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250 Cards in this Set

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Dementia

*alzheimer's is MCC of dementia
GRADUAL progression of multiple cognitive deficits

*Short-term memory affected more than long term memory

Terms:
- aphasia & paraphasic errors (grass is greel)
- Apraxia: fail motor task despite normal strenth
- Agnosia & Prosopagnosia
- Distrubed executive functioning
ALZHEIMER'S

- GENETICS
- AGE OF ONSET
ONSET > 60 YO
- incidence doubles every 5 yr after 60
- more common in blacks & women

Genetics:
- Linkages to chrom 21, 14, 1 = EARLY onset
- Chrom 19 apolipoprotein E4 allele = LATE onset

**familial AD is only 7% of all AD cases

Risk factors = VASCULAR
- obesity, age, apo E4, hypercholesterolemia, HTN, insulin resistence

*100% DOWN'S SYN = AD by 40 yo*
Pathology of AD

- cholinergic hypothesis
- amyloid hypothesis
1.B-Amyloid Plaques: Extracell
- can be normal
2. Neurofibrillary tangles: Intracell
- tau & ubiquitin
- also in PSP
3. Hippocampal Pyramidal cell degen
- basal forebrain cholinergic neurons
4. Diffuse cerebral atrophy
- Hydrocephalus ex vacuo

Glutamate excitotoxicity & excess NMDA stim may play a role too

amyloid hypothesis
- plaques trigger inflamm, abnl tau phosphorylation, free radical tox
--> neuronal loss & cholinergic dysfxn
SYMPTOMS & SIGNS OF AD


**ask family members about new deficits
1. Loss of Insight
2. EARLY: mental slowing, lose interest, language problems, apraxia, spatial disorientation, impaired judgement, perseveration
- family members take over finances, etc
3. Maintain Social Skills: friendly, jocular
- pt looks normal superficially
4. LATE: become a different person – behavior, depression, delusions, hallucinations, frontal lob release signs
5. LATE MOTOR SIGNS: gait instability, parkinsonian
- don’t respond to Parkinson meds
AD DX
CLINICAL DX
- PT. HISTORY (family )
- MENTAL STATUS EXAM

*atypical memory loss & FOCAL FINDINGS --> MRI

MRI: DIFFUSE ATROPHY, HYPOMETABOLISM in temporo-parietal region, small hipocampus
AD MEDS:


**important to recognize & tx behavioral symptoms
- agitation
- psychosis
- aggression
AChE-inhibitors = mild-moderate

1. donepezil (aricept) = major
2. rivastigmine
3. galantamine

4. Memantine ( namenda): moderate-advanced AD
- noncomp NMDA-R antagonist
- blocks glutamate

*use atypical neuroleptics for psych symptoms
*Use antidepressant also if needed*
multi-infarct dementia
2nd / 3rd MCC dementia
STEPWISE, ABRUPT DECLINES
- can be cortical or subcortical

+ FOCAL defects

Subcortical:
- pseudobulbar palsy
- parkinsonian features
- emotional incontinence
- more apathy, depression, withdrawal, etc than cortical

**dx is based on hx of multiple storkes & focal defects**
DEMENTIA W/ LEWY BODIES
TRIAD:
1.EARLY: Fluctuating cognition w/ big variations in attn & alertness bw days & hours

*2. Recurrent hallucinations (75% pts)

3. EARLY: motor signs of parkinson's
- less tremors

*hallucinations are huge
DLB PATHOLOGY
1. Diffuse Lewy Bodies
- alpha-synuclein inclusions
2. Loss of Dopaminergic neurons in SN
3. Loss of Ach neurons in basal forebrain
4. Also senile plaques & hippocampal degeneration

**subcortical AND cortical lewy bodies
PARKINSON'S VS AD
PD: EARLY MOTOR, LATE DEMENTIA
+ TRAP

AD: EARLY DEMENTIA, LATE MOTOR
HUNTINGTON'S VS AD

- path
HUNTINGTON'S:
+ family hx & genetic testing
- movement disorder: chorea
- EARLY behavioral problems
- late parkinsoniam features

path:
- gen. atrophy
- focal atrophy of caudate nucleus
CREUTZFELDT-JAKOB DISEASE

- ONSET
- DESCRIPTION
- FEATURES
- path & dx
RARE, FATAL
onset: 50-70

TRIAD:
1. RAPIDLY PROGRESSIVE DEMENTIA
2. non-epileptic myoclonic jerks
3. ataxia
- die w/in 6 mo onset

PRION DISEASE
- Spongy degen
- neuronal loss
- astrocytic proliferation

dx:
EEG: periodic sharp waves
- elevated 14-3-3 PROTEIN IN csf
FRONTOTEMPORAL DEMENTIA
(FTD; PICK'S DISEASE)

- ONSET
- VS. AD)
EARLIER ONSET THAN AD

FEATURES:
- VERY SIMILAR TO AD
- Spared motor & sensory
- EARLY behavior & personality changes
- Progressive aphasia (out of proportion to dementia)

MRI:
- FOCAL ATROPHY OF FRONTAL & TEMPORAL LOBES
- PICK BODIES
KORSAKOFF'S SYNDROME

- THIAMINE DEF
- OFTEN 2' CHRONIC ALCOHOLISM
Sleep-confused patient (encephalopathy)
- Wernicke’s triad: ophthalmoplegia, encephalopathy, gait instable
- precipitated by IV glucose admin in hospital
- Korsakoff’s = residual amnesia: both antero & retrograde
(PATHY MEMORY DEFICITS UNLIKE AD)

Little insight
&
major confabulation (confuse imagination w/ real)
NORMAL PRESSURE HYDROCEPHALUS

- features
- mechanism

**VERY OVER-DIAGNOSED**
1. EARLY Gait apraxia (initiation)
2. Subcortical dementia (depressed)
3. Urinary incontinence

mechanism:
Arachnoid granulations can't reabsorb CSF
--> Communicating hydrocephalus
- Ventricles enlarge & push against MIDLINE PATHWAYS
--> urinary incontinenc & leg control

*MRI: VERY LITTLE CORTICAL ATROPHY
AD vs. age-related cognitive decline
NORMAL; PT OF AGING
- pt is still highly functional
- NOT progressive memory loss
- mildly diminished
AD vs. depression/pseudodementia
SUBJECTIVE COMPLAINT
- onset is variable;esp in younger
- abrupt onset; fluctuates
- POOR effort; focuses on failures
- sad, teary, personality changes evident
- aware & distressed abt memory loss
- Inconsistent, spotty deficits
ENCEPHALOPATHY VS DEMENTIA
ENCEPHALOPATHY:
Acute/subactue onset
- fluctuating course
- attention is majorly impaired; sleepy
- often reversible
EVALUATION OF HEADACHE:

OMINOUS SIGNS & SYMPTOMS
(warranting further eval)
1. NEW ONSET headache in person not previously predisposed to headaches

2. NEW ONSET of headache in older pt

3. SUDDEN ONSET

4. FEVER

5. FOCAL NEURO FINDINGS

6. Signs of increased ICP
- drowsy, sleepy, papilledema
EVALUATION OF HEADACHE:


DIAGNOSIS: CONSIDER THE FOLLOWING IN ALLL PTS PRESENTING W/ HEADACHE
1. Subarachnoid hemorrhage
neg Head CT --> lumbar puncture

2. MRI: non-migraine or tension headahce
- r/o mass lesion

3. Temporal arteritis
- sedimentation rate & temporal a. biopsy

4. Meningitis or pseudotumor cerebri
- LP

5. Sinusitis: sinus series
NEUROVASCULAR THEORY OF MIGRAINES

- also genetics?
- tx?
BENIGN DISEASE PROCESS

Wave of neuronal excitation
-->. Waves of cortical spreading depression
--> Blood vessels dilate & constrict

= Release of K+ & Glutamate --> CSD

*PET shows dec CBF to brain areas involved in migraine

*MEDS for serotonin receptors tx headaches

50% migraine pts = FAMILY HX
HEADACHES
- SYMTOMATIC VS ESSENTIAL
LOOK AT THE TABLE!
MIGRAINE HEADACHES

- ABORTIVE TX
1. OTC: aspirin, tylenol, NSAIDs
- also used to tension type

2. CAFFEINE: CNS stimulant that vasoconstricts
- assc'd with rebound headaches

3. Triptans = 5HT agonists
- contraindicated in CAD & uncontrolled HTN
- Frovatriptan: preventive; used for menstrual migraines

4. IV DA-blockers
- antiemetics: Metoclopramide & Prochlorperazine

5. Narcotics: used in preggers w/ migraine
MIGRAINE HEADACHES

- PREVENTIVE TX
1. TRICYCLIC ANTIDEPRESSANTS
- block NE & 5HT reuptake
- SEs: confusion & urinary retention
- esp. Nortriptyline: great SE profile

2. Beta-blockers: propranolol
- Beta1-R: blocks NE release
- inhibits Locus ceruelus firing - some effects on 5HT-R
- AVOID in pts w/ asthma & depression

3. Anti-convulsants
- Topiramate (topamax): #1 megraine prevention
(also causes wt. loss)
- other SEs: numbness, tingle, kidney stones, confusion, behavior change, word finding difficulty
- Valproate is other option


4. BOTOX: expensive!
- more effecitve in chronic daily headache
Categories of myelin diseases
1. DE-myelinating (myelinoclastic)
- primary destruction of myelin (MS)
- primary destruction of OG cell (PML)
- primary destruction of axon (infarct or trauma)

2. DYS-myelinating (leukodystrophies)
PERIVENOUS ENCEPHALOMYELITIS (PEM)

aka postinfectious/postvaccinal encephalomyelitis
CNS demyelinating diseases that are PRECEDED BY AN INFXN
- but the infectious agent is gone by the time of demyelination

1. Infxn precedes pathology
2. cellular immune response
3. lesions are perivenous
4. demyelination
PEM

- ADEM
- AHLE
Acute disseminated encephalomyelitis (ADEM)
- Viral infxns (MMR)

Acute hemorrhagic leukoencephalitis (ahle)
- systemic viral infxn or respt infxn (m. penumoniae)

** difference is severity/mortality: AHLE IS FATAL**
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

- causes
- histo
- viruses


**IMMUNOCOMPROMISED***
SLOW viral infxn in immunodef pt. (lymphoma, AIDS, long term steroids)
- gray matter lesions also possible
- virus grows in OG cells

Histo:
- focal loss of myelin
- big OG nuclei with viral inclusions
- Atypical, reactive astrocytes
- foamy macros

POLYOMA VIRUSES:
- JCV
- bk
-sv40
LEUKODYSTROPHIES
DYSMYELINATING DISEASES (defects in formation or remodeling)
- genetic enzymopathies
- diseases of childhood

**mental retardation + neuro problems = most common finding **

- U FIBERS ARE SPARED (association fibers connecting gyri neighbors)
- PNS myelin MAY be involved
METACHROMATIC LEUKODYSTROPHY (MLD)

- clinical
- mechanism
- genetic
Prog. Motor disability & psychosis / behavioral problems in adulthood

**CNS & PNS MYELIN INVOLVED**

- Lysosomal disorder: Aryl sulfatase A deficiency
- Chr 22 recessive
- Metachromatic macros & inclusions in white matter = red macros

**no seizures **
GLOBOID LUEKODYSTROPHY
(GLD)
AKA KRABBE'S DISEASE
- Developmental fail
- tonic spasms & myoclonic jerks
- GAIT DISORDER
- progressive spasticity
- VISUAL disturbances
- MICROcephaly

