Block 10

Front 1

What is responsible for central chromatolysis of neurons?

Back 1

Axonal trans-section – in central chromatolysis, the nucleus moves to the periphery and nucleolus becomes more prominent (in an attempt to produce more RNA to regenerate more axonal proteins)

Front 2

What is an example of an inclusion body in oligodendrocytes?

Back 2

PML viral infection (JC virus) --> leads to intra-nuclear inclusions + glassy appearance of oligodendrocytes

Front 3

What is the most commonly seen cell in white matter?

Back 3

Oligodendrocytes: make myelin – if injured, result in demyelination

Front 4

What are astrocytic responses to injury?

Back 4

Gliosis (proliferation of astrocytes in response to injury (fibrosis-like), seen w/ any pathologic process)
Rosenthal fibers: intracytoplasmic inclusions in astrocytes
Corpora amylacea: non-pathologic (seen with aging), look like Lafora bodies of neurons
Alzheimer type 2 astrocytes: seen in metabolic diseases (not Alzheimer’s!)

Front 5

What are the different types of astrocytes?

Back 5

Gray-matter astrocytes (Protoplasmic astrocytes);
White-matter astrocytes (Fibrillary astrocytes) --> involved most commonly in disease processes of astrocytes – astrocytes in white matter are not obvious on microscopy, have role in formation of BBB

Front 6

What are examples of intra-cytoplasmic inclusions in neurons?

Back 6

Pathologic: Rabies infection (Negri bodies), neurofibrillary tangle (pathologic, seen in aging and Alzheimer’s disease), Lewy bodies (seen in pigmented neurons affected by Parkinson’s), Lafora bodies
Non-pathologic: Lipofuscin (non-pathologic, golden-brown material, seen with wear-and-tear of neurons), Colloid inclusion (non-pathologic)

Front 7

What are examples of intranuclear inclusions in neurons?

Back 7

Pathologic: CMV infection
Non-pathologic: Marinesco body (seen with aging, positioned next to nucleolus of neuron)

Front 8

What characterizes neuron cells?

Back 8

Large nucleus with prominent nucleolus is usually seen in neurons – variations exist

Front 9

What changes are seen in the cell morphology of neurons at death?

Back 9

Nucleus becomes more condensed and less well-defined, and cytoplasm becomes more eosinophilic (“red and dead”) – in gross brain, atrophy shows as narrowing of gyri and deepening of sulci

Front 10

What are neuronal reactions to injury?

Back 10

Acute neuronal injury, atrophy, central chromatolysis/axonal reaction, neuronal inclusions

Front 11

What characterizes cerebral edema?

Back 11

Increased brain volume due to increased water content, may complicate any pathologic process, types include: vasogenic, cytotoxic, interstitial/hydrocephalic

Front 12

What is subfalcine herniation?

Back 12

Herniation of cingulate gyrus underneath the falx, most commonly caused by asymmetric space-occupying lesion above the tentorium (supratentorial) --> brain herniation thru falx causes compression of adjacent ACA, leading to 2’ infarct

Front 13

What are the major types of herniation in brain?

Back 13

Cerebellar tonsillar herniation, subfalcine (cingulate) herniation, transtentorial herniation (types: lateral/uncal, central), “upward” herniation

Front 14

What is seen grossly in all types of cerebral edema?

Back 14

Flattening of gyri with narrowing of sulci – cerebral edema is a gross diagnosis (e.g. by imaging the entire brain), rather than a microscopic diagnosis (however, if do microscopic analysis, may see vacuolation of parenchyma, cell swelling, enlarged extracellular spaces, fluid around blood vessels)

Front 15

What characterizes interstitial/hydrocephalic edema?

Back 15

CSF accumulates in extracellular spaces of periventricular white matter --> reduces volume of periventricular white matter; usually due to obstruction of CSF flow, may be reversible surgically by shunting CSF out of the ventricular space

Front 16

What characterizes cytotoxic edema?

Back 16

Intra-cellular swelling due to increased cellular concentration of osmotically active solutes, gray and white matter affected equally, usually a complication of hypoxia/ischemia-induced damage to Na/K pump in affected cells

Front 17

What is the most common type of cerebral edema?

Back 17

Vasogenic edema: results from increased permeability of blood vessels across BBB, white matter is most severely affected, fluids mainly in extracellular spaces

Front 18

What occurs in an injury to ependymal cells and choroid plexus?

Back 18

Little regenerative capacity of the single epithelial layer of the ependyma --> (instead, will get) proliferation of glial cells beneath the ependyma, leading to bumps on the ependyma known as “granular ependymitis”

Front 19

What are the various types of response to injury in microglial cells?

Back 19

Become elongated --> “Rod cells” --> when rod cells proliferate, may cause “Microglial nodules”
Acquire foamy cytoplasm --> “Glitter cells”; Neuronophagia

Front 20

What are the macrophages/histiocytes of the brain?

Back 20

Microglia (BM derived like other histiocytes)

Front 21

What characterizes lateral (uncal) transtentorial herniation?

Back 21

Displacement of uncus and parahippocampal gyrus over the free edge of the tentorium --> can lead to PCA compression (supplies visual cortex --> may see blindness), can lead to Kernohan’s notch

Front 22

What lesions are most commonly responsible for obstructive hydrocephalus?

