCA is often CN V1)

(Blumenfeld)
Clinical findings to distinguish ischemic brain stem involvement from hemispheric involvement
a. Brain stem involvement
b. Hemispheric involvement
a. Brain stem involvement
I. Crossed signs
(Decreased sensation on one side of the face and contralateral body, or weakness on one side of the face and contralateral body)

II. Cranial nerve abnormalities
1. Dysconjugate gaze
2. Wrong-way eyes
3. Pupillary abnormalities
4. Nystagmus

b. Hemispheric involvement
I. Aphasia
II. Hemineglect
III. Hemianopia
IV. Seizures

(Blumenfeld)
Clinical signs and symptoms to differentiate brain stem lesions
a. Midbrain
b. Pons
c. Medulla
a. Midbrain
1. CN III palsy
I. Uni- or bilateral pupil dilation
2. Ataxia
3. Flexor\Decorticate posturing
4. Impaired consciousness
5. Central neurogenic hyperventilation or Cheyne-Stokes

b. Pons
1. Bilateral Babinski's sign
2. Generalized weakness
3. Perioral numbness
4. "Salt and pepper" (pins and needles) facial tingling
5. Bilateral upper or lower visual loss or blurring
(Usually from impaired blood flow from the basilar artery to both PCA)
6. Ocular bobbing
(Eyes dip downward quickly and then return gradually to mid position before dipping again)
7. Shivering
8. Palatal myoclonus
(Affect the central tegmental tract)
9. CN VI palsy
10. Bilateral small but reactive pupils
(Disruption of descending sympathetic fibers)
11. Extensor\decerebrate posturing
12. Impaired consciousness
13. Apneustic respiration
(By damaging medial parabrachial Kolliker-Fuse area)

c. Medulla
1. Vertigo
2. Ataxia
3. Nystagmus
4. Nausea and vomiting
6. Respiratory arrest
7. Autonomic instability
8. Hiccups
9. Ataxic respiration

(Blumenfeld)
Focal vascular syndrome of medial medulla
a. Syndrome name
b. Vascular supply
c. Involved structures and their relevant anatomical clinical findings
a. Medial medullary syndrome

b. Paramedian branches of vertebral and anterior spinal arteries.

c.
1. Pyramidal tract -> Contralateral arm or leg weakness
2. Medial lemniscus -> Contralateral decreased position and vibration sense
3. CN XII nucleus and exiting fascicles -> Ipsilateral tongue weakness

(Blumenfeld)
Focal vascular syndrome of lateral medulla
a. Syndrome name
b. Usual cause
c. Vascular supply
d. Involved structures and their clinical features
a. Wallenberg's syndrome\Lateral medullary syndrome

b. Vertebral thrombosis

c. Vertebral artery
(More commonly than PICA)

d.
1. Inferior cerebellar peduncle ->
I. Ipsilateral ataxia
II. Nystagmus

2. Trigeminal nucleus and tract -> Ipsilateral facial decreased pain and temperature sense

3. Spinothalamic tract -> Contralateral body decreased pain and temperature sense

4. Descending sympathetic fibers -> Ipsilateral Horner's syndrome

5. Nucleus ambiguus and exiting CN X -> Hoarseness, Dysphagia

6. Nucleus solitarius -> Ipsilateral decreased taste

7. Vestibular nuclei ->
I. Vertigo
II. Nausea and vomiting

(The most common brainstem infarct along with medial basis pontis infarct)

(5&6 help to differentiate it from pons lesions)

(Blumenfeld)
Focal vascular syndromes of medial pontine basis
a. Syndrome name (2)
b. Vascular supply
c. Involved structures and their clinical features
d. Usual cause
a.
1. Dysarthria hemiparesis\Pure motor hemiparesis
2. Ataxic hemiparesis

b. Paramedian penetrating branches of basilar artery

c.
I. 1&2 - Corticospinal and corticobulbar tracts -> Contralateral hemiparesis
II. Only 2 - Pontine nuclei and pontocerebelar fibers -> Contralateral ataxia
(Occasionally ipsilateral)

d. #1 Lacunar infarcts resulting from small-vessel lipohyalinosis in the setting of chronic hypertension
(Or microemboli, small-vessel thrombosis, occlusion of the opening of small penetrating vessels by atherosclerotic disease where they arise from the wall of the basilar artery)

(Blumenfeld)
AICA syndrome
a. Involved region
b. Involved structures and their clinical features
a. Lateral caudal pons

b.
1. Middle cerebellar peduncle -> Ipsilateral ataxia
2. Vestibular nuclei -> Vertigo, Nystagmus
3. Trigeminal nucleus and tract -> Ipsilateral facail decreased pain and temperature sense
4. Spinothalamic tract -> Contralateral body decreased pain and temperature sense
5. Descending sympathetic fibers -> Ipsilateral Horner's syndrome
6. Inner ear by labyrinthine artery coming of AICA -> Ipsilateral hearing loss

(Blumenfeld)
Midbrain infarcts
a. Vascular supply
b. Syndromes, their involved structures and the clinical features
a. Branches of PCA and top of basilar artery

b.
1. Weber's syndrome - Midbrain basis
I. CN III fascicles -> Ipsilateral CN III palsy
II. Cerebral peduncle -> Contralateral hemiparesis

2. Claude's syndrome - Midbrain tegmentum
I. CN III fascicles -> Ipsilateral CN III palsy
II. Red nucleus, Superior cerebellar peduncle fibers -> Contralateral ataxia

3. Benedikt's syndrome - Combined 1&2

(Blumenfeld)
Top-of-the-basilar syndrome
a. Usual cause
b. Clinical features
c. Basilar scrape syndrome
a. Lodged embolus at the top of the basilar artery.

b. Clinical features
1. Visual cortex -> Visual disturbances
2. Bilateral medial thalami or temporal lobes -> Memory disturbances
3. CN III nucleus fascicles
4. Midbrain reticular formation ->
I. Somnolence
II. Delirium
III. Vivid visual hallucinations (peduncular hallucinosis)
5. Cerebellum -> Ataxia

c. Basilar scrape syndrome
I. Seen as an embolus migrates up the basilar artery toward the top, occluding various penetrator arteries in the pons on the way, and end lodging in the top of the basilar artery.

(Blumenfeld)
Extraocular nuclei, which are
a. Contralateral
b. Bilateral
c. Ipsilateral
a. Contralateral
1. CN III nuclei innervating superior rectus
(Central caudal CN III)
2. CN IV nuclei

b. Bilateral
1. Edinger-Westphal
2. Nuclei innervating levator palpebrae superior
(Central caudal)

c. Ipsilateral
Rest

(Blumenfeld)
Functional regions of the cerebellum - give function and motor pathways influenced
a. Lateral hemispheres
b. Intermediate hemispheres
c. Vermis and flocculonodular lobe
d. Other functions associated to cerebellar pathways
a. Lateral hemispheres
I. Motor planning for extremities
II. Lateral corticospinal tract
('Lateral\appendicular motor system')

b. Intermediate hemispheres
I. Distal limb coordination
II. Lateral corticospinal tract and rubrospinal tract
('Lateral\Appendicular motor system')

c. Vermis and flocculonodular lobe
1. Vermis - Proximal limb and trunk coordination via
I. Anterior corticospinal tract
II. Reticulospinal tract
III. Vestibulospinal tract
IV. Tectospinal tract
(Medial\truncal motor system)

2. Flocculonodular lobe - Balance and vestibulo-ocular reflexes via MLF

d.
I. Speech articulation
II. Respiratory movements
III. Motor learning
(IV. Certain higher-order cognitive processes)

(Blumenfeld)
Cerebellar lesions and principles for localization
a. Is ataxia ipsilateral or contralateral to the side of a cerebellar lesion
b. Midline lesions of the cerebellar vermis or flocculonodular lobes ->
c. Lesions lateral to the cerebellar vermis\hemispheric lesions ->
a. Ipsilateral.

b. Midline lesions of the cerebellar vermis or flocculonodular lobes ->
I. Unsteady gait\Truncal ataxia
II. Eye movement abnormalities

c. c. Lesions lateral to the cerebellar vermis\cerebellar hemispheric lesions ->
I. Ataxia of the limbs\appendicular ataxia

(Blumenfeld)
Cerebellum
a. Which structure separates the anterior and posterior lobes
b. Which structure separates the posterior lobe from the flocculonodular lobe
c. What are the components of the flocculonodular lobe
a. The primary fissure
(The deepest cerebellar fissure)

b. The posterolateral fissure

c. Flocculonodular lobe
I. Two flocculi
(Important connections to vestibular nuclei via MLF)
II. Nodulus
(Midline structure, most inferior part of cerebellar vermis, connected to flocculi by thin pedicles)

(Blumenfeld)
The cerebellum
a. Function of the superior, middle, and inferior cerebellar peduncles
b. Synonyms
a. Function
I. Superior cerebellar peduncle - Mainly output from cerebellum
II. Middle and inferior cerebellar peduncle - Mainly carry input

b. Synonyms
I. Superior cerebellar peduncle\Brachium conjunctivum ('connecting')
(Decussate in the midbrain at the level of the inferior colliculi)

II. Middle cerebellar peduncle\Brachium pontis

III. Inferior cerebellar peduncle\Restiform body ('ropelike')

(Blumenfeld)
Deep cerebellar\roof nuclei
a. Responsible for all
b. List them from lateral to medial
c. List their input
d. What is the deep cerebellar nuclei analog that receive input from the inferior vermis and flocculi
a. Outputs from the cerebellum.
(Also receive collateral fibers of cerebellar inputs on their way to the cerebellar cortex)

b. Deep cerebellar nuclei from lateral to medial
1. Dentate
2. Emboliform
3. Globose
(3-4 = Interposed nuclei)
4. Fastigial
(Don't Eat Greasy Foods)

c.
I. Dentate nuclei - <- Lateral cerebellar hemispheres
(Active just before voluntary movement)
II. Interposed nuclei - <- Intermediate part of the cerebellar hemispheres
(Active during movement)
III. Fastigial nuclei - <- Vermis, part from flocculonodular lobe

d. Vestibular nuclei

(Blumenfeld)
Cerebellum
a. In the cerebellum gyrus are called
b. The three layers of the cerebellar cortex from white matter and peripherally
c. What are the two kinds of synaptic inputs to the cerebellum
a. Folium

b.
1. Granule cell layer
(Small granule cells, almost as many as in cerebrum)
2. Purkinje cell layer
(Cell bodies of large, flask-shaped Purkinje cells)
3. Molecular layer
(Unmyelinated granule cell axons, Purkinje cell dendrites, interneurons)

c. Synaptic input to the cerebellum
1. Mossy fibers
(<- Pontine nuclei ++, excitatory synapses with granule cells)
2. Climbing fibers

(Blumenfeld)
(<- Contral inferior olivary nucleus, connect with cell body and dendrites of Purkinje cells, modulatory\inhibitory effect on the stimulatory effect received by parallel fibers)
Microscopic circuitry of the cerebellum
a. How is synaptic input from Mossy fibers (from pontine nuclei ++) transmitted to affect Purkinje cells
b. Which cells carry all the output of the cerebellum to the deep cerebellar and vestibular nuclei
a.
1. Mossy fibers synapse with granule cells in granule cell layer ->
2. Granule cells send axons into the molecular layer ->
3. The axons bifurcate and form parallel fibers ->
(Run perpendicular to direction of Purkinje cells)
4. Forms excitatory synapses with Purkinje cells

b. Purkinje cells
(Form inhibitory synapses)

(Blumenfeld)
Interneurons of the cerebellum - Location, connection, and function
1. Basket and Stellate cells
I. Molecular layer
II. <- Excited by granular cells, -> inhibit Purkinje cells
(Basket cells form a 'basket' around Purkinje cell bodies in Purkinje cell layer, Stellate cells synapse with Purkinje dendrites in molecular layer)
III. Function = Lateral inhibition of Purkinje cells
(-> Enhanced signal resolution in the spatial domain)

(All axons projecting upward\peripherally are excitatory (Mossy fibers, climbing fibers, granule cell parallel fibers), while all axons projecting downward are inhibitory (Purkinje cells, stellate cells, basket cells, golgi cells)

(Blumenfeld)

2. Golgi cells
I. Granule cell layer
II. <- Excited by granule cell parallel fibers in molecular layer, -> feedback inhibition to granule cell dendrites
(This shortens the duration of excitatory inputs to the granule cells -> enhanced signal resolution in the time domain)
Cerebellar output pathways
a. Why does coordination deficits occur ipsilateral to the lesion
b. Does vermis-lesions cause ipsilateral or contralateral deficits
a. The pathway are double-crossed
1. Decussation of superior cerebellar peduncle in the midbrain
2. As the corticospinal (pyramidal decussation) and rubrospinal tract (ventral tegmental decussation) decussate while descending to the spinal cord
(Input to cerebellum also follows this pattern)

Or the connections are ipsilateral.

b. Bilateral because the medial motor systems influence the proximal trunk muscles bilaterally.
Lateral hemispheres of cerebellum - Output pathway (deep cerebellar nuclei, cerebellar peduncle...)
1. Lateral hemisphere ->

2. Dentate nucleus ->

3. Superior cerebellar peduncle ->
(Decussate in midbrain)

4a. Ventral lateral nucleus of thalamus ->
(Posterior VL (VLp\VL pars caudalis, basal ganglia terminate in VLa\pars oralis)
(Via thalamic fasciculus)

5b. Cortex
I. Premotor cortex
II. Supplementary motor area
III. Parietal lobe
(Influence motor planning in the corticospinal system)
(Some evicende that it also reach prefrontal association cortex and is in this way involved in cognitive function)

4b. Parvocellular red nucleus ->

5b. Central tegmental tract ->

6b. Inferior olivary nucleus ->

7b. Olivocerebellar fibers -> cerebellum

(Blumenfeld)
Intermediate hemispheres of cerebellum - Output pathway (deep cerebellar nuclei, cerebellar peduncle...)
1. Intermediate hemispheres ->

2. Interposed nuclei ->
(Emboliform, globose nuclei)

3. Superior cerebellar peduncle ->
(Decussate in midbrain)

4a. Ventral lateral nucleus of thalamus ->
(Posterior VL (VLp\VL pars caudalis, basal ganglia terminate in VLa\pars oralis)
(Via thalamic fasciculus)

5a. Motor, supplementary motor, premotor cortex to influence lateral corticospinal tract
(For ongoing distal limb coordination)

4b. Magnocellular red nucleus ->

5b. Rubrospinal tract

(Blumenfeld)
Vermis of cerebellum - Output pathway (deep cerebellar nuclei, cerebellar peduncle...)
1. Vermis ->

2. Fastigial nucleus ->

3a. Superior cerebrellar peduncle ->

4a. Ventral lateral nucleus of thalamus ->
(Posterior VL (VLp\VL pars caudalis, basal ganglia terminate in VLa\pars oralis)
(Via thalamic fasciculus)

(Also goes to tectum)

5a. Motor cortex and association cortex
(Influence anterior corticospinal tract)

3b. Uncinate fasciculus ->
('Hook bundle')
(Travel with superior cerebellar peduncle)

4b. Juxtarestiform body ->

5b. Vestibular nuclei

3c. Juxtarestiform body
(Next to restiform body\inferior cerebellar peduncle)
(Carries fibers in both directions between the vestibular nuclei and the cerebellum, this is important for equilibrium and balance)

4c. Vestibular nuclei (-> Vestibulospinal tract) and reticular formation (Reticulospinal tract)

(Medial motor system)

(Blumenfeld)
Inferior vermis and flocculonodular lobe - Output pathway (deep cerebellar nuclei, cerebellar peduncle..)
1. Inferior vermis and flocculonodular lobe ->

2. Vestibular nuclei ->

3. Juxtarestiform body ->
(Travels with inferior cerebellar peduncle\restiform body)

4. MLF
(Eye movement pathways - smooth pursuit, vestibulo-ocular reflex..)

(Vestibulocerebellum = flocculonodular lobes, inferior vermis)

(Blumenfeld)
Cerebellar input pathways
a. Which fibers are responsible for input to the cerebellum
b. What are the main cerebellar input pathways
a. Mossy fibers, except for climbing fibers from inferior olivary nucleus.

b. Main cerebellar input pathways
1. Pontocerebellar fibers
2. Spinocerebellar pathways
I. Dorsal spinocerebellar tract
II. Cuneocerebellar tract
III. Ventral spinocerebellar tract
IV. Rostral spinocerebellar tract
3. Climbing fibers
4. Vestibular inputs

(Blumenfeld)
Pontocerebellar fibers
a. Main origins of input
b. Cells projecting to cerebellum
c. Cerebellar peduncle or equivalence
a. Main origins of input
I. Cortex
(Via corticopontine fibers in internal capsule and cerebral peduncles)
(Most from primary sensory and motor cortices and visual cortex)

b. Cells projecting to cerebellum - Pontine nuclei
(Where the corticopontine fibers synapse, interspersed among corticospinal and corticobulbar fibers)

c. Cerebellar peduncle or equivalence - middle cerebellar peduncle in pontocerebellar fibers
(Cross the midline and give rise to Mossy fibers)
Cerebellar glomerulus
a. What
b. Structure
c. Inputs, synapse on
a. Sites of complex synaptic interactions in the granule cell layer.

b. Look like small clearings among the granule cells, contain axons and dendrites encapsulated in a glial sheath.

c. Mossy fiber axon terminals and Golgi cell axon terminals. Synapse on granule cell dendrites.

(Blumenfeld)
Spinocerebellar fibers - Main origin of input, cells projecting to cerebellum\nucleus, cerebellar peduncle
a. Dorsal spinocerebellar tract
b. Cuneocerebellar tract
c. Ventral spinocerebellar tract
d. Rostral spinocerebellar tract
a. Dorsal spinocerebellar tract
I. Leg proprioceptors
II. Nucleus dorsalis of Clark
(Column in intermediate gray matter zone of spinal cord, C8-L2\3)
III. Inferior cerebellar peduncle
(Ipsilateral)

b. Cuneocerebellar tract
I. Arm proprioceptors
II. External cuneate\Accessory\Lateral nucleus
(In medulla lateral to cuneate nucleus)
III. Inferior cerebellar peduncle

(Ipsilateral)

c. Ventral spinocerebellar tract
I. Leg interneurons
II. Spinal cord neurons
(Cross in ventral commissure)
III. Superior cerebellar peduncle
(Cross again)

d. Rostral spinocerebellar tract
I. Arm interneurons
II. Spinal cord neurons
III. Superior and inferior cerebellar peduncles

(These are not conscious)

(Blumenfeld)
Climbing fibers - Main origins, cells\nuclei projecting to cerebellum, cerebellar peduncle or equivalent
1. Parvocellular red nucleus, cortex, brainstem, spinal cord ->

2. Central tegmentum (Only from parvocellular red nucleus) ->

3. Inferior olivary nucleus ->

4. Olivocerebellar fibers ->
(Decussate)

5. Climbing fibers

(The lateral reticular nucleus is located dorsal to the inferior olive and also receives similar input and projects to the cerebellum via the inferior cerebellar peduncle, but it gives rise to mossy fibers instead of climbing-fiber terminals)

(Blumenfeld)
Cerebellar arterial perfusion areas
a. PICA
b. AICA
c. SCA
a. PICA
I. Lateral medulla
II. Most of the inferior half of the cerebellum
III. Inferior vermis

b. AICA
I. Caudal lateral pons
II. Middle and inferior cerebellar peduncle
III. Part of ventral cerebellum between PICA and SCA territories, include flocculi

c. SCA
I. Rostral lateral pons
II. Superior cerebellar peduncle
III. Most of the superior half of the cerebellar hemispheres (include deep cerebellar nuclei)
IV. Superior vermis

(Infarcts are least common in AICA territory)

(Blumenfeld)
Cerebellar infarcts
a. In which of the cerebellar arteries are infarcts most common
b. Typical signs and symptoms
c. Infarcts that spare the lateral brainstem and involve mainly the cerebellum itself are more common with ...
a. PICA and SCA

b. Signs and symptoms
1. Vertigo
2. Nausea and vomiting
3. Nystagmus
I. Horizontal
II. Vertical
III. Gaze paretic
4. Limb ataxia
5. Unsteady gait
6. Headache - Occipital, frontal, upper cervical
7. Unilateral hearing loss with AICA infarct
(Labyrinthine artery branch of AICA)
8. Large infarcts -> Swelling -> tonsillar herniation
I. Hydrocephalus
(Compress 4th ventricle)
II. Brain stem findings - among them impaired consciousness
III. Head tilt
9. Postural\Rubral tremor
(Form of action\intention tremor, thought to involve red nucleus, this is now questioned)
10. Myoclonus
11. Speech
I. Slurred
II. Scanning\explosive speech
11. Failure of suppression of vestibulo-ocular reflex
12. Ocular dysmetria
c. SCA infarcts
(AICA and PICA more often involve the lateral brainstem as well)

(Blumenfeld)
Ataxia
a. Definition
b. The movements can be said to consist of continuous
c. Ataxic movements have abnormal timing and rhythmicity - what is this called
d. Ataxic movements have abnormal trajectories through space (overshooting\past-pointing and undershooting) - what is this called
a. An inability to coordinate muscle activity during voluntary movement.
Characterized by disordered contractions of agonist and antagonist muscles and the lack of normal coordination between movements at different joints.

b. Overshooting, overcorrecting, and then overshooting again around the intended trajectory.

c. Dysrhythmia

d. Dysmetria
(Refer to distance, power, and speed of an act, component of ataxia)

(Ataxia - taxis: order)

(Blumenfeld)
Ataxia
a. Lesions of the cerebellar vermis cause what type of ataxia, what is it characterized by
b. Lesions of the intermediate and lateral portions of the cerebellar hemisphere can cause what type of ataxia
c. Which area of the cerebellum can be injured unilaterally without causing a appreciable deficit
a. Truncal ataxia
I. Wide-based, unsteady, "drunk-like" gait
(Affect medial motor system)

b. Appendicular ataxia
(Affect lateral motor system)

c. Unilateral portion of the cerebellar hemisphere.