- Lysosomal disorder: Galactocerebroside-beta-galactosidase deficiency
- chr 14 recessive: 14q31

- multinucleated, globoid macros with tubular inclusions in white matter
- severe diffuse dysmyelination
- severe reactive astrocytosis
- MICROCEPHALY
ADRENAL LEUKODYSTROPHY
(ALD)

"Lorenzo's oil"

BOARDS - NOT CAO

- adult onset type: adrenal myeloneuropathy (more SC damage instead of adrenal problems)
X-linked
- boys
- adrenal glands & testis
- storage of very LCFAs

CLINICAL: FTT, seizures, retinal degen, hearing & educational problems, clumsiness, schizo, dementia

- peroxisomal defect
- diffuse demyelination (esp posterior cerebellum)
- perivascular lymphocytic infiltration & foamy macros

** intracytoplasmic crystalloid structures in adrenal cortex & testis **
ALEXANDER'S DISEASE

dON'T NEED TO KNOW!
- macro-cephaly
- seizures, spasticity
- psych problems & dementia

- rosenthal fibers = excessive GFAP + gliosis
- osmophilic densities
VINCRISTINE

- type of PN
- type of drug
- mechanism
CHEMOTHERAPY DRUG (which are #1 cause of drug-induced PN)

MECH:
Inhibits microtubule polymerization & interferes with axonal transport

PN TYPE:
- stocking glove dist. --> profound distal weakness (esp foot drop)

**symptoms of PN may WORSEN for several months after you d/c vincristine**

n biopsy: intra-axonal filaments
WHAT SURROUND MUSCLE BUNDLES vs FASCICLES vs. FIBERS??
What surrounds muscle bundles?
Epimysium

What surrounds muscle fascicles?
Perimysium

What surrounds a muscle fiber?
endomysium
WHAT IS ALS & WHAT KIND OF pathologic changes would you expect to see?
Amyotrophic lateral sclerosis
- LMN problem

muscle biopsy shows NEUROGENIC CHANGES (not myopathic)
- Cn-HATR
TYPE 1 mm vs. TYPE 2 mm

(type 1 mnemonic)
What is the mnemonic for Type 1 muscles?
One Slow Red Fat Ox:
Type 1
Slow-twitch, sustained force
Red - high Mb
Wide z bands, abundant fat
Oxidative

*type 2 is opposite, fast, white, glycolytic, abundant glycogen, scant fat, & few mitos
5 types of neurogenic pathologic skeletal muscle reactions?
"Cn-HATR" since a neurogenic pathologic reaction is Central Nervous (Cn) hater.

1. Central nuclei (normally @ edges)

2. Hypertrophy (grouped)

3. Atrophy (grouped)

4. Target fibers (re-innervation)

5. Ring fibers (myotonic dystrophy)

+ Angular fibers = Stain darkly; deinnervation
**reinnervation: grouped type 1 or type 2 fibers (evangelize?)
What are the 5 types of myopathic pathologic reactions of skeletal muscle?
1. Myophagocytosis = Necrosis
(Multiple nuclei 2' macros)

2. Inflammation - Infiltration of WBCs

3. Necrosis

4. Fiber-splitting

5. Central cores

+ more hypertrophy
What are the acquired neurogenic disorders?

Neurogenic --> 2' involvement of muscle
(Denervation atrophy)

Genetic = Spinal muscular atrophies (SMA)
“TINI”
Trauma
Inflammatory --> Guillan Barre
Neoplasms
Iatrogenic (Vincristine, drugs, surgery)
+ Endocrine --> Diabetes

**Type II disuse atrophy: Assc'd with steroid use

MECH: Damaged peripheral nerves, axonal degen, and/or demylination
- Re-innervation can be seen after neurogenic changes
--> Would change the muscle fiber type --> Mosaicism of fiber types
What are the acquired myopathic disorders?

1' disease of muscles
Polymyositis**
Inclusion Body Myositis**
Dermatomyositis
Infections

It's a "PIDI" to acquire a myopathic disorder
What are the category and examples of NMJ disorders?
Neurogenic:
Myasthenia Gravis
Lambert-Eaton (paraneoplastic)
What are the genetically determined myopathic disorders?
X-linked:
Duchenne/Becker MD


Autosomal:
Congenital MD
Limb-Girdle type
Myotonic dystrophy
What is "floppy baby"?
Spinal Muscular Atrophy (infantile motor neuron disease);
Abnormality of the anterior horn cells
MOST SEVERE SMA TYPE? genetics?

**SMA is like ALS for kids
- Progressive LMN degeneration
SMA type 1: Werdnig-Hoffman dz
= Floppy baby @ birth
- dies w/in 3 years

CHROM 5: deletion of SMN OR NAIP gene
SMA

- PATHOLOGY
1. grouped atrophy of fibers = CLASSIC
(1 neuron feeds a motor unit)

2. Angular shrunken fibers (panfascicular)

3. Rare hypertrophic fibers (compensatory)
What are the early pathologic signs of DMD/BMD?

and what about late?
EARLY:

Myopathic changes (necrosis, myophagocytosis, etc)
Variation in fiber size, splitting, internal nuclei
Raised serum CK (myolysis)


LATE:
Endomysial CT and fibrosis
What is the pathogenesis of DMD/BMD?
Dystrophin on Xp21 encoding Dystrophin
DMD - no protein
BMD - milder deficiency of protein

DMD = Doesn't Make Dystrophin
BMD = Badly Made Dystrophin
Course/Onset of DMD/BMD
NORMAL AT BIRTH
- DMD onset = 5yo; pelvic girdle 1st
- pseudo hypertrophy of calf
- die by early 20s

**BMD is way milder & more normal life span**
What is the pathogenesis of Limb-Girdle dystrophy?
Mutation in sarcoglycan complex

AUTOSOMAL
What is the pathogenesis of Myotonic Dystrophy?

- basic presentation
Type 1: Chr 19q13.2-13.3
= CTG rpts

Type 2: Chr 3

AUTOSOMAL***

Myotonia, cataracts, heart problems, frontal balding
What is the pathogenesis of congenital dystrophies?
Abnormalities of merosin gene expression
(Merosin-negative)

autosomal (recessive)
- neonatal hypotnia & delayed milestones
ION CHANNEL MYOPATHIES

- hyperkalemic = hyper/myotonia
- Hypokalemia = hypotnia
- Normokalemic

- genetics & pathology

*not on exams i don't think*
AUTOSOMAL dominant
- intermyofibril vacuoles & electrolyte abnormalities
What triggers malignant hyperthermia?

results?
What triggers malignant hyperthermia?
- Halogenated anesthetic agents

What is the result of malignant hyperthermia?
- Tachycardia, hyperpyrexia
(Hypermetabolic state)

*multiple genes are involved - Ca channel & Ryanodine

*know for boards not cao
What is the characteristic pathology of mitochondrial myopathy?

- transmission?
“ragged red fibers”

eg, MERFF:
Myoclonic Epilepsy with Ragged Red Fibers


maternal transmission usually
INFLAMMATORY MYOPATHIES

presentation?
muscle biopsy?
mechanism?

- usually females (except IBM = males)
PROXIMAL MUSCLE WEAKNESS
(except IBM)


1. Non-suppurative inflammation
2. Lymphocytic INFILTRATION in endomysium, perimysium
3. Muscle necrosis
4. Myophagocytosis
5. Regenerative activity

(Myopathic changes)

**AUTOIMMUNE PROCESS**
POLYMYOSITIS

- CAUSE
- AGEGROUP
- HISTO
CAUSE: CD8+ T cells & macros destroy muscle
- trigger unknown

SEE: lymphocytic infiltration & myophagocytosis
- also myonecrosis: ^ nuclei (macrophages)

Age group > 20 yo (doesn't affect kids like DM does)

Triggers
DERMATOMYOSITIS (DM)

- ^ risk of?
- age groups
- cause
- presentation
- path
INCREASED LUNG CA RISK

CAUSE:
CD4+ T cells, B cells, IgG, IgM, MAC attack myocytes
= Blood vessel disease of skeletal muscle
(Microangiopathy & Atrophy)
age groups: (PM does NOT affect kids)
- Kids: Perifascicular atrophy
- Adults: Active myositis

LOOKS: racoon eyes (violet upper eyelids), face, trunk rash
What is shown on muscle biopsy of Inclusion Body Myositis (IBM)?

NOT ON EXAM
Rimmed vacuoles with inclusions

OUTLIER of inflamm myopathies bc affects older MEN more & has more DISTAL mm weakness
What type of muscle fiber does steroid-induced myopathy cause atrophy of?
Type 2


**Type 2 atrophy (disuse atrophy) also seen in denervation atrophy
= neurogenic atrophy
What are the pathologic features of Myasthenia Gravis?

- muscle biopsy
- tests
- increased risk/assc'd findings
- presentation?

**Congenital MG has NO ACh-R Abs
Near-normal light microscopic changes
Simplified post-synaptic membrane
Reduced number of ACh-Receptors
Increased circulation of ACh Receptor antibodies

+ Tensilon test & Decremental response on nerve conduction study
^ Risk of thymus issues
- present w/ extra-ocular muscle problems (diplopia, droopy eyelid)
With what is Lambert-Eaton most associated with?

- also mechanism?
- tests?
Small cell carcinoma of the lung

- Pre-synaptic Ca2+ channel Abs
- NEGative tensilon test & incremental response on nerve conduction study
- Proximal muscle weakness
TOXIC MYOPATHIES

- cuases
1. Thyrotoxic myopathy
2. Ethanol myopathy

*also drug induced - Steroids (type 2 atrophy), statins, AZT, chloroquine
What are two types of immune-mediated neuropathies?
AIDP (Guillain-Barre Syndrome)
CIDP (Chronic Inflammatory Demyelinating Polyradiculoneuropathy)
LMN PATHOLOGY

- segmental demyelination vs axonal degeneration
1. Segmental: individual segments of myelin lost
- NO DAMAGE TO AXON

2. Axonal degen:
- Axon damage --> secondary demyelination

3. Myopathy (denervation atrophy)
TYPES OF PERIPHERAL NEUROPATHIES

- Inflamm / Immune -mediated
- Infectious
- Hereditary
- Acquired
- Traumatic
INFLAMM
1. AIDP (GBS): ascending weakness; PNS demyelination
2. CIDP: polyradiculoneruopathy

Infectious: Leprosy, diphtheria, chickenpox

Hereditary:
- onion bulb formation (segmental demyel & remyel)
- Charcot-Marie Tooth

ACQUIRED
- Diabetes, Uremia, Thiamin def, b12 def
- CA
- Drugs, chemicals

TRAUMATIC:
- laceration
- Carpal Tunnel syndrome
What is the most common acquired metabolic neuropathy?
Neuropathy from adult-onset diabetes mellitus
ACUTE INFLAMM DEMEYLINATING POLYNEUROATPHY
(AIDP; GUILLAIN BARRE SYNDROME)

- PRESENTATION
- TX
- CAUSES
Preceded by flu-like illness
(C. jejuni infxn?)