Back 22

Obstructive lesions in 3rd ventricle or cerebral aqueduct

Front 23

What characterizes hydrocephalus?

Back 23

Increase in water content of brain within the ventricular system (leading to dilation of ventricular system), can be obstructive (communicative or non-communicative), non-obstructive (increased CSF production, impaired absorption), or Hydrocephalus ex vacuo (loss of white matter volume leading to compensatory dilation of ventricular system)

Front 24

What characterizes tonsillar herniation?

Back 24

Herniation of cerebellum thru the foramen magnum, most commonly seen with posterior fossa or cerebellar space-occupying lesions, leads to respiratory arrest by medullary compression

Front 25

What characterizes central transtentorial herniation?

Back 25

Downward displacement of brainstem (e.g. hypothalamus and rostral brainstem) through the incisura --> can lead to “Duret hemorrhage” in the middle of brainstem (immediately fatal)

Front 26

What is Kernohan’s notch?

Back 26

Infarction of cerebral peduncle (opposite to brain lesion) as well as compression of CNIII (same side as brain lesion) --> leading to unopposed sympathetic stimulation of pupils causing pupillary dilation on same side as brain lesion + paralysis on same side as brain lesion (e.g. right hemisphere uncal lesion --> left cerebral peduncle infarct --> decussation of fibers --> right-sided paralysis)

Front 27

What is dementia?

Back 27

Progressive loss of cognitive function independent of the state of attention

Front 28

What is seen microscopically in Alzheimer’s brain?

Back 28

Senile plaques (due to β Amyloid deposition either in diffuse or neuritic fashion)
Neurofibrillary tangles (made up from Tau proteins – shows as elongated, flame-shaped intra-cytoplasmic Tau protein inclusions)
Granulovacuolar degeneration (“dot and halo”) + Hirano bodies (only in hippocampus), Amyloid angiopathy

Front 29

What is seen pathologically in Alzheimer’s brain?

Back 29

Diffuse cortical atrophy with disproportionately prominent atrophy of hippocampi (leading to small hippocampi), loss of white matter leading to hydrocephalus ex vacuo – vision and ability to move is lost very late in AD

Front 30

What characterizes clinical features of Alzheimer’s?

Back 30

Initial symptoms: forgetfulness and memory problems (AD initially affects hippocampus)
Later symptoms: language problems, loss of math skills, loss of learned motor skills
Final symptoms: incontinence, mutism, inability to walk
Death: due to other diseases (esp. pneumonia), Progression is slow and relentless

Front 31

What is associated with genetic forms of Alzheimer’s?

Back 31

Mutations affecting the β Amyloid (Aβ) production/processing;
APP gene (chr. 21) --> Down syndrome (Trisomy 21) can lead to Alzheimer’s due to having 3 copies of Amyloid Precursor Protein (APP); PS1 gene (chr. 14), PS2 gene (chr. 1)

Front 32

What is the pathogenesis of Alzheimer’s?

Back 32

Involves a combination of β-amyloid protein (Aβ) and Tau protein abnormalities

Front 33

What is the most common cause of dementia in the elderly?

Back 33

Alzheimer’s – most important risk factor is increasing age (40% in 85-89yo), 10% of cases are familial, true diagnosis made only on autopsy of brain, F > M

Front 34

How are neurodegenerative disorders defined?

Back 34

Progressive loss of neurons that typically arise without any inciting events – classified based on site of involvement and/or type of protein aggregates present

Front 35

What are the various types of protein aggregates present in neurodegenerative disorders?

Back 35

Amyloid (Aβ): seen in Alzheimer’s, Tau proteins (seen in tauopathies), α-synuclein (seen in synucleinopathies), ubiquitin (seen in almost all of neurodegenerative diseases)

Front 36

What are the various types of neurodegenerative disorders based on site of involvement?

Back 36

Cerebral cortex --> dementing disorders, subcortical areas (basal ganglia, brainstem) --> movement disorders, cerebellum and spinal cord --> spinocerebellar ataxias, motor neurons in spinal cord --> motor neuron diseases

Front 37

What characterizes Progressive Supranuclear Palsy?

Back 37

Hybrid disease (dementing and movement disorder) – mild progressive dementia + movement disorder (truncal rigidity, vertical gaze palsy), M > F, fatal within 5-7 years;

Front 38

What characterizes Frontotemporal Dementia with Parkinsonism linked to Chromosome 17?

Back 38

Familial disease with frontotemporal dementia and Parkinsonism, due to mutation in Tau gene (Tauopathy) – will have only neurofibrillary tangles (similar to AD) without any plaques found in AD

Front 39

What characterizes Motor Neuron Disease Inclusion Dementia?

Back 39

May or may not be associated with motor neuron disease; shows Tau-negative, silver-negative, ubiquitin-positive inclusions – most commonly found in the dentate fascia of the hippocampus

Front 40

What characterizes pathology of Corticobasal Degeneration?