(Blumenfeld)
False localization of ataxia - list the conditions that can cause ataxia symptoms
1. Lesions of the cerebellar peduncles or pons
(-> Severe ataxia)

2. Hydrocephalus
(Can damage frontopontine pathways)

3. Lesions of the prefrontal cortex

4. Spinal cord lesions
(2-4 -> cerebellar truncal ataxia-like gait)

5. Ataxic hemiparesis
I. <- Lacunar infarcts in corona radiata, internal capsule or pons that involve both corticospinal and corticopontine fibers
II. Unilateral UMN signs and ataxia, usually on same side
(Can also be seen in lesions of the frontal or parietal lobes, sensorimotor crtex, or in midbarin lesions that involve fibers of the superior cerebellar peduncle or red nucleus)

6. Sensory ataxia
I. When the posterior column-medial lemniscal pathway is disrupted
II. Truncal and appendicular ataxia
(Differentiate by impaired joint position sense on exam and with worsening of symptoms when visual feedback is removed (close eyes))
(lesions of peripheral nerves or posterior columns cause ipsilateral ataxia, lesions of thalamus, thalamic radiations, or somatosensory cortex cause contralateral ataxia)

(Blumenfeld)
Appendicular ataxia
a. Most abnormalities can be described as a combination of
b. Finger-nose-finger test
c. Heel-shin test
d. Tests for dysrhythmia
a. Dysrhythmia and dysmetria.

b. Finger-nose-finger test
I. The patient touches their nose and then the examiner's finger alternately
(Can increase the sensitivity of the test by holding the target finger at the limit of the patient's reach, and by moving the target finger each time)

c. Heel-shin test
I. The patient rubs one heel up and down the length of the opposite shin in as straight a line as possible in supine position
(Not standing since gravity will be involved in the downward sliding)

d. Dysrhythmia tests
1. Rapid tapping of the fingers together
2. Rapid tapping of the hand on the thigh
3. Rapid tapping of the foot on the floor

(Blumenfeld)
Testing for appendicular ataxia
a. Dysdiachokinesia - What, how can it be tested
b. How can the examiner test for overshoot
a. Dysdiadochokinesia
I. Impairment of the ability to perform rapidly alternating movements
II. Alternately tapping one hand with the palm and dorsum of the other hand

b. Overshoot test
I. Have the patient raise both harms suddenly from their lap or lower them suddenly to the level of the examiner's hand
II. Examiner can apply pressure to the patient's outstretched hands, and then suddenly release it

(Blumenfeld)
Truncal ataxia
a. Characteristics of gait
b. How can it be tested
a. Wide-based, unsteady, 'drunk-like' or toddler gait
(Alcohol impairs cerebellar function and cerebellar pathways are not fully myelinated in infancy)

b. Tests
1. Tandem gait
I. The patient walk with the heel touching the toe with each step
(Force the patient to assume a narrow stance, the patient tend to fall\deviate toward the site of the lesion)

2. Romberg test
I. Patient stand with feet approximated, if closing the eyes increase the unsteadiness, a loss of proprioceptive control is indicated, and the test is positive

3. Titubation - tremor of trunk or head

(Blumenfeld)
Cerebellar lesions - Eye movement abnormalities
a. Ocular dysmetria
b. How can the saccades change
c. What type of nystagmus is present
d. What happens to the vestibulo-ocular reflex, how can this be tested for
a. Saccades over- or undershoot their target.
(Rapid eye movement to redirect the line of sight)

b.
1. Slow saccades
(Present in some degenerative conditions of the cerebellum)
2. Jerky saccadic intrusions during attempted smooth pursuit eye movements
(Particularly when the flocculonodular lobe is involved)

c. Nystagmus
1. Gaze paretic type
(When the patient looks toward a target in the periphery, slow phases occur toward the primary\rest position and fast phases occur back toward the target)
(Change direction, unlike nystagmus in peripheral vertigo)
2. Vertical nystagmus

d. Vestibulo-ocular reflex
I. The normal suppression can be impaired
(Particularly if the flocculonodular lobe is involved)
II. Ask the subject to fixate on their tumbs, held together at arm's length while they turn their head from side to side. Nystagmus occurs in patients with impaired VOR suppression

(Blumenfeld)
Cerebellar lesions and associated S&S
a. Speech involvement
b. How can the reflexes be affected
a. Speech involvement
1. Scanning\Explosive speech
I. Irregular fluctuations in rate and volume

2. Slurred speech
(Ie. alcohol intoxication)

b. They can have a pendular\swinging quality

(Blumenfeld)
Differential diagnosis of acute or recurrent ataxia in adults
1. Toxin ingestion
I. Ethanol
II. Anticonvulsants
2. Stroke - ischemic and hemorrhagic
3. Basilar migraine
(A migraine accompanied by transient brainstem signs (vertigo, tinnitus, perioral numbness, diplopia..) thought to be due to vasospastic narrowing of the basilar artery)
4. Benign paroxysmal vertigo
(<- Labyrinthine dysfunction)
5. Conversion disorder
6. Postconcussion syndrome
7. Traumatic hematoma
8. MS
9. Infectious or postinfectious cerebellitis
10. Celiac disease
(Recent evidence suggest that celiac disease without GI symptoms may be an important cause of ataxia in patients with no clear diagnosis)
11. Brainstem encephalitis
12. Wernicke's encephalopathy
13. Toxoplasmosis
14. Brain abscess
15. Brain tumor (usually chronic)
16. Hereditary episodic ataxias
17. Metabolic disorders
I. Hartnup disease
(Aminoaciduria due to defective renal tubular transport of neutral amino acids -> increased excretion of tryptophan and its derivatives -> pellegra-like symptoms)
II. Maple syrup urine disease
III. Pyruvate DH deficiency
18. Paraneoplastic syndromes
I. Breast cancer
II. Ovarian cancer

(Blumenfeld)
Differential diagnosis of chronic or progressive ataxia in adults
1. Cerebellar or other metastasis
I. Lung carcinoma
II. Breast carcinoma
III. Melanoma

2. MS

3. Chronic toxin exposure
I. Alcohol\nutritional deprivation
II. Phenytoin
III. Mercury
IV. Thallium
V. Toluene (glue, spray paint)

4. Degenerative disorders
I. Olivopontocerebellary atrophy
II. Machado-Joseph disease
III. Dentatoruboropallidolulysian atrophy (DRPLA)

5. Celiac disease
(Recent evidence suggest that celiac disease without GI symptoms may be an important cause of ataxia in patients with no clear diagnosis)

6. Progressive multifocal leukoencephalopathy (PML)
(<- JC virus (human polyoma virus), subacute afebrile disease characterized by areas of demyelinization surrounded by markedly altered neuroglia, including inclusion bodies in neuroglial cells, usually in leukemia and AIDS patients)

7. Toxoplasmosis

8. Creutzfeldt-Jakob disease

9. AVMs

10. Paranoeplastic syndromes
I. Breast cancer
II. Ovarian cancer

11. Wilson's\hepatolenticular disease

12. Vitamin E deficiency

(Blumenfeld)
Differential diagnosis of acute or recurrent ataxia in infants and children
1. Toxin ingestion
I. Anticonvulsants
I. Ethanol

2. Infectious or postinfectious cerebellitis

3. Brainstem encephalitis

4. Basilar migraine

5. Benign paroxysmal vertigo

6. Conversion disorder

7. Postconcussion syndrome

8. Traumatic hematoma

9. Brain tumor
(Usually presents as chronic progressive ataxia)

10. Hereditary episodic ataxia
(7 types, many are related to dysfiring of Purkinje cells)

11. Metabolic disorders
I. Hartnup disease
II. Maple syrup urine disease
III. Pyruvate DH deficiency

12. Neuroblastoma syndrome

13. MS

14. Stroke - hemorrhagic and ischemic

15. Kawasaki disease
(Idiopathic systemic vasculitis, primarily in children < 8 years)

(Blumenfeld)
Differential diagnosis of chronic or progressive ataxia in infants and children
1. Posterior fossa tumors
I. Medulloblastoma
(Undifferentiated cells of medullary tube, usually in vermis)
II. Cerebellar astrocytoma
III. Ependyoma
IV. Hemangioblastoma
V. Pontine glioma

2. Congenital malformations
I. Dandy-Walker malformation
(Atresia of foramina of Luschka and Magendie -> hydrocephalus, cerebellary hypoplasia)
II. Cerebellar aplasias

3. Degenerative disorders
I. Friedreich's ataxia
(Trinucleotide repeat expansion in Friedreich ataxia gene (FRDA), various signs)
II. Ataxia-telangiectasia
III. Olivopontocerebellar atrophy
IV. Machado-Joseph disease

4. MS

5. Metabolic disorders
I. Abetalipoproteinemia
II. Adrenoleukodystrophy
III. Juvenile GM2 gangliosidosis
IV. Juvenile sulfatide lipidosis
V. Hartnup disease
VI. Maple syrup urine disease
VII. Pyruvate DH deficiency
VIII. Marinesco-Sjogren syndrome
IX. Respiratory chain disorders
X. Ramsay-Hunt syndrome\Progressive cerebellar tremor
(Start as intention tremor)

(Blumenfeld)
An embolic workup after an cerebral thromboembolic event usually include
1. Transesophageal echocardiogram

2. 24-hour Holter monitor

3. Transcranial Doppler studies

4. MRA

(Blumenfeld)
Basal ganglia
a. The two types of movements disorders with examples
b. Components
c. (Neo)Striatum
d. Lenticular\Lentiform nucleus
e. Location of basal ganglai nuclei
a. Basal ganglia movement disorders
1. Hyperkinetic movement disorders
I. Huntington's disease
(Uncontrolled involuntary movements produce a random pattern of jerks and twists)

2. Hypokinetic movement disorders
I. Parkinson's disease
(Rigidity, slowness, marked difficulty initiating movements)

b. Basal ganglia
1. Caudate
2. Putamen
(Lateral)
3. Globus pallidus\Pallidum
(Medial to putamen, pale from all the white matter passing through, internal and external segment)
4. Subthalamic nucleus
5. Substantia nigra
(Some include nucleus accumbens and ventral pallidum which is involved in the limbic system as well)

c. (Neo)Striatum
1. Caudate
(C-shaped, head body and tail. The amygdala lies close to the tail, nucleus accumbens lie close to the head)
2. Putamen
(Receive virtually all input to the basal ganglia, separated by penetrating fibers of the internal capsule, connected by cellular bridges)

d. Lenticular\Lentiform nucleis
1. Putamen
2. Globus pallidus

e. Collection of gray matter nuclei located deep within the white matter of the cerebral hemispheres.

(Blumenfeld)
Internal capsule relative to basal ganglia
a. Which structures does the anterior limb of the internal capsule pass through
b. Which structures does the posterior limb of the internal capsule pass through
c. Which 2 structures are always medial to the internal capsule and which structure is always lateral to it
a. Between the lentiform nucleus and the head of the caudate.

b. Between the lentiform nucleus and thalamus.

c.
I. The caudate and the thalamus are always medial to the internal capsule.
II. The lentiform nucleus is always lateral to it.

(Blumenfeld)
Basa ganglia blood supply
1. Striatum and globus pallidus is mainly supplied by lenticulostriate branches of MCA

2. Medial globus pallidus is often supplied by anterior choroidal artery of ICA

3. The caudate head and anterior portions of the lentiform nucleus are often supplied by the recurrent artery of Heubner from ACA

(Blumenfeld)
Basal ganglia
a. Virtually all inputs to the basal ganglia arrive via
b. Outputs leave the basal ganglia via
c. Basal ganglia are involved with
a. The striatum
(And nucleus accumbens)

b.The internal segment of the globus pallidus and the closely related substantia nigra pars reticulata
(Inputs and outputs through the basal ganglia are thus easily visualized as a funnel, with the spout pointing medially)

c. Basal ganglia
1. General motor control
2. Eye movements
3. Cognitive functions
4. Emotional functions

(Blumenfeld)
Inputs to basal ganglia - List the four major sources of input and list the major neurotransmitter for each input
The basal ganglia receive input from
1. Cerebral cortex
I. Glutamate
(Mainly to putamen)

2. Substantia nigra pars compacta - Nigrostriatal pathway
I. Dopaminergic
(Excitatory to some cells and inhibitory to others in the striatum)

3. Intralaminar nuclei - Especially the centromedian and parafascicular nuclei
I. Glutamate
(Within the internal medullary lamina of the thalamus)

4. Raphe nuclei
I. Serotonergic

(All input converge on striatum)

(Blumenfeld)
Basal ganglia outputs
a. List the four major thalamic nuclei to which the basal ganglia project
b. List two additional basal ganglia outputs
c. From what structures do the basal ganglia outputs arise
d. What is the major neurotransmitter for all outputs from the basal ganglia
a. List the four major thalamic nuclei to which the basal ganglia project
1. Ventral lateral (VL) nucleus
(VL anterior\oralis from basal ganglia, VL posterior\caudalis from cerebellum (Caudalis = Cerebellum))

2. Ventral anterior (VA) nucleus
(1-2 via thalamic fasciculus, and project further to the entire frontal lobe - Motor information travels mainly to the premotor, supplementary motor, and primary motor cortices)

3. Intralaminar nuclei - Centromedian, Parafascicular
(These project back to the striatum)

4. Mediodorsal nucleus
(Involved primarily in limbic pathways)

b. List two additional basal ganglia outputs
1. Pontomedullar reticular formation (Thus influence reticulospianl tract)
2. Superior colliculus
(Influence tectospinal pathways)

c. From what structures do the basal ganglia outputs arise
I. Internal segment of Globus pallidus
I. Substantia nigra pars reticulata

d. What is the major neurotransmitter for all outputs from the basal ganglia - GABA
(All are inhibitory)

(Blumenfeld)
Intrinsic basal ganglia connections
a. Direct pathway - Components and neurotransmitter, net effect
b. Indirect pathway - Components and neurotransmitters, net effect
a. Direct pathway
1. Cortex (+, Glu) ->
1. Striatum (-, GABA) ->
(Also substance P)
2. Internal segment of globus pallidus\substantia nigra pars reticulata (- GABA) ->
3. Thalamus (VL, VA) (+, Glu) ->
4. Cortical motor areas

Net effect - excitatory by inhibiting inhibition
((-1)(-1) = +1)

b. Indirect pathway
1. Cortex (+, Glu) ->
2. Striatum (-, GABA) ->
(Also Enkephain (Enkephalin to External pallidum)
3. External segment of globus pallidus (-, GABA) ->
4. Subthalamic nucleus (+, Glu) ->
5. Internal segment of globus pallidus\Substantia nigra pars reticulata (-, GABA) ->
6. Thalamus (VA, VL) (+, Glu) ->
7. Cortical motor areas

Net effect - inhibition
(Indirect inhibits)
((-1)(-1)(+1)(-1) = -1)

(Blumenfeld)
Basal ganglia
a. Explain the mechanism of the hypokinetic movement disorder Parkinson's disease by the indirect and direct basal ganglia pathways
b. Explain the mechanism of how anticholinergic drugs can be beneficial in the treatment of Parkinson's disease
c. Explain the mechanism of the hyperkinetic movement disorder hemiballismus in terns of the direct and indirect basal ganglia pathways. In hemiballismus there are unilateral wild flinging movements of the extremities contralateral to a lesion most often in the subtahalamic nucleus
d. Explain the hyperkinetic movement disorder Huntington's disease --||--.
a. Parkinson's disease
I. Dopaminergic neurons in the substantia nigra pars compacta degenerate
II. Dopamine have excitatory effects on striatal neurons of the direct pathway and inhibitory effects on striatal neurons of the indirect pathway -> Less dopamine cause inhibition via both pathways
III. This may account for the paucity of movements seen in Parkinson's disease
(Drugs that bolster dopaminergic transmission can improve the symptoms of the disease)

b. The striatum contains large interneurons called aspiny neurons, some of which are cholinergic. Some evidence suggests that these preferentially form excitatory synapses onto striatal neurons of the indirect pathway.

c.
1. Loss of excitatory Glu from subthalamic nucleus ->
2. Decreased inhibition of thalamus from internal segment of globus pallidus and substantia nigra pars reticulata ->
3. Hyperkinetic movement disorder

d.
1. Striatal neurons degenerate, some evidence suggest that enkephalin containing striatal neurons of the indirect pathway are more severely affected ->
2. Removal of inhibition from the external segment of the globus pallidus -> decreased inhibition of the indirect inhibitory pathway -> hyperkinetic movement disorder

(In more advanced stages, both the direct and indirect pathways degenerate and a rigid hypokinetic parkinsonian state results)

(Blumenfeld)
Basal ganglia
a. The four channels
b. Group them into dorsal and ventral striatal pathways
a. The four channels
1. Motor channel
2. Oculomotor channel
3. Prefrontal channel
4. Limbic channel

b.
I. Dorsal striatal pathways - 1-3
II. Ventral striatal pathway - 4

(Blumenfeld)
Basal ganglia - motor channel
a. Sources of cortical input
b. Basal ganglia input nuclei
c. Basal ganglia output nuclei
d. Thalamic relay nuclei
e. Cortical targets of output
Basal ganglia - motor channel
a. Sources of cortical input
I. Somatosensory cortex
II. Primary motor cortex
III. Premotor cortex

b. Basal ganglia input nuclei
I. Putamen

c. Basal ganglia output nuclei
I. Globus pallidus - internal segment
II. Substantia nigra pars reticulata

d. Thalamic relay nuclei
I. Ventral lateral (VL) and ventral anterior (VA)

e. Cortical targets of output
I. Supplementaory motor area
II. Premotor cortex
III. Primary motor cortex

(Blumenfeld)
Basal ganglia - Oculomotor channel
a. Sources of cortical input
b. Basal ganglia input nuclei
c. Basal ganglia output nuclei
d. Thalamic relay nuclei
e. Cortical targets of output
Basal ganglia - Oculomotor channel
a. Sources of cortical input
I. Posterior parietal cortex
II. Prefrontal cortex

b. Basal ganglia input nuclei
I. Head of caudate

c. Basal ganglia output nuclei
I. GPi
II. SNr

d. Thalamic relay nuclei
I. VA
II. MD (Mediodorsal)

e. Cortical targets of output
I. Frontal eye fields
II. Supplementary eye fields

(Regulation of eye movements)

(Blumenfeld)
Basal ganglia - Prefrontal channel
a. Sources of cortical input
b. Basal ganglia input nuclei
c. Basal ganglia output nuclei
d. Thalamic relay nuclei
e. Cortical targets of output
Basal ganglia - Prefrontal channel
a. Sources of cortical input
I. Posterior parietal cortex
II. Premotor cortex

b. Basal ganglia input nuclei
I. Head of caudate

c. Basal ganglia output nuclei
I. GPi
II. SNr

d. Thalamic relay nuclei
I. VA
II. MD

e. Cortical targets of output
I. Prefrontal cortex

(Probably important in cognitive processes involving the frontal lobes)

(Blumenfeld)
Basal ganglia - Limbic channel
a. Sources of cortical input
b. Basal ganglia input nuclei
c. Basal ganglia output nuclei
d. Thalamic relay nuclei
e. Cortical targets of output
Basal ganglia - Limbic channel
a. Sources of cortical input
I. Temporal cortex
II. Hippocampus
III. Amygdala

b. Basal ganglia input nuclei
I. Nucleus accumbens
II. Ventral caudate
III. Ventral putamen
(Ventral striatum)

c. Basal ganglia output nuclei
I. Ventral pallidum
(A region just ventral to the globus pallidus)
II. GPi
III. SNr

d. Thalamic relay nuclei
I. VA
II. MD

e. Cortical targets of output
I. Anterior cingulate
II. Orbital frontal cortex
(Involved in limbic regulation of emotions and motivational drives)

(Another component of this pathway is the dopaminergic projections from the ventral tegmental area, which lie just medial to the substantia nigra of the midbrain. It provides dopaminergic inputs to nucleus accumbens as well as to other limbic structures and to the frontal lobes. Related to schizophrenia and other psychiatric disorders and addictions)

(Blumenfeld)
Tracts of basal ganglia
a. Ansa lenticularis
b. Lenticular fasciculus
c. Thalamic fasciculus
d. Subthalamic fasciculus
a. Ansa lenticularis
I. Fibers from direct pathway going from GPi to thalamus
II. Goes ventral (in a loop) under internal capsule

b. Lenticular fasciculus\H2 field of Forel
I. Fibers direct pathway from GPi to thalamus
II. Goes through internal capsule, ventral to zona incerta (ventral part of thalamic reticular nucleus) and dorsal to subthalamic nucleus

c. Thalamic fasciculus\H1 fields of Forel
I. The joined fibers of ansa lenticularis and lenticular fasciculus

d. Subthalamic fasciculus
I. Carries fibers of the indirect pathway from GPe to STN
(The point where the two join is called h field of Forel or prerubral field)

(Blumenfeld)
Movement disorders
a. Common definition for movement disorders caused by basal ganglia dysfunction
b. Is a unilateral movement disorder caused by focal basal ganglia lesions such as infarct, hemorrhage, abscess, tumor, or degeenration contralateral or ipsilateral
a. Dyskinesias
(As opposed to spasticity with corticospinal tract, ataxia..)

b. Contralateral.

(Blumenfeld)
Basal ganglia symptoms - Bradykinesia, hypokinesia, and akinesia
a. Bradykinesia
b. Hypokinesia
c. Akinesia
d. Besides basal ganglia disorders, in which other conditions can these conditions be found
a. Bradykinesia
I. Slowed movements

b. Hypokinesia
I. Decreased amount of movements

c. Akinesia
I. Absence of movements

(These terms are usually reserved for localizations above UMNs)

d.
1. Abulia\Akinetic mutism
I. From diffuse lesions of the frontal lobes, subcortical white matter, thalami, brainstem reticular formation

2. Catatonia
I. Extreme cases of psychomotor retardation from psychiatric conditions such as depression and schizophrenia

(Blumenfeld)
Basal ganglia symptoms - Rigidty - Describe the rigidity seen in
a. Corticospinal disorders
b. Basal ganglia disorders
c. Frontal lobe dysfunction
a. Corticospinal disorders - Clasp-knife rigidity
I. Resistive tone intially increase as the msucles of the limb are stretches, but it may then decrease

b. Basal ganglia disorders - Plastic\waxy\lead pipe rigidity
I. More continuous character
(Cogwheel rigidity in parkinsonian disorders - ratchet-like (skralle) interruptions in tone can be felt as the limb is bent. Thought of as rigidity with a superimposed tremor)

c. Frontal lobe dysfunction - Paratonia\gegenhalten
I. More active, inconsistent character

(Rigidity - increased resistance to passive movement of a limb)

(Blumenfeld)
Basal ganglia symptoms - Dystonia
a. Dystonia
b. Name the focal dystonia involving neck muscles
c. Name the focal dystonia involving the facial muscles around the eyes
d. Name the focal dystonia involving the laryngeal muscles
e. Name the focal dystonia affecting the hand
f. Cause of dystonias
a. The patient assumes abnormal, often distorted positions of the limbs, trunk, or face. Can be generalized, unilateral, or focal.
(More sustained or slower than in athetosis)

b. Torticollis
('Twisted' neck)

c. Blepharospasm

d. Spasmodic dysphonia
(Altered voice production)

e. Writer's camp
(Induced by excessive use of a writing instrument)

f. Causes
1. Tumor, abscess, infarct or other structural lesion of basal ganglia
2. Huntington's disease
3. Parkinson's disease
4. Wilson's\Hepatolenticular disease
5. Certain seizures
6. Primary idiopathic torsion dystonia\dystonia musculorum deformans
(Hereditary disorder causing generalized dystonia)
7. Use of dopaminergic antagonists - antipsychotics, antiemetics
(Delayed\tardive dyskinesia, in which oral and lingual choreic dyskinesias are often prominent can develop after long term use. Remains severe despite discontinuation of drug in 1\3 of cases)
(Some effect with botulinum toxin treatment)

(Blumenfeld)
Wilson's\ disease\Hepatolenticular degeneration
a. What
b. S&S
c. Laboratory tests
d. Treatment
a. AR disorder of biliary copper excretion that causes progressive degeneration of the liver and basal ganglia.

b. S&S
1. Dysarthria
2. Dystonia
(Some patients have facial dystonia causing a wry smile called risus sardonicus)
3. Rigidity
4. Tremor
(Wing-beating - abduction)
5. Choreoathetosis
6. Psychiatric disturbances
7. Liver failure
8. Kayser-Fleischer rings
(Brownish outer corneal deposits of copper, in nearly all patients with neurologic manifestations)

b. Diagnostic tests
1. Elevated 24-hour urine copper levels
2. Serum ceruloplasmin < 20 mg\dl

d. Treatment
1. Copper-chelating agents - Penicillamine, zinc

(Blumenfeld)
Athetosis
a. Athetosis
b. Causes
a. Athetosis ('Without position')
I. Writhing, twisting movements of the limbs, face and trunk.
(When it merge with faster choreic movements its called choreoathetosis)

b. Causes
1. Perinatal hypoxia involving the basal ganglia
2. Kernicterus caused by severe neonatal janudice
3. Wilson's disease
4. Ataxia telangiectasia
5. Huntington's disease
6. Antipsychotic or antiemetic dopamine antagonists
7. Parkinson patients who are treated with levodopa