Present w/ Ascending weakness that starts at distal limbs
- Also ANS: heart & Hypotension
- CSF: ^ pressure, ^ protein, decreased cells

PT NEEDS RESPIRATORY SUPPORT

cause: PNS demyelination
INFECTIOUS POLYNEUROPATHY

- MECHANISM
VASCULITIS

- WBC infiltration of blood vessels --> granulomas of nn --> neuropathy
NEUROPATH OF MEDICAL DISEASES
READ YOUR EFFING HANDOUT IN WORD
Superficial injuries & severity of the intracranial injury

- how are they related?
THEY'RE NOT RELATED

DON'T JUDGE A BOOK/SCALP INJURY BY ITS COVER
- the worst cases may have no external presentation
What distinguishes a laceration from an incision?
Lacerations have "tissue bridges" or areas where the underlying tissue did not tear.
types of scalp wounds
1. Contusion / Hemorrhage

2. Abrasian

3. laceration

4. INCISION
WHAT FACTOR OF HEAD TRAUMA CORRELATES W/ THE SEVERITY OF INTRACRANIAL INJURY?
THE LOCATION OF OF THE INJURY
- where was the force applied?
- where did the hemorrhage or bleeding occur?
- where was the infection?
Are most skull fractures associated with severe intracranial injuries?
No, about 1/4th of fatal head injuries have no fractures. As with the scalp injuries (contusion, laceration, etc.), the severity of the intracranial injuries depends on where the force was applied.
Linear Fractures: definition and clinical significance.

- types
Types:
- closed ("simple")
- break in the overlying skin ("compound")

- Are significant normally because they indicate that trauma has occurred at a site.

Sometimes they are of more significance b/c they cross a superficial artery (like the middle meningeal)
- or open a space b/w two cavities and thus serve as a portal for infection.
Comminuted Fractures: definition and clinical significance.
- Skull is broken into multiple fragments.

- Force may be the same as a linear fracture but the effects are different. Causes more intracranial injury than linear fractures b/c the fracture can be depressed.
Stellate Fracture: definition and clinical significance.
- Multiple fracture lines radiate from a single focus.

- More commonly found in the curved areas of the skull. More commonly caused by being struck by a force (hammer) over a small area of contact. Can be confused with multiple blow trauma (false + for child abuse by radiologist)
Diastatic Fracture: definition and clinical significance.
- Fractures that extend along a suture.

- Commonly occur before complete closure of the suture.
(kids - child abuse?)
Depressed Fracture: definition and clinical significance.
- One edge of the fracture is at least 1/2 the thickness of the skull below the original contour.

- Downward edges can cause significant lacerations and intracranial injuries.
What is the classic presentation of an epidural hematoma?

epidural: bw skull & dura
- diploic vein lives here too
1. Blow to the head
2. Rendered unconscious
3. Regain consciousness
4. Short period of alertness
5. SUDDENLY develops evidence of INCREASE intracranial pressure.
- Headache, Nausea, Vomiting
6. Progresses slowly then rapidly to coma, if not treated.
What is the most common mechanism of epidural hematoma formation?

- what type of blood?

**Incidence decreases w/ age bc dura adheres better to skull as you get older
- Usually due to a LINEAR FRACTURE through the TEMPORAL BONE, which passes across the MIDDLE MENINGEAL ARTERY and associated veins, lacerating them.

*Thin Temporal

Brain is not INITIALLY injured
- 2' injury from increased ICP

ARTERIAL BLOOD
(subdural = venous)
EPIDURAL HEMATOMA

- GROSS appearance & changes seen in the handout pictures
1. Brain edema (greater on hematoma side)

2. Midline shift

3. Cingulate and uncale herniations

4. Duret hemorrhage

5. Cortical infarcts

6. Dusky discoloration = respirator brain

THERE IS NO BLOOD IN THE GYRI
(but there was major increased ICP)
SUBDURAL HEMATOMAS

- classic presentation
- mC pattern of injury
- normal location?
NO CLASSIC PRESENTATION - super variable

MC PATTERN:
1. rotary motion of brain relative to skull
- usually associated with other cerebral injury (like atrophy)
2. TEAR bridging veins
(bw arachnoid & superior sagittal sinu)
- location is usually over dorso-lateral brain (UL bc falx cerebri stops it)

VENOUS BLOOD
(epidural hematoma is arterial)
- slower increase in volume
Subdural Hematoma: Arterial or Venous Bleed?

- what causes increase in size of hematoma?
VENOUS.
- the increase in volume is usually SLOWER than an Epidural Hematoma.

- Sequelae is a pattern of bleeding, stabilization, healing, bleeding -> increase size of bleed.

- Note: some believe that lysis of RBCs within the bleed and subsequent osmotic shift of fluid into the bleed is what causes the increase in size of the hematoma.
How do subdural hematomas heal?

acute hematoma:
Formation of granulation tissue from the dura -> Neomembrane formation -> neomembrane (outer membrane thickness > inner membrane) extends from the edges of the hematoma -> cyst formation.

- Progression can be used to determine when the injury occurred, though this method determines a range and not a specific time like that seen in CSI.
What is the most common cause of subarachnoid hemmhorage?
TRAUMA

2nd MC cause is...ruptured Berry Aneurysm
(esp @ COW)

**Sudden ^^ in Systolic BP can rupture a weak blood vessel**
SUBDURAL HEMORRHAGE

- gross appearance from handout pic
1. NO blood in gyri still

2. Falx Cerebri: keeps the hematoma Unilateral

3. Compressed brain + Midlline shift
--> Uncal & cingulate herniation

4. EDEMA

5. Fibrous membrane
- cyst filled with blood?
How can a pathologist tell the difference b/w a contusion and an infarct in the brain?
Contusions primarily affect the crowns of the gyri, are wedge-shaped, and SPARE THE SULCI.

Infarcts more commonly AFFECT THE DEEPER PORTIONS OF THE SULCI with less involvement or SPARING THE CROWNS OF THE GYRI.

Learn one, know the other is the exact opposite.
Blunt Force Lesion Definitions: Coup
An intracranial lesion BENEATH the site of IMPACT.

- Injury usually due to an actual collision of brain and interior skull structures. MC is to see frontal brain injuries in a Coup lesion due to the fact that the anterior skull has many fixed projections (cribiform plate, etc.) that can cause lacerations when the brain slides over these areas.
difference bw subarachnoid hemorrhage & basilar injury from distinct INJURY to blood vessels
Distinct injury to blood vessels
- usually in vertebral arteries
- follow blood here

*lesions usually due to hyperextension or hyperrotation
Blunt Force Lesion Definitions: Contrecoup
An injury that occurs OPPOSITE the site of IMPACT.

- Injury is usually due to rotational forces that are occurring to a brain being moved AWAY from the skull. Larger impacts actually cause a negative pressure gradient to form and subsequent bubble formation, which is also damaging to the brain. Coup and Contracoup injuries most frequently occur anteriorly, however.

**most occipital impacts --> contrecoup injuries
Blunt Force Lesion Definitions: Intermediary Coup
Injuries that occur ALONG THE LINE OF FORCE (in b/w one side of the skull and the other)

- Thought is that brain may be striking stationary structures such as the falx, tentorium, or foramina, that are more centrally located.
What is the most likely lesion you will see in an occipital impact?
Contracoup: 90%

Coup: 17%

Percentages must take into account that some pts get both contracoup and coup injuries at the same time. Since the force hits the back of the head, contracoup injuries are occurring to the anterior brain, WHICH IS THE MC SITE FOR DRAIN BAMAGE!!!
What is the most likely lesion you will see in an frontal impact?
Coup: 93%

Contracoup: 21%

Majority of brain injuries from blunt force trauma hit the anterior brain. MORE PROOF!
What is the most likely lesion you will see in a Lateral impact?
Contracoup: 60%

Coup: 50%

What type of injury should you see more of here...intermediary coup methinks.
Predict what injuries you will see in a stationary but moveable head struck by a moving object (watermelon to the face)?
Coup injuries more common (watermelon hits skull, skull moves backwards, brain hovers in CSF, skull strikes brain).
Predict what injuries you will see in a stationary and supported (unmoveable) head struck by a moving object?
Most of the energy is transmitted to the SCALP and SKULL and not the brain (nothing hits the brain b/c the skull doesn't move). Thus, SCALP and SKULL INJURIES ARE MORE COMMON IN THIS INCIDENT.
Define concussion.

- What is always present in a concussion?
- When should you suspect a severe cerebral injury?
- Can you see the injuries histiologically?
Def: Temporary, reversible neurological deficiency caused by trauma which results in immediate, temporary loss of consciousness.

always present: RETROGRADE AND POST-TRAUMATIC AMNESIA

BE CONCERNED IF: symptoms persist for >24 hours.

NO HISTO changes only see non-specific signs of injury
What are the general cerebral consequences of trauma?
Brain swelling secondary to EDEMA or HYPEREMIA (increased blood flow) in and around the site of injury.
What are the vascular consequences of cerebral trauma?
Vessels may be contused, lacerated, or have torn intimas. This increases risk for thrombosis, aneurysm formation, or AV malformation upon healing.
Which cranial nerve is most commonly affected by brain injury?
CN III (severe ptosis, mydriasis, downward and outward pointing eye).
What are the systemic consequences of cerebral trauma?
More common effects include pulmonary congestion, vagal effects in the heart (increased???), and GI ulceration.
What are the delayed CNS effects of cerebral trauma?

- subarachnoid hemorrhage
- contusions & intracerebral hemorrhages
Healing of intracranial lesions in subarrachnoid hemorrhages may block CSF flow, leading to communicating hydrocephalus

**arachnoid granulations are all effed up**


Contusions and intracerebral hemorrhages -> focal gliosis, seizures.
What type of brain trauma can occur from a broken femur?
Fat emboli can travel from the site of trauma to the brain causing diffuse PETECHIAL hemorrhages in the WHITE MATTER. Decreasing cerebral function may ensue.
Where do spinal injuries most commonly occur?
Cervical or Lumbar spine (thoracic is supported by the ribs).
NEURODEGENERATIVE DISEASES

- general characteristics
- broad categories

*neurodegenerative disorder = loss/abnormal activity of functionally related groups of neurons
GENERAL CHARACTERISTICS:
1. Mostly old folk (rarely young pts)

2. Mostly PNS

3. Clinical manifestations vary depending on specific neuron population lost
- cortical --> dementia
- Basal ganglia --> movement
- Cerebellar --> ataxia
- Motor --> weakness


BROAD categories:
1. Movement disorders
- Involuntary ( PD, huntington's)
- Voluntary (ALS)
- Spinocerebellar (Friedrich Ataxia)

2. Cognitive / Dementia
- Alzheimer's
- Lewy Body
- Pick's disease
- Prion
KNOWN etiologies associated with neurodegenerative diseases

hint: alzheimer's
APP gene on Chr 21 (familial alzheimer disease)

also:
- trinucleotide rpts (huntington's
- Virus (influenza)
- toxins (MPTP)
- oxidative stress

lots others
NEURODEGENERATIVE DISEASES & LOCATIONS

- huntington's
- Alzheimer's
- Parkinson's
- Friedreich ataxia
- Amyotrophic lateral sclerosis
1. HUNTINGTON:
caudate nucelus & frontal cortex

2. ALZHEIMER:
frontal & hippocampal cortex

3. PARKINSON:
Substantia nigra

4. FRIEDREICH ATAXIA:
ONLY SC - posterior & lateral columns

5. ALS:
- Lateral columns of SC
negative vs. positive symptoms in involuntary/extrapyramidal type movement disorders

(neurodeg dz)
POSITIVE SYMPTOMS
- excess of involuntary movements

NEGATIVE symptoms
- reduction of voluntary movements
STRUCTURAL basis of involuntary movement disorders
(pathogenesis)
Degenerative changes in NIGROSTRIATAL PATHWAYS
(brain stem & basal ganglia)
- normally modulate feedback from thalamus to motor cortex

**Accompanied by disturbnace in specific NTs (DA or GABA, etc)
PARKINSONISM

- clinical syndrome/symptoms
- disorders in this group
Negative & Positive symptoms
(TRAP - tremor, rigid, akinesia, postural instability)