Back 40

Cortical atrophy (less prominent than AD), ballooned neurons
Tauopathy in gray and white matter: Tau-positive inclusions in neurons (tangle-like) as well as astrocytes (astrocytic plaques and tufted astrocytes) and oligodendrocytes (coiled bodies)
Note: know that this disease extensively involves white matter as well as gray matter

Front 41

What is Corticobasal Degeneration?

Back 41

Cognitive decline with sensory cortical dysfunction (cortical) + movement disorder such as rigidity and asymmetric motor disturbances (basal); affects elderly

Front 42

How does Progressive Supranuclear Palsy differ from Alzheimer’s?

Back 42

M > F; Neurofibrillary tangles are globose (rounded) as opposed to elongated, flamed-shaped in AD, no plaques present --> pure Tauopathy; brain atrophy is less prominent and is more focused in deep gray structures (globus pallidus)

Front 43

What characterizes pathology of Progressive Supranuclear Palsy?

Back 43

Neuronal loss is more in deep gray structures (globus pallidus, substantia nigra, inferior/superior colliculus, etc), shows Globose (rounded) neurofibrillary tangles (Tau protein), no plaques (no amyloid role), Tauopathy

Front 44

What are different types of frontotemporal dementias?

Back 44

Pick disease, Progressive supranuclear palsy, Corticobasal degeneration, Motor neuron disease inclusion dementia, Frontotemporal dementia with Parkinsonism linked to chromosome 17, Dementia lacking distinctive histology

Front 45

What are the pathologic findings in Pick Disease?

Back 45

Lobar atrophy (mainly in frontal and temporal lobes, sparing the posterior 2/3rd of superior temporal gyrus --> “knife-edge atrophy”), deeper atrophy (caudate and putamen), Pick bodies (mainly seen in dentate fascia of the hippocampus), Tauopathy (stains positive for Tau proteins)

Front 46

What characterizes Pick Disease?

Back 46

Early on affects temporal lobes (not hippocampus) mainly --> characterized by early onset of behavioral changes (e.g. aggression) together with alterations in personality and language disturbances (no memory loss)

Front 47

What characterizes the pathology of Parkinson’s disease?

Back 47

Pallor of substantia nigra and locus ceruleus, loss of pigmented neurons with associated gliosis and pigment incontinence, Lewy bodies (!)
Lewy bodies = if see inclusion in cytoplasm in pigmented neurons --> think about PD

Front 48

What is Friedrich Ataxia?

Back 48

Spinocerebellar ataxia due to GAA trinucleotide repeat; hereditary (AR) due to changes on frataxin gene on 9q12; begins in 1st decade with gait ataxia, high incidence of CV disease, and concominant diabetes; death is due to pulmonary infection or CV disease

Front 49

What are spinocerebellar ataxias?

Back 49

Diseases affecting cerebellum and spinal cord – most are trinucleotide repeat disorders (CAG or GAA); includes the hereditary form of olivopontocerebellar atrophy
Note: if see atrophy of olive, pons, and cerebellum in young patient AND familial --> think Spinocerebellar ataxias
Note: if see the same in older patient with NO family history --> think Multiple System Atrophy

Front 50

What is Multiple System Atrophy?

Back 50

A group of movement disorders characterized by presence of glial cytoplasmic inclusions; include:
Sporadic form of olivopontocerebellar atrophy: ataxia, cerebellar dysfunction
Striatonigral degeneration: Parkinsonism without Lewy bodies (instead have glial cytoplasmic inclusions)
Shy-Drager syndrome (Parkinsonism with autonomic dysfunction)
Inclusions are positive for alpha-synuclein, ubiquitin, and alphaB-crystallin (hence, a synucleinopathy) and are present in oligodendrocytes and astrocytes (rather than neurons as in Parkinson’s disease)

Front 51

What characterizes the pathology of Huntington’s disease?

Back 51

Atrophy of caudate and putamen with loss of medium-sized spiny (GABAergic) neurons with corresponding gliosis

Front 52

What movement disorder is seen with Huntington’s disease?

Back 52

Chorea: jerky, hyperkinetic movements affecting all parts of the body
May also have dementia and depression (increased risk of suicide)

Front 53

What characterizes Huntington’s disease?

Back 53

Hereditary (AD) due to CAG trinucleotide repeat expansion in the gene (chromosome 4) encoding huntingtin; Paternal transmission is associated with anticipation (earlier onset in succeeding generations); larger repeats are also associated with earlier onset

Front 54

What is a likely diagnosis in a presentation of dementia with “fluctuating course” and hallucinations?

Back 54

Dementia with Lewy Bodies – dementia is fluctuating and associated with hallucinations and prominent frontal signs – important to ID because some drugs to treat AD (cholinesterase inhibitors) will worsen Dementia with Lewy Bodies – can see Lewy bodies (ubiquitin-positive) in brainstem as well as cortex, is a synucleinopathy (stains positive with synuclein)

Front 55

What characterizes Parkinson’s disease?

Back 55

Synucleinopathy: rare cases of juvenile AR Parkinson’s disease are due to mutations in the α-synuclein and parkin genes – patients present with Parkinsonism, 10-15% with dementia; treatment includes L-dopa and neurosurgery

Front 56

What is Parkinsonism?