(Blumenfeld)
Chorea
a. Chorea
b. Causes
a. Chorea ('Dance')
I. Movement disorders characterized by nearly continuous involuntary movements that have a fluid or jerky, constantly varying quality.
(Can involve proximal and distal extremities, trunk, face, neck, and respiratory muscles)

b. Causes
1. Huntington's disease

2. Benign familial chorea
(AD, non-progressive chorea, not accompanied by cognitive or emotional decline)

3. Sydenham's\Rheumatic chorea
(Rheumatic fever - post group A streptococcal infections, antistreptococcal antibodies that cross-react with striatal neurons, accompanied by emotional lability, recurrent events in 1\5 of patients)

4. SLE
(Can be the first manifestation)

5. As dyskinetic side effect of levodopa
I. Parkinson's disease
II. Antipsychotics
III. Anti-emetics

(Perinatal anoxia, CO poisoning, hyperthyroidism, electrolyte and glucose abnormalities, Wilson's disease, Lesch-Nyhan syndrome, lysosomal storage disorders)

(Blumenfeld)
Tics
a. Tics
b. Motor tics
c. Vocal tics
d. Gilles de la Tourette's syndrome\Tourette's syndrome
a. A sudden brief action that is preceded by an urge to perform it and followed by a sense of relief.

b. Motor tics
I. Usually involve the face or neck, less often the extremities

c. Vocal tics
I. Brief grunts, coughing sounds, howling or barking noises, words (obscene words - coprolalia)

d. Tourette's syndrome
I. AD pattern with incomplete penetrance
II. Persistent vocal and motor tics
III. Higher incidence of ADHD disorder and OCD disorder
IV. Can only be diagnosed clinically
(No structural lesions)
(Some effect with treating with antidopaminergics like haloperidol and central alpha-2-antagonists like clonidine)

(Blumenfeld)
Myoclonus
a. Myoclonus
b. Possible locations of dysfunction
c. Causes
a. Myoclonus
I. The 'fastest' movement disorder
II. Sudden, rapid muscular jerk
III. Can be focal, unilateral, or bilateral

b. Locations of dysfunction
1. Cerebellum
2. Cerebral cortex
3. Basal ganglia
4. Brain stem
5. Spinal cord
(All CNS)

c. Causes
1. Anoxic brain injury

2. Encephalitis

3. Toxic\metabolic encephalopathies
(See liver flap a form of flapping tremor\asterixis with hepatic failure)

4. Epileptic cortical activity
I. Juvenile myoclonic epilepsy
II. progressive myoclonic epilepsy

5. Paraneoplastic syndromes
I. Small cell lung carcinoma
II. Ovarian carcinoma
III. Breast carcinoma
IV. Neuroblastoma

6. Prion-related illnesses

7. late in the course of Lewy body disease or Alzheimer's disease

(Blumenfeld)
Tremor
a. Resting tremor - Characteristics, Types
b. Postural tremor - Characteristics, Types
c. Intention\Ataxic tremor - Characteristics, Types
d. Other disorders resembling tremor
a. Resting tremor
I. Most prominent when the limbs are relaxed, decrease\stop when patient move the limbs
II. Often asymmetrical and involve mainly the hands and upper extremities ('pill-rolling tremor)
III. Types
1. Parkinsonian tremor
2. Cerebellar disorders\Rubral tremor
(<- MS or brain stem infarct of cerebellum or superior cerebellar peduncle)
3. Palatal tremor
(Persist during sleep, <- central tegmental tract by brain stem infarcts or MS)
(3-5 Hz)

b. Postural tremor
I. Most prominent when the patient's limbs are actively held in a position, disappears at rest
II. Types
1. Essential\Familial\Senile\Benign tremor
(Most common movement disorder, 5-8 Hz, most commonly involve hands or arms, most often bilateral but can be asymmetrical, increase with stress, often improved by beta blockers, ventrolateral thalamotomy, or thalamic stimulation. Very slow progression)
2. Toxic\metabolic causes
(Drugs, medications, alcohol withdrawal)
3. Exaggerated physiological tremor
(8-13 Hz, enhanced with caffeine)
4. Neuromuscular disorders
(Also intention tremor)
5. Cerebellar disorders - Rubral tremor, trunk and head titubation
(Titubation associated with vermis lesions)
6. Parkinsonism
(Non-typic)

c. Intention\ataxic tremor
I. Usually a feature of appendicular ataxia
II. As the patient attempts to move their limb toward a target
III. Types - cerebellar appendicular ataxia

d. Other disorders resembling tremor
1. Clonus
2. Myoclonus
3. Flapping tremor (asterixis)
4. Dystonic tremor
5. Fasciculatiosn
6. Motor seizures

(Action tremor - postural, intentional, or both tremors. Static tremor - resting or postural tremor)

(Blumenfeld)
Parkinson's disease
a. Epidemiology
b. Pathologic changes
c. Classic presenting triad
d. Other S&S
a. 1% of people over 65 years, general onset between 40-70 years.
(No familial tendency except in rare familial cases)

b. Pathologic changes
I. Loss of pigmented dopaminergic neurons in the substantia nigra pars compacta
(-> Pale appearance)
II. Remaining dopaminergic neurons often contain characteristic cytoplasmic inclusions called Lewy bodies - eosinophilic (pink), contain ubiquitin and alpha-synuclein and have a lighter halo

c. Classic presenting triad
1. Resting tremor - pill rolling tremor'
2. Bradykinesia
3. Cogwheel rigidity
(Often initially unilateral but later become bilateral, although the severity often remains asymmetrical, nearly always improves with levodopa)

d. Other S&S
1. Postural instability -> unsteady gait - Parkinsonian gait
(Postural instability - the diminished ability to make reflex postural adjustments to maintain balance)
I. Retropulsion - If pulled backward slightly, they take several backward steps to regain balance, or may fall
II. Festinating gait - Walk with small shuffling steps
III. Anteropulsion - Continually falling and shuffling forward

2. Masked facies\Hypomima
(Decrease in spontaneous blink rate and facial expression)

3. Voice - Hypophonic
(Speech has a hurried, muttering quality)

4. Micrographia - Writing becomes small

5. Myerson's sign - Inability to suppress blinking when the glabella\brow ridge is tapped repeatedly
(Unspecific finding seen in other neurodegenerative disorders as well)

6. Dementia
(15-40% of patients, from comorbidity with Alzheimer's or Lewy body disease?)

7. Bradyphrenia - Response to questions are slowed
(But may be accurate if enough time is allowed)

8. Depression and anxiety

9. Seborrhea and hypersalivation

(Blumenfeld)
Parkinson's disease
a. Pharmacological treatment options
b. Side-effects of dopamine therapy
c. Other treatment options
a. Pharmacological therapy
1. Levodopa
I. Usually given with carbidopa
(Carbidopa is a decarboxylase inhibitor that cannot cross the BBB)

2. MAO-B inhibitors - Selegiline, Rasagiline

3. Anticholinergics - Benztropine mesylate, trihexyphenidyl

4. Amantadine - Antiviral, anticholinergic, antiglutamatergic, probably also release dopamine in striatum

5. Other dopamine agonists - Ropinirole, Pramipexole

b. Side-effects of dopamine therapy
1. The most common peripheral side effects are GI disturbances and orthostatic hypotension
(These are both substantially reduced by carbidopa)
2. Psychiatric symptoms - Psychosis
3. Dyskinesias
(When the drug wears off the patient can experience 'freezing', where the patient becomes almost unable to move. In severe cases patients fluctuate almost only between dyskinetic and freezing states)

c. Stereotactic surgery
I. Subthalatomy or DBS of the subthalamic nucleus
(DBS - Deep brain stimulation cause 'depolarization block')
II. Internal pallidotomy or DBS of the internal segment of globus pallidus

(Blumenfeld)
Parkinsonism - Differential diagnosis
1. Parkinson's disease

2. Drug-induced parkinsonism
(Dopamine antagonists - haloperidol, procholorperazine, onset is usually abrupt and symptoms are symmetrical)

3. Multisystem atrophy
I. Striatonigral degeneration
II. Shy-Drager syndrome
(Accompanied by intermediolateral cell column degeneration -> marked orthostatic hypotension, impotence, urinary incontinence)
III. Olivopontocerebellar atrophy
(Parkinsonism with ataxia)
(This group (#3) have atypical parkinsonism with symmetrical symptoms, absence of resting tremor, early appearance of postural instability, little response to dopaminergic agents because other parts of the basal ganglia (ie striatum) are lesioned as well)

4. Progressive supranuclear palsy (PSP)\Steele-Richardson-Olszewski syndrome
(Multiple structures around the midbrain-diencephalon junction degenerate -> superior colliclus (decreased vertical eye movement), red nucleus, dentate nucleus, subthalamic nucleus, GP)

5. Diffuse Lewy body disease
(Lewy bodies found in substantia nigra and throughout the cerebral cortex, prominent psychiatric problems early, visual hallucinations)

6. Cortical basal ganglionic degeneration
(Asymmetrical parkinsonism, limb dystonia, apraxia, wandering\alien limb syndrome ('mind of its own')

7. Machado-Joseph disease\Spinocerebellar ataxia type 3

8. Dentatorubropallidoluysian atrophy (DRPLA)
(7-8 - Rare, AD pattern, neruodegenerative, expanded trinucleotide repeats)

9. Huntington's disease
(Atypical, more common in early onset cases)

10. Wilson's disease

11. CO poisoning
(Delayed effect after several weeks)

12. Von Economo's encephalitis lethargica

13. Dementia pugilistica
(Boxers, parkinsonism and cognitive decline)

14. MPTP toxicity\abuse
(By product of illicitly manufactured meperidine (narcotic analgesic) that cause parkinsonism. Used experimentally in parkinson's research)

15. Vascular parkinsonism
(<- Lacunar strokes in striatum or substantia nigra

16. Disorders resembling parkinsonism
(Bradykinesia, rigidity or paratonia, hypohponia, unstable gait)
I. Hydrocephalus
II. Frontal lobe lesion (abulia)
III. Advanced schizophrenia (catatonia)
IV. Severe depression
V. Severe hypothyroidism

(Blumenfeld)
Huntington's disease
a. Epidemiology
b. Inheritance
c. Pathologic hallmark
d. General classification of signs
e. Radiographic diagnosis
a. Epidemiology
I. 4-5 \ 100 000
(Higher in those with northern European ancestry)
II. Usual age of onset - 30-50 years
III. Median survival time from the onset of the first symptoms is 15 years
(Usually die of respiratory infections)

b. Inheritance
I. AD
II. Huntingtin protein
III. Caused by expanded trinucleotide repeats. > 40 CAG repeats

c. Progressive atrophy of the striatum, especially involving the caudate nucleus.
(The putamen and to a lesser extent the nucleus accumbens is also involved

d. Include abnormalities in all four domains of basal ganglia function discussed earlier - body movements, eye movements, emotions, cognition

e. Enlarged ventricles seen on coronal CT and MRI scans. From loss of bulging of head of caudate on the walls of the lateral ventricles.

(Blumenfeld)
Huntington's disease
a. S&S
b. Treatment options
a. S&S
Motor channel
1. Chorea
(Mild masked fidgety or jerking motions initially, can be made more obvious by having the patient hold their arms outstretched eyes closed)
2. Tics
3. Athetosis
4. Dystonic posturing
(More parkinsonian phenotype in the rare cases of juvenile onset)

Oculomotor channel
1. Slow saccades
2. Impaired smooth pursuit
3. Sluggish optokinetic nystagmus
4. Difficulty initiating saccades without moving the head

Limbic channel
1. Depression
2. Anxiety
3. OCD
4. Manic-like behavior
5. Psychosis

Prefrontal channel
1. Behavioral disturbances
2. Decreased attention
3. Memory impairment - Both recent and remote memories
4. Anomic\Nominal aphasia
(The principal deficit is in naming persons or objects perceived)
5. Impaired executive functions
6. Dementia

b. Treatment options - Symptomatic
1. Chorea can be reduced by dopamine-depleting agents such as tetrabenzine or by dopamine receptor blocking neuroleptics
2. Psychiatric manifestations can be treated with counselign and psychotropic medications

(Blumenfeld)

(Blumenfeld)
Parkinson's disease - S&S indicating non-idiopathic parkinsonism
1. Lack of response to levodopa
(Seen in multisystem atrophy (Striatonigral degeneration, Shy-Drager syndrome, Olivopontocerebellar atrophy) due to non-specific damage of basal ganglia circuitry)

2. Early gait instability
(Multisystem atrophy)

3. Symmetrical findings
(Drugs\Toxins, Multisystem atrophy)

4. Absence of resting tremor

5. Impaired vertical eye movements
(Progressive supranuclear palsy (PSP)\Steele-Richardson-Olszewski syndrome
(Multiple structures around the midbrain-diencephalon junction degenerate -> superior colliclus (decreased vertical eye movement), red nucleus, dentate nucleus, subthalamic nucleus, GP))

6. Orthostatic hypotension
(Shay-Drager syndrome)

7. Early psychiatric features
(Diffuse Lewy body disease)

8. Acute onset
(-> Toxin\Drug-induced)

(Blumenfeld)
Pituitary and hypothalamus
a. The four functions of hypothalamus
b. Embryological origin of the pituitary
c. Hypothalamus - Location, separated from thalamus by
a. The four functions (HEAL)
1. Homeostasis mechanisms - Control appetite, thirst, sexual desire, sleep-wake cycles and thermoregulation
2. Endocrine control, via the pituitary
3. Autonomic control
4. Limbic mechanisms

b. Embryological origin of the pituitary
1. The anterior pituitary\adenohypophysis is formed by a thickened area of ectodermal cells on the roof of the developing pharynx that invaginate, forming Rathke's pouch
2. The posterior pituitary\neurohypophysis forms from an evagination of the floor of the ventricular system

c. Hypothalamus
I. Under the thalamus, separated by a groove on the wall of the third ventricle called the hypothalamic sulcus
II. Forms the walls and floor of the inferior portion of the third ventricle
III. Right dorsal to the optic chiasm

(Blumenfeld)
Hypothalamus - Describe the location of
a. Tuber cinerum
b. The mammillary bodies
c. The infundibulum
d. The pituitary stalk
e. The median eminence
a. Tuber cinerum ('Gray protuberance')
I. Bulge between the optic chiasm and mammillary bodies.

b. The mammillary bodies
I. Paired structures that form the posterior portion of the hypothalamus.

c. The infundibulum
I. Arise from the tuber cinerum and continues inferiorly as the pituitary stalk

d. The pituitary stalk
I. The continuation of the infundibulum

e. The median eminence
I. The anterior portion of the infundibulum
(Slightly elevated)
(Site where inhibitory and releasing factors are secreted into the primary capillary plexus)

(Blumenfeld)
Pituitary and hypothalamus
a. What is the dura covering the superior portion of the pituitary fossa called, and which structure penetrates it
a. The diaphragma sella, the pituitary stalk.
Major hypothalamic nuclei
3 Groups from medial to lateral

1. Periventricular area - Periventricular nucleus

2. Medial hypothalamic area - 4 Groups from anterior to posterior
I. Preoptic area
a. Medial preoptic nucleus
b. Lateral preoptic nucleus
(Derived from the telencephalon, while the rest of the hypothalamus is derived from the diencephalon)

II. Anterior\Supraoptic region
a. Anterior hypothalamic nucleus
b. Supraoptic nucleus
c. Paraventricular nucleus
(b-c: Contain oxytocin or vasopressin and project to the posterior pituitary)
d. Suprachiasmatic nucleus
(The master clock for circadian rhythms, <- specialized retinal ganglion cells via retinohypothalamic tract from optic chiasm)

III. Middle\tuberal region
a. Arcuate nucleus
b. Ventromedial nucleus
c. Dorsomedial nucleus

IV. Posterior\Mammillary region
a. Medial mammillary nucleus
b. Intermediate mammillary nucleus
c. Lateral mammillary nucleus
d. Posterior hypothalamic nucleus

3. Lateral hypothalamic area
I. Lateral preoptic nucleus
II. Lateral hypothalamic nucleus
(The medial forebrain bundle (MFB) pass through it, this carries many connections to and from the hypothalamus)

(The fibers of the fornix pass through the hypothalamus on the way to the mammillary body, dividing the medial and lateral areas)

(Blumenfeld)
Hypothalamic control of the autonomic nervous system
a. Descending autonomic fibers originate mainly from
b. Path
c. Other descending autonomic pathways from the brain
d. Important sources of input
a. Paraventricular nucleus mainly, also from dorsomedial, lateral, and posterior hypothalamic nuclei.

b. Path
1. Medial forebrain bundle (MFB) ->
2. Polysynaptic pathway via dorsolateral brainstem and periaqueductal gray matter ->
3a. Preganglionic parasympathetic nuclei in the brainstem and intermediate zone of the sacral spinal cord
3b. Preganglionic sympathetic neurons in the intermediolateral cell column of the thoracolumbar spinal cord.

c. From
1. Nucleus solitarius
2. Noradrenergic nuclei - locus ceruleus
3. Raphe nucleus
4. Pontomedullary reticular formation

d. Amygdala and certain regions of the limbic cortex (orbital frontal, insular, anterior cingulate, temporal cortices)

(Blumenfeld)
Medial forebrain bundle
a. From-to
b. Which other fibers does it carry
a. Hypothalamus (lateral zone) <--> midbrain tegmentum

b.
1. Connected with various components of the limbic system
2. Raphe nuclei
3. Locus ceruleus
(2-3 from brainstem to hypothalamus and cerebral cortex)
4. Dopaminergic fibers from substantia nigra to striatum

(Stedman)
Hypothalamic-limbic pathways
a. What is the main input and output connections between the limbic system and the hypothalamus
b. Implications
a.
1. The subiculum of the hippocampal formation --Fornix--> Mammillary bodies

2. Mammillary bodies --Mammillothalamic tract--> Anterior thalamic nucleus <--> Limbic cortex in cingulate gyrus

3. Amygdala
I. <--Stria terminalis--> Hypothalamus
II. <--Ventral amygdalofungal pathway--> Hypothalamus

b. Explain emotion-autonomic NS linkage, explain depression-increased infection susceptibility connection
(Hypothalamic hamartoma can cause seizures consisting of laughter (gelastic epilepsy), irritability and aggression, and endocrine abnormalities)

(Blumenfeld)
Hypothalamus
a. What are the effect of anterior hypothalamic lesions on sleep and heat regulation, why
b. What are the effect of posterior hypothalamic lesions on sleep and heat regulation, why
c. What are the effects of lateral hypothalamic lesions on weight and water intake
d. What are the effects of medial hypothalamic lesions on weight and water intake
a. What are the effect of anterior hypothalamic lesions on sleep and heat regulation, why
1. Insomnia
I. GABAergic neurons in the ventral lateral preoptic area (VLPO) contribute to nonREM sleep by inhibiting the arousal systems
(histaminergic neurons in the tuberomammillary nucleus (TMN), orexin-containing neurons in the posterior lateral hypothalamus, brainstem serotonergic, noradrenergic, dopaminergic and cholinergic nuclei)
2. Hyperthermia
I. Normally detect increased body temperature and activates mechanisms of heat dissipation

b. What are the effect of posterior hypothalamic lesions on sleep and heat regulation, why
1. Hypersomnia
I. Destroy arousal systems - histaminergic neurons in the tuberomammillary nucleus TMN) and orexin-containing neurons in the posterior lateral hypothalamus
2. Poikilothermia
I. Posterior hypothalamus conserver heat

c. What are the effects of lateral hypothalamic lesions on weight and water intake
1. Decrease in body weight
I. Lateral hypothalamus is important in appetite
II. Ghrelin is produced by gastric mucosal cells, binds in hypothalamus, and stimulates appetite
2. Decrease water intake
(Osmoreceptors is in the anterior regions of hypothalamus)


d. What are the effects of medial hypothalamic lesions on weight
I. Obesity
II. Ventromedial nucleus suppress appetite
III. Leptin is a hormone produced by adipose tissue that binds to Ob receptors in hypothalamus and reduce appetite

(Blumenfeld)
Hypothalamo-pituitary axis
a. Nuclei projecting to the primary capillary plexus in the median eminence, name of tract
b. Nuclei projecting to the posterior pituitary, name of tract
c. Blood supply and drainage of anterior pituitary
d. Blood supply and drainage of posterior pituitary
a.
I. Arcuate, periventricular, medial preoptic, paraventricular (parvocellular part) nuclei.
II. Tubero-infundibular tract

b.
I. Paraventricular (magnocellular portion) and supraoptic (magnocellular portion) nuclei
II. Supraoptico-hypophysial tract

c. Anterior pituitary
1. ICA -> Superior hypophysial artery ->
2. Primary capillary plexus in median eminence ->
3. Portal hypophysial veins ->
4. Secondary capillary plexus in anterior pituitary ->
5. Veins to cavernous sinus
(This arrangement makes it very susceptible to ischemia)

d. Posterior pituitary
1. ICA -> Inferior hypophysial artery and branch of superior hypophysial artery ->
2. Veins to cavernous sinus

(Blumenfeld)
Pituitary adenoma
a. Epidemiology - % of intracranial neoplasms, mean age of diagnosis
b. How many of the pituitary adenomas secrete hormones
c. What are the three hormones most commonly secreted
d. Mass lesion effects
e. Other lesions in the sellar and suprasellar regions
a.
I. 12%
II. 40 years

b. 85% -> 15% are nonfunctioning\silent.
(This is problematic because they do not respond to hypothalamic suppression)

c.
#1. Prolactin (50%)
#2. GH
#3. ACTH
(Very rare that the tumor secrete more than one hormone)

d.
1. Compression of optic chiasm -> Bitemporal hemianopia
2. Hydrocephalus
3. Brainstem compression

e.
1. Craniopharyngioma
2. Aneurysms
3. Meningioma
4. Optic glioma
5. Hypothalmic glioma
6. Chordoma
7. Teratoma
8. Rathke's pouch cysts
9. Sarcoidosis
10. Lymphoma
11. Metastases
(Epidermoid, dermoid, empty sella syndrome, lymphocytic hypophysitis, Langerhans cell histiocytosis..)