1. Tremor
2. Rigidity
3. Bradykinesia
4. Forward propulsion
5. Pill-rolling movements
6. Mask-like facies

** Idiopathic PD
** Post-encephalitic Parkinsonism

also: progressive supranuclear palsy, cortico-basal degen, multiple system atrophy
PARKINSON DISEASE (IDOPATHIC PD, PARALYSIS AGITANS)

- ONSET
- POPULATION
- Pathogenesis/genetics
(Acute PD, familial PD
SPORADIC disease in OLDER people

TRAP symptoms

PATHOGENESIS
- NOT ENOUGH DOPAMINE
- acute PD = MPTP toxin (methylpheynltetrahydropyridine)
- Familial = Alpha-synuclein
IDIOPATHIC PD

PATH & HISTO FINDINGS
PATH:
- BS & basal ganglia
- Pallor of Substantia nigra in midbrain and/or Locus Ceruleus in Pons

HISTO:
- ATROPHY of substantia nigra/locus ceruleus
- Reduced pigmentation
- LEWY BODIES!!! in these areas (eosinophilic inclusions)
- Loss of dopa neurons going to striatum
POST-ENCEPHALITIC PARKINSONISM

(von economo's disease)

- setting?
Seen in aftermath of pan-influenza epidemic of 1914-19
(spanish influenza?)

probalby NOT on the test bc it has almost vanished ever since
HUNTINGTON'S DISEASE

- clinical features
- pathogenesis
onset: 20-40 yrs
- Involuntary choreiform/dancey movements
- Psych symtpoms (dementia & psychosis)
- Can --> Parkinson's
- Die in 10-15 yrs

PATHOGENESIS: AUTO DOM
- Chromsome 4p: Trinucleotide rpts --> Polyglutamine rpts
--> Huntingtin protein aggregation & intraNUClear inclusions

**Anticipation: Increasing severity & earlier onset w/ successive generations
HUNTINGTON'S DISEASE

- PATHOLOGY
Anatmoc focus: Basal ganglia (caudate & putamen)

Gross:
BL Caudate Atrophy
**Lateral aspect of lateral ventricles become CONCAVE (normal = convex)

MICROSCOPIC:
- Atrophy of caudate
- LOSS of medicum sized spiny neurons
(normally utilize GABA
- INTRANUCLEAR INCLUSIONS
AMYOTROPHIC LATERAL SCLEROSIS

(amyotrophic --> flaccid)
(Lateral --> lateral columns)

- clinical features & onset
- pathology
AFFECTS ALL AGE GROUPS

CLINICAL: UMN & LMN affected
- Asymm weakness first
- LMN problem: Atrophy & fasciculation
- UMN prob: Weakness & spasticity (babinski)

PATH:
1. Apoptosis of AHC & cranial nerve nuclei
**EXCEPT EYE MOVEMENT** - SPARED

2. Atrophy of anterior spinal nerve roots

3. Neurogenic atrophy of skeletal muscles
(Cn-HATR)

4. UMN: Betz cells in motor cortex atrophy
--> CST atrophy
DEGENERATIVE DISORDERS AFFECTING THE SPINAL CORD

- LOCATIONS OF
a. tabes dorsales
b. FA
c. als
d. Subacute combined degeneration
A. TABES DORSALIS
Meningovascular syphilis
--> Fibrosis of meninges
--> Pinches/kills dorsal roots going to Dorsal Columns & Clarke's nucleus
= Stomping giat

B. Freidreich ataxis:
1. Dorsal roots (afferent) --> Posterior columns & CLarke's
2. Desc UMN to CST
3. Ascending Spinocerebellar tracts

C. ALS
1. UMN to CST
2. AHC

D. SACD
1. Dorsal Columns
2. Spinocerebellar Tracts
3. AHC
SPINOCEREBELLAR DEGENERATION

- FEATURES
- EXAMPLE
- CLNICAL PRESENTATION
Affects:
1. Cerebellar Cortex: Ataxia & balance messed up
2. Spinal Cord:
- Spinocerebellar tracts
- Dorsal columns/Clarke's nucleus
- UMN: pyramidal nn. --> spastic
3. PNS: Dorsal roots
Sensorimotor periph neuropathy

*Example = Friedreich's ataxia
- GAA rpts on Chromsome 9p13 (frataxin gene)

NO DEMENTIA OR COGNITIVE CHANGES BC CEREBRUM IS NOT INVOLVED
DEMENTIA VS. MENTAL RETARDATIONS


2 common & 1 uncommon degenerative cause of dementia
Dementia: Progressive deterioration of higher cognitive fxns
- you're losing previously attained knowledge

Mental retardation: NEVER achieve certain milestones

(Delirum = temporary; not relentlessly progressive)

Common causes: Alzheimers (65%- frontal & hippocampus) & Dementia w/ Lewy bodies

Uncommon cuase: Pick's dz (5%) = lobar sclerosis
ALZHEIMER'S DISEASE

- CLINICAL & PATHOGENESIS
MCC of dementia
- onset: 50-65 yo

CLINICAL FEATURES:
- Progressive decline
- LATE: psych,mood changes & mute, immobile

PATHOGENESIS:
1. Early onset Familial AD
- Chr 21 APP (amyloid precurosr protein)
- Down's syndrome: < 45yo
ALZHEIMER'S DISEASE

- PATHOLOGY
ANATOMIC FOCUS:
1st: Hippocampus & temporal cortex
Later: Neocortex, deep grey, & BS

+ Cerebral aTROPHY
+ Senile Plaques
a.) A beta-amyloid protein = extracellular
b.) Tau Neurofibrillary Tangles = intracellular
- correlate w/ clinical dementia

(also see granulovacuolar degen & amyloid angiopathy)

**Aggregates = neurotoxic
PICK'S DISEASE

(FRONTAL LOBE DEMENTIAS)
Continuum of overlapping pathologic abnormalities

**Selective areas of lobar atrophy

**Do a silver stain to see pick bodies*8
PRIMARY VS METASTATIC TUMORS
PRIMARY:
- arise w/in CNS or coverings
- Low or High
- DO NOT METASTASIZE (exceptions)
- MALIGNANT behavior even if benign bc it's inside the skull


METASTATIC
- Always HIGH grade
- arises outside CNS
- COMMON
TUMORS OF THE NERVOUS SYSTEM

- CNS VS. PNS
--> primary vs. metastatic
PNS:
- Schwannoma
- Neurofibroma
- Neurofibroscarcoma

CNS:
PRIMARY:
1. Neuroepithelial (glioma)
- Astrocytoma
- Oligodendroglioma
- Epndymoma
2. Embryonal
3. Meningioma
4. Primary Lymphoma
(also germinoma, choroid plexus papilloma, colloid cyst)

METASTATIC
1. Lymphoma
2. Breast, GI, Lung (blood borne)

** Carcinomatous meningitis?
FACTORS TO CONSIDER IN MAKING UR DX
1. Anatomic Distribution
2. Age of pt
DIFFERENTIATING A BENIGN FROM MALIGNANT GLIAL TUMOR
1. TYPE: histological appearance

2. GRADE: degree of malignancy
- how ugly is it?

3. STAGE: metastasized?
- not important in CNS tumors bc they rarely metastasize
(EXCEPT for MEDULLOBLASTOMAS/PNETs)
MORPHOLOGIC (histologic) CRITERIA FOR GRADING TUMORS
More Important Criteria
1. MITOTIC ACTIVITY
2. NUCLEAR ANAPLASIA (ATYPIA) - how ugly it is
3. VASCULAR PROLIFERATION
4, NECROSIS

Less Important Criteria
- Abnormal Mitotic Figures
- Degree of Phenotypic Differentiation
- Cellular Density and Pleomorphism


**numeric description
**Descriptive = blastoma = HIGH grade
What are gliomas?

- MC types of gliomas?

**nerve tumors are also types of neuroepithelial tumors
What are gliomas?

Gliomas are a sub-category of neuroepithelial tumors. Neuroepithelium is anything derived from the embryological neural tube or its derivatives.

What are the most common histological types of gliomas?
1. Astrocytoma
2. Oligodendroglioma
3. Ependymoma
What is an astrocytoma?
A type of glioma that has...

1. GFAP (Glial Fibrillary Acidic Protein)
- int. filament protein
2. Elongated, broad-based processes with a star-like appearance (exception: gemistocytic astrocytes are large and round/oval)
THE ONLY TUMORS YOU NEED TO REMEMBER SAYS CAO

- DIVIDE THEM BY THE AREAS WHERE THEY ARE
1. Glioma (cerebrum)

2. Meningioma (meninges)

3. Ependymoma (fourth ventricle)
- mostly benign

4. Pontine Glioma

5. Astrocytoma of childhood (cerebellum)

6. Medulloblastoma (vermis of cerebellum)

7. Acoustic Schwannoma

8. Craniopharyngioma: above pituitary
TYPES OF ASTROCYTOMAS

(general)
1. Diffuse: poorly demarcated; diffuse margins

2. Special variants: well-demarcated
- mostly below the tentorium (cerebellar)
- maybe removed totally by sx?
DIFFUSE ASTROCYTOMAS

- what are they ?
- characteristics (originate, prevalence, prognosis)
- classic picture
Low-Grade Astrocytomas
- diffuse infiltration of neuropile
--> low grade always turns into high grade

1. Originates & infiltrates WHITE matter
2. MC POST-childhood astrocytoma (adult)
3. POOR prognosis
- so diffuse; hard to resect/radiate

**Fibrous, germistocytic, & protoplasmic types are all diffuse

CLASSIC picture of diffuse astrocytoma
- swollen temporal lobe (diffuse infiltration)
- hippocampus involved
- NO HEMORRHAGE OR NECROSIS**
ASTROCYTOMA GRADING

- numeric vs descriptive

**grading based on cellular density, nuclear atypia, mitotic index, vascular proliferation, & necrosis**
1. Astrocytoma: Grade 1 & 2

2. Anaplastic Astrocytoma: Grade 3
+ Mitosis, but NO vasc proliferation or necrosis

3. Glioblastoma = Grade 4
UGLIEST
+ mitosis, necrosis, AND vasc. proliferation
most cellular, severest anaplasia & pleomorphism
DIFFUSE ASTROCYTOMAS & AGE OF PT

- ADULTS VS. KIDS
ADULTS:
2/3 supratentorial (cerebrum)
& 2/3 are anaplastic @ dx
**more likely high-grade**

CHILDREN:
2/3 Infratentorial (mostly cerebellar)
- 2/3 low grade @ dx (grade 1 or 2)
LOW-GRADE DIFFUSE ASTROCYTOMA

- BEHAVIOR
- exceptions
Grow SLOWLY
- spread along intact myelinated axons
- do NOT destroy axons or BBB

*Symptoms start when tumor bulk = ^ ICP
(brain stem gliomas are early symptomatic)

2 EXCEPTIONS to slow growth/symptom onset
1. Tumor associated intracranial HEMORRHAGE
2. Invasion of grey matter --> SEIZURES
HIGH GRADE DIFFUSE ASTROCYTOMAS

- behavior
1. Grow faster
2. Wide variety of symptoms (depending on location)

**majority of glioblastoma originate from low-grade diffuse astrocytomas**
= ticking time bomb
(by the time it becomes malignant, it's already infiltrated a huge area of the brain)
GLIOBLASTOMA

- what is it?
- what does it look like (and on ct?)
HIGHEST GRADE ASTROCYTOMA
- ugliest


1. Ugly, highly anaplastic cells
2. Necrosis (jigsaw shapes)
3. Vascular Tufts = glomeruli-ish
4. Ring-like lesions on CT ??