Back 56

Clinical syndrome characterized by TRAP: Tremor (“pill-rolling”), Rigidity, Akinesia (diminished facial expression, slowness of voluntary movement), Posture and gait abnormalities (“festinating” gait: progressively shortened, accelerated steps) – all symptoms are due to damage to the nigrostriatal DA neurons (if damage is due to neurodegenerative disease --> Parkinson’s disease; other cause of damage include infectious, meperidine, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy)

Front 57

What are the diseases affecting motor neurons?

Back 57

ALS (progressive muscular atrophy and bulbar palsy)
Hereditary: Bulbospinal atrophy (Kennedy syndrome), Spinal muscular atrophy

Front 58

What is a hereditary form of motor neuron diseases?

Back 58

Bulbospinal atrophy (Kennedy syndrome) – X-linked due to CAG repeat in androgen receptor gene; presents as young adults with LMN disease as well as androgen problems (gynecomastia, testicular atrophy, low sperm count)

Front 59

What microscopic findings are seen in ALS?

Back 59

Bunina bodies in anterior horn neurons of spinal cord, loss of anterior horn cells, motor neurons in CN nuclei, myelinated axons in corticospinal tracts; neurogenic atrophy of skeletal muscle

Front 60

What gross findings are seen in ALS?

Back 60

Thinning of anterior roots of spinal cord, atrophy of precentral gyrus (UMN located here)

Front 61

How does a patient with ALS present?

Back 61

Early signs: asymmetric weakness of the hands, cramping and spasticity of the arms and legs
Later: fasciculations, Death: involvement of pulmonary muscles leading to pulmonary infections

Front 62

What characterizes ALS?

Back 62

Loss of LMN and UMN; M > F; 10% cases are familial with mutations in Cu-Zn SOD1 gene on chromosome 21

Front 63

What is the general presentation of diseases affecting motor neurons?

Back 63

Signs of LMN disease: Denervation of muscles (atrophy, weakness)
Sings of UMN disease: hyperreflexia, Babinski sign (positive if toes upgoing on scratch)

Front 64

What is the pathology involved in Friedrich Ataxia?

Back 64

Loss of neurons in cerebellar vermis (Purkinje cells) and dentate nucleus, brainstem (CN VII, X, XII), and in Clarke column of spinal cord; also, loss of axons and gliosis in posterior tracts, corticospinal, and spinocerebellar tracts in spinal cord

Front 65

How is the pathology of AT different from FA?

Back 65

In addition to spinocerebellar degeneration (e.g. loss of cerebellar Purkinje cells), will see telangiectasias and amphicytes (bizarre, enlarged nuclei due to inability to repair DNA) in many organs

Front 66

How is Ataxia-Telangiectasia (AT) different from Friedrich Ataxia (FA)?

Back 66

AR and childhood onset but due to mutation of ATM gene on chromosome 11; also in addition to cerebellar ataxia, patients have increased risk of x-ray-induced chromosome abnormalities; patients have telangiectasias in conjunctiva and skin, increased risk of lymphoid malignancies, and immunodeficiency

Front 67

What is spinal muscular atrophy?

Back 67

Group of AR diseases due to Survival Motor Neuron (SMN1) gene on chromosome 5; infantile form is the most significant with lowest survival (Werding-Hoffman disease)

Front 68

Which drugs are best for 1st, 2nd, and neuropathic pain, respectively?

Back 68

2nd: NSAIDs; 1st/2nd: Opioids; Neuropathic: Na+ channel antagonists and Gabapentin (Neurontin)

Front 69

What is the effect of Substance P at the spinal nociceptive synapse?

Back 69

It works synergistically with the NMDA receptor

Front 70

What is the effect of Glutamate at the spinal nociceptive synapse?

Back 70

Acts on AMPA receptor to generate APs; Acts on NMDA receptor to cause an influx of Ca2+ which subsequently leads to increased protein phosphorylation, NO production, and prostaglandin synthesis (can be blocked by NSAIDs), all of which lower the threshold to electrical excitability

Front 71

How does Acetaminophen work?

Back 71

It inhibits central prostaglandin formation (but not peripheral)

Front 72

What noxious chemicals cause electrical activation of primary afferents (e.g. C-fibers)?

Back 72

5-HT, Histamine, H+, Bradykinin

Front 73

How are NSAIDs effective against inflammatory or 2nd pain?

Back 73

They block molecular alterations that lead to the sensitization of nociceptive neurons (i.e. they block the peripheral sensitization of C-fibers to noxious chemicals by inhibiting the formation of prostaglandins), sensitization in the CNS may also be attenuated (by inhibiting central prostaglandin formation)

Front 74

What happens in the primary afferents and in the neurons of the spinal cord in response to acute injury?

Back 74

Primary afferents: immediately --> massive burst of action potentials, later on --> peripheral sensitization (regularly occurring APs); Neurons in spinal cord: immediately --> same as primary afferent, later on --> wind-up (progressively increasing frequency of APs) followed by central sensitization (maintenance of hyperexcitable state)

Front 75

What is meant by endogenous pain inhibition?