(Blumenfeld)
Pituitary adenoma
a. Treatment options
b. Diagnosis of prolactin-secreting tumors
c. Diagnosis of GH-secreting tumors
d. Diagnosis of ACTH-secreting tumors
a. Treatment options
1. Pharmacological
I. Prolactin-secreting tumor - Dopaminergic agonists such as bromocriptine and cabergoline
II. GH-secreting tumors - Somatostatin analogues - octreotide
2. Surgical
I. Transsphenoidal approach
3. Radiotherapy with gamma knife
(If surgery fails or in patients who cannot undergo surgery due to operative risk)

b. Prolactin-secreting tumor
1. Amenorrhea in women, hypogonadism in men, infertility
(PRL inhibit LHRH, function to delay menses and fertility during lactation)
2. Galactorrhea
3. Hair loss
4. decreased libido
5. Weight gain
6. Excessive elevated PRL levels are virtually diagnostic of pituitary adenoma (> 150 ug\L in nonpregnant patients)
(Microadenomas as small as 0.5 mm can be visualized on MRI indirectly through their effect on the shape of the pituitary)

c. GH-secreting tumor
1. Acromegaly in adults, gigantism in children
I. Carpal tunnel syndrome
II. Arthritis
III. Infertility
IV. Hypertension
V. Diabetes
2. Elevated IGF-1 and GH levels

c. ACTH-secreting tumors\Cushing's disease
1. Cushing's syndrome
I. Cushingoid appearance - Round "moon-shaped" face, truncal obesity
II. Acne
III. Hirsutism
IV. Purple skin striae
V. Hypertension
VI. Diabetes
VII. Immunosuppression
VIII. Osteoporosis
IX. Amenorrhea
X. Psychiatric disturbances - Mania, psychosis, depression

(Blumenfeld)
Thyroid hormone
a. Neurologic manifestations of hyperthyroidism
b. Neurologic manifestations of hypothyroidism
a. Hyperthyroidism
1. Proximal muscle weakness
2. Tremor
3. Dyskinesias
4. Dementia
(In the elderly, any of the other clinical manifestations can be absent, and it can mimic dementia or depression)
(Others: Cushingoid appearance (moon face, truncal obesity, buffalo neck), acne, hirsutism, purplish skin striae, easy brusing and poor wound healing, hypertension, diabetes, edema, immunosuppression, osteoporosis, avascular necrosis of the femoral head, amenorrhea, decreased libido, myopathy, fatigue, psychiatric disturbances..)

b. Hypothyroidism
1. Depression
2. Neuropathy
3. Ataxia
4. Dementia
(--||--)
(Others: Lethargy, weight gain, cold intolerance, smooth, dry skin, hair loss, constipation, myxedema coma, cardiac involvement, carpal tunnel syndrome)

(Blumenfeld)
Panhypopituitarism
a. Causes
a. Causes
1. Pituitary tumors
2. Treatment of pituitary tumors
3. Pituitary apoplexy
(Sometimes caused by spontaneous hemorrhage from pituitary tumors, -> sudden headache, meningeal signs, uni\bilateral cavernous sinus syndrome, visual loss, hypotension..)
4. Head trauma
5. Pituitary infarct
6. Postpartum pituitary necrosis\Sheehan's syndromes
7. Congenital abnormalities
8. Others - Mass lesions and inflammatory conditions - Meningioma, craniopharyngioma, hypothalamic tumors, metastases, sacroidosis, lymphocytic hypophysitis, infections, autoimmune disorders

(Blumenfeld)
The limbic system
a. The four basic categories of its function, give the main structure for each function
b. Give the main components of the limbic system
a. HOME
1. Homeostasis - Including autonomic and neuroendocrinal control, Hypothalamus
2. Olfaction - Olfactory cortex
3. Memory - Hippocampal formation
4. Emotions and drives - Amygdala

b. The limbic system
1. Limbic cortex\Paralimbic cortex\Limbic association cortex
(Forms a ringlike limbic lobe around the edge of the cortical mantle, which surrounds the corpus callosum and upper brainstem-diencephalic junction)
I. Parahippocampal gyrus
II. Cingulate gyrus
III. Medial orbitofrontal cortex
IV. Temporal love
VI. Anterior insula

2. Hippocampal formation
I. Dentate gyrus
II. Hippocampus
III. Subiculum

3. Amygdala

4. Olfactory cortex

5. Diencephalon
I. Hypothalamus
II. Thalamus
a. Anterior nucleus
b. Mediodorsal nucleus
III. Habenula

6. Basal ganglia
I. Ventral striatum
a. Nucleus accumbens
b. Ventral caudate and putamen
II. Ventral pallidum
(Those parts of the globus pallidus located ventral to the anterior commissure)

7. Basal forebrain
I. Substantia innominata\Nucleus basalis of Meynert
(Provide the major cholinergic innervation for the entire cerebral cortex)
II. Olfactory tubercle
III. Ventral pallidum
IV. The nucleus of the diagonal band of Broca
V. The preoptic area
(Rostral extension of hypothalamus)

8. Septal nuclei
(Participates in limbic pathways, within or just caudal to the subcallosal and paraterminal gyri)
I. Medial septal nucleus
II. Lateral septal nucleus
(Cholinergic, Hippocampal formation -> lateral septal -> medial septal -> hippocampal formation)

9. Brainstem
(Sometimes considered part of the limbic system)
(Interpeduncular nucleus, superior central nucleus, dorsal tegmental nucleus, ventral tegmental nucleus, parabrachial nucleus, periaqueductal gray, reticular formation, nucleus solitarius, dorsal motor nucleus of the vagus)
(May help link limbic pathways to mechanisms for autonomic and behavioral arousal)

(Blumenfeld)
The limbic system
a. Which virus have a special tropism for the limbic cortex
b. Hippocampal formation - Location, special feature
c. Allocortex
d. Mesocortex
e. Corticoid areas
a. Herpes simplex
(Due to certain shared immunological surface markers)
(Parahippocampal gyrus, cingulate gyrus, medial orbitofrontal cortex, temporal pole, anterior insula)

b. Hippocampal formation
1. Location
I. The medial and dorsal continuation of the hippocampal gyrus.
II. Form the floor of the temporal horn of the lateral ventricle within the temporal lobe
2. 3 layers -> Archicortex
(95% of cortex is 6-layered neocortex\isocortex\neopallium)

c. Allocortex (Other cortex)
I. Archicortex\archipallium (first cortex), 3-layered hippocampal cortex, Hippocampus
II. Paleocortex\paleopallium (old cortex), 3-layered olfactory cortex, Piriform cortex of the olfactory area

d. Mesocortex\transitional cortex\Limbic cortex\Paralimbic cortex
I. The regions between 3 and 6-layered cortex
II. Limbic cortex: parahippocampal gyrus, cingulate gyrus, anterior insula, orbitofrontal cortex, temporal pole

e. Corticoid areas
I. Simple-structured cortex-like regions that overlie or merge with subcortical nuclei
II. Don't contain consistent cortical layers
III. Amygdala, Substantia innominata, septal region
(Considered the most rudimentary form of cortex)

(Blumenfeld)
Amygdala
a. Location
b. Components
c. General function
a. Location
I. In the anteromedial temporal lobe
II. Overlaps anterior end of the hippocampus
III. Its dorsal part lies just underneath the uncus

b. Components
1. Corticomedial nuclei
2. Basolateral nuclei
3. Central nuclei
(In addition, the C-shaped bed nucleus of the stria terminalis is considered part of the amygdala)

c. Involved in emotional, autonomic, and neuroendocrine circuits of the limbic system.

(Blumenfeld)
Major limbic pathways - Fornix - 5 main fibers
Fornix
1. Subiculum -> Medial and lateral mammillary nuclei, lateral septal nuclei

2. Hippocampus -> Lateral septal nuclei

3. Hippocampal formation -> Anterior thalamic nucleus

4. Medial septal nucleus -> Hippocampal formation

5. Nucleus of the diagonal band of Broca -> Hippocampal formation

(Blumenfeld)
Major limbic pathways
a. Mammillothalamic tract
b. Cingulum
c. Anterior commissure - Anterior and posterior part
a. Mammillothalamic tract
Medial mammillary nucleus -> Anterior thalamic nucleus

b. Cingulum
Cingulate gyrus -> Parahippocampal gyrus

c. Anterior commissure
I. Anterior part: Anterior olfactory nucleus -> contralateral anterior olfactory nucleus
II. Posterior part: Amygdala -> Contralateral amygdala, Anterior temporal cortex -> Contralateral anterior temporal cortex

(Blumenfeld)
Major limbic pathways
a. Medial olfactory stria
b. Lateral olfactory stria
c. Stria terminalis
d. Uncinate fasciculus (temporal stem)
a. Medial olfactory stria
Anterior olfactory nucleus <--> Anterior commissure

b. Lateral olfactory stria
Olfactory bulb ->
1. Piriform cortex
2. Periamygdaloid cortex
3. Corticomedial cortex

c. Stria terminalis
1. Corticomedial amygdala -> Hypothalamus
2. Amygdala -> Septal nuclei

d. Uncinate fasciculus (temporal stem)
1. Piriform and entorhinal cortex -> Orbitofrontal olfactory cortex
2. Amygdala -> Orbitofrontal and cingulate cortex

(Blumenfeld)
Major limbic pathways
a. Inferior thalamic peduncle
b. Ventral amygdalofungal pathway
c. Medial forebrain bundle (MFB)
d. Stria medullaris
a. Inferior thalamic peduncle
Amygdala, anteromedial temporal cortex, and insula -> Medial diencephalon

b. Ventral amygdalofungal pathway
Amygdala ->
1. Hypothalamus
2. Nucleus basalis
3. Ventral striatum
4. Brainstem nuclei

c. Medial forebrain bundle
Amygdala and other forebrain structures <--> Brainstem nuclei

d. Stria medullaris
Medial septal nuclei -> Habenula

(Blumenfeld)
Major limbic pathways
a. Habenulointerpeduncular tract\Fasciculus retroflexus
b. Mammillotegmental tract
c. Perforant pathway
d. Alvelar pathway
a. Habenulointerpeduncular tract\Fasciculus retroflexus
Habenula -> Interpeduncular nucleus

b. Mammillotegmental tract
Mammillary bodies -> Brainstem

c. Perforant pathway
Entorhinal cortex -> Dentate gyrus granule cells

d. Alvelar pathway
Entorhinal cortex -> Hippocampal pyramidal cell

(Blumenfeld)
Olfaction
a. Interneurons in the olfactory bulb
b. Olfactory pathway from olfactory receptor neuron
c. Anterior olfactory nucleus and its connections
d. Secondary olfactory cortex
a. Periglomerular cells and granule cells.

b. Olfactory pathway
1. Olfactory receptor neuron ->
2. Tufted and mitral cells ->
(Synapse in glomerulus)
3. Olfactory tract ->
4. Lateral olfactory stria ->
5a. Primary olfactory cortex
I. Piriform cortex
(Pear-shaped in some animals)
II. Periamygdaloid cortex
(Rostral and dorsal to amygdala)
5b. Corticomedial nucleus of the amygdala
(-> Emotional and motivational aspects of olfaction)
5c. Olfactory tubercle
(In the anterior perforated substance)

c. Anterior olfactory nucleus
I. Collaterals in the olfactory tract synapse onto neurons forming the anterior olfactory nucleus
II. The neurons feed back to the ipsilateral olfactory bulb and to the contralateral olfactory bulb via the medial olfactory stria and anterior part of anterior commissure

d. Secondary olfactory areas
I. Anterior entorhinal cortex
(<- Piriform cortex, involved in olfaction-memory connection)
II. Orbitofrontal olfactory area
(Directly and indirectly via the entorhinal cortex or the mediodorsal nucleus of the thalamus)
(Lesion -> deficit in olfactory discrimination)
III. Basolateral amygdala
IV. The lateral preoptic area
V. The nucleus of the diagonal band of Broca

(Blumenfeld)
Memory
a. Which two main regions of the brain appears to be critical to memory formation
b. Which two other structures are also very important
a.
1. The medial temporal lobe memory areas
I. Hippocampal formation (dentate, hippocampus, subiculum)
II. Adjacent cortex of the parahippocampal gyrus

2. The medial diencephalic memory areas
I. Thalamic medio-dorsal nucleus
II. Anterior nucleus of the thalamus
III. Other diencephalic nuclei lining the third ventricle

b.
1. The white matter network connections between the structures in a.
2. The basal forebrain
(Through its widespread cholinergic projections to the cerebral cortex, including the medial temporal lobes)

(Blumenfeld)
The medial temporal lobe memory systems
a. Hippocampal formation - Structure and components
b. Hippocampal formation - Unique histological feature
c. Choroid fissure
a. Hippocampal formation
I. S-shaped (on the left) on coronal sections
(-> Hippocampus (sea horse), Cornu Ammonis (horn of the ancient Egyptian ram-headed god Ammon)
I. From top of S to bottom
1. Dentate gyrus
2. Hippocampus
3. Subiculum ('Support')
(4. Parahippocampal gyrus)
(Hippocampal sulcus between 1-3, collateral sulcus between 4 and adjacent gray matter)

b. Archicortex - Three-layered hippocampal formaton

c. Choroid fissure
I. The groove in the medial temporal lobe just dorsal to the hippocampal formation.

(Blumenfeld)
The hippocampal formation
a. Dentate gyrus - Principal neurons, layers
b. Hippocampus and subiculum - Principal neurons, layers
c. The hippocampal formation - Pes hippocampi\hippocampal head, hippocampal tail, indusium griseum
a. Dentate gyrus
I. Granule cells
II. Inward from pia
1. Molecular layer
2. Granule cell layer
3. Polymorphic layer

b. Hippocampus and subiculum
I. Pyramidal cells
II. From pia inwards
1. Molecular layer
(Stratum lacunosum moleculare, stratum radiatum)
2. Pyramidal cell layer
(Stratum pyramidale)
3. Polymorphic layer
(Stratum oriens)

c. The hippocampal formation
1. Pes hippocampi\Hippocampal head
I. Anterior part
2. Hippocampal tail
(Curves back along the floor of the temporal horn, disappears under the ventral posterior edge of the splenium of the corpus callosum)
3. Indusium (Membranous layer\covering) griseum (gray)
I. Remnant of the hippocampal formation that continues along the dorsal surface of the corpus callosum.

(Blumenfeld)
The parahippocampal gyrus
a. Components (8)
b. Which structure serves as the major input and output relay between association cortex (frontal, parieto-occipital, and temporal) and the hippocampal formation
c. Which sulci delineates it laterally
a. Components
1. Entorhinal cortex (Area 28)
(In the anterior portions of the parahippocampal gyrus, adajcent to the subiculum)
2. Prorhinal cortex
3. Perirhinal cortex
(Area 35, 36. on the medial and lateral walls of the rhinal sulcus, also continues laterally onto the occipitotemporal gyrus)
4. Parahippocampal cortex
(Posterior portion of parahippocampal gyrus)
5. Piriform cortex
6. Perimaygdaloid cortex
7. Presubicular cortex
8. Parasubicular cortex
(Entorhinal cortex -> parasubiculum -> presubiculum -> subiculum)
b. Entorhinal cortex.
(2\3 of the input reaches it via relays in the perirhinal cortex and parahippocampal cortex

c. The collateral sulcus posteriorly, and the rhinal sulcus anteriorly.

(Blumenfeld)
The hippocampal formation
a. List the hippocampal pyramidal cell sectors
b. Intrinsic circuitry of the hippocampal formation - List each of the five synapses forming the
circuit from the entorhinal cortex via the perforant pathway to the hippocampal formation and back to the entorhinal cortex

c. Explain the trisynaptic and direct pathway from entorhinal cortex to CA1

d. Which synapses have been found to exhibit long-term potentiation (LTP), a form of synaptic plasticity
a. CA1-4 (Cornu Ammonis)
C1 near subiculum, C4 near dentate gyrus.

b. Intrinsic circuitry of the hippocampal formation
1. The perforant pathway
(Perforates subiculum)
I. Entorhinal cortex -> Granule cell layer of the dentate gyrus
(From pyramidal cells in layer 2 and 3 of the entorhinal cortex)

2. Granule cells of the dentate gyrus -> mossy fibers\axons -> synapse on CA3 pyramidal cells

3. CA3 axons leave the hippocampal formation via the fornix and also give rise to Schaffer collaterals -> synapse on CA1 pyramidal cells

4. CA1 axons leave the hippocampal formation via the fornix and also project and synapse with subiculum

5. Pyramidal cells of the subiculum send fibers to fornix and back into the entorhinal cortex

(Assumed to play a vital role in human memory)

c.
1. Trisynaptic pathway - via perforant pathway
2. Direct pathway - alvear pathway directly from entorhinal cortex to CA1 and CA3
(The direct pathway may be the dominant one, earlier assumed to be the trisynaptic)

d.
1. Perforant pathway-granule cell
2. Mossy fiber-CA3
3. Schaffer collateral-CA1

(Blumenfeld)
The hippocampal formation - Output and input
a. What is the main source for output fibers from the hippocampal formation
b. How does input reach the hippocampus from the contralateral hippocampus
c. Where does the hippocampal formation receive important cholinergic modulatory input from and via
a. The subiculum
(It projects to both the fornix and the entorhinal cortex. It also sends connections to amygdala, orbitofrontal cortex, and ventral striatum)

b.The hippocampal commissure

c. From the medial septal nucleus and the nucleus of the diagonal band of Broca. Via the fornix.
(Additional modulatory influences also reach the medial temporal lobes from cholierngic inputs from the nucleus basalis of Meynert, and from noradrenergic, dopaminergic, and serotonergic nuclei in the brainstem)

(Blumenfeld)
The fornix
a. Fornix - What, from-to
b. Alveus and fimbria
c. Crura and body
d. The columns is the continuation of the body, what are its three main targets
a. Fornix ('Arch')
I. Arched white matter structure
II. From hippocampal formation to the diencephalon and septal areas.

b. Alveus and fimbria
I. Alveus - White matter layer from hippocampi to fimbria of fornix.
II. Fimbria - Continuation of alveus when it assumes a bundle-shape

c. Crura and body
I. Crura - Continuation of fimbria when it leaves the hippocampal formation and run under corpus callosum. Connected by hippocampal commissure.

II. Body - Change name into body when they run adjacent to each other in the midline.

d. Fornix
1. Subiculum -> postcommissural fornix -> medial and lateral mammillary nuclei
2. Subiculum and hippocampus -> precommissural fornix -> lateral septal nucleus
3. Hippocampal formation -> anterior thalamic nucleus

(Blumenfeld)
The limbic system
a. The Papez circuit
a. The Papez circuit
1. Subiculum ->
2. Fornix ->
3. Medial and lateral mammillary nuclei ->
4. Medial mamillary nucleus -> mammillothalamic tract -> anterior thalamic nucleus ->
(Anterior thalamic nucleus also receives a direct projection from the fornix)
5. --Internal capsule--> Cingulate gyrus ->
6. --Cingulum\Cingulate bundle--> Parahippocampal gyrus -->
7. Entorhinal cortex and hippocampal formation

(Blumenfeld)
Memory
a. Declarative memory - Synonym, what does it include
b. Nondeclarative memory - Synonym, what does it include
c. Amnesia is typically used for which a. or b.
d. Loss of declarative memory is typical of lesions affecting which structures
a. Declarative memory\Explicit
I. Facts and events

b. Nondeclarative memory\Implicit
I. Skills and habits -
(Non-localized - Motor cortex, basal ganglia, cerebellum)
II. Simple classical conditioning (Cerebellum)
(Amygdala in conditioned fear)
III. Nonassociative learning - habituation and sensitization
(Decreased and increased response to a stimulus)
IV. Priming

c. Declaratie

d. Bilateral medial temporal lobe or bilateral medial diencephalic lesions.

(Blumenfeld)
Memory
a. Unilateral lesions of the dominant and non-dominant medial temporal or medial diencephalic structures can result in
b. Associates structures of deficits of nondeclarative\implicit memory
a.
I. Dominant -> Deficits in verbal memory
II. Non-dominant -> Deficits in visual-spatial memory

b. Not localized to the same extent as declarative memory. Probably involve plasticity in several areas -basal ganglia, cerebellum, and motor cortex.

(Blumenfeld)
Cellular mechanisms involved at different times in memory storage
a. Seconds to minutes
b. Minutes to hours
c. Hours to years
a. Seconds to minutes
I. Ongoing electrical activity of neurons
II. Changes in intracellular Ca and other ions and second messenger systems

b. Minutes to hours
I. Protein phosphorylation and other covalent modifications
II. Expression of immediate early genes

c. Hours to years
I. Additional changes in gene transcription and translation resulting in structural changes of protein and neurons

(Blumenfeld)
Anatomical structures involved at different times in storage of explicit memories
a. Attention\Registration - < 1 second
b. Working memory - Seconds to minutes
c. Consolidation - Minutes to years
d. Years
a. Attention\Registration - < 1 second
I. Brainstem-diencephalic activating systems
II. Frontoparietal association networks
III. Specific unimodal and heteromodal cortices

b. Working memory - Seconds to minutes
I. Dorsolateral prefrontal association cortex
II. Specific unimodal and heteromodal cortices
(Working memory involves holding a particular concept briefly in awareness while a mental operation, such as the carrying function in arithmetic is performed)

c. Consolidation - Minutes to years
I. Medial temporal structures
II. Medial diencephalic structures
III. Specific unimodal and heteromodal cortices
(Cause consolidation of declarative memories in the neocortex)

d. Years
I. Specific unimodal and heteromodal cortices

(Blumenfeld)
Memory - Give examples of test for
a. Attention and working memory
b. Recent memory
c. Remote memory
a. Attention and working memory
I. Ask the patient to repeat back lists of digits or words forward and backward

b. Recent memory
I. Give the patient several words to remember and then test for recall of these after 4-5 minutes.

c. Remote memory
I. Ask about verifiable personal information (previous addresses or schools) and well-known current events

(Blumenfeld)
Memory
a. Anterograde amnesia
b. Retrograde amnesia
c. Which of these does lesions of the medial temporal lobe or medial diencephalic memory systems effect
d. Types of normal memory loss
a. Anterograde amnesia
I. Deficit in forming new memories - consolidation.

b. Retrograde amnesia
I. Loss of memories from a period of time before the brain injury.

c. Both. Retrograde amnesia for recent memories up to several years.
(-> Suggest that these recent memories are dependent on the normal functioning of tehse structures

d. Normal memory loss
1. Infantile amnesia
(For the first 1-3 years of life, result of ongoing CNS maturational processes, such as myelination)

2. During or shortly after awakening from sleep
(Dreams)

3. Passage of time - forgetting

4. Benign senescent forgetfulness
(The normal mild decline in memory function that occurs gradually over the decades (as opposed to years in Alzheimer's))

(Blumenfeld)
Differential diagnosis of memory loss with anatomical lesions usually visible on imaging studies
1. Bilateral medial temporal lesions, from
I. Surgery
II. Cerebral contusions
(Contusions often involve the anteromedial temporal lobes and the basal orbitofrontal cortex -> permanent memory deficits)
(Contusion - Mechanical injury resulting in hemorrhage beneath unbroken skin)
III. Infarct - PCA
IV. Hippocampal sclerosis
(Usually with chronic epilepsy)
V. Herpes encephalitis
VI. Paraneoplastic limbic encephalitis
VII. Neoplasm
VIII. Inflammatory process - Sarcoidosis

2. Bilateral medial diencephalic lesions, from
I. Wernicke-Korsakoff syndrome
II. Infarct - Thalamoperforating arteries
(<- PCA and basilar artery)
III. Whipple's disease
(<- Tropheryma Whippleii)
IV. Neoplasm

3. Basal forebrain lesions
I. ACA aneurysmal rupture
II. Neoplasms

4. Diffuse disorders
I. MS
II. Numerous other diffuse disorder
(Additional deficits are common)

(Blumenfeld
Differential diagnosis of memory loss without anatomical lesions visible on conventional imaging
1. Seizures
(Including electroconvulsive therapy)
(Memory loss of period during and postical)

2. Concussion\Commotio cerebri
(Brain concussion - a clinical syndrome due to mechanical, usually traumatic, forces; characterized by immediate and transient impairment of neural function, such as alteration of consciousness, disturbance of vision and equilibrium, etc.)
(Memory loss is usually reversible, except for the hours around the time of injury)

3. Ischemia - Bilateral medial temporal (PCA) or medial diencephalic (paramedian thalamoperforator arteries <- PCA) structures
(Artery of Percheron refers to the cases where a single paramedian thalamoperforator artery bifurcates shortly after its origin from the top of the basilar artery and supplies both medial thalami. An occlusion here will cause memory loss)

4. Diffuse cerebral anoxia
(CA1 is especially vulnerable to anoxic injury)

5. Transient global amnesia
(Idiopathic, often induced by emotional stress or exertion. Retrograde and anterograde. Lasts for 4-12 hours. Recurs in 15%. Postulated to be a migraine-like phenomenon, a history of migraines is common in this patient group)

6. Early Alzheimer's disease and other degenerative disorders
(Alzheimer's tend to preferentially affect the bilateral hippocamapal, temporal, and basal forebrain structures)

7. Diffuse infectious or toxic\metabolic encephalopathies
(Additional deficits are common, including those caused by medications such as benzodiazepines)

8. Psychogenic amnesia
I. Dissociative disorder
II. Repression
III. Conversion disorder
IV. Malingering

(Blumenfeld)
Wernicke-Korsakoff syndrome
a. Common patients
b. Cause
c. Pathologically affected structures
d. S&S, Acute triad
a. Alcoholics, occasionally in patients on chronic parenteral nutrition.

b. Thiamine deficiency.

c. Mechanism
I. Bilateral necrosis of the mammillary bodies and of a variety of medial diencephalic and other periventricular nuclei.

d. S&S
1. Acute triad
I. Ataxia
II. Eye movement abnormalities - Horizontal gaze paresis, Nystagmus, Ophthalmoplegia
III. Confusional state

2. Anterograde and retrograde amnesia

3. Confabulation - Provide spurious answers to questions rather than saying that they do not remember
(Probably related to frontal lobe dysfunction, which cause disinhibition and a loss of self-monitoring capabilities)

4. Frontal lobe symptoms - Impairments in judgment, initiative, impulse control, and sequencing tasks

(Blumenfeld)
The Amygdala\Amygdaloid nuclear complex ('Almond')
a. Location
b. Components
c. Function of amygdala in emotions and drive
d. Syndrome of bilateral lesions of the amygdala - Name, what
e. Manifestations of seizures involving the amygdala and adjacent cortex
a. In the anteromedial temporal lobe, just dorsal to the anterior tip of the hippocampus and the temporal horn.

b. Components
1. Basolateral nucleus
(Largest, <--> diverse cortical areas, basal forebrain, medial thalamus)
2. Central nucleus
(Smallest, <--> hypothalamus, brainstem)
3. Corticomedial nucleus
(<--> olfaction, hypothalamus (appetitive states))
(4. The bed nucleus of the stria terminalis)

c. Important for attaching emotional significance to various stimuli perceived by the association cortex.

d. Kluver-Bucy syndrome
I. Placid, non-aggressive behavior along with other behavioral changes
(Most cases are induced in monkey studies)

e. Cause powerful emotions of fear and panic.