**butterfly glioblastoma**
- crosses the corpus callosum
SPECIAL VARIANT OF ASTROCYTOMA THAT CAO WILL TEST ON

- characteristics/differences from a regular low grade astrocytoma
- histo features
- neuroanatomical sites
hint: ben carson
1. Low grade
2. Well-demarcated margins (NOT diffuse)
3. MUCH better prognosis =)

PILOCYTIC ASTROCYTOMA

1. Bipolar astrocytes w/ 2 long hair-like processes
- degenerated vacuolated cells
2. Rosenthal fibers (eosinophilic sausagey extracellular stuff)
3. Lack of overt mitotic activity

**YOUNG PATIENTS**

MOST ARE IN CEREBELLUM
- not in cortex
PILOCYSTIC ASTROCYTOMA

- where is it usually?
- how does it grow?
Special variant of low-grade astrocytoma

Childhood tumor mostly in CEREBELLUM

1. As tumor grows it degenerates
2. Forms small cysts
3. Become confluent & form larger cysts --> necrotic
4. Cyst wall beocmes gliotic scar w/ only nidus/rest of viable tumor
**Total removal of NIDUS stops growth of tumor
OLIGODENDROGLIOMA

- what is it?
- what does it look like?
- where do you usually find it?
1. Type of glioma (neuroepithelial tumor)

2. Round dark nuclei (size of lymphocyte) surrounded by clear cytoplasm
- looks like a NORMAL OG cell

3. Found in WHITE matter (duh)
- tendency to INFILTRATE gray matter (more gross infiltration than astrocytoma)
--> SEIZURES
OLIGODENDROGLIOMA

- MICROSCOPIC FEATURES
1. Sheets of clear cells ~ Honeycomb / fried egg

2. Calcifications

3. Spontaneous bleeding (2' neovascularization)

4. Chicken wire patten from capillaries
EPENDYMOMA

- prevalence
- site
- results
- special features
3RD MC glial tumor
- originates in periventricular area (site of normal ependyma)
- esp 4th ventricle**

**Forms epndymal ROSETTES**
= perivascular pseudorosette (central blood vessel)
- look like precursors of normal ependyma

--> NONCOMMUNICATING HYDROCEPHALUS
MEDULLOBLASTOMA
(primary cerebellar PNET)

- what is it?
- site
- characteristics
- grade


**PNET = primitive neuroectodermal tumor**
- medulloblastomas that occur elsewhere in the brain
Embryonal tumor; undifferentiatied w/o any phenotypic expression
- HIGH GRADE (blastoma) that originates from brain stem

CHARACTERISTICS:
1. Cerebellar tumor (vermis
- can grow into 4th ventricle
2. Smal blue cells!
- also in Rb & small cell CA of lung
- High nuclear:cytoplasmic ratio
3. Anaplastic nuclei
4. TONS of mitotic figures
5. Metastasizes along SC
(LOVES to grow in Subarachnoid space --> compress SC)


ALWAYS GRADE 4 DAMMIT
- but quite txable
OTHER PRIMARY CNS TUMORS

- germinoma
- choroid plexus papilloma
- Colloid cyst
1. GERMINOMA: germ cell tumors CAN occur in the brain
- usu midline

2. Choroid plexus papilloma
- benign, intraventricular, hypersecretion of CSF
= communicating hydrocephalus

3. COLLOID CYST: tumor like
** CHANGE IN POSITION CAUSING ^ ICP **
- located in lateral ventricle near foramen of Munro
- acts like ball valve: pt. leans forward & makes obstructive, noncommunicating hydrocephalus

-
PNS NERVE SHEATH TUMORS

- schwannoma vs. neurofibroma
Schwannoma does NOT infiltrate the nerve
- it's just pushing on it & causing dysfxn
- Can be resected --> restore fxn
- ONLY schwann cells (no fibroblasts)
- they NEVER progress to neurofibrosarcoma


NEUROFIBROMA diffusely infiltrates nerve
- need to sacrifice the nerve to remove it
- find Schwann cells AND fibroblasts
- HIGH risk of progressive to neurofibrosarcoma
SCHWANNOMAS

- biphasic histological pattern
- acoustic neuroma
ANTONI A: NUCLEAR PALLISADING
- stacks of parallel, elongated nuclei
KNOW THIS COLD

ANTONI B: Macro/microvesicular degeneration/necrosis


*Acoustic neuroma = schwannoma of VESTIBULAR portion of CN8

DOES NOT INFILTRATE THE NERVE
NEUROFIBROMA

- MC type
- what is it?
- histo features
MC is Solitary types
- benign nerve sheath tumor
- associated w/ neurofibromatosis (neurocutaneous syn; Von Recklinhausen dz)
+ Cafe-au-lait spots (hyperpig'd spots)

HISTO:
- >1 elongated cell type (schwann, fibroblasts)
- loose matrix w/ wavy spindle cells


*HIGH CHANCE OF TURNING INTO NEUROFIBROSARCOMA
- esp w/ radiation
MALIGNANT PERIPHERAL NERVE SHEATH TUMOR

- neurofibrosarcoma & malignant schwannoma

characteristics?
1. Extremely infiltrative
2. Can metastasize
3. Assc'd w/ Neurofibromatosis
4. Can result from prior irradiation (increased risk)
MENINGIOMA

- WHAT IS IT?
- HOW IT HARM?
- MORPH?
INTRADURAL TUMOR
- do NOT invade CNS

1. Compress
2. Increase ICP --> ischemia, edema, herniation
3. Obstruct CSF (non-communicating hydrocephalus)

MORPH:
1. Well demarcated; shell it out
2. Sheets of syncytial cells
3. WHORLS (transitional type)
4. Psammoma bodies (calcified spheres)
5. Meningothelial rests

*malignant meningiomas infiltrate the neuropile
SCHWANNOMAS

- biphasic histological pattern
- acoustic neuroma
ANTONI A: NUCLEAR PALLISADING
- stacks of parallel, elongated nuclei
KNOW THIS COLD

ANTONI B: Macro/microvesicular degeneration/necrosis


*Acoustic neuroma = schwannoma of VESTIBULAR portion of CN8

DOES NOT INFILTRATE THE NERVE
NEUROFIBROMA

- MC type
- what is it?
- histo features
MC is Solitary types
- benign nerve sheath tumor
- associated w/ neurofibromatosis (neurocutaneous syn; Von Recklinhausen dz)
+ Cafe-au-lait spots (hyperpig'd spots)

HISTO:
- >1 elongated cell type (schwann, fibroblasts)
- loose matrix w/ wavy spindle cells


*HIGH CHANCE OF TURNING INTO NEUROFIBROSARCOMA
- esp w/ radiation
MALIGNANT PERIPHERAL NERVE SHEATH TUMOR

- neurofibrosarcoma & malignant schwannoma

characteristics?
1. Extremely infiltrative
2. Can metastasize
3. Assc'd w/ Neurofibromatosis
4. Can result from prior irradiation (increased risk)
MENINGIOMA

- WHAT IS IT?
- HOW IT HARM?
- MORPH?
INTRADURAL TUMOR
- do NOT invade CNS

1. Compress
2. Increase ICP --> ischemia, edema, herniation
3. Obstruct CSF (non-communicating hydrocephalus)

MORPH:
1. Well demarcated; shell it out
2. Sheets of syncytial cells
3. WHORLS (transitional type)
4. Psammoma bodies (calcified spheres)
5. Meningothelial rests

*malignant meningiomas infiltrate the neuropile
PRIMARY CNS LYMPHOMA

- incidence
- where?
Increasing incidence (2' AIDS)

LIKE WHITE MATTER (periventricular)
- Start in VR spaces; perivenular
- Diffusely infiltrate parenchyma
(edema & necrosis)
- Usually B cell type (high grade)

**reticulin stain = concentric rings of perivascular tumor**
METASTATIC LYMPHOMA

- where?
- characteristics
Originate from OUTSIDE CNS
- usually involve subdural (hodgkin's) or SAH spaces & Meninges
- multiple tumor deposits
- similar phenotype to primary lymphoma from which they originate
METASTIC CNS TUMORS

- FROM WHERE?
- routes
KILL BIL
(Breast, GI, Lung)

uncommon tumors that like to go to cns
- Melanoma**deadliest
- Choriocarcinoma

ROUTE = BLOOD mainly
also adj stuff & along nerves
CARCINOMATOUS MENINGITIS

- WHAT IS IT?
Meningeal carcinomatosis

- metastasis to Subarachnoid space
LAYERS OF MENINGES

- spaces
1. DURA: periosteum of the skull
+ venous blood

2. LEPTOMENINGES: arachnoid & pia
- meningitis is usually here
+ arteries

- Epidural space: potential space; doesn't normally exist
- Subdural: very narrow
- Subarachnoid space
CSF FLOW
4 ventricles
- foramen of Monro connects lateral ventricles
- Sylvian aqueduct connects 3rd & fourth ventricle

OUTLETS:
- 2 foramina of Luschka
- Foramen of Magendie
--> SAS
--> Arachnoid granulations
--> Venous sinuses (mostly superior saggital sinus

**when arachnoid granulations are occluded by pus/hemorrhages (meningitis)
--> COMMUNICATING HYDROCEPHALUS
INFLAMM OF THE CNS

- meningitis
- ventriculitis
- encephalitis
- cranial neuritis
**MC routes of entry**
MC routes of entry for meningitis = OM & Sinusitis & Meningeal vessels (hematogenous)

Leptomeningitis = Meningitis
- Pachymeningitis = dura
- Subdural inflamm = Subdural empyema

Ventriculitis: rare in meningitis bc of direction of CSF flow

Encephalitis: inflamm of brain parenchyma or Myelitis of SC
- still rare bc difficult to penetrate the pia (unless infarct)

- cranial neuritis = inflamm of cranial nn.
Types of meningitis
(7)
1. Bacterial/purulent
+ pus (except meningococcal - hemorrhagic)

2. Fungal/Granulomatous
- chronic or acute

3. Parasitic
- cysticercosis or amoebic

4. Viral: lymphocytic

5/6: Allergic / Chemical: also lymphocytic

7. Carcinomatous meningitis: assc'd with neoplasia of SAS
ACUTE BACTERIAL MENINGITIS

- gross features
CLOUDY MENINGES = PUS
- tons of neutrophils (PMNs)
(Meningococcal meningitis = exception)
- Pus on cerebral convexitis (sulci) & Posterior SC

- Bacteria grows in SAS & ventricles
--> immune response (Igs & neutrophils)
- encaphlitis is NOT usually an issue (tough pia)

EMPIRICAL TX IS IMPORTANT
bacteria causing meningitis in the usa

- neonates
- infants/kids
- adolescents / young adults
- elderly /debilitated
NEONATES: Fecal contamination
- E. coli
- GBS (strep agalactiae)
( & Listeria?)