Back 75

Neuronal processes that arise primarily in the midbrain/brainstem periaqueductal gray (PAG), travel downwards to the spinal cord, and inhibit transmission of pain at the spinal synapses;
they contain NE and 5-HT neurons – the system may be activated consciously in response to learned reactions, emotionally, by noxious input or by drugs

Front 76

What types of pain are associated with neuropathic pain (e.g. with diabetic neuropathy)?

Back 76

Inflammatory pain as well as an intense, episodic, lightning-like pain with sensitivity to touch

Front 77

What is meant by 1st pain and 2nd pain?

Back 77

1st pain is pain in the acute phase: intense/sharp; 2nd pain is pain in the tonic/chronic phase: occurs as tissues become inflamed, aching/burning/throbbing/sensitivity to touch (allodynia)

Front 78

Which α2-adrenergic agonist has a greater effect on the nervous system than on the cardiovascular system?

Back 78

Dexmedetomidine

Front 79

How does the anti-depressant Amitriptyline block chronic pain?

Back 79

It alters the “affective reaction” to pain, and it blocks reuptake of monoamines (e.g. 5-HT) thus affecting noxious input

Front 80

What are the effects of general anesthetics at safe doses?

Back 80

They block the perception of pain by inhibiting synapses in route to the cortex to create unconsciousness; at these safe doses most agents attenuate, but do not eliminate transmission of impulses at synapses in the CNS – because of this the patient will be unaware, but reflex movements and autonomic responses will still occur (supplementation with opioids is often required to block pain reflex actions)

Front 81

How do local anesthetics work?

Back 81

Prevent conduction of pain impulses by blocking Na+ flux into nerves; applied peripherally or spinally

Front 82

What characterizes Capsaicin?

Back 82

Extract from hot red peppers, applied topically; Depletes Substance P from pain sensory afferents (attenuates peripheral/central sensitization phenomenon); Takes a few weeks to become maximally effective

Front 83

What adverse effects are associated with Tramadol?

Back 83

Dizziness, vertigo, constipation, n/v, pruritus, xerostomia

Front 84

What characterizes Tramadol (Ultram)?

Back 84

MOA: weak affinity for opioid receptors, and blocks reuptake of NE/5-HT;
Metabolized to O-desmethyltramadol (M1, has a much greater affinity for the opioid receptor);
Tramadol can act as an opioid antagonist when the patient is taking a full opioid agonist like Morphine, partially reversing the analgesia generated by the Morphine, as well as initiating mild withdrawal actions in chronic Morphine users

Front 85

What are the actions of Opioids?

Back 85

They block the release of Glutamate and Substance P from nociceptive presynaptic terminals of primary afferents (which are upregulated during inflammation); They hyperpolarize postsynaptic neurons; They change the affective reaction to pain

Front 86

What is the mechanism of action of α2-adrenergic agonists (e.g. Clonidine) on neurons?

Back 86

They mimic the action of endogenous NE released from descending pain inhibitory pathways (blocks Glutamate/Substance P release from primary afferents), require spinal/epidural delivery

Front 87

What are the effects of Opioids on spinopetal neurons (from PAG)?

Back 87

They block the inhibitory actions of the GABAergic neurons, thus leading to disinhibition and a subsequent increase in NE/5-HT release (since NE/5-HT are inhibitory to pain input, this will decrease the perception of pain)

Front 88

What can be said about the treatment of neuropathic pain?

Back 88

Does not respond well to NSAIDs or Opioids; Responds to anticonvulsants (e.g. Carbamazepine or local anesthetics like Mexiletine) and Gabapentin/Pregabalin (inhibit Ca2+ flux which may potentiate GABA, though not via direct interaction with the GABA receptor) – best response is found with a combination of drugs directed at different parts of the problem

Front 89

What is the most common congenital malformation of the brain in human fetus?

Back 89

Anencephaly: F >M, develops at gestation day 28, with folate (!) deficiency being a possible risk factor *** KNOW

Front 90

What is polymicrogyria?

Back 90

Excessive folds of “micro-gyri” (small folds) that may be fused together or piled on top of each other, resembling cobblestones or Moroccan leather, resulting in an abnormally thin, laminated, excessively folded cortical ribbon – may be due to intrauterine infections (CMV), intrauterine hypoperfusion, or metabolic disorders (Zellweger syndrome)

Front 91

What are disorders of cell migration?

Back 91

Too many gyri: Polymicrogyria
Too few gyri, smooth brain: Lissencephaly (agyria, type I: failure in normal cell migration, type II: over-migration of neurons)
Neuronal heterotopias

Front 92

What organs are affected in Meckel-Gruber syndrome?

Back 92

Occipital encephalocele, polydactyly, polycystic kidneys, hepatic fibrosis with bile duct proliferation

Front 93

What is encephalocele?

Back 93

Diverticulum of malformed CNS tissue through a defect in the cranium – mostly in occipital region

Front 94

What are the pathological findings in anencephaly?

Back 94

Area cerebrovasculosa (flattened remnant of disorganized brain tissue with admixed ependyma, choroid plexus, and meningothelial cells), shallow orbits with eye protrusion, calvarium is hypoplastic or absent, descending fiber tracts are absent, brainstem and cerebellum are often spared

Front 95

How is anencephaly detected prenatally?