(Blumenfeld)
The limbic system - Emotions and drives
a. Emotions and drives are mediated by complex interactions among numerous brain regions - Give some examples
b. Which area are especially active during states of fear, anxiety, and aggression
c. Which areas of the before-mentioned are especially active in pleasurable states
a.
1. The heteromodal association cortex
2. Limbic cortex
3. Amygdala
(Central role, important for attaching emotional significance to various stimuli perceived by the association cortex)
4. Septal area
5. Ventral striatum
6. Hypothalamus
7. Brainstem autonomic and arousal pathways

b. Amygdala

c. The septal area
(Ie orgasm, experimental animals continuously press lever stimulating it. Lesion -> Sham-rage in animals (also from certain regions of the midbrain tegmentum)

(Blumenfeld)
The heteromodal association cortex\area - Definition (Structures, function)
Heteromodal association areas in the frontal, temporal, and parietal lobes integrate sensory data, motor feedback, and other information with memories. This integration facilitates learning and creates thought, expression, and behavior.

(Merckmanuals)
The amygdala
a. Main connections - From where, via
a. Main input connections

Cortical connections
1. <--> Diverse cortical areas - Heteromodal association cortex, limbic cortex
I. Indirectly via the anterior temporal and insular cortices
II. Uncinate fasciculus
(Amygdala <--> medial orbitofrontal and cingulate cortices)

2. The hippocampal formation
(Emotional aspect of memory, fear memory)

Subcortical connections
3. Stria terminalis ('The long way around')
I. Hypothalamus and septal area
(C-shaped, run along the wall of the lateral ventricle, the fornix of the amygdala)
(Corticomedial amygdala -> ventromedial hypothalamus probably carry olfactory information that increase or decrease appetite)

4. Ventral amygdalofungal pathway
('The short cut')
I. Septal area (via diagonal band of Broca), basal forebrain (nucleus basalis), ventral striatum, mediodorsal nucleus of the thalamus
(Mediodorsal nucleus - limbic relay that project to the frontal lobes)

5. Medial forebrain bundle -> Hypothalamus, brainstem nuclei
I. Nucleus solitarius
II. parabrachial nucleus
III. Dorsal motor nucleus of the vagus
IV. Periaqueductal gray
V. Reticular formation

Olfactory connections (input)
6. Olfactory bulb via lateral olfactory stria
(To corticomedial nucleus, also indirectly related in the piriform cortex to reach the basolateral nucleus)

(Blumenfeld)
Neuroendocrinological functions of the limbic system
a. Example
b. Mediated by
a. Decreased immune function in depression.

b. Connections between the limbic cortex, amygdala, and the hypothalamus.


(Blumenfeld)
The diagonal band of Broca
a. What type of structure
b. Connections
a. A white-fiber bundle

b. Connections
1. Amygdala -> septal nuclei (part of ventral amygdalofungal fibers)
2. Septum <--> hypothalamus
3. Cortex <--> Striatum
4. Cholinergic neurons with projections to the medial temporal lobes

(Blumenfeld)
Seizures and epilepsy
a. Seizure - What, causes, prevalence
b. Epilepsy - What, causes, prevalence
c. Ictal, postictal, interictal
a. Seizure
I. An episode (symptom) of abnormally synchronized and high-frequency firing of neurons in the brain
II. Results in abnormal behavior or experience of the individual
(Varies by location, duration, and type of abnormal electrical activity)
III. <- Epilepsy, electrolyte abnormalities, alcohol withdrawal, electroshock therapy, toxins
IV. 10-15%
(Single seizure during lifetime)

b. Epilepsy (Epilepsia - seizure)
I. A disorder in which there is a tendency to have recurrent unprovoked seizures.
II. <- Genetic, structural, metabolic, or other abnormalities
III. 1%

c. Ictal, post-ictal, interictal (Ictus - stroke)
I. Ictal - During a seizure
II. Post-ictal - Immediately after a seizure
(Todd's paresis describes the focal weakness experienced after a seizure)
III. Interictal - Between seizures

(Blumenfeld)
International classification of epileptic seizures
I. Partial (focal, local) seizures
A. Simple partial seizures
1. With motor signs
2. With somatosensory or special sensory signs
3. With autonomic symptoms or signs
4. With psychiatric symptoms
B. Complex partial seizures
1. Simple partial onset followed by impairment of consciousness
2. With impairment of consciousness at onset
C. Partial seizures evolving to secondarily generalized seizures
1. Simple partial seizures evolving to generalized seizures
2. Complex partial seizures evolving to generalized seizures
3. Simple partial seizures evolving to complex partial seizures evolving to generalized seizures

II. Generalized seizures
A. Absence seizures
1. Typical absence (peptit mal)
2. Atypical absence
B. Myoclonic seizures
C. Clonic seizures
D. Tonic seizures
E. Tonic-Clonic (Grand mal) seizures
F. Atonic seizures

III. Unclassified epileptic seizures

(The international league against epilepsy, 1980)
Seizures and epilepsy
a. Simple partial seizure
b. Aura
c. Complex partial seizure
a. Simple partial seizure
I. Consciousness is spared
II. Positive (arm twitching) or negative (language impairment) symptoms

c. Complex partial seizure
I. Impairment of consciousness
(Affect wider regions or affect deep brainstem and diencephalic regions)
II. The most common location is the temporal lobes
(Temporal lobe\psychomotor epilepsy)

b. Aura ('Breeze')
I. Epileptic ictal phenomenon\a perceived only by the patient.
II. They can occur in isolation, or they may serve as a warning for a larger seizure or migraine headache
Clinical manifestations of partial and complex partial seizures in different brain regions
a. Occipital lobe - Primary visual cortex
b. Occipital lobe - Inferior tempero-occipital association cortex
c. Parietal lobe
a. Occipital lobe - Primary visual cortex
1. Sparkles and flashes
2. Scotoma
3. Hemianopia in contralateral visual field

b. Occipital lobe - Inferior tempero-occipital association cortex
1. Visual hallucinations
2. Nystagmoid or oculogyric jerks
3. Palpebral jerks and eye blinking
4. Sensations of eye oscillation

c. Parietal lobe
1. Vertigo
2. Contralateral numbness, tingling, or burning
3. Aphasia (dominant hemisphere)
4. Contralateral hemineglect (non-dominant hemisphere)

(Blumenfeld)
Clinical manifestations of partial and complex partial seizures in different brain regions
a. Frontal lobe - Dorsolateral convexity (Primary motor cortex, prefrontal cortex, frontal eye fields)
b. Frontal lobe - Supplementary motor area
c. Frontal lobe - Orbitofrontal and cingulate area
a. Frontal lobe - Dorsolateral convexity
1. Contralateral tonic or clonic activity
(Primary motor cortex)
2. Strong version (turning) of eyes, head, and body away from the side of the seizure
(Prefrontal cortex and frontal eye fields)
3. Aphasia
(Dominant hemisphere)

b. Supplementary motor area
1. Fencing posture
(extensions of contralateral upper extremitiy)
2. Other tonic postures
3. Speech arrest
4. Unusual sounds

c. Orbitofrontal and cingulate gyri
1. Elaborate motor automatisms
2. Making unusual sounds
3. Autonomic changes
4. Olfactory hallucinations
(Orbitofrontal)
5. Incontinence
(Cingulate)

(Seizures are often brief, occur multiple times per day, and may have no post-ictal deficits. Nocturnal exacerbations is common. Elaborate motor automatisms without LOC or postictal deficits often lead to misdiagnosis of psychogenic episodes)

(Blumenfeld)
Clinical manifestations of partial and complex partial seizures in different brain regions
a. Medial temporal lobe
b. Medial temporal lobe - Duration of seizure
a. Medial temporal lobe
1. 'Butterflies' in the stomach
(Rising visceral sensation in the epigastric area)
2. Nausea
3. Deja vu
(Most often right\nondominant side, also other mystical or religious phenomena)
4. Fear, panic, and unpleasant odor
(Amygdala or nearby structures)
5. Autonomic phenomena - Tachycardia, mydriasis, piloerection, borborygmi, flushing
6. Bland (blid) staring with unresponsiveness
7. Oroalimentary automatisms - Lipsmacking, chewing, swallowing
8. Contralateral dystonia with ipsilateral automatisms
(<- Ipsilateral basal ganglia)

b. 1-2 minutes usually.

(Often with post-ictal amnesia, tiredness, headache, emotional changes, or other focal deficits. Its the most common cause of complex partial seizures. Head or eye deviation commonly seen probably results from spread to frontal or parietal lobes.)

(Blumenfeld)
Clinical manifestations of partial and complex partial seizures in different brain regions
a. Lateral temporal lobe
a. Lateral temporal lobe
1. Vertigo
(Temperoparietal operculum)
2. Inability to hear
3. Simple auditory hallucinations - Buzzing, roaring, engine, tones
4. Elaborate auditory hallucinations - Voice, music
(Voice more in seizures of non-dominant side)
5. Aphasia
I. Dominant side - Aphasia with inability to understand what people are saying
II. Non-dominant side - Saying words or phrases repeatedly
Generalized seizures
a. What is the most common type
b. Typical event of a tonic-clonic seizure
a. Tonic-clonic (Grand mal) seizure

b. Tonic-clonic seizure
1. Tonic phase
I. LOC
II. Generalized contractions -> Stiff extension
III. 10-15 seconds
IV. Expiratory gasp
(Force air past epiglottis)

2. Clonic phase
I. Rhythmic bilateral jerking
(1 Hz)
II. Gradually slow down and stop
III. Incontinence or tongue biting is common
IV. 30 s-2 min
V. Massive autonomic release - Tachycardia, hypertension, hypersalivation, mydriasis

3. Post-ictal period
I. Immobile and flaccid
II. Unresponsive with eyes closed
III. Breathe deeply to compensate for the mixed metabolic and respiratory acidosis produced by the seizure
III. Usually regain consciousness within a few minutes
(Deficits lasts from minutes to hours and include profound tiredness, confusion, amnesia, headache..)

(Blumenfeld)
Absence seizures
a. Typical duration
b. Classification
c. Characterizing features
d. How can they be differentiated from complex partial seizures - Aura, Duration, Automatisms, Post-ictal deficits, Frequency, Interictal brain function, Ictal EEG
a. < 10 seconds

b. Generalized

c. Lack of awareness of the event, normally no post-ictal phase

d. Differentiation from complex partial seizures
(A - absence, CP - Complex partial)
1. Aura
CP - Can be present
A - Not present

2. Duration
CP - 30-120s
A - < 10s

3. Automatisms
CP - Can be
A - None
(Minor clonic movements of the eyelids or corners of the mouth can sometimes occur)

4. Post-ictal deficits
CP - Can be
A - None

5. Frequency
CP - 3-4 \ month
A - Multiple daily

6. Interictal brain function
CP - Focal abnormalities
A - Normal

7. Ictal EEG
CP - Unilateral or asymmetrical, rhythmic activity over the temporal lobe (5-8 Hz)
A - Generalized, Spike-waves (3-4 Hz)

(Most common in children, up to 80% remit spontaneously)

(Blumenfeld)
Seizures
a. Status epilepticus
b. Diagnostic tools\methods
c. When is the risk highest for new-onset seizures
d. Causes
a. Seizures of any type occurring continuously or repeatedly in rapid succession.
(Generalized tonic-clonic status epilepticus is a medical emergency, first pharmacological line of treatment is benzodiazepines or phenytoin)

b. Diagnostic tools
1. History & physical
2. Basic blood tests
3. MRI
(Special thin coronal cuts and pulse sequences used to view the medial temporal, cortical and subcortical structures in detail)
4. Interictal EEG
5. Continuous video and EEG monitoring to get ictal recording
6. Ictal and interictal nuclear medicine tests - SPECT, PET
c.
I. Infancy and childhood
(Most common causes are febrile, congenital, and perinatal injury)
II. In the elderly
(Most common are cerebrovascular disease, brain tumors, and neurodegenerative conditions)

d. Causes
1. Head trauma
2. Cerebral infarct
3. Intracranial hemorrhage
4. Vascular malformation
5. Cerebral venous thrombosis
6. Anoxia
7. Mesial temporal (hippocampal) sclerosis
(Necrosis and gliosis)
(<- complex febrile seizure in children through damage of CA1?, head trauma, CNS infections)
8. Electrolyte abnormalities
I. Hypo\Hypernatremia
II. Hypocalcemia
III. Hypomagnesemia
9. Hypoglycemia
10. High fever
(Febrile seizures occur in 3-4% of all children, usually between 6 months and 5 years, simple febrile seizures are generalized tonic-clonic, complex febrile seizures last > 15 minutes, occur > 1\day, have focal features and are associated with increased risk of epilepsy)
11. Toxins
12. Alcohol, benzodiazepines, barbiturate, or barbiturate withdrawal
13. Meningitis and encephalitis
14. Brain abscess
15. Vasculitis
16. Neoplasm
17. Inborn error of metabolism
18. Neuronal migrational abnormality
19. Hereditary epilepsy syndromes
I. Rolandic epilepsy
(AD with incomplete penetrance, often mild nocturnal seizures, centrotemporal spikes on EEG)
II. Childhood absence epilepsy (pyknolepsy)
III. Juvenile myoclonic epilepsy
20. Neurodegenerative disorder
21. Nonepileptic seizures\Pseudoseizures
(Psychogenic episodes, syncopes, arrhythmias..)

(Blumenfeld)
Epilepsy
a. How many % of patients can achieve satisfactory control over the seizures with medications
b. Other treatment strategies for medically refractory epileptic conditions
a. > 70%

b. Other treatment strategies
1. Ketogenic diet

2. Epilepsy surgery
I. Focal surgical resection
(Best result (>90%) with unilateral medial temporal lobe epilepsy)
II. Multiple subpial transection
(Severe cortical-cortical connections when the foci are localized to an important functional area)
III. Callosotomy
(If multiple locations)
IV. Hemispherectomy
(In patients < 2-3 years with
debilitating epilepsy)

3. Neurostimulation
I. Vagus nerve stimulators
(Rarely stop the seizure completely. Vagus -> nucleus solitarius -> para-brachial nuclei of pons -> limbic system and other forebrain structures)
II. Deep brain stimulation
(Under investigation, Thalamic nuclei)
III. Responsive neurostimulation
(Under investigation, function like implanted defibrillator in heart)

(Blumenfeld)
Schizophrenia
a. S&S
b. Associated dysfunctional structures
c. Associated neurotransmitter abnormality
a. S&S
1. Abnormalities of thought
I. Delusions and hallucinations
II. Disorganized, tangential speech
2. Flat affect
3. Catatonia
4. Decreased cognition - Particularly working memory

b.
1. The limbic system - Amygdala, hippocampal formation, parahippocampal gyrus
(<- MRI, pathologic studies)
2. The frontal lobes - The dorsolateral prefrontal cortex
(<- PET, fMRI)
(3. Basal ganglia)

c. Dopamine
(Psychotic symptoms improve with antidopaminergic agents, dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens and ventral striatum, as well as to the prefrontal cortex and limbic cortex)

(Blumenfeld)
OCD
a. S&S
b. Associated dysfunctional structures
c. Associated neurotransmitter abnormality
a. S&S
1. recurrent, obsessive thoughts cause the patient much anxiety, while the performance of repetitive, compulsive behaviors such as hand washing provide temporary relief.

b. Head of caudate, anterior cingulate gyrus, and orbitofrontal cortex
(Form loop which may be considered analogous to hyperkinetic movement disorders, but with unwanted thoughts\compulsions instead of movements. 50% of patients with Tourette's have OCD, it is also more frequent in Huntington's and Sydenham's chorea)

c. Serotonin

(Blumenfeld)
Depression and mania
a. Associated neurotransmitter abnormalities
b. Functional differences
c. Structural differences
a. Serotonin and norepinephrine.

b.
1. Global decrease in activity of the cerebral cortex, especially frontal lobes
2. Increased cortisol
(40% of patients, <- increased CRH in hypothalamus)
3. Decreased neurotrophic factors such as BDNF (brain-derived neurotrophic factor) and VEGF in critical brain regions
(<- Cortisol, inflammatoryr cytokines)

c.
1. Decreased number and density of glial cells and some interneurons in the prefrontal cortex
(Some studies suggest that left frontal lesions are more likely to produce a depressed mood, while right frontal lesions tend to produce an abnormally elevated mood)
2. Decreased volume of hippocampus

(Blumenfeld)
Association cortex
a. Unimodal association cortex - Synonym, Examples
b. Heteromodal association cortex - Synonym, Examples
c. Heteromodal association cortex - difference from unimodal association cortex
a. Unimodal association cortex\Modality-specific association cortex
I. Somatosensory association cortex
II. Visual association cortex
III. Auditory association cortex
IV. Premotor cortex
V. Supplementary motor area

b. Heteromodal association cortex\Higher-order association cortex
I. Prefrontal association cortex
II. Parietal and temporal heteromodal association cortex

c. Heteromodal association cortex
I. Bidirectional connections with both motor and sensory association cortex of all modalities. Unimodal association cortex primarily have unidirectional connection with its associated primary cortex.
II. Heteromodal association cortex also have bidirectional connections with limbic cortex
(-> Highest-order mental functions. These functions apparently require integration of abstract sensory and motor information from unimodal association cortex, together with emotional and motivational influences provided by limbic cortex)

(Blumenfeld)
Hemispheric specialization
a. Hemispheric specialization - What, postulated reason
b. Functions lateralized to the dominant (usually left) hemisphere
c. Functions lateralized to the nondominant (usually right) hemisphere
a. Hemispheric specialization
I. The tendency of some functions to be lateralized to the left or right hemisphere.
II. Maybe allow certain functions to be processed mainly within one hemisphere, eliminating delays caused by long callosal transmission times.

b. Examples
1. Skilled motor formulation - praxis
(90% are right handed, skilled complex motor tasks for both right and left limbs are programmed mainly by the dominant, usually left, hemisphere. -> Left hemisphere lesions are more often associated with apraxia)

2. Language
(Left in > 95% of right-handers, left in about 70% of left-handers. Many left-handers have a significant bilateral representation of language)

3. Arithmetics
(Sequential and analytical calculating skills)

4. Musical ability - Sequential and analytical skills in trained musicians

5. Sense of direction
(following a sense of written directions in sequence)

c. Nondominant hemisphere
1. Prosody - Emotions conveyed by tone, rhythm, stress of voice
(Both the ability to produce and to recognize it)

2. Visual-spatial analysis and spatial attention

3. Arithmetic - Ability to estimate quantity

4. Musical ability - In untrained musicians and for complex musical pieces in trained musicians

5. Sense of direction - Finding one's way by overall sense of spatial orientation

(Blumenfeld)
Language processing
a. Primary auditory cortex - Location
b. Wernicke's area - Location, Brodmann's area
c. Wernicke's area - Function
d. Wernicke's area - Important connections and their functions
a. Primary auditory cortex
I. Brodmann's area 41
II. Heschl's gyrus and superior temporal gyrus (in Sylvian fissure)

b. Wernicke's area
I. The posterior 2\3 of the superior temporal gyrus in the dominant hemisphere
II. Brodmann's area 22
III. Many authors also include inferior temporal language area (area 37), angular gyrus (39), and supramarginal gyrus (40), because lesions to these regions also cause Wernicke's aphasia

c. Wernicke's area - Function
I. Auditory association cortex
II. The initial steps of language processing that enable particular sequences of sound to be identified and comprehended as meaningful words
(Neural representations for sound are converted into words)

d.
1. Supramarginal gyrus (40), angular gyrus (39), inferior temporal language area (37) - Lexicon, Assist language comprehension, Angular gyrus connects visual association cortex with Wernicke's area when reading

(Blumenfeld)
Language processing
a. Area for articulation of sound
b. Broca's area - Location, Brodmann's area
c. Broca's area - Function
d. Broca's area - Important connections and their functions
a. The face area of the primary motor cortex (area 4).

b. Broca's area
I. Brodmann's area 44, 45
(2x Wernicke's which is 22)
II. In the opercular and triangular portions of the inferior frontal gyrus
(Broca's aphasic area extend to prefrontal cortex area 9,10,46,47 and premotor and supplementary motor cortex area 6)

c. Broca's area - Function
I. Constitute the motor program that activates particular sequences of sounds to produce words and sentences.
(Neural representations for words are converted back into sounds)
II. Syntax\Grammatical structure

d.
1. Prefrontal cortex - Assist in Syntax
2. Premotor and supplemental motor areas- Assist in higher-order motor aspects of speech formulation and planning

(Blumenfeld)
Language processing
a. Connections between Wernicke's and Broca's area
b. Connections to the contralatera hemisphere - Via, Function
c. Other connections which when lesioned can produce aphasia
a. Connections between Wernicke's and Broca's area
1. Arcuate fasciculus
I. Subcortical white matter pathway
2. Numerous polysynaptic connections along the peri-Sylvian cortex

b. Connections to the contralateral hemisphere
I. Via corpus callosum
II. Important for recognition and production of the affective elements of speech.
III. In lesions of the dominant hemisphere, callosal connections may allow the nondominant hemisphere to take over some functions of the damaged areas and to participate in at least partial recovery

c. Thalamus, basal ganglia.