INFANTS/KIDS:
- H. influenzae (no Abs)

ADOLESCENTS/OUNG ADULTS
- Neisseria Meningitidis

ELDERLY/DEBILITATED
- S. pnuemo
- Listeria monocytogenes
ACUTE EFFECTS OF BACTERIAL MENINGITIS

- long term dreaded effects
1. Vascular thrombosis & vasospasms --> Infarcts (and 2' infxn of infarcts)

2. Edema --> ^ ICP --> herniations

3. Neurotoxicity = blindness & deaf (permanent)

4. Plugged arachnoid granulations
= Acute obstructive communicating hydrocephalus

**LONG TERM DREADED EFFECTS**
- dead/blind
- hydrocephalus
- mental retard
meningococcal meningitis
(neisserial)

- why is it particularly worrisome?
1. Kill's pt w/o prodromal symptoms
2. High mortality rate (50=90%)
3. Necrotizing vasculitis of the SKIN & many other organs
- including adrenal glands (waterhouse-Friderichsen syn)
- hemorrhage

**PROPHYLACTIC rifampin or serum if contact is suspected**

ALSO, IT'S NOT CLOUDY; MORE HEMORRHAGIC
FUNGAL MENINGITIS

- which organisms
- basic forms
1. cryptococcus neoformans (MC in both types)

2. Coccidiodes immitis

3. Blastomyces Dermatitis

4. Histoplasma capsulatum

A.) Chronic - non-opportunistic
- GRANULOMATOUS meningitis
(Epithelioid cells, giant multinucleated cells, lymphs)

B.) ACUTE: opportunist
- mixed cellular meningitis
- can be hemorrhagic
VIRAL MENINGITIS

- assc'd with?
- characteristics
MILD disease; usu transiet, nonspecific symptoms
- high LYMPHs
- NORMAL glucose
- assc'd with VIRAL ENCEPHALITIS**
(hsv encephalitis)
PARASITIC MENINGITIS

- organisms
- characteristics
1. Cysticercosis (T. solium) = Chronic
- Chronic granulomatous rxn

2. Acute = Amebic (naegleria*)

3. Meningitis caused by flukes/worms (helminths)
- ABUNDANT EOSINOPHILS
- common in immigrants
LYMPHOCYTIC MENINGITIS

- what kinds of infections?
common in
- viral
- chemical / allergic (also show eosinophils)
- Lymphomas involving SAS

**CSF has almost all lymphs
CSF PROFILES OF MENINGITIS

- DIFFERENTIATE BW
Bacterial / Granulomatous (fungal, TB) / Parasitic / Viral / Carcinomatous

KNOW THIS COLD
- cell type is best guide in making distinctions (then cx & serology)
ALL HAVE ELEVATED PRESSURE (carcinomatous can be normal)

1. Bacterial
- HIGHEST cells
- mostly PMNs
- HIGHEST protein
- LOWEST glucose

2. Granulomatous Meningitis = Fungal/TB
^ Cells
Mostly Lymphs
^ Protein
Normal or decreased Glucose

3. Parasitic
^ cells
lymphs, monocytes, plasma cells, EOSINOPHILS
^ Protein
Normal-Dec Glucose

4. Carcinomatous:
- can have normal opening pressure
Mononuclear cells; can see tumor cells
Mild ^ Protein
Normal-Dec Glucose

5. VIRAL:
- NORMAL glucose
^ lymphs
^ protein
BRAIN ABSCESS

- WHAT IS IT?
- TYPES?
- SOURCES OF INFXN
Focal, well demarcated collections of purulent tissue confined

tYPES:
- Intra cerebral
- subdural empyema
- epidural

SOURCES:
- MC = blood (bacteremia; infected embolus)
- also OM/mastoid or trauma
ACUTE ABSCESS

- what is it?
- when is it lethal?
- characteristic pathology
NON-encapsulated abscess
- can form a capsule and become chronic

Lethal in IMMUNOCOMPROMISED

PATH:
- Necrotic
- Microorg is present
- CNS edema
- Neovascularization
COMMON microorganisms causing abscess

(same for acute & chronic)
1. Bacteria: Strep / Bacteroides / Staph aureus
(SBS)

2. FUNGI: Candida aLBICANS, aspergillus, Zygomycetes

3. Parasites = Toxoplasma, Amoebae (GI) - usu Entamoeba histolytica

**chronic abscess are more common in immunocompetent pts
CHRONIC ABSCESS

- WHAT IS IT?
- DESCRIBE THE LAYERS
Chronic abscess are more common in immunocompetent pts
= ENCAPSULATED ABSCESS

Three layers:
1. Necrotic, pus filled center
2. Intermediate: fibrous capsule (+ Collagen - rare in CNS)
3. Periph: Reactive astrogliosis
(inflamm cells)
**Clinically silent = protects CNS from further spread, but resistant to abx
--> surrounding edema & space occupying lesion --> herniation??


+ Neovascularization --> Edema
TUBERCULOSIS OF THE CNS

- agent
- types
Mycobacterium TB & atypical forms

TYPES:
1. Miliary TB --> Meninges or parenchyma
(Little foci of TB all over ur body)

2. Granulomatous: Similar to fungal meningitis
- meninges only
- thick secretions @ base of skull --> communicating hydrocephalus
- Caseating necrosis, lymphs, epithelioid histiocytes, giant cells
**AIDS pt WONT' have granuloma**
- just see histiocytes w/ organisms (like in TB)

3. Tuberculomas (parenchyma)
- Embolus; few sites of inxn
ENDARTERITIS OBLITERANS

- WHAT IS IT?
- WHEN DO YOU SEE IT?
- RESULTS?
Huebner's arteritis

- Occlusive proliferation of the intima of large blood arteries

- Seen in TB & Tertiary syphilis

--> MASSIVE CEREBRAL INFARCTS
AIDS infections of CNS

- common opportunists
Cryptococcus neoformans
- frequent in Ohio valley
--> Granulomatous meningitis or Cerebritis/enceph

**Toxoplasma will do same thing**

NO GRANULOMATOUS INFLAMM IN AIDS PTS
- just histiocytes w/ organism

dx: PAS or GMS (silver) stain for crypto (india ink?)
CNS SYPHILIS

- main presentations
- time course
- asymptomatic
1. Meningovascular (7 yrs post-infxn)
- Inflamm causes vascular compromise
- Obliterated endarteritis
= cerebral infarcts

2. Tabes Dorsalis (stomp
around)
- 15-20 yrs post-infxn
- DRG compromised --> dorsal roots killed --> Atrophy of dorsal columns
--> 2' joint damage (excess wear)

3. General Paresis of the insane / Dementia Paralytica
- 10-20 yrs post-infxn
- severe atrophy of brain (dementia)
- major prolif of microglial cells

4. Asymptomatic:
- no real neuro symptoms
- CSF pleocytosis (reactive lypmhocytosis)
- Increased Ig concentration
+ csf syphilis serology

*also gummatous syphilis, congenital neurosyphilis,

syphilitic meningitis--> 1-2 yrs post-infxn
VIRAL CNS INFXNS TO KNOW

- polio
- rabies
- measles
- mumps
- JC

**what type of virus
RNA:
- Polio: Picorno
- Rabies: Rhabdo
- Measles/Mumps: Paramyxo
(SSPE / Encephalitis)
- HIV Retro

DNA:
- HSV (encephalitis)
- JC = Human papova virus
(PML)
**symptoms depend on distribution of the brain
- NOT the type of virus
CNS VIRAL INFXNS

DX, ANATOMICAL SITE, EXAMPLE

- Polioencephalitis
- Poliomyelitis
- Leukoencepahlitis
- Panencephalitis
1. POLIO ENCEPH
- Cerebral GRAY matter
- EEE

2. POLIOMYELITIS
- SC GRAY matter
- polio
= AHC & Bulbar motor nuclei

3. LEUKOENCEPH
- Cerebral WHITE matter
- PML

4. PANENCEPH
- BOTH cerebral & SC, gray AND white matter
= SSPE (cerebrum)
DISTRIBUTION OF LESIONS IN VIRAL ENCEPHALITIDES

- HSV
- PML
- SSPE
- PRION CJD
- POLIO
- RABIES
1. SSPE: Cerebrum

2 PML: cerebral white matter
(JC virus --> oligodendroglia)

3. CJD: Cerebral cortex & cerebellum

4. Polio: AHC & Bulbar motor nuclei
(Poliovirus --> motor neurons)

5. Rabies encephalitis
- BS & Cerebellum

6. HSV enceph
- temporal lobe = Hallucinate!!
ROUTES OF CNS VIRAL INFXN
MOSTLY BLOOD VIREMIA

- along the nerves = Rabies (retrograde axoplasmic flow)
conventional viral infection

- characteristics
- neuronal changes seen in conventional type
1. Conventiional
- Pathology follows limited period of incubation
- Virus can be Isolated from Lesion

GRAY MATTER IS AFFECTED

Neuronal changes:
1. Neuronal dropout (apoptosis)
2. Neuronophagia (gitter cells)
3. Cytopathic changes (cellular atypia)
4. Inclusion bodies (Nonspecific)
5. Perivascular Cuffing
- Lymphs aggregate around blood vessels (VR space connects to SAS)
--> lymphs can go into CSF and look like meningitis
6. Microglial nodule:
esp in HIV/AIDS
3 types of cns viral infxns
1. conventional
2. Slow
3. Atypical (prion)

**see perivascular cuffing in slow & conventional types**
types of inclusion bodies seen in viral CNS infxns
**inclusion bodies are nonspecific**

HSV: intranuclear Cowdry Type A

Rabies: Negri = intra cytoplasmic

JCV: Big huge intranuclear mass in oligodendroglia
- obscures nucleus

**mostly eosinophilic**
POLIOVIRUS

- results
- where?
- agent
- targe
Encephalitis / Myelitis
- poor immunization

Enterovirus (Picorna) - RNA

Target: Motor neurons of SC, brain stem, or cortex
(myelitis, bulbitis, encephalitis)
HERPES SIMPLEX VIRUS

- results
- prevalence
- characteristics
- where?
MC non opportunistic spontaneous viral encephalitis

DX: CT/MRI
- Characteristic mesial temporal hemorrhagic/necrotic lesions
- become BL over time

Cowdry type A inclusions = intra nuclear
HIV-1/AIDS associated nervous system lesions
1. Vacuolar myelpathy
- vacuolarization of neurons/nerves

2. Opportunists
- Toxo
- Crypto
- CMV encephalitis
- Mycobacterial infxns
- HSV & Herpes zoster

3. PML (JCV)
slow viral infections

- characteristics
- examples
LONG TIME bw infection & clinical manifestation of symptoms

- see perivascular cuffing

examples:
1. Subacute sclerosing panecephalitis
- Measles virus
Lesions: Panenceph, Extensive necrosis, Cowdry Type A inclusions

2. PML
- JCV
- Leukoencephalitis
- huge intranuclear lesion
ATYPICAL OR UNCONVENTIONAL (PRION) INFECTIONS OF CNS

- main result
- main organisms
- tranmission
- path
"Evangelism"
- mutant protein converts normal proteins

1. Spongiform encephalopathy
- dementia
- vacuolation (holes in neuropile)
2. Reactive astrocytosis/gliosis
3. No infectious microorg
4. Instead, mutant prion protein
5. Latent period (slow)
6. NO EVIDENT INFLAMM OR NEURONOPHAGIA********

Mostly a gray matter process
- cerebellum & deep grey can be affected

Human forms = dementia
- CJD
- Kuru: cerebellum mainly = ataxia
conventional viral infection

- characteristics
- neuronal changes seen in conventional type
1. Conventiional
- Pathology follows limited period of incubation
- Virus can be Isolated from Lesion

GRAY MATTER IS AFFECTED

Neuronal changes:
1. Neuronal dropout (apoptosis)
2. Neuronophagia (gitter cells)
3. Cytopathic changes (cellular atypia)
4. Inclusion bodies (Nonspecific)
5. Perivascular Cuffing
- Lymphs aggregate around blood vessels (VR space connects to SAS)
--> lymphs can go into CSF and look like meningitis
6. Microglial nodule:
esp in HIV/AIDS
3 types of cns viral infxns
1. conventional
2. Slow
3. Atypical (prion)