Back 95

Detected prenatally by screening maternal blood for elevated alpha-fetoprotein (!) *** KNOW

Front 96

What are neural tube defects caused by failure of neural tube closure?

Back 96

Anencephaly (cranial end closure defect), Myelomeningocele (caudal end closure defect), Craniorachischisis, Exencephaly

Front 97

What are neural tube defects caused by herniation of neural tissue/meninges thru a defect in skull or vertebtral column?

Back 97

Encephalocele (cranial end protruding out), Meningocele (spinal cord protruding out)

Front 98

What is myelomeningocele?

Back 98

Neural tissue and meninges herniate through a vertebral defect – mostly in lumosacral region  mostly affect lower extremities (motor, sensory) and bowel/bladder control; may be associated with Chiari II syndrome; the protrusion may be covered by skin or thin membrane, and central spinal canal may open and blend into skin

Front 99

What are midline patterning defects?

Back 99

Problems with separation of brain hemispheres; include Holoprosencephaly (incomplete or faulty separation of cerebral hemispheres), Agenesis of the corpus callosum, Septo-optic dysplasia

Front 100

What are different types of Chiari malformations? (types III and IV not on exam)

Back 100

Chiari I = cerebellar tonsils extend into the upper cervical canal, not due to increased intracranial pressure – not serious and surgically treatable
Chiari II = Arnold-Chiari = displacement of vermis into the upper cervical canal, always associated with a myelomeningocele, main risk factor is maternal Vitamin A deficiency

Front 101

What are cerebellar malformations?

Back 101

Chiari malformations
Too big posterior fossa: Dandy Walker malformations

Front 102

What characterizes agenesis of corpus callosum?

Back 102

Incidental finding, may be seen with other malformations; patients have higher incidence of mental retardation and seizures; will show slightly dilated ventricles with an irregular “batwing” contour

Front 103

What conditions often accompany holoprosencephaly in the affected individual?

Back 103

Craniofacial anomalies: single eye (cyclopia), proboscis (instead of nose) in severe cases; hypotelorism, cleft lip/palate in moderate cases; single midline incisor in mild cases – note: craniofacial abnormalities are often a clue to the severity of underlying holoprosencephaly
Brain abnormalities: single ventricle (instead of two lateral ventricles), fusion of deep gray structures in midline (basal ganglia, thalami), absent corpus callosum/olfactory bulbs/tracts
Note: least severe abnormalities: absence of one olfactory bulb/tract (cannot smell on one side), single midline incisor

Front 104

Mutation in what gene has been associated with holoprosencephaly?

Back 104

Mutations in the Sonic hedgehog gene have been identified in AD cases

Front 105

What conditions are associated with holoprosencephaly?

Back 105

Trisomy 13 and maternal diabetes

Front 106

What is the most common type of Lissencephaly?

Back 106

Type I: inherited; due to under-migration of neurons - cortex is too thick for gestational age, and only contains 4 layers of cells; in localized form, it is referred to as “pachygyria”

Front 107

What is cerebral heterotopia?

Back 107

Misplaced brain tissue; a lesser form of migration abnormality than lissencephaly and polymicrogyria; include cortical dysplasia (heterotopic neurons in layer 1); are associated with focal epilepsy (treatable by surgery)

Front 108

What is Type II Lissencephaly (cobblestone lissencephaly)?

Back 108

Due to over-migration of neurons – brains shows highly disordered cerebral cortical structure; may lead to cerebellar and ocular abnormalities & congenital muscular dystrophy; is due to defect in O-mannosylation

Front 109

What pathologic findings are seen in Chiari II malformation?

Back 109

Lumbosacral myelomeningocele, displacement of vermis into the upper cervical canal, 2’ Hydrocephalus (due to obstruction from vermis displacement)
4th ventricle, pons, and medulla are elongated, Kinked (“S”-shaped) lower medulla, Fusion (“beaking”) of the inferior tectum/colliculi
Note: any time have a baby with lumbosacral myelomeningocele --> scan for Chiari II

Front 110

What are spinal cord malformations?

Back 110

Hydromyelia (dilation of central canal lined with normal ependymal cell)
Syringomyelia (dilation of central canal not lined with ependymal cells – instead, have glial lining)
Note: syringomyelia has association with neoplasms of spinal cord
Duplication of spinal cord: diplomyelia
Partial duplication of spinal cord: diastematomyelia

Front 111

What drug use is associated with Dandy Walker malformation?

Back 111

Isotretinoin use during pregnancy

Front 112

What is Dandy Walker malformation?

Back 112

4th ventricle dilation causing hypoplasia or absence of cerebellar vermis --> causing enlargement of posterior fossa --> causing elevation of tentorium (between cerebrum and cerebellum) and transverse sinus; also can see hydrocephalus

Front 113

What is seen grossly in brain with diffuse hypoxic/ischemic encephalopathy?

Back 113

Diffuse cerebral edema with dusky-colored gray matter lesions, pseudolaminar necrosis of neocortex (infarct of layers III and V), “watershed” infarcts in regions with blood supply overlap

Front 114

What are the gross and microscopic findings in subacute infarct?