(Blumenfeld)
Aphasia
a. Aphasia\Dysphasia
b. Disorders commonly mistaken for aphasia
c. Causes of aphasia
a. Aphasia\Dysphasia
I. Defect in language processing caused by dysfunction of the dominant cerebral hemisphere.
II. Both spoken and written language are affected.
III. Not caused by impaired audition or articulation

b. Disorders commonly mistaken for aphasia
1. Disorders of speech production
I. Dysarthria
II. Aphemia (Verbal apraxia)
III. Mutism

2. Auditory disorders
I. Peripheral hearing loss
II. Pure word deafness
III. Cortical deafness

3. Defects in arousal and attention
I. Global confusional state
II. Narcolepsy
(Toxic\metabolic disorders, post-ictal state, brainstem ischemia..)

4. Psychiatric disorders
I. Schizophrenia
(Nonsensical, neologisms)
II. Conversion disorder and other somatoform disorders

5. Uncooperative patient

c. Causes of aphasia
1. Cerebral contusion, subdural or epidural hematoma

2. Ischemic or hemorrhagic vascular events

3. Ictal or post-ictal deficits with focal seizures in dominant hemisphere

4. Mass lesions - Brain tumors, abscess, toxoplasmosis

5. Inflammatory or autoimmune disorders - MS, vasculitis

6. Developmental disorders - Language delay, Autism

7. Degenerative disorders - Progressive nonfluent aphasia, semantic dementia, Alzheimer's, Huntington's

(Blumenfeld)
Broca's aphasia
a. Most common etiology
b. S&S
c. Associates features
d. Synonyms
e. Normal pattern of recovery
a. Infarct in the territory of the superior division of the left MCA.

b. S&S
1. Decreased fluency
(Phrase length of < 5 words, number of content words (ie nouns) exceeds the number of function words (ie prepositions, articles..), -> lack of grammatical structure)

2. Lacking prosody
(-> Monotonous telegraphic speech)

3. Naming difficulties

4. Impaired repetition
(<- Disconnection of this structure from Wernicke's area, Especially of sentences with high content fo function words - no, ifs, ands, buts)

5. Comprehension is relatively intact

6. Reading and writing is equally affected

7. Impaired comprehension of syntactically dependent structures

c. Associated features
1. Dysarthria
2. Right hemiparesis affecting face and arm more than leg
3. Apraxia
(Affect the nonparetic left side of the body)
4. Frustration and depression

d. Expressive\Motor\Anterior\Non-fluent aphasia

e. Normal pattern of recovery
-> Transcortical motor aphasia -> Anomic aphasia

(Blumenfeld)
Wernicke's aphasia
a. Most common etiology
b. S&S
c. Associated features
d. Synonyms
e. Normal pattern of recovery
a. Infarct in the inferior division of left MCA.

b. S&S
1. Markedly impaired comprehension
(Respond incorrectly and fail to follow commands)

2. Impaired lexical function -> Empty, meaningless speech full of nonsensical paraphasical errors
(However, normal fluency, prosody, and syntax)
(Paraphasia - phonemic (pish instead of fish), semantic (ink instead of pen))

3. Neologisms

4. Impaired naming

5. Impaired repetition
(<- Disconnection from Broca's area)

6. Reading and writing is equally affected

c. Associated features
1. Contralateral visual field cut - especially of the right upper quadrant
(<- Optic radiation lesion)

2. Apraxia

3. Anosognosia
(Not seen in Broca's aphasia)

4. Angry or paranoid behavior
(Misdiagnosis for schizophrenia)

d. Receptive\Sensory\Posterior\Fluent aphasia

e. Normal pattern of recovery
-> Transcortical sensory aphasia -> Anomic aphasia

(Blumenfeld)
Aphasia
a. Classification scheme - The 3 questions
b. List the eight syndromes from the classification scheme
a. Classification scheme, Yes\No gives 7 syndromes
1. Fluent
2. Comprehends
3. Repeats

b. Syndromes
1. 1N, 2N, 3N -> Global aphasia
(<- Large left MCA stem infarcts, or large left MCA superior division infarcts initially, large subcortical infarcts, hemorrhages)
(Normal recovery - -> Broca's aphasia)

2. 1N, 2N, 3Y -> Mixed transcortical aphasia
(<- Mixed ACA-MCA and MCA-PCA watershed infarcts or subcortical lesions)

3. 1N, 2Y, 3N -> Broca's aphasia

4. 1N, 2Y, 3Y -> Transcortical motor aphasia
(<- ACA-MCA watershed infarct, affect prefrontal and association motor cortex)

5. 1Y, 2N, 3N -> Wernicke's aphasia

6. 1Y, 2N, 3Y -> Transcortical sensory aphasia
(<- MCA-PCA watershed infarct

7. 1Y, 2Y, 3N -> Conduction aphasia
(<- Subcortical lesions involving the arcuate fasciculus or by cortical lesions of the peri-Sylvian region in the dominant hemisphere that disrupt the polysynaptic connections)

8. 1Y, 2Y, 3Y -> Anomic aphasia\Anomia\Dysnomia
(Naming difficulties and some paraphasias. Naming is often the first function to be impaired in aphasias. Ie naming parts of a shirt - collar, sleeve, cuff)

(All patients are assumed to have impaired naming and some paraphasic errors)
(Transcortical aphasia are characterized by spared repetition. Clasically caused by watershed infarcts which spare Broca's area, Wernicke's area, and their interconnections, but damage other language areas in the frontal or temperoparietal cortices. Also common in basal ganglia or thalamic lesions.)

(Blumenfeld)
Apraxia
a. Apraxia\Ideomotor apraxia
b. Testing
c. Sites of lesions, association with other disease
a. The inability to carry out an action in response to verbal command, in the absence of any
I. comprehension deficit,
II. Motor weakness, or
III. Incoordination
(Caused by an inability to formulate the correct movement sequence)

b. Imaginary actions such as brushing their hair or lighting a match and blowing it out.

c. It can be caused by lesions in many locations. > 1\3 of aphasic patients have some apraxia, where apraxia of the oral and buccal muscles is the most common.

(Blumenfeld)
Aphemia
a. Synonyms
b. What
c. Usual cause
a. Synonyms
I. Foreign accent syndrome
(For their effortful, poorly articulated speech)
II. Verbal apraxia
(If developmental disorder in children without findings on imaging)

b. Severe apraxia of the speech articulatory apparatus.
(Differentiated from Broca's aphasia by their normal written language)

c. Small lesion in the dominant frontal operculum restricted to Broca's area.

(Blumenfeld)
Disconnection syndromes
a. What
b. Examples
c. Corpus callosotomy - S&S
a. Cognitive dysfunction is caused by damage to pathways that connect one cortical area to another.

b. Examples
1. Conduction aphasia
(Severe arcuate fasciculus between Broca's and Wernicke's area)

2. Alexia without agraphia
(<- Lesion in dominant occipital cortex extending to the corpus callosum. Often by PCA infarct. -> Prevents the transmission of visual information to Wernicke's area from both sides since it damages corpus callosum)

3. Impaired repetition in Broca's and Wernicke's aphasia
(<- Damage part of connecting pathway)

4. Pure word deafness\Verbal auditory agnosia
(<- Infarct in the auditoary area of the dominant hemisphere that extends to the subcortical white matter, cutting off auditory input from the contralateral hemisphere as well)
(Agnosia - Normal percept stripped of its meaning)

5. Left superior MCA infarcts can cause apraxia of the ipsilateral hand

c. Corpus callosotomy - S&S
1. Agraphia of the left hand
2. Agnosia of the left hand
3. Alexia in left hemifield
(If left hemisphere is dominant)
(Done to prevent seizures to becoming generalized in patients where fall is a major problem)

(Blumenfeld)
Attention
a. Dependent on which structures
b. Which hemisphere is most involved
a. Dependent on which structures
1. Medial and intralaminar thalamic nuclei
2. Widespread projecting neuromodulatory systems in the upper brain stem
3. Hypothalamus and basal forebrain
4. The cingulate gyrus
5. Medial and lateral fronto-parietal association cortex
(Basal ganglia? cerebellum?)

b. The right\nondominant
(-> Left neglect. The left hemisphere appear to respond to stimuli on the right side, while the right hemisphere responds to both left- and right-sided stimuli but more strongly to stimuli on the left. Like left premotor cortex and apraxia)

(Blumenfeld)
Spatial analysis and integration
a. Which region is especially important
b. Visual information is analyzed by two streams of higher-order information processing - Which are these and where do they go
c. Disorders of spatial analysis such as impaired visual-spatial judgment or spatial constructional abilities are most commonly seen in lesions of
a. The parietal association cortex, the nondominant hemisphere is more important than the left.
(At the junction of the parietal, temporal, and occipital cortex)
(The frontal association cortex is also involved.)

b.
1. What? stream
I. Ventral pathway - occipitotemporal association cortex and prefrontal cortex
(Analyze form with specific regions identifying colors, faces, letters..)

2. Where? stream
I. Dorsal pathway - occipito-parietal association cortex and prefrontal cortex
(Analyze location and movement of visual objects in space)
(The posterior parietal cortex is ideally located to receive integrative information from visual, proprioceptive, vestibular, auditory and other information from adjacent cortex)

c. The right parietal cortex.

(Blumenfeld)
Hemineglect syndrome
a. Most often caused by
b. S&S\Testing - 4 classes
a. Lesions of the right parietal or frontal cortex.
(Often the right inferior division of the MCA)

b. S&S
1. Sensory neglect - Visual, tactile, auditory
I. Extinction on double simultaneous stimulation
II. Allesthesia
(Erroneously report the location of a stimulus given to the left side of the body as being on the right)

2. Motor-intentional neglect
I. Motor extinction
(Ask patient to close eyes and randomly intermix commands to raise the right arm, left arm, or both)
II. Allokinesia
(The patient inappropriately moves the normal limb when asked to move the neglected limb)
III. Tactile response test
(Raise hand when touched)
IV. Directional motor bias
(As the patient to close their eyes and then point to a spot directly in front of their sternum)
V. Spatial akinesia
(Limb movements are impaired when the limbs are located in the hemineglected space)

3. Combination of sensory and motor neglect
I. Line-bisection task
(Bisect line on the midline)
II. Cancellation tasks
(Cross out lines, cross out a certain letter in a paper filled with spread letters)
III. Drawing - Clock face

4. Conceptual neglect
I. Anosognosia
(Lack of awareness of the illness. Also seen in patients with Wernicke's aphasia, frontal lobe disorders, Wernicke-Korsakoff syndrome, cortical blindness)
II. Anosodiaphoria
(Aware that they have severe deficits yet show no emotional concern or distress about it)
(Diaphoria - difference)
III. Hemiasomatognosia
(Patients deny that the left half of their body belongs to them)

(Blumenfeld)
Right hemisphere lesion syndromes
a. Capgras syndrome
b. Fregoli syndrome
c. Reduplicative paramnesia
a. Capgras syndrome
I. Patients insist that their friends or family members have all been replaced by identical-looking imposters

b. Fregoli syndrome
I. Patients believe that different people are actually the same person who is in disguise.

c. Reduplicative paramnesia
I. Patients believe that a person, place, or object exists as two identical copies.
(Paramnesia - False recollection)

(Blumenfeld)
Functions of the frontal lobe
a. Functions important for restraint (Inhibition of inappropriate behaviors)
b. Functions important for initiative
(Motivation to pursue positive or productive activities)
c. Functions important for order (The capacity to correctly perform sequencing tasks and a variety of other cognitive operations)
a. Functions important for Restraint
1. Judgment
2. Foresight
3. Perserverance
4. Delaying gratification
5. Inhibiting socially inappropriate responses
6. Concentration\Selective attention

b. Functions important for initiative
1. Curiosity and creativity
2. Spontaneity
3. Motivation and drive
4. Personality

c. Functions important for order
1. Abstract reasoning
2. Working memory
(The ability to hold a limited amount of information in an immediate store while a variety of cognitive operations are performed involving them)
(<- Dorsolateral prefrontal cortex)
3. Perspective taking
4. Planning
5. Organization
6. Sequencing
7. Temporal order

(Organization scheme postulated by philosophers and scientists from Plato to Freud)

(Mnemonic RIO)

(Blumenfeld)
The prefrontal cortex - Connections
Cortical connections
1. Association cortex of the temporal, parietal, and occipital lobes - Unimodal and heteromodal
2. Limbic cortex - Especially anterior cingulate and posteromedial orbitofrontal (Both are the closest parts of the limbic system)

Subcortical connections
3. Amygdala and other parts of the anteromedial temporal cortex- via Uncinate fasciculus

4. Hippocampal formation - via the cingulate gyrus and parahippocampal gyrus

5. Thalamic nuclei - Mediodorsal nucleus
(Also medial pulvinar and intralaminar nuclei)

6. Basal ganglia - Via head of caudate

(Also connections from every other region - hypothalamus, septal region, subthalamic region, cerebellum, midbrain, subcortical and brainstem modulary neurotransmitter systems)

(Blumenfeld)
Frontal lobe disorders
a. Why is there such a big variety in symptoms
b. Two structural classifications for grouping symptoms
a.
1. Big - Encompass many different functional areas
2. Lesions must often be bilateral to become clinically detectable. Bilateral lesions results in more complex behavioral disorders
3. The functions of the frontal lobes themselves are complex

b.
1. Dorsolateral convexity lesions and orbitofrontal lesions
I. Dorsolateral convexity lesions - Apathetic, lifeless, abulic state
II. Orbitofrontal lesions - Impulsive, disinhibited behavior and poor judgment

2. Left and right frontal lesions
I. Left -> Depression-like symptoms
II. Right -> Behavioral disturbances resembling mania
(Many exceptions)

(Blumenfeld)
Frontal lobe disorders
a. S&S
a. S&S
1. Abulia
(Passive, apathetic, little spontaneous activity, markedly delayed responses, tendency to speak briefly or softly. Extreme -> Akinetic mutism - Immobile, akinetic, mute, but awake with eyes open)

2. Disinhibition
(Silly behavior, crass jokes, aggressive outbursts)

3. Witzelsuch\Inappropriate jocularity
(A morbid tendency to pun, make poor jokes, and tell pointless stories, while being oneself inordinately entertained thereby.)
(Witzeln - to affect wit, sucht - mania)

3. Utilization behavior or environmental dependency
(Tend to respond to whatever stimuli are at hand, even when unappropriate. Ie 'the next bed over syndrome' answering unappropriately to questions asked to other patients)

4. Perserveration or impersistence
(Perservation - Luria sequencing task: copy a sequence until a certain point. Patient with perservation will draw one part of the sequence repeatedly and 'close in' on the examiner's example (above). Luria manual sequencing task - tap thigh with fist, palm, and side of open hand repeatedly)

5. Frontal release signs

6. Incontinence
(Frontal inhibiting micturition center in medial frontal regions in supplemental motor area)

7. Confabulation

8. Attention disorders
(-> Digit span testing, months forward and backward)

9. Memory disorders
(<- Attention disorders and problems with memory retrieval caused by frontal lobe lesions)

10. Decreased ability to spontaneously generate lists
(Tested by word generation tasks, used to detect subtle decreases in verbal fluency and are a sensitive measure of dominant frontal dysfunction, FAS test - 60 seconds to produce words beginning with a excluding places and persons, --||- for A,S)

11. Impaired abstract reasoning ability
(Tests for this are proverbs (what does it mean to say..?), similarities (how are ... and ... alike?), and logic problems)

12. Non-fluent aphasia
(If dominant hemisphere)

13. Contralateral hemineglect
(If nondominant hemisphere, most common with nondominant parietal lesions)

14. Large palpable bump on the frontal bone
(Meningiomas can cause hyperostosis resulting in a large palpable bump on the head)

15. Olfactory dysfunction
(Tumors in the orbitofrontal area often cause anosmia)

16. Impaired saccades away from the lesion
(If the frontal eye fields are involved, OKN test (decreased fast phase) is sensitive)

17. Motor impersistence
(Test by having the patient sustain an action such as holding out both arms or sticking out the tongue for 20 seconds)

18. Paratonia\Gegenhalten
(Increased tone, feel like patient is resisting in a voluntary way)

19. Frontal release signs\Primitive reflexes
(Grasp reflex, grasp when examiner strokes patients palm and can't release)
(Suck <- touch patients lip with cotton swab, snout <- tap the patient's lips)

20. Frontal gait abnormalities - Shuffling, unsteady, magnetic gait
(Feet barely leave the floor)

(Blumenfeld)
Frontal lobe disorders - Differential diagnosis
1. Disorders commonly affecting the frontal lobes
I. Head trauma
II. ACA or MCA infarcts
III. Hemorrhage <- Hypertension, tumor, AComm aneurysm
IV. Neoplasms - Gliomas, metastases, meningiomas..
V. Brain abscesses - Toxoplasmosis, Herpes simplex encephalitis (limbic cortex)
VI. Frontotemporal lobar degeneration (FTLD)
VII. Developmental abnormalities
VIII. Frontal lobe seizures

2. Diffuse processes causing frontal-like syndromes
I. Toxic or metabolic disorders
II. Hydrocephalus
(Compress ACA or frontal subcortical white matter pathways)
III. Binswanger's encephalopathy
(-> Multi-infarct dementia, many infarcts and lacunae in white matter with relative sparing of cortex and basal ganglia)
IV. Diffuse anoxic injury
V. Demyelination and other subcortical degenerative disorders
VI. Advanced Alzheimer's disease
(#2 tend to affect frontal lobes since they make up 1\3 of the cortex)

3. Other disorders causing frontal-like syndromes
I. Schizophrenia
(Negative symptomatology)
II. Depression
III. Parkinson's disease
IV. Huntington's disease
V. Cerebellar lesions
VI. Lesions of brainstem ascending RAS or thalamus

(Blumenfeld)
disorders of visual processing
a. Syndromes of primary visual cortex
b. Syndromes of the inferior occipito-temporal cortex
a. Syndromes of primary visual cortex
1. Cortical blindness\Anton's syndrome
(<- Bilateral lesions of the primary visual cortex, have anosognosia, loss of blink to threat, OKN, loss of eye closure in response to bright light..)
(Also seen with combined frontal and occipital lesions (+confabulation) and combined occipital and right parietal lesions (+neglect))

2. Visual halluzinations from seizures and migraine-related phenomena

3. Alexia without agraphia, associated with color anomia
(Left PCA infarct extending to corpus callosum -> disrupt input from both visual cortices to Wernicke's area)

b. Syndromes of the inferior occipito-temporal cortex
(In what-stream path)
1. Complex formed visual hallucinations with seizures

2. Prosopagnosia
(Unable to recognize people by looking at their faces, <- bilateral inferior occipitotemporal cortex\fusiform gyrus lesion)
(Also extend to animal faces)
(Associated with achromatopsia, alexia, and upper-quadrant or bilateral upper visual field defects)

3. Achromatopsia (Chroma - color, opsis - vision)
(Cortical color blindness, not equivalent to color agnosia (perception without meaning), see shades of gray, can be in one quadrant, hemifield, or entire visual field (then often associated with prosopognsoia))

4. Category-specific visual agnosias
(Human tools, living things.., <- atrophy of the temporal neocortex in semantic dementia)

5. Generalized visual-object agnosia
(<- Large bilateral lesions, apply to both generic and specific recognition of all visual objects)

6. Visual static agnosia
(Only able to recognize objects when they move)

7. Micropsia\Macropsia
(Objects appear unusually small or large, less specifically localized to this region)

8. Metamorphopsia
(Objects have a distorted shape and size, 'Alice in Wonderland syndrome', <- migraine, infarct, hemorrhage, tumors..)

9. Visual reorientation
(The environment appears tilted or inverted, <- more associated with vestibular or lateral medullary dysfunction)

10. Cerebral diplopia or polyopia
(<- inferior occipito-temporal association cortex, occipital lesions, corneal lesions)

11. Erythropsia
(Gold, red, purple, or other unnatural coloring of the visual fields, <- non-specific localization)

(Digitalis can give objects a yellowish halo)

(Blumenfeld)
Balint's syndrome
a. S&S
b. Associated features
c. Usual cause
Balint's syndrome - Clinical triad of
I. Simultanagnosia
(Impaired ability to perceive parts of a visual scene as a whole, perceive only small parts at a time, problem with identifying moving objects),
II. Optic ataxia
(impaired ability to reach for or point to objects in space under visual guidance. In contrast to cerebellar ataxia, once an object has been touched, a patient with optic ataxia can perform smooth movements back and forth with it even with the eyes closed)
III. Ocular apraxia
(Difficulty voluntarily directing one's gaze toward objects in the peripheral vision through saccades)

b. Associated signs can be aphasia on dominant side or neglect on nondominant side and inferior-quadrant visual field cuts

c. Bilateral lesions of the dorsolateral parieto-occipital cortex, classically caused by MCA-PCA watershed infarcts.
(Can also be caused by hemorrhage, tumors, dementia with posterior cortical atrophy..)