**see perivascular cuffing in slow & conventional types**
types of inclusion bodies seen in viral CNS infxns
**inclusion bodies are nonspecific**

HSV: intranuclear Cowdry Type A

Rabies: Negri = intra cytoplasmic

JCV: Big huge intranuclear mass in oligodendroglia
- obscures nucleus

**mostly eosinophilic**
POLIOVIRUS

- results
- where?
- agent
- targe
Encephalitis / Myelitis
- poor immunization

Enterovirus (Picorna) - RNA

Target: Motor neurons of SC, brain stem, or cortex
(myelitis, bulbitis, encephalitis)
HERPES SIMPLEX VIRUS

- results
- prevalence
- characteristics
- where?
MC non opportunistic spontaneous viral encephalitis

DX: CT/MRI
- Characteristic mesial temporal hemorrhagic/necrotic lesions
- become BL over time

Cowdry type A inclusions = intra nuclear
HIV-1/AIDS associated nervous system lesions
1. Vacuolar myelpathy
- vacuolarization of neurons/nerves

2. Opportunists
- Toxo
- Crypto
- CMV encephalitis
- Mycobacterial infxns
- HSV & Herpes zoster

3. PML (JCV)
slow viral infections

- characteristics
- examples
LONG TIME bw infection & clinical manifestation of symptoms

- see perivascular cuffing

examples:
1. Subacute sclerosing panecephalitis
- Measles virus
Lesions: Panenceph, Extensive necrosis, Cowdry Type A inclusions

2. PML
- JCV
- Leukoencephalitis
- huge intranuclear lesion
ATYPICAL OR UNCONVENTIONAL (PRION) INFECTIONS OF CNS

- main result
- main organisms
- tranmission
- path
"Evangelism"
- mutant protein converts normal proteins

1. Spongiform encephalopathy
- dementia
- vacuolation (holes in neuropile)
2. Reactive astrocytosis/gliosis
3. No infectious microorg
4. Instead, mutant prion protein
5. Latent period (slow)
6. NO EVIDENT INFLAMM OR NEURONOPHAGIA********

Mostly a gray matter process
- cerebellum & deep grey can be affected

Human forms = dementia
- CJD
- Kuru: cerebellum mainly = ataxia
POLYSOMNOGRAPHY

- what are you measuring?
1. EEG: brain potentials

2. Elecctroculogram: EOG
- eye movements

3. EMG: muscle activity
- submentalis muscle of the chin
EEG FREQUENCIES
Delta: < 4 hz

Theta: 4-7 hz

Alpha: 8-14 hz

Beta: > 13 Hz
STAGES OF SLEEP
2 States:

1. NREM
Stage 1: Low amp theta
Stage 2: K-complexes & sleep spindles
Stage 3: 20-50% high amp delta
Stage 4: > 50% high amp delta

- no eye movements excpet maybe slow rolling ones in stage I, reduced EMG activity
- Stage II is present > 50% of sleep
- Stages 3 & 4 diminish as sleep progresses

2. REM:
- EEG pattern similar to NREM Stage I
- Low ampt, mixed freq waves
+ Rapid conjugate eye movments
- ABSENT EMG activity (muscle paralysis)
ORGANIZATION OF HUMAN SLEEP

NORMAL

**dreams occur during alll stages of sleep.
- vivid dreams with good story lines usually seen in REM
After sleep onset
- Progress through Stages I-IV in 46-60 min.
- Slow wave (stage 3 &4) dominate first third of the night
(15-25% of total nocturnal sleep in young adults)

**After 1st slow wave sleep episode, progression of nREM stages reverses
--> Then you get REM sleep

Average cycle: 90-110 minutes
(4-6 cycles / night)

**After first REM, intervals bw successive REMs decrease through the night
- Length of REM increases each time.

REM = 20-25% OF SLEEP
Stage 2 = 50%
Stage 3 & 4 = 15%
EFFECT OF AGE ON SLEEP PATTERNS
Daily sleep requirements DECREASE WITH AGE
- level off during middle age
- decline further with old age

BABIES: greater REM sleep (50% vs 25% adults)
- elderly have even less rEM

STAGE 4 Declines throughout developing/middle years
--> disappears after 60 yrs
NEUROANATOMY OF SLEEP

- BRAIN AREAS INVOLVES
1. RAS
- induce sleep & wakefulness
- Rostral RAS: needed to wake up
- Caudal RAS: needed to fall asleep
**Raphe nuclei & Nucleus of the solitary tract in medulla also involved in falling asleep (?)

2. Suprachiasmatic Nucleus
- of the hypothalamas
- "Biologic clock" for circdatian rhythms
- regulates diurnal secretion ofhormones
- direct input from the retina (retinohypothalamic fibers)
--> helps reset intrinsic rhythmicity of the suprachiasmatic nucleus (coincides w/ day/night)
NEUROCHEMISTRY OF SLEEP
- MAIN NT?
SEROTONIN
- raphe nuclei in the brain stem
- promotes sleep
- w/o it = insomnia
TYPES OF INSOMNIA
1. Sleep misperception syndrome
2. Pschophysiologic insomnia:
- not on exam
- poor sleep habits acquired during stress persist

3. Psychopathological insomnia
- of anxiety/depression

4. Limb Movement Insomnia
- Nocturnal myoclonus: bothers spouse
- Restless legs syndrome: bothers pt

5. Circadian rhythm insomnia
- jet lag
PSYCHOPATHOLOGICAL INSOMNIA

anxiety vs depression
Insomnia associated w/ emotional disturbances

Anxiety: Difficulty falling asleep

Depression: early awakenings

**chronic schizophrenics actually sleep well
LIMB MOVEMENT INSOMNIA

- RESTLESS LEG SYNDROME
VS
- NOCTURNAL MYOCLONUS
Restless legs: Bother pt more
- creepy crawlies in their legs
- get up to move around and feels better
- delays sleep onset
- tx w/ DA agonists (parkinson's med) like Ropinerol & Pramiprexole
- SEs: hallucinations, gambling, nausea

2. Nocturnal Myoclonus: Bothers spouse more
- Pt is asleep
- Let twitches every 20-40 seconds during STAGE 1 AND 2 SLEEP
TREATMENT OF INSOMNIA
1. Benzodiazepenes: DOC for insomnia
- potent suppressors of deep slow wave sleep
- enhange subjective quality of sleep
- sharply reduce the # of microwakes
= more restorative/refreshing sleep
- NOT long term drug 2' tolerance

2. TCAs:
- long term tx of insomnia AND migraines

3. Barbiturates are NO LONGER USED
- rapid tolerance
--> rebound intolerance
- suppress REM sleep
PARASOMNIA

- types of disorders
- what stage of sleep?
Undesirable behavior that occurs during sleep or is exacerbated by sleep

1. Nocturnal Enuresis: Stage 4
- more in boys/young adults
- maturational lag in neurological control

2. Somnambulism: Stage 3-4
- sleep walking; remain unconscious

3. Night terrors: Stage 3-4

4. REM Behavior Disorder: REM
NIGHT TERRORS VS. NIGHTMARES

- memory
- stage
- intensity
Nightmare
- Stage: REM
- STRONG memory when you wake up
- Intense

Night Terror:
- Stage 3-4
- NO MEMORY when you wake up
(memorable for the parents)
- SUPER DUPER INTENSE
+ ANS activity
*occurs during first several hours of sleep
PSYCHOPATHOLOGICAL INSOMNIA

anxiety vs depression
Insomnia associated w/ emotional disturbances

Anxiety: Difficulty falling asleep

Depression: early awakenings

**chronic schizophrenics actually sleep well
LIMB MOVEMENT INSOMNIA

- RESTLESS LEG SYNDROME
VS
- NOCTURNAL MYOCLONUS
Restless legs: Bother pt more
- creepy crawlies in their legs
- get up to move around and feels better
- delays sleep onset
- tx w/ DA agonists (parkinson's med) like Ropinerol & Pramiprexole
- SEs: hallucinations, gambling, nausea

2. Nocturnal Myoclonus: Bothers spouse more
- Pt is asleep
- Let twitches every 20-40 seconds during STAGE 1 AND 2 SLEEP
TREATMENT OF INSOMNIA
1. Benzodiazepenes: DOC for insomnia
- potent suppressors of deep slow wave sleep
- enhange subjective quality of sleep
- sharply reduce the # of microwakes
= more restorative/refreshing sleep
- NOT long term drug 2' tolerance

2. TCAs:
- long term tx of insomnia AND migraines

3. Barbiturates are NO LONGER USED
- rapid tolerance
--> rebound intolerance
- suppress REM sleep
PARASOMNIA

- types of disorders
- what stage of sleep?
Undesirable behavior that occurs during sleep or is exacerbated by sleep

1. Nocturnal Enuresis: Stage 4
- more in boys/young adults
- maturational lag in neurological control

2. Somnambulism: Stage 3-4
- sleep walking; remain unconscious

3. Night terrors: Stage 3-4

4. REM Behavior Disorder: REM
NIGHT TERRORS VS. NIGHTMARES

- memory
- stage
- intensity
Nightmare
- Stage: REM
- STRONG memory when you wake up
- Intense

Night Terror:
- Stage 3-4
- NO MEMORY when you wake up
(memorable for the parents)
- SUPER DUPER INTENSE
+ ANS activity
*occurs during first several hours of sleep
REM Behavior disorder

- population
- tx
OLDER MEN

NO normal muscle paralysis during REM
- patients act out their dreams
- injure themselves or sleeping partners

tx: anti-convulsants work very well
HYPERSOMNIA

- types of disorders
1. SLEEP APNEA

- Obstructive: upper airway obstruction

- Central: rare; Myotonic dystrophy is related to it
(damaged brain stem centers)

- Mixed: Central respiratory pause followed by obstructive ventilatory efforts

2. Narcolepsy: 4 symptoms
SLEEP APNEA

- clinical features
- complications
- epidemiology
FEATURES:
- Loud pharyngeal snoring
- nighttime apnea
- day time HYPERSOMNOLENCE
- MORNING HEADACHES***

COMPLICATIONS:
- Pickwickian syndrome (obese)
- pulmonary issues + right heart failure & polycythemia

Epidemiology: more common in older obese men
SLEEP APNEA TX
1. WT LOSS. 1ST TX

2. CPAP: "pneumatic splint" of the airway
- people don't liek the mask

3. Sx: enlarge upper airway

*don't need to know drugs for this
NARCOLEPSY

- DEFINITION
- EPIDEM
REM sleep INTRUSION into wakeful
--> excessive sleepiness & abnormalities of REM sleep

EPIDEM:
- Onset: 15-35
- Can persist into old age
- family hx - autosomal dominant
NARCOLEPSY SYMPTOMS
1. Excessive daytime somnolence
- occurs in boring, sedentary situation
- alleviated by motor activity & mental simulation
- CAN'T be fully relieved by any amt of sleep
- Brief episodes of sleep --> wake up feeling good & super refreshed
- vivid dreams can occur here

2. CATAPLEXY:
- muscular weakness/paralysis
- precip'd by excitement/emotion
- pt is conscious
- complete paralysis excpet respiratory & eye muscles

3. Sleep paralysis
- inability to move during the onset of sleep or on awakening

4. Hypnagogic hallucinations: dreams while you're awake
- accompany the onset of sleep or awakening


1 & 2 = PRESENT ALL THE TIME
3 & 4 = present 50% of the time
NARCOLEPSY PATHOPHYSIOLOGY