Back 114

Gross: gelatinous, friable tissue (“cracking artifact”), more distinct boundary between normal/abnormal
Microscopic: macrophage predominance, reactive astrocytes --> gliosis

Front 115

What are the gross and microscopic findings in acute infarct?

Back 115

Gross: soft, edematous tissue; corticomedullary junction becomes indistinct
Microscopic: pale tissue, “red and dead” neurons, neutrophils

Front 116

What are the sources of emboli in cerebral vessels?

Back 116

Cardiac mural thrombi, plaques within carotid arteries, paradoxical emboli (congenital heart disease), tumor/fat/air emboli – most commonly involves MCA region

Front 117

What are the most common sites for thrombosis in cerebral vessels?

Back 117

Carotid bifurcation, origin of the MCA, ends of the basilar artery; major contributing cause for thrombosis is cerebral atherosclerosis (risk factors: HTN, diabetes)

Front 118

How are infarcts categorized based on time?

Back 118

Acute: up to 48hrs – Subacute: 2-3 days to several weeks – Remote: >1 month

Front 119

What are various types of infarcts?

Back 119

Non-hemorrhagic (pale, bland, anemic): due to arterial thrombosis (usually from atherosclerosis), can be treated with anticoagualants/fibrinolytics, may become hemorrhagic
Hemorrhagic (red): due to embolism or venous thrombosis, anticoagulant is CI
Note: do imaging studies to determine if hemorrhagic or non-hemorrhagic --> determine treatment
Note: ischemic infarct may become hemorrhagic 2’ to anti-coagulant therapy

Front 120

What is stroke?

Back 120

Abrupt onset of focal or global neurological symptoms caused by hypoxia/ischemia or hemorrhage lasting more than 24 hours – if symptoms resolve in <24hrs, it is called “transient ischemic attack” (TIA)
Note: hypoxia is low pO2 supply to tissue for any reason (low inhaled O2, CO poisoning, inhibition of oxygen use by tissue); ischemia is due to reduction in perfusion pressure (hypotension) or obstruction of blood vessels

Front 121

What are pathologic findings in diffuse hypoxic/ischemic encephalopathy?

Back 121

Selective vulnerability: death of gray matter more than white matter (neurons more sensitive to hypoxia than glial cells) – within gray matter, CA1 region of hippocampus, Purkinje cells of cerebellum, and pyramidal neurons in neocortex (layers III and V) are the most susceptible

Front 122

What types of ischemic damage can occur in brain?

Back 122

Focal cerebral ischemia (infarct) due to thrombosis or embolism
Global cerebral ischemia (diffuse hypoxic/ischemic encephalopathy) due to cardiac arrest, shock, severe hypotension --> Mild cases: leads to transient confusion with recovery;
Severe cases: PVS, brain death, role for mechanical ventilation to save the brain (“respirator brain”)

Front 123

What are different types of aneurysms?

Back 123

Saccular (berry) aneurysms – “congenital” (not present at birth, but predisposing factors present at birth)
Atherosclerotic (fusiform) aneurysms; mycotic (infectious) aneurysms; traumatic, dissecting aneurysms

Front 124

What are the most common sites for hypertensive hemorrhage?

Back 124

Basal ganglia (putamen), thalamus, pons, cerebellum (HTN hemorrhage occurs deep in the brain)

Front 125

What is the most common cause of intracerebral hemorrhage?

Back 125

Hypertension – accounts for 50% of clinically significant hemorrhages; thought to cause weakening of arterial vessels or small microaneurysms (Charcot-Bouchard)

Front 126

What are various hypertensive cerebrovascular diseases?

Back 126

Hypertensive intracerebral hemorrhage, lacunar infarcts, hypertensive encephalopathy

Front 127

What is the classic presentation of saccular aneurysm rupture?

Back 127

“Worst headache I’ve ever had” with collapse – associated with increased intracranial pressure (straining at stool, sexual orgasm) – 25-50% of patients die with first rupture, rebleeding common in survivors, rupture may lead to vasospasm of adjacent vessels leading to ischemic injury/infarcts, reorganized blood in CSF space can cause obstructive hydrocephalus

Front 128

What are the predisposing factors for saccular (berry) aneurysms?

Back 128

Most important: cigarettes, HTN, AD polycystic kidney disease, CT-related problems (Ehlers-Danlos, Marfan, neurofibromatosis, fibromuscular dysplasia)

Front 129

What characterizes saccular (berry) aneurysms?

Back 129

2% of post-mortem brains, mostly sporadic, due to underlying defect in tunica media
Most common locations: anterior circulation (ACA-Acomm junction), bifurcation of MCA, MCA-internal carotid junction, tip of basilar artery where PCA comes off

Front 130

What are the gross and microscopic findings in remote infarct?

Back 130

Gross: cystic cavity
Microscopic: cavity (clear space) surrounded by gliosis

Front 131

What are the two most common settings causing subarachnoid hemorrhage?

Back 131

Trauma (#1 answer on exam), rupture of a saccular (berry) aneurysm

Front 132

How does hemorrhagic acute/subacute/remote infarct differ from non-hemorrhagic?

Back 132

Hemorrhagic will have extravasated blood cells in an otherwise similar-looking lesion

Front 133

What is the disease that causes amyloid deposition in cerebral vessels?