(Some patients may experience only optic allesthesia (a false localization of objects in space) or cerebral akinetopsia (an inability to perceive moving objects)

(Blumenfeld)
Disturbances of auditory processing
a. Tinnitus - What, <-
b. Self-audible bruits - What, <-
c. Release phenomenon - What, analogous to
d. Auditory hallucinations - causes
a. Tinnitus
1. Persistent ringing tone or buzzing in one or both ears
2. <- Peripheral auditory disorders affecting the
I. Tympanic membrane
II. Middle ear ossicles
III. Cochlea
IV. CN VIII

b. Self-audible bruits
1. Pulsatile "whoosing" sounds
2. <- Turbulent flow in
I. AVMs
II. Carotid dissections
III. The extracranial-to-intracranial pressure gradient that is elevated in increased ICP

c. Release phenomenon
I. Elaborate auditory hallucinations (music, voices..) in patients with sensorineural deafness
II. Analogous to Bonnet syndrome - Visual hallucinations caused by visual loss

c. Auditory hallucinations - <-
1. Release phenomenon

2. Lesions or ischemia of the pontine tegmentum
(Involving the trapezoid body, superior olivary nucleus, or other auditory circuits, often elaborate auditory phenomena such as music Analogous to visual phenomena of peduncular hallucinosis)

3. Paracusis
(A sound that is heard once is then heard repeatedly, analogous to palinopsia)

4. Psychotic disorders

5. Seizures
I. Primary auditory cortex -> Simple auditory phenomena
(<- From contralateral side often)
II. Auditory association cortex -> elaborate auditory phenomena - music or voices
(Music more often from nondominant hemisphere)

(Blumenfeld)
The consciousness system
a. Consciousness was described by Plum and Posner as having two components - What are these and explain them
b. Consciousness can be described in terms of three distinct but related processes that maintain ...
c. Which structures are involved in maintaining the level of consciousness
a. Plum and Posner - Consciousness
1. Content of consciousness
I. The substrate upon which consciousness acts
II. Includes most of the systems - sensory, motor, emotional, memory

2. Level of consciousness
I. Regulated by several brain networks - both cortical and subcortical networks that carry out specialized functions

b.
1. Alertness
2. Attention
3. Awareness of self and environment
(Awareness - Our ability to combine various forms of sensory, motor, emotional and mnemonic information into an efficient summary of mental activity that can potentially be remembered at a later time)
(AAA)

c. Substrates for maintaining level of consciousness
1. Upper brainstem
2. Thalamic activating systems
3. Hypothalamic activating systems
4. Basal forebrain activating systems
5. Medial and lateral frontoparietal association cortex and cingulate gyrus

(Blumenfeld)
Attention
a. Which two major functions do attention include
b. Anatomical substrates of attention
c. Anatomical structures linked to self-reflection, introspection, and self-awareness
a.
1. Selective\directed attention
(Focusing attention on a particular domain above others)

2. Sustained attention - Vigilance ('wakefulness'), concentration, nondistractibility
(Vigilance - An watchfulness for whatever may occur)
(Both involve an enhanced activity in stimulus-relevant regions of the brain ("signal") and decreased activity in stimulus irrelevant brain regions ("noise"))

b. Anatomical substrates of attention
1. Widespread projection systems
I. Upper brainstem
(Cholinergic (pedunculopontine, laterodorsal tegmental nuclei) and noncholinergic (pontomesencephalic reticular formation, maybe glutamatergic) -> thalamus, hypothalamus, basal forebrain structures, noradrenergic (locus ceruleus, lateral tegmental area), serotonergic (dorsal and medial raphe) -> cortical structures ++, dopaminergic (SNpr, ventral tegmental area) -> striatum, limbic cortex, prefrontal cortex)
II. Thalamus
(Intralaminar, midline, ventral medial transfer input from upper brainstem reticular formation, thalamic reticular nucleus 'gates' information. It receives input from thalamus, cortex, and brainstem systems and sends inhibitory GABAergic projections to thalamus and brainstem)
III. Hypothalamus
(Tuberomammillary\posterior lateral nucleus (histaminergic), receive input from anterior hypothalamus and brainstem and project to cortex and thalamus)
IV. Basal forebrain
(Nucleus basalis of Meynert, Diagonal band of Broca, medial septal cholinergic and GABAergic neurons, <- brainstem, -> cortex and thalamus)

2. Frontal and parietal association cortex
(The lateral parietal cortex\parieto-tempero-occipital (TPO) cortex lie at the nexus of auditory, visual, and somatosensory unimodal association cortex -> perfect for heteromodal integration in attention)
(Prefrontal cortex - frontal eye fields -> direct attention toward contralateral side and initiate eye movements toward attended targets, motor-intentional aspects of attention toward the contralateral side, more generalized aspects of attention)

3. Anterior cingulate cortex and limbic pathways
(Motivational aspects of attention - motivating directed and sustained attention)

4. Tectum - Superior colliculi, pretectal area, and pulvinar
(Participate with the PTO cortex and frontal eye fields in directing visual attention toward relevant visual stimuli for saccadic eye movements)

5. Other structures - Cerebellum, basal ganglia

(The right\nondominant hemisphere is usually more involved)

c. The medial parietal region - Precuneus, Posterior cingulate, and retrosplenial cortex

(Blumenfeld)
Attentional disorders
a. Tests for attention
b. Mild inattention can cause patients to have problems with
c. Severe inattention can cause to
d. Common causes of impaired general attention
a. Tests for attention
1. Digit span
I. A random series of numbers is recited to the patient, and the patient is asked to repeat them back immediately, normal is 5-7 digits
II. Backward is more difficulty and the normal is about 2 less than forward

2. Months of the year forward and backward

3. Count backward by sevens from 100

4. Motor impersistence
I. The patient is asked to stick out their tongue or hold up their arms for 20 seconds, without subsequent prompting. Failure -> Motor impersistence

5. "A" random letter test
(For vigilance, tap every time A is read by the examiner from a random sequence of letters)

(There is some overlap between the definitions of sustained attention and working memory. Attention - related to stimulus selection, working memory - temporary storage depot without necessarily being directly involved in stimulus selection. The frontal lobes play an important role in both functions)

b. Registering new information and completing tasks.

c. Severe inattention can cause patients to be completely unresponsive to outside stimuli. They may still be fully awake.

d. Common causes of impaired general attention
1. Diffuse encephalopathy
(Can, especially when acute in onset, also be associated with an impaired level of alertness ranging from mild lethargy to coma)

2. Focal lesions
I. Frontal or parietal lobes
II. Brainstem-diencephalic activating systems
(And others)

3. Attention-deficit hyperactivity disorder (ADHD)
(Affect 1-5% of elementary school children, Varies if inattention or hyperactivity is most pronounced,

4. Psychiatric disorders
I. Depression
II. Mania
III. Schizophrenia

(Blumenfeld)
Attention-deficit hyperactivity disorder (ADHD)
a. Epidemiology
b. How many % show remission upon entering adolescence
c. S&S
d. Treatment
a. Epidemiology
I. 1-5% of all elementary school children
II. 3-5x as many boys as girls
III. Onset typically around 3 years, problems emerge with school
(Genetic - higher concordance in siblings)

b. 70%

c. S&S
1. Whether attention-deficit or impulsive and hyperkinetic behaviors dominates varies

2. The attention-deficit is more likely to cause problems with higher-order functioning such as high-level executive functions, organizational skills..As opposed to simple functions such as tested by digit span

d. Treatment
1. Individual and family behavioral therapy

2. CNS stimulants - Methylphenidate (Ritalin)
(Reuptake inhibition of monoamine transporters, increase levels of dopamine and NA especially)

2. Selective NA reuptake inhibitors - Atomoxetine
(-> Stimulants that enhance dopaminergic and NAergic neurotransmission is beneficial)

(Blumenfeld)
Encephalopathies
a. Encephalopathy
b. Toxic and metabolic encephalopathies
a. Encephalopathy
I. Diffuse brain dysfunction

b. Toxic and metabolic encephalopathies
1. Medication, drug or alcohol toxicity
(Medications - Anti-cholinergics, sedative-hypnotic, narcotic)

2. Withdrawal from alcohol or other sedatives

3. Electrolyte abnormality - Hypernatremia, hypercalcemia,
hypermagnesemia

4. Diffuse anoxia

5. Hypothyroidism, hyperthyroidism

6. Hypoadrenalism

7. Thiamine deficiency - Wernicke-Korsakoff encephalopathy

8. Hepatic failure

9. Renal failure

10. Pulmonary failure

11. Sepsis

12. Inborn errors of metabolism

13. Paraneoplastic syndromes

14. Hereditary endogenous benzodiazepine production

(Blumenfeld)
Mental status changes
a. Acute\subacute vs chronic changes in mental status - Duration, Associated conditions
b. Acute mental status changes - Synonyms
c. Acute mental status changes - S&S
a.
1. Acute\subacute mental status changes
I. Hours to a few months
II. Causes
#1 Toxic or metabolic disorders
#2 Infections
#3 Head trauma and seizures
(-> Often treatable)

2. Chronic mental status changes
I. Months to years
II. Often represents neurodegenerative disorders in the elderly
(Dementia is a broad terming meaning literally 'decline in mental function', its usually applied more specifically to gradually progressive disorders such as Alzheimer's disease)

b. Acute mental status changes
I. Acute confusional states
II. Acute global confusion states
III. Organic psychosis
IV. Acute organic brain syndrome
V. Delirium
(Delirium is commonly used for acute confusional state in which agitation and hallucinations are prominent. Ie delirium tremens which occurs in the setting of alcohol withdrawal)

c. Acute mental status changes - S&S
1. Prominent inattention

2. Confusion

3. Waxing and waning levels of alertness and confusion over the course of hours
(Often exacerbated in the evening -> 'Sundowning')

4. Difficulty registering new memories
(<- Inattention, diffuse dysfunction of the memory network)

5. Often problems with writing, calculations, and constructional abilities
Causes of acute and subacute mental status changes
1. Toxic or metabolic encephalopathies
I. Medication, drug or alcohol toxicity
II. Withdrawal from alcohol (Delirium tremens) or other sedatives
III. Electrolyte abnormalities - Hypernatremia, hypercalcemia, hypermagnesemia in particular
IV. Hypoglycemia
V. Diffuse anoxia
VI. Hypothyroidism, hyperthyroidism
VII. Hypoadrenalism
VII. Thiamine deficiency - Wernicke-Korsakoff encephalopathy
VIII. Hepatic, renal, or pulmonary failure
IX. Sepsis
X. Inborn errors of metabolism
XI. Paraneoplastic syndromes
XII. Hereditary endogenous benzodiazepine production

2. Head trauma

3. Diffuse or focal cerebral ischemia or infarct

4. Intracranial hemorrhage

5. Migraine

6. Seizure or post-ictal state

7. Hydrocephalus

8. Elevated ICP

9. Diffuse cerebral edema

10. -Itis - Meningitis, encephalitis, brain abscess, vasculitis

11. Diffuse subcortical demyelination - MS

12. Intracranial neoplasm

13. Paraneoplastic syndrome

14. Mild insult in setting of underlying impaired mental status
(Ie UTI or change in environment)

15. Psychiatric disorders - Depression, mania, schizophrenia

16. Sleep deprivation

17. Visual deprivation or more generalized sensory deprivation
(Patients in ICU are prone to acute confusional states from the combination of sedative use, immobilization, and sleep and sensory deprivation)

18. Hypotension

19. Posterior reversible encephalopathy syndrome

(Blumenfeld)
Chronic mental status disorders
a. Dementia
b. Other terms for chronic mental status disorders
c. How is cortical and subcortical dementias differentiated
a. Dementia
I. Decline in cognitive abilities including memory
II. Its more typically used when there is gradually progressive deterioration over the course of months to years
(-> Dementia\chronic mental status disorders as opposed to delirium\acute mental status disorders)

b. Other terms for chronic mental status disorders
1. Static encephalopathy
(Permanent nonprogressive brain damage as a result of head injury, anoxia, or congenital abnormalities of brain development)

2. Mental retardation
(Impaired general intellectual and social adaptive function originating during development that is > 2 SD below average)

c.
I. Cortical dementias are characterized by dysfunction of higher-order functions - agnosia, apraxia, aphasia
II. Subcortical dementias are characterized by the absence of these.
(<- Huntington's disease, Progressive supranuclear palsy\Steele-Richardson-Olszewski disease)

(Blumenfeld)
Chronic mental status changes\Dementia
a. How many % of cases are Alzheimer's disease responsible for
b. How many % of cases has a treatable cause
c. Causes of chronic mental status changes
a. >50%
(10-15% is caused by vascular dementia)

b. 10%

c. Causes of chronic mental status changes
1. Primary neurodegenerative disorders
I. Alzheimer's disease
(#1)
II. Dementia with Lewy bodies
(Begin with fluctuating dementia, parkinsonism, and visual hallucinations)
(#2)
III. Frontotemporal lobar degeneration (FTLD)
(Frontotemporal dementia, progressive nonfluent aphasia, semantic dementia, other related disorders)
(#3)
IV. Parkinson's disease with dementia
V. Huntington's disease
VI. Progressive supranuclear palsy (PSP)\Steele-Richardson-Olszewski syndrome
VII. Cerebellar atrophies
VIII. Cortica-basal ganglionic degeneration\Cortico-basal degeneration
(Usually asymmetrical onset of movement disorder (ie dystonia) with cortical features, often apraxia)
IX. Dentatorubropallidoluysian atrophy (DRPLA)
X. Wilson's disease
(Treatable cause, often present in adolescence with hepatic dysfunction, dysarthria, movement disorders, or psychotic manifestations)

2. Vascular dementia
(Second most common cause, 10-15% of cases)
I. Multi-infarct dementia
II. Binswanger's disease
III. Intracranial hemorrhage
IV. Cerebral amyloid angiopathy
(Cause dementia through multifocal recurrent hemorrhages and white matter ischemic disease)

(When diffuse and severe white matter degeneration of any cause are present, a clinical picture emerges consisting of dementia, pseudobulbar affect (crying and laughing without the emotions), and frontal lobelike featrues such as shuffling, magnetic gait, and gegenhalten)

3. Psychiatric pseudodementia
(<- Depression, schizophrenia, conversion disorder)

4. Thiamine deficiency\Wernicke-Korsakoff encephalopathy and other alcohol-related disorders
(Alcoholism cause dementia via thiamine deficiency, other nutritional deficits, multiple head injuries, seizures, and probably a direct degenerative on the cerebellum)

5. Intracranial neoplasms and paraneoplastic syndromes
(Paraneoplastic syndromes of the nervous system occur when cancer-fighting agents of the immune system attack nerve or muscle cells. Cancers commonly associated with these disorders include lung, breast and ovarian cancer. Depending on the location of the cell damage, these syndromes can cause problems with muscle movement or coordination, sensory perception, memory or thinking skills, or sleep.)

6. Nornal-pressure hydrocephalus and noncommunicating hydrocephalus

7. Head trauma, including chronic subdural hematoma and dementia pugilistica\Chronic Boxer's encephalopathy\Boxer's dementia
(<- Repetitive concussions)

8. Infections
I. HIV-associated neurodegenerative disorder (HAND)
(Metabolic encephalopathy fueled by immune activation of brain macrophages and microglia, responds to treatment with antiretroviral therapy)
II. Meningitis
(Cryptoccal as seen in elderly or HIV patients often cause dementi)
III. encephalitis
IV. Neurosyphilis
V. Lyme disease
VI. Creutzfeldt-Jakob disease and other prion diseases
VII. CNS Whipple's disease
VII. Progressive multifocal leukoencephalopathy (PML)
(A rare, subacute, afebrile disease characterized by areas of demyelinization surrounded by markedly altered neuroglia, including inclusion bodies in glial cells; it occurs usually in individuals with AIDS, leukemia, lymphoma, or other debilitating diseases, or in those who have been receiving immunosuppressive treatment. Caused by JC virus, a human polyoma virus)

9. Vitamin-deficiencies
I. Vitamin B12 deficiency
(-> Megaloblastic anemia, subacute combined degeneraton (affect spinal cord (posterior columns more than corticospinal tract) and can involve cerebral white matter. Reversibility depends on when treatment is started)
II. Folic acid deficiency
(Associated with increased risk of dementia)
III. Pellegra
(<- B3\niacin deficiency, -> 3Ds - Dementia, Dermatitis, Diarrhea)

10. Heavy-metal toxicity
(Often with peripheral neuropathy, aluminimum in dialysate solutions used to cause dialysis dementia)

(Blumenfeld)
Frontotemporal lobar degeneration (FLTD)
a. Synonym
b. Give the three most common primary neurodegenerative disorders causing dementia in correct order
c. Variants, which is most common
d. Pathological changes\mechanism
a. Pick's disease

b.
#1 Alzheimer's disease
#2 Diffuse Lewy body disesae
#3 FTLD

c. Initial S&S
1. Variants
I. Frontotemporal dementia - Most common
II. Progressive nonfluent aphasia
(Left hemisphere perisylvian atrophy and nonfluent aphasia with relative sparing of language comprehrension)
III. Semantic dementia
(<- Temporal neocortex of both hemispheres. Prominent left lesion -> more impaired word comprehension)

(In some patients there is a concurrent motor neuron disease resembling ALS)

d. Pathological changes\mechanism
I. Neuronal inclusions containing ubiquinated TDP-43 (Transactive response (TAR) DNA-binding protein of 43 kDA)
(Appx 50%)
II. Neuronal inclusions bodies containing the microtubule-associated protein tau - Pick's bodies
(Appx 50%)

(Many genetic forms)

(Blumenfeld)
Alzheimer's disease
a. Pathological changes and their mechanism
b. Where are these changes most severe initially
a. Pathological changes and their mechanism
1. Cerebral atrophy

2. Neuronal loss

3. Amyloid\Senile plaques
I. Extracellular accumulation
II. Insoluble protein core containing beta-amyloid and apolipoprotein E surrounded by a rim of abnormal axons and dendrites called dystrophic neurites
(Dystroph - Progressive changes that may result from defective nutrition of a tissue or organ)
(Amyloid is a general term for insoluble protein deposits that can occur in various organ systems in different forms of amyloidosis)
(Beta-amyloid is derived from proteolytic cleavage of a transmembrane protein of unknown function called amyloid precursor protein (APP), cleavage by gamma-secretase intracelluarly is assumed to promote pathological cleavage)

4. Neurofibrillary tangles
I. Intracellular accumulations
I. Contain tau proteins
(Hyperphosphorylated microtubule-associated proteins\paired helical filaments)

b.
1. Medial temporal lobes
I. Amygdala
II. Hippocampal formation - Esp CA1
III. Entorhinal cortex

2. Basal temporal cortex
(Extend over the lateral posterior temporal cortex, parieto-occipital cortex, and posterior cingulate gyrus)

3. Frontal lobes

4. Where cholinergic neurons arise - Nucleus basalis, septal nuclei, nucleus of the diagonal band

(To a lesser extent in the locus ceruleus (NA) and raphe nuclei (serotonin))

(Blumenfeld)
Alzheimer's disease
a. Are most cases sporadic or genetic
b. Which gene\protein is associated with increased risk both with heterozygotes and homozygotes
c. AD varieties of Alzheimer's disease
a. Most cases are sporadic.
(And occur after the age of 60 years)

b. Epsilon4 alelle of apolipoprotein E (Apoe4)
(3x increase with heterozygotes, 15x increase with homozygotes)
(Dysfunctional plaque (lipid) clearance or modulation, or other unknown mechanism)

c. AD varieties of Alzheimer's disease
1. The APP gene
(chromosome 21, -> Down's syndrome connection)
2. The presenilin 1 gene
(Chromosome 14, involved in APP cleavage)
3. The presenilin 2 gene
(Chromosome 1, involved in APP cleavage)

(These can have onset as early as in the third or fourth decade of life)

(Blumenfeld)
Alzheimer's disease
a. Risk factors
b. The median time of survival from onset
b. S&S
a. Risk factors
1. Age
(1% when < 65 years, 40% when > 80 years)
2. ApoE4 allele
3. Other rare hereditary forms
4. History of TBI

b. 8 years

c. S&S - Typical Chronology
1. Memory loss, particularly for recent memories
(Dominant early feature)
(Recent events - Where they left their keys, what they're planning to buy in the store)
(<- Medial temporal lobe involvement)

2. Anomic aphasia - Difficulty finding words
(<- Posterior TPO involvement, other TPO findings include apraxia and visual-spatial deficits)

3. Behavioral abnormalities
(Paranoia, sexually inappropriate, aggressive or agitated, perform unusual activities)

4. Frontal lobe dysfunction - Gait impairment, abulia, incontinence

(Anosognosia is common)

(Late\severe Alzheimer's -> Akinetic, mute, unresponsive, bedridden. Ultimately succumb to infection or other illnesses)

(Blumenfeld)
Alzheimer's disease
a. Treatment options
b. Agents under investigation
a. Treatment options
1. Symptomatic treatment

2. Counseling of patient and family members

3. NMDA glutamate receptor antagonists - Memantine
(At normal levels, glutamate aids in memory and learning, but if levels are too high, glutamate appears to have an excitotoxic effect, killing neurons.)

4. Cholinesterase inhibitors
I. Donepezil
II. Rivastigmine
III. Galantamine

b. Agents under investigation
1. Gamma-secretase inhibitors

2. Specific beta-amyloid antibodies

3. Inhibition of amyloid-related inflammatory responses by blocking RAGE (Receptors for advanced glycated endproducts)

(Blumenfeld)
Where is the circle of Willis located in relation to the meninges?
In the pia.

(Goldberg)
Medial and lateral striate arteries and anterior choroidal artery
a. Where do they arise from
b. Which important structure can be damaged due to occlusion of these vessels
a. Medial striate from ACA, the other two from MCA.
(All in the region of the midbrain.)

b. The internal capsule.
(The narrow zone of a funnel of motor and sensory fibers that converge upon the brain stem from the cerebral cortex.)
(These small vessels can cause substantial tissue damage by hemorrhaging in situations of hypertension or arteriosclerosis)

(Goldberg
Sensory tracts in the spinal column - Name the four functionally different modalities, which tracts they travel with, and where they cross
1. Pain-temperature
I. Spinothalamic tract
II. Crosses over within 1-2 spinal cord vertebral segments after entering the spinal cord
(-> A lesion of the spinothalamic tract will result in loss of pain-temperature sensation contralaterally, below the level of the lesion)

2. Conscious proprioception - stereognosis
I. Posterior columns-medial lemniscus
II. Cross over in the junction between the spinal cord and brain stem right after synapsing in the nuclei gracilis and cuneatus
(+Vibration sense)
(Enable you to describe the position of your limb)
(A lesion of the posterior columns results in a decrease in conscious proprioception, stereognosis and vibration sense ipsilaterally below the level of the lesion)

3. Light touch
Combine 1&2 - Partly decussate in medulla (Posterior columns-medial lemniscus) and partly immediately in the spinal cord (spinothalamic tract)
(-> Why light touch typically is spared in unilateral spinal cord lesions)
(1-3 terminate in thalamus)

4. Unconscious proprioception
I. Spinocerebellar tract
II. Don't decussate
(Enables you to walk and perform other complex acts subconsciously without having to think which joints are flexed and extended)
(-> In contrast to cerebral lesions, cerebellar lesions tends to produce ispilateral malfunctioning)
(Enter cerebellum via inferior (via medulla) and superior (via midbrain) cerebellar peduncles)

(Goldberg)
Diseases affecting various portions of the spinal cord - give the location for the following conditions
a. Amyotrophic lateral sclerosis
b. Tertiary syphilis\Tabes dorsalis
c. Pernicious anemia
d. Polio
e. Guillain-Barre syndrome
f. Syringomyelia
a. Amyotrophic lateral sclerosis
I. Anterior horns of gray matter
(LMN lesion signs)
II. Corticospinal tracts
(UMN lesion signs)

b. Tertiary syphilis\Tabes dorsalis
I. Posterior columns, especially fasciculus gracilis
(Lower body)
(Proprioceptive loss and pain from posterior root irritation)

c. Pernicious anemia
I. Posterior columns
(-> Proprioceptive loss)
II. Corticospinal tracts
(-> UMN lesion)

d. Polio
I. Anterior horn cells of gray matter

e. Guillain-Barre syndrome
I. Peripheral nerve involvement
(Sensory and LMN loss)

f. Syringomyelia
I. Central part of spinal cord or brainstem
(Affect #1 the crossing pain-temperature fibers, #2 the corticospinal tract)
(Syringo - tube, myelos: marrow)
(Longitudinal 'tubes' in the spinal cord lined by gliogenous tissue)

(Goldberg)
Cranial nerve nuclei
a. General mnemonic
b. Exceptions
a. General mnemonic
1-4 in midbrain
5-8 in pons
9-12 in medulla

b. Exceptions
1. CN I and II lie more rostrally near the diencephalon
2. The sensory nucleus of CN V extend from the midbrain to the spinal cord
(Although it enters the pons)
3. CN VII and VIII nuclei lie in pons and medulla

(Goldberg)
Cranial nerves
a. Which two structural characteristics is unique to CN IV
b. Location of the spinal nucleus of CN V
c. Which tract carries CN V input from its nuclei to thalamus
d. Parts of the trigeminal nucleus and their modalities
e. Which CNs project into the trigeminal nucleus
a. Exits dorsally and crosses over.

b. From pons to C2.

c. Trigeminal lemniscus
(Cross over immediately)

d.
I. Mesencephalic nucleus CN V - Proprioception
II. Main sensory nucleus CN V (pons) - Light touch
III. Spinal nucleus (medulla and upper spinal cord) - Pain, temperature
(Tractotomy for trigeminal neuralgia is performed in medulla)

e. 5, 7, 9, 10
(Last 3 only for ear)

(Goldberg)
Cranial nerves
a. Which cranial nerve loops around abducens nucleus before exiting
b. What is the name of the visceral sensory nucleus, and which CNs project into it
c. What is the name
a. CN VII
(This naughty nerve heard there was some sex to be had over by the 4th ventricle and began in early development to grow in reverse direction, into the core of the brain stem. On arriving at the 4th ventricle it realized that it misunderstood. It was six, not sex, and the facial nerve did an U-turn, traveling around CN VI nucleus to exit anterolaterally)

b. Nucleus solitarius - CN VII, IX, X
(S for sensory)
(Located solely in medulla)
(Taste - VII, IX, X. Carotid sinus and carotid body - IX, massive sensory return along CN X)

(Goldberg)
Vertigo
a. The two main causes
b. Method for differentiation
a. Causes
I. Dysfunction of the vestibular apparatus of the inner ear.
II. Dysfunction of the vestibular nuclei in the brain stem

b. Nucleus solitarius and ambiguus lie near the vestibular nuclei. Therefore, if the patient not only has vertigo, but also difficulty with taste (NS), swallowing (NA), or speech (NA), this increases the suspicion of a brain stem lesion.