- sleep study
REM sleep occurs at the ONSET of sleep or within 10 MIN.
- impaired sleep-wake regulation
(not an excessive NEED for REM sleep)

Day time sreepies bc REM intrudes into wakefulness
- hallucinations, paralysis, & cataplexy are dissociated manifestations of REM
NARCOLEPSY DX
1. Tetrad of Symptoms
2. Positive family hx
3. Multiple sleep latency test
- onset of REM sleep w/in 10 minutes
- observe for day time somnolence (fall asleep w/in 10 min of laying down)
- direct transitions from wakefulness --> REM sleep
NARCOLEPSY TX
Not on exam really

- Hypersomnolence: CNS stimulants
(Methylphenidate or dextroamphetamine)

- Other symptoms: give SSRIs
(cataplexy, sleep paralysis, hypnagogic hallucinations)
DEFINE

- COMA
- STUPOR
- OBTUNDATION
- LETHARGY
COMA
Total or near total unresponsiveness

STUPOR
Severely impaired arousa
- SOME response w/ VIGOROUS stimuli

OBTUNDATION
NOT as severe
- some response to TOUCH/VOICE

LETHARGY/somnolence
Decreased arousal, but still maintained; esp with light stimulation
DEFINE:

- CONFUSION / ENCEPHALOPATHY
- DELIRIUM
CONFUSION:
Impaired attention but aroused enough to perform certain mental tasks

DELIRIUM:
Confusion PLUS periods of agitation, hypervigilence, irritability, & hallucinations
- alternating w/ periods of decreased arousal
PATHOPHYSIOLOGY OF COMA

- Main areas of consciousness
- excitatory inputs to cortex
Main areas = Cerebral hemispheres & BS-RAS
- need at least 1 hemisphere & RAS
--> UL strokes don't usually cause coma


EXCITATORY INPUTS (bypass thalamus)
1. Basal forebrain (Ach) - Alzheimer's
2. Raphe nuclei (serotonin)
3. Locus ceruleus (NE)
4. Substantia Nigra: VTA (DA)
5. Posterior hypothalamus (Histamine)
4 general causes of coma
Coma: BL stroke or BS lesion (around RAS)

1. Supratentorial Mass Lesions
- head trauma: epidural/subdural hematoma
- HTN --> intracranial hemorrhage
- cerebral abscess
- Massive stroke w/ edema
**find ASYMMETRICAL FINDINGS**

2. INFRATENTORIAL MASS LESIONS
- BS or cerebellar strokes/hemorrhages/tumors
--> compress RAS --> BS signs
**CROSS FINDINGS***
(Ipsilat CNs & CL hemisphere)

3. METABOLIC: diffuse cortical knockout
- drug OD
- severe electrolyte disorders
- glucose
- sAH, meningitis, renal fail, etc
***BS FXN USUALLY REMAINS INTACT**

4. PSYCHOGENIC COMA:
- physiologically awake; appears comatose
(doesn't respond to environment)
- WILL respond to painful stimuli
NEUROLOGIC EXAM IN COMATOSE PATIENTS
1. ASK THEM A QUESTION
- test language fxn

2. USE PAINFUL STIMULI
- if pt doesn't respond to verbal
- deep nailbed, sternal rub, cotton swab in nasopharynx
--> report grimace, asymm, withdrawal, etc.

**glasgow coma scale**
- motor / verbal / eye response
Spontaneous respirations

- from what lesion?
- progression
Abnormal patterns of respiration
- MC in supratentorial mass lesion causing Brain Herniation

Patient Deteriorates --> Progress:
1. Cheyne-Stokes
- BL hemispheres/diencephalic
- Hyperpnea & Apnea
- least specific

2. Central neurogenic hyperventilation
- Hypothalamic - Midbrain damage
- rostral BS tegmentum

3. APNEUSTIC breathing
- prolonged inspiratory cramp (pause w/ full breath)
- Uncommon; most specific
- Mid/Caudal-pontine lesion

4. Ataxic/Biot's breathing
- Medullary damage
- Deep & shallow breaths together
- Reticular formations of medulla
(normal to-fro breathing)
Medullary / Upper cervical cord lesions

- what kind of breathing problems results?
Anatomical separation of AUTOMATIC and VOLUNTARY influences on breathing

- Lesion in medullary reticulospinal projections to SC
(--> automatic respirations)

**Spared CST --> Spinal respiratory motor neurons
(voluntary breathing)

Patients have to "remember" to breath
- PROBLEMS AT NIGHT

= ONDINE'S CURSE
PUPILLARY SIZE

- what is it dependent on?
- SMALL VS LARGE
- WHAT KIND OF LESION?


**BRAIN DEAD PATIENTS HAVE FIXED AND DILATED PUPILS
Balance bw
1.) Paraysym (CN 3 - miosis)
2.) Sym (mydriasis)

SMALL: (pinpoint pupils)
- Mess up desc. sympathetic paths
- Pontine lesion (#3 MC HTN hemorrhage)
--> BL, small, fixed pupils
- UL miosis & ptosis = HORNER'S
(ipsilateral brain stem)


LARGE: broad causes
- Central herniation --> BL CN 3 palsies
- Uncal herniation: IL CN3 palsy
- PCOM: CN3 palsy + headahce
- SAH: comatose/lethargic too!
DAMAGE TO PRETECTAL AREA

- what is it?
- what results? (eye)
Pretectum: Region of neurons found between the thalamus and midbrain. It receives binocular sensory input from retinal ganglion cells of the eyes, and is the region responsible for maintaining the pupillary light reflex.



**Damage pretectal area - interrupts pupllary light reflex
- spared accomodation
- nonreactive 2 light
- retained ciliospinal reflex (dilates to painful stimulation)
EYE MOVEMENTS

- Doll's eyes
- when do you use this?
COMATOSE PATIENTS

Oculocephalic (Doll's eyes)
- CN8 carries info from Semicirc canals --> CL PPRF
- Right SCC tells eyes to move Left

*Warm water stimulates this pathway
*Cold water INHIBITS this pathway
EYE MOVEMENTS

- COLD CALORIC TESTING IN COMATOSE PTS
- results in cortical vs. BS lesion vs. brain dead pt.
COLD CALORIC TESTING
- Cold water in ear INHIBITS oculocephalic reflex
a.) SLOW nystag to IPSI
- opp SCC is taking over
b.) FAST nystag to CL
- brain compensates
(normal response - BS & Cortex intact)

ex// Cold water in RIGHT ear causes LEFT beating nystagmus
- named for fast phase

1.) Lesion in hemispheres (BL)
- Cold in RIGHT ear
- SLOW Right nystag
- ABSENT fast nystag (no cortical function)
**r/o brain stem pathology**

2.) Lesion in BRAIN STEM
- asymm eye movements w/ cold calorics

3.) BRAIN DEAD
- NO RESPONSE
(slow or fast)

4.) Psychogenic coma: normal slow/fast phase
TESTS TO DO IN COMATOSE

**DIFFERENTIATE BW PSYCHOGENIC & REAL**
1.) MENTAL STATUS
- Painful stimulation

2.) Spontaneous respirations?
- Cheyne Stokes, Central neurogenic hypervent, Apneustic, Biot's, Ondine's curse

3.) Small vs Large pupils
- light reflex

4.) Eye movements
- Doll's eyes
- Cold caloric testing

5.) Motor:
- Decorrical vs. Decerebrate posturing

6.) Reflexes
- Bainski, clonus, hyperreflexia

7.) Sensory
- painful stimulation
- look for asymm response
MOTOR RESPONSE IN COMATOSE PATIENTS
Response to painful stimuli
- look for asymm

1.) Decortical posturing
- Flexed arms & Extended legs
- Lesion @ Diencephalon or above
(Above BS; Thalamus or higher)

2.) Decerebrate posturing
- Extended arms & legs
- Overactive Lateral vestibulospinal tract
(powerful extensor pathway)
- Rostral/upper BS lesions
(midbrain; upper pons)

**In brain herniation, pt can progress from decorticate --> decerebrate posturing as lesion progresses deeper
DIAGNOSTIC STUDIES TO RUN ON COMATOSE PATIENTS
1. Blood studies
- infxn?
- OD?
- LIVER or renal failure?
- metabolic issue?

2.) Urine Tox screen & Blood alcohol level
- drug & alcohol abuse = causes for confusion & coma

3.) HEAD CT / MRI scan
- look for supra/infra tentorial structural lesion
- CT: r/o hemorrhagic
(less sensitive ,but fast)

4.) LP
- if normal CT/MRI

5.) EEG:
- Non-convulsive status epilepticus
AUDITORY PATHWAY
1. Cochlear n.
2. cochlear nucleus
3. Acoustic striae
- crosses midline
- largest = trapezoid body
4. Sup. olivary nucleus (CL)
5. Lateral lemniscus
6. Inferior colliculus
7. Medial geniculate body (thalamus)
8. Auditory cortex (heschl's gyrus)
Fxn of

- superior olivary nucleus
- lateral lemniscus
- medial geniculate body
SON
- detects time differences in sound arrival
- useful in directionality
- uses low Freq sounds


LATERAL LEMNISCUS
- startle response / reflex

MEDIAL GB
- ability to focus/discern specific quality of sound
- cocktail party effect
PATHWAYS TO DAMPEN SOUND
DESTRUCTION OF ANY OF THESE PATHWAYS
= HYPERACUSIS & icreased startle response

1. Descending efferents
- inhibitory
- lets you tune in to specific sounds

2. CN 7 : dampen ossicles via stapedius muscle

3. CN 5: Dampens tympanic membrane
Causes of auditory hallucinations
1.) CNS tumor/lesion in 1' auditory cortex or association cortex
- LOUD ROARING coming from unaffected hemisphere

2. AV malformation
- bruits

3. PONS lesions
- tapping, buzzing, tones

4. PSYCHOENIC
- schizphrenia or other neurosis

6. Tympanic membrane lesion
- hear heart beats/vascularity
AUDITORY GO/NO-GO TEST
Response to taps

- abnormal: frontal release signs = frontal lobe damage
CENTRAL VS PERIPHERAL VERTIGO

AND TESTS
CENTRAL: Cerebellar + BS
- less common
- can reflect posterior fossa hemorrhag eor stroke
- also see neuro deficits
- IMMEDIATE ONSET OF NYSTAGMUS w/ positional testing
*no adaptation*

PERIPHERAL
- INNER EAR
- DELAYED onset of vertigo w/ positional testing
- never vertical nystag
- ADAPTATION IS PRESENT
What kinds of vertigo do you tx w/ diuretics
1. Benign positional vertigo
- calcium carbonate crystals

2. Meniere's disease
- endolymphatic hydrops/high pressure
VESTIBULAR NERVE INFXNS

- TX & SEs
Vestibular neuritis
- horrible awful vertigo for weeks to months

TX;
Neurectomy, Gentamicin otic drops

SEs: permanent hearing loss
- destory labyrinth
TREATMENTS OF

PARTIAL VS GENERALIZED SEIZURES
- mech of treating partial vs generalized seizures
PARTIAL SEIZURES: inactivate V-gate Na+ or Increased GABA
1.) Simple / Complex / with 2' generalization
a. carbamazepine
b. phenytoin
c. phenobarbital
d. valproate

new meds:
a. lamotrigine
b. gabapentin
c. topiramate**
d. levetiracetam**
e. tiagabine
f. zonisamide

GENERALIZED SEIZURES:
V-gate Ca2+ - thalamaocortical radiations

New meds: Lamotrigine for ALL

Conventional meds: valproate for all
- absence: can give ethosuximide too