(Goldberg)
Argyll-Robertson pupil
a. Clinical sign
b. Assumed lesion
c. Cause
a. A pupil that accommodate but don't react.
(Constricts during accommodation, but don't constrict to light)

b. Pretectal area of the superior colliculus.

c. Syphilis

(Goldberg)
Conjugate gaze
a. Damage to the motor areas of the cerebral cortex produces contralateral hemiplegia. How does it affect the eye movements
b. Which Brodmann's area is responsible for voluntary conjugate gaze, involuntary conjugate gaze
c. Internuclear ophthalmoplegia - synonym, from lesion to, most common cause, S&S
c. Mechanism
a. It cause a loss of the ability of either eye to look toward the contralateral environment.
(Site with plegia, -> look toward site with lesion)

b.
I. Voluntary conjugate gaze - Brodmann's area 8 - Visuomotor area
(In frontal cortex, just anterior to premotor cortex)
II. Involuntary conjugate gaze - Brodmann's area 17,18,19

c.
1. Input from cortex (8\17-19) synapse in contralateral lateral gaze center\paramedian pontine reticular formation (PPRF) in pons
2. Project to ipsilateral CN VI nucleus and contralateral CN III nucleus (medial rectus) via MLF
(Ipsilateral = same site as after it has crossed over\opposite site of involved hemisphere, -> left cortex innervate left medial rectus and right lateral rectus)

c. Internuclear ophthalmoplegia (INO)\MLF syndrome
I. Bilateral MLF lesion
II. MS
III. Decreased ability for either eye to look medially, but both eyes can converge and perform vertical gaze
(Different pathways)

(Goldberg)
Nystagmus
a. What
b. What is the most common form, characteristics
c. Vertical nystagmus - Cause
d. Pendular nystagmus - Characteristics, Cause
a. Repetitive, tremor-like oscillating movements of the eye

b. Horizontal jerk nystagmus
I. The eyes repetitively move slowly toward one side and then quickly back
(Normal to have a slight degree of such nystagmus on attempted extreme lateral gaze, but marked degrees are abnormal and found in a variety of clinical conditions)

c. Vertical nystagmus
I. Always pathological
II. Signify brainstem dysfunction

d. Pendular nystagmus
I: The eye moves at equal speeds in both directions
II. Congenital or present after prolonged periods of blindness

(Goldberg)
Cold calorics testing
a. Method
b. Result in lethargic\stupor\obtundation patient, why
c. Result in patient in coma, why
a. Inject some cold water into one of the ears. The normal response is slow movement toward the site of the cold water and fast movement back to center of vision, with no net deviation of the eyes.
(Imagine slow movement mediated by the slow brainstem to see what's going on, while fast movement back is mediated by the cortex to keep eyes on the important part of the visual field)

b. The fast component of nystagmus becomes less pronounced and there is net deviation of the eyes, because the cortex is affected most at first.
(The fast component gradually disappears)

c. No movement at all because the brain stem becomes depressed as well.

(Goldberg)
What deficits will occur in the cranial nerves following destruction of the left cerebral hemisphere
1. CN I - Loss of olfaction on the left

2. CN II - Right homonymous hemianopia

3. CN III, IV, VI - Loss of right conjugate gaze

4. CN V - Right facial hemianesthesia, only slight motor defect in chewing on the right, owing to bilateral innervation of the motor nucleus of CN V

5. CN VII - Lower-right facial paralysis

6. CN VIII - Little defect owing to bilateral representation

7. CN IX, X - No significant defect - bilateral innervation

8. CN XI - Decreased function on the right (minimal)

9. CN XII - Variable contralateral tongue paresis

(You can remember the motor defects with most CN upper MN lesions by noting which muscle maneuvers you find difficult to perform. Most of us will experience difficulty in raising one eyebrow, trying to move but one eye, biting down exclusively on one side, or swallowing or talking on one side only. These difficulties coincide with bilateral innervation of the cranial nerves.)

(Goldberg)
Identify the type of respiration and site of lesion of the following breathing pattern
a. Rapid respirations of increasing and decreasing depth, alternating with periods of absent respiration
b. Rapid respiration
c. Irregular rate and depth of respiration
d. Slow, gasping respiration
a. Cheyne-Stokes, cerebrum

b. Central neurogenic hyperventilation, midbrain

c. Ataxic respiration, medulla

d. Apneustic respiration, pons

(Ataxic respiration - very irregular breathing pattern, may progress to respiratory arrest)
(Apneustic respiration - has 2-3 second respiratory pauses at full inspirations
(Rarely, involve medial parabrachial Kolliker-Fuse area dorsal to the motor nucleus of CN V))
(Cheyne-Stokes
(Crescendo-Decrescendo, also seen in high-altitude sickness and medical conditions such as cardiac failure))

(Goldberg)
Papez circuit
a. Involved with
b. Intercommounications
a. Believed to be involved in the emotional content of conscious thought processes and in memory.

b. Hippocampus, hypothalamus, thalamus, and cerebral cortex.

(Goldberg)
Korsakoff syndrome
a. Typical patients
b. S&S
c. Associated structure
a. Alcoholics and undernourished.

b. S&S
1. Memory loss
2. Confusion and confabulation

c. Mamillary bodies.

(Goldberg)
Riley-Day syndrome
a. Synonym
b. Structural associations
c. S&S
a. Familial dysautonomia.

b. Degenerative changes in the CNS and peripheral autonomic system.

c. S&S
1. Decreased lacrimation
2. Transient skin blotching
3. Attacks of hypertension
4. Episodes of hyperpyrexia and vomiting
5. Impairment of taste discrimination
7. Relative insensitivity to pain
8. Emotional instability

(Goldberg)
Thalamus
a. Explain the mechanism of the thalamic pain syndrome
a. Thalamic pain syndrome
I. The thalamus is capable of perceiving pain but not of accurate localization -> a tumor affecting the thalamus can cause a vague sense of pain without the ability to accurately localize it.
Give function or connection of the following thalamic nuclei
a. Ventral posterolateral (VPL) nucleus
b. Ventral posteromedial (VPM) nucleus
c. Anterior thalamic nucleus
d. Ventral lateral (VL) nucleus
a. Ventral posterolateral (VPL) nucleus
I. Synaptic region for ascending spinal sensory pathways

b. Ventral posteromedial (VPM) nucleus
I. Synaptic region for the trigeminal lemniscus

c. Anterior thalamic nucleus
I. Part of the papez circuit

d. Ventral lateral (VL) nucleus
I. Receives input from the cerebellum

(Goldberg)
Cerebellar disorders
a. Generally, how can the movements of cerebellar and basal ganglia disorders be differentiated
a. Differentiation
I. Cerebellar disorders - Awkwardness of intentional movements
II. Basal ganglia disorders - Meaningless unintentional movements occurring unexpectedly

(Goldberg)
Basal ganglia disorders - S&S for
a. Parkinsonism
b. Chorea
c. Athetosis
d. Hemiballismus
a. Parkinsonism
1. Rigidity
2. Slowness
3. Resting tremor
4. Mask-like face
5. Shuffling gait
(Associated with degeneration in the basal ganglia and substantia nigra)

b. Chorea
I. Sudden jerky and purposeless movements
(Sydenham's chorea found in rheumatic fever, Huntington's chorea, an inherited disorder)

c. Athetosis
I. Slow-writhing, snake-like movements, especially of the fingers and wrists

d. Hemiballismus
I. A sudden wild flail-like movement of one arm

(Goldberg)
In what clinical conditions would you expect a positive Romberg, how can these conditions be differentiated.
In proprioceptive or vestibular defects.
(To keep one's balance requires at least 2\3 senses that help maintain balance - vision, vestibular sense and proprioception. These three modalities feed into the cerebellum.)

In proprioceptive defects the patient is unable to determine joint position as tested by the examiner.

In vestibular defects that patient may experience vertigo, nystagmus, or abnormal cold-caloric testing.

(Goldberg)
How can cranial nerves 10, 12, and 7 be tested by speech
KLM

1. Kuh, kuh, kuh - The soft palate (CN X)

2. La, la, la - The tongue (CN XII)

3. Mi, mi, mi - The lips (CN VII)

(Goldberg)
Cerebral cortex
a. Agnosias
b. Apraxias
a. Agnosias (Gnosis - knowledge)
I. Complex cerebral receptive disabilities.

b. Apraxias (Praxia - to do)
I. Complex cerebral motor disabilities.

(Goldberg)
Cerebral lesions - Give the S&S and Brodmann's area for
a. Primary motor area
b. Supplemental motor area
c. Frontal eye fields
d. Prefrontal cortex - only S&S
a. Primary motor area
I. Brodmann's area 4
II. Flaccid paralysis

b. Supplemental motor area
I. Brodmann's area 6
II. Spasticity and increased deep tendon reflex

c. Frontal eye fields
I. Brodmann's area 8
II. Difficulty with voluntary conjugate gaze to contralateral side

d. Prefrontal cortex
I. Changes in judgment, abstract thinking, tactfulness and foresight. -> Irresponsibility in dealing with daily affairs, vulgar speech, and clownish behavior.

(Goldberg)
Cerebral lesions - Give the S&S and Brodmann's area for
a. Broca's speech area
b. Primary somasthetic\somatosensory arae
c. Auditory area
d. Wernicke's area
a. Broca's speech area
I. Brodmann's area 44,45
II. Motor aphasia when the dominant hemisphere is involved
(The patient knows what he wants to say but speech is slow, deleting many prepositions and nouns)

b. Primary somasthetic\somatosensory area
I. Brodmann's area 3,1,2
II. Contralateral impairment of touch, pressure, and proprioception
(Pain will be impaired if the lesion lies in the secondary somesthetic sensory area which receives pain information)

c. Auditory area
I. Brodmann's area 41,42
II. Unilateral lesions have little effect on hearing due to bilateral representation of the auditory pathways.

d. Wernicke's area
I. Brodmann's area 22
II. Lesions in the dominant hemishpere result in auditory aphasia
(The patient hears but don't understand. He speaks but makes mistakes unknowingly owing to his inability to understand his own words)

(Goldberg)
Cerebral lesions - Give the S&S and Brodmann's area for
a. Supramarginal gyrus
b. Angular gyrus
c. Visual cortex (17,18,19)
d. Secondary visual cortex (18,19)
a. Supramarginal gyrus
I. Brodmann's area 40
II. Lesions in the dominant hemisphere results in tactile and proprioceptive agnosia, left-right confusion, disturbances of body iamge, and apraxia.

b. Angular gyrus
I. Brodmann's area 39
II. Dominant hemisphere: alexia, agraphia (inability to read and write)

c. Visual cortex (17,18,19)
I. Total destruction cause blindness in the contralateral visual field

d. Secondary visual cortex (18,19)
I. Visual agnosia (Difficulty in recognizing and identifying objects)

(Goldberg)
1-3 - Structure, Effect of lesion
1. Corticomesencephalic tract carrying information for lateral conjugate gaze to the contralateral side
(It originates from both the frontal lobe (area 8) for voluntary gaze and occipital lobe (areas 17,18,19) for involuntary gaze movements)
I. A lesions results in inability to look to the contralateral side.
(The eyes look toward the lesion)

2. Medial longitudinal fasciculus (MLF)
I. Lesion -> Internuclear ophthalmoplegia (INO) - Inability of the ipsilateral eye (CN3) to adduct on lateral conjugate gaze. There is also nystagmus of the abducting contralateral eye.
(Convergence is unaffected because convergence, while using CN3, involves a different pathway than that of lateral conjugate gaze)

2. Lateral gaze center\Paramedian pontine reticular formation (PPRF)
I. Lesion -> Deficit in lateral conjugate gaze to ipsilateral side

(Goldberg)
1-4 - Give the cerebellar effects of lesions and explain why
1. Thalamus
I. Contralateral ataxia
II. Since connections come from the contralateral cerebellum
(Which in turn receives ipsilateral connections from the spinocerebellar tract (not shown))

2. Red nucleus
I. Contralateral intention tremor and ataxia
II. Since it receives input from the contralateral cerebellum
(Decussate as seen in midbrain)
(Sensory input to the cerebellum is essentially from the ipsilateral spinocerebellar tract)

3. Superior cerebellar peduncle
I. Lesion cause ipsilateral ataxia
I. Since it comes from the ipsilateral cerebellum
(Which in turn receives sensory input from ipsilateral spinocerebellar tract. Information crosses over to the red nucleus via the decussation of the superior cerebellar peduncle at the midline of the midbrain)

4. Cerebellum
I. Lesion -> Ipsilateral ataxia

(Goldberg)
1-4 - Structure, Effect of lesion
1. Corticomesencephalic tract
I. Lesion -> Deficit in contralateral lateral conjugate gaze
(On the double-headed gingerbread man's big toe)

2. Corticospinal and corticobulbar tracts
I. Lesion -> Contralateral weakness of the extremities (corticospinal tract) and contralateral weakness of the tongue and lower face (corticobulbar tract)
(The double-headed gingerbread man's middle toe)

3. Corticobulbar tract
I. Unilateral lesion -> Little damage to cranial nerve function, since it sends overlapping bilateral connections to most cranial nerve nuclei. But the patient will have weakness of the lower face (CN7) and sometimes opposite tongue (CN12) since connections to these areas are commonly totally crossed.

4. Corticospinal tract
I. -> Contralateral palsy of extremities

(Goldberg)
A lesion to one side of the cerebral cortex or internal capsule will not significantly affect most CN nuclei, because of bilateral innervation from the cerebral cortex. Thus if one side is injured, the other side takes over function. What are they key motor and sensory exceptions
1. Paralysis of the contralateral lower face, and in some patients weakness of the contralateral tongue

2. Sensation loss to the entire contralateral face

3. Inability of either eye to look conjugately to the contralateral side

(If other cranial nerves show a deficit, it implies that the lesion lies either within the cranial nerve itself or in the nucleus of the nerve within the brain stem. Alternatively, there are bilateral cerebral cortex or internal capsule lesions (pseudobulbar palsy))

(Goldberg)
Case
Pain in right upper extremity with a Babinski sign on the same side. Where is the smallest possible location?
Right spinal cord

(Pain suggests involvement of peripheral nerve or nerve root, since CNS lesions tend to cause loss of localized pain instead of causing it.
To account for a single unilateral lesion, the Babinski sign, an UMN sign, would have to arise within the cervical cord in the corticospinal tract on the right, near the simultaneous peripheral nerve root lesion that cause the pain.)

(Goldberg)
Case
Only decreased pain and temperature in the upper extremities. Where is the smallest possible lesions
Bilateral spinal cord injury caused by sryingomyelia.

(In syringomyelia the center of the (generally cervical) cord is hollowed out ->
1. Pain-temperature is the only sensory modality involved, because the condition destroys pain-temperature axons that cross over in the affected area, the anterior white commissure.

2. The condition specifically affects the upper extremities, not lower parts of the body, because of cervical cord involvement.

3. Sometimes the condition may extend more laterally, damaging the anterior horns and causing LMN paralysis in the cervical nerve distribution)

(Goldberg)
Case
Patient shows
1. Decreased sensation on both sides of the face
2. Hoarseness with paralyzed left vocal cord
3. Decreased proprioception - Stereognosis in the right upper extremity
4. Decreased pain-temperature sensation in the right upper and lower extremities
5. Left Horner's syndrome
Left medulla

(Hoarseness with paralyzed left vocal cord suggests direct involvement of nucleus ambiguus in medulla, or or its peripheral extensions out along the vagus nerve (CN10). Lesions to internal capsule or cerebral cortex, do not cause hoarseness or vocal cord paralysis unless, since projection of each side of the cerebrum to both sides of the brain stem affords coverage against most cranial nerve problems with unilateral cerebral lesions.

The long tract signs then confirms the lesion is in the left medulla, affecting not only CNX but left medial lemniscus (decreased proprioception), left spinothalamic tract (decreased pain-temperature), left nucleus and tract of CNV and trigeminal lemniscus (-> bilateral decreased facial sensation), and reticular formation (Horner's syndrome))

(Goldberg)
Case
A patient cannot read better than the 20\200 line on the Snellen chart at 20 feet. At 7 feet, she still can read no better than the 20\200 line.

She complains of diplopia, which does not disappear on covering one eye.

She reports lack of smell sensation (anosmia), including no response to ammonia, while other sensory modalities, namely pinprick and light touch the the face are intact.

She reports numbness of the hands and feet in a glove-and-stocking distribution.
These signs as a whole are nonphysiologic:

The closer one views a Snellen eye chart, the smaller the lines one should be able to read.

Diplopia is caused by one eye looking in one direction and the other eye looking in another direction. It should disappear on covering one eye. (Rarely, though, diplopia may be due to retinal detachment or dislocated lens).

Ammonia does not test the sense of smell (CN I), but rather tests the pain endings of CN V. With absent sense of smell (anosmia) there still should be response to ammonia.

Sensory deficit in a glove-and-stocking pattern distribution commonly represents hysteria or malingering, but may also be due to peripheral neuropathy.

(Goldberg)
1-5 - Area, Result of lesion
1. Prefrontal cortex
I. Changes in judgment, abstract thinking, tactfulness and foresight.
II. Symptoms - Irresponsibility in dealing with daily affairs, vulgar speech, clownish behavior
(Lesions of the right frontal lobe may be associated with inappropriate cheerfulness, including pathological laughter. Lesions of the left frontal lobe are more associated with depression including pathological crying)

2. Broca's speech area (44,45)
I. Motor aphasia if the dominant side is involved - The patient knows what he wants to say but speech is slow, deleting many nouns and connector words like but, or, and and.
(In severe cases, the patient may be unable to read or write. In lesser cases (aphemia) there may be a deficit in speech but not in writing.
(Aphemia (pheme - voice) - Form of motor aphasia in which the ability to express ideas in spoken words is lost)

3. The frontal eye fields (8)
I. Difficulty in voluntarily moving the eyes to the opposite side
(The same symptoms could result from a lesion to the ipsilateral corticomesencephalic tract or contralateral pontine lateral gaze center)

4. Corticobulbar zone of the primary motor area (4)
I. Supplies the head and cranial nerves
II. CN VII - the lower face part of the nucleus CNVII and sometimes CN XII are affected, resulting in weakness of the contralateral lower face and sometimes weakness of the contralateral tongue
(Most CNs are not affected by corticobulbar area lesions since there is overlap bilateral connections to both sides of the brain stem)

5. The primary motor area (4)
I. Initial contralateral flaccid paralysis followed in several months by partial recovery of function and a possible Babinski reflex
(Spasticity and increased deep tendon reflexes may occur if area 6 - the supplemental motor area is included)

(Goldberg)
1-5 - Area and effect of lesion
1. Primary somesthetic area (3,1,2)
I. Contralateral impairment of touch, pressure and proprioception
(Pain sensation will be impaired if the lesion lies in the secondary somesthetic sensory area, indicated by xxx, which lies above the lateral fissure and receives pain information)

2. Secondary somesthetic area
I. Impairment of pain sensation

3. Wernicke's area (22)
I. Lesions in the dominant hemisphere result in auditory aphasia - The patient hears but does not understand
II. He speaks but makes mistakes unknowingly owing to his inability to understand his own words
III. Hem crams into his speech inappropriate word substitutes (paraphasia) and neologosims.
(-> A word salad)
IV. In the temporal lobe lesions, the patient commonly exhibits problems with verbal memory, whereas nonverbal memory is affected with right temporal lobe lesions.

4. Auditory area (41,42)
I. Unilateral lesions have little effect on hearing owing to bilateral representation of the auditory pathways.
(Significant auditory defects generally involve either CN VIII or its entry point in the brain stem, for bilateral representations begins beyond this point)

5. Angular gyrus (39)
I. Dominant side lesion -> Alexia and agraphia, Gerstmann's syndrome
(Agraphia, left-right disorientation, finger agnosia, acalculia)
II. Bilateral lesion -> Balint's syndrome
III. Large nondominant lesions -> Hemineglect

(Goldberg)
Cerebral cortex
a. How is the occipital lobe delineated
b. How can the central sulcus be identified laterally
c. How can the supramarginal gyrus be located
d. How can the angular gyrus be located
a. By drawing a line from the parieto-occipital fissure to the preoccipital notch.

b. By noting that the pre- and postcentral gyri, which surround it, run more or less vertically, in comparison with the more horizontal frontal gyri

c. The supramarginal gyrus lies around the posterior tip of the lateral fissure

d. The angular gyrus lies around the posterior tip of the superior temporal sulcus (which lies between superior and middle temporal gyri)

(Goldberg)
Cerebral cortex
a. Temporal lobe - 3 gyri on lateral side, 3 gyri on medial side
a.
I. Lateral side - Superior, middle, inferior temporal gyri
II. Medial side - Uncus, parahippocampal, occipitotemporal gyri

(Goldberg)
The cerebral cortex
a. The calcarine fissure divides the visual area of the brain into which two structures
b. The third ventricle - Lateral and midline borders (clockwise from 6 o' clock)
a. The cuneus above and the lingular gyrus below.

b. The third ventricle
I. Lateral border - Thalamus and hypothalamus
(Separated by hypothalamic sulcus)
II. Midline borders - Clockwise from 6 o'clock
1. Pituitary stalk
2. Optic chiasm
3. Lamina terminalis
4. Anterior commissure
5. Anterior tip of fornix
6. Interventricular foramen
7. Stria medullaris
8. Pineal gland
9. Posterior commissure
10. Aqueduct of Sylvius
11. Rostral tip of midbrain

(Goldberg)
Trigeminal pathways
1-7 - Name of structure, effect of lesion related to the face
1. Sensory cortex -> Contralateral decrease in all facial sensation

2. Thalamus -> Contralateral decrease in facial sensation

3. Trigeminal lemniscus -> Contralateral decrease in facial sensation
(Also called the ventral trigeminothalamic tract)

4. Mesencephalic nucleus subdivision of sensory nucleus of CN V -> Ipsilateral decrease in facial proprioception
(Ie telling how hard one has bit down on one's teeth)

5. Main sensory nucleus subdivision of sensory nucleus of CN V -> Ipsilateral decrease in facial light touch

6. Spinal nucleus subdivision of the sensory nucleus of CN V -> Ipsilateral facial pain-temperature sensation

7. Spinal tract of CN V -> Ipsilateral decrease in facial sensation

(Goldberg)