Back 133

Cerebral amyloid angiopathy: Amyloidogenic proteins (usually Aβ40) deposit in the walls of medium- and small-caliber meningeal and cortical vessels – microscopically, vessels will have apple-green birefringence under polarized light with congo-red stain due to amyloid deposition
Note: if see hemorrhage in a place that’s uncommon for HTN hemorrhage, think about amyloid angiopathy

Front 134

What is suspected in a young patient presenting with recurrent strokes, free of any risk factors for stroke, and a strong FH of stroke?

Back 134

CADASIL: rare, hereditary form of stroke due to mutations in Notch3 gene; Characterized clinically by recurrent strokes (usually subcortical infarcts, sometimes hemorrhages); diagnosed by finding Notch3 mutations or by biopsying vessels of skin/muscles (looking for concentric thickening of media and adventitia, as well as basophilic, PAS-positive deposits)

Front 135

What is primary angiitis of CNS?

Back 135

Inflammation of blood vessels only in CNS (aka granulomatous angiitis of CNS); some cases may be due to VZV reactivation; treatment is steroids/immunosuppressants
Note: granulomatous inflammation of blood vessels only in CNS --> think primary angiitis

Front 136

How can vasculitis lead to cerebral hemorrhage?

Back 136

Infectious vasculitis, primary angiitis of CNS, systemic vasculitis (most common cause is polyarteritis nodosa)

Front 137

How is cavernous angioma different from AV malformations?

Back 137

Distended, thin-walled vessels without intervening brain tissue - bleed less often than AV malformations, but can cause clinically insignificant bleeds forming old hemorrhages/calcifications

Front 138

What characterizes AV malformations?

Back 138

M>F, more in 10-30yo men; can cause seizures, intracerebral hemorrhage, or subarachnoid hemorrhage; is seen as tangled mass of abnormal vessels separated by gliotic brain tissue

Front 139

What vascular malformations in brain tend to bleed (clinically significant)?

Back 139

AV malformations (#1 type), cavernous angiomas (capillary telangiectasia and venous angioma are incidental findings that tend not to bleed)

Front 140

What changes are seen in hypertensive hemorrhage?

Back 140

Thickening of arterioles (hyaline change), extravasation of blood with compression of surrounding tissue, hypoxic/ischemic change and edema in adjacent tissue;
Old lesions: hemosiderin-laden macrophages and gliosis

Front 141

What is hypertensive encephalopathy?

Back 141

Clinical syndrome – if due to acute HTN, patient can come in with diffuse cerebral dysfunction (headaches, confusion, vomiting, coma); if due to chronic HTN, patient can have “multi-infarct dementia” (dementia, gait abnormalities, focal neurological deficits)

Front 142

Besides intracerebral hemorrhage, what can occur in the brain as a result of HTN?

Back 142

Single or multiple small cavitary infarcts called “lacunar infarcts”, <15mm in size, occur in same locations as HTN hemorrhage – cavitary lesions contain macrophages and gliosis; microscopically, appear as vessels with widened perivascular spaces (État crible)

Front 143

What characterizes peripheral neuropathy?

Back 143

Most common cause of weakness; starts in feet/hands/stocking and glove principal b/c longest nerves are affected first; length-dependent in origin/nature; can affect any/all parts of nerve; knowing which components of nerve are affected helps narrow DD

Front 144

Is ALS a central or peripheral disease?

Back 144

Both; involves UMN & LMN; affects corticospinal tract so get brisk reflexes; ONLY EMG

Front 145

What characterizes ALS?

Back 145

Combination of UMN signs (brisk reflexes) with LMN signs (atrophy, fasciculations); EMG helps support dx when shows fasciculations (but NO sensory loss); no other dx tests; must r/o others

Front 146

What are examples of anterior horn cell/motor neuron diseases?

Back 146

ALS, SMA, polio, radiation, lymphoma

Front 147

What characterizes anterior horn cell diseases?

Back 147

Motor neuron diseases; motor only, NO sensory; can start anywhere even speech/swallowing

Front 148

What tests are used in peripheral neuropathy?

Back 148

EMG/nerve conduction studies, blood tests, spinal tap, biopsy

Front 149

What are the causes of peripheral neuropathy?

Back 149

Hereditary (CMT), metabolic (DM, thyroid, vit B12), infectious (leprosy, HIV), entrapment (CTS), inflammatory (Guillan-Barre, CIDP, vasculitis), toxic, tumors

Front 150

What are the steps in determining the type of neuromuscular problem you have?

Back 150

1) central vs peripheral, 2) component/localization of the central or peripheral, 3) timing/history

Front 151

Working from the top down, what are the possibilities as sources of weakness?

Back 151

Motor cortex, anterior horn cell, peripheral nerves, NMJ, muscle

Front 152

What are the possible peripheral components (prox to distal)?

Back 152

Anterior horn cell (ALS, SMA), peripheral nerve, which could include roots, plexus, nerves, etc (CMT, DM), NMJ (Myasthenia Gravis, Lambert Eaton), muscle (Duchenne’s, polymyositis)

Front 153

What characterizes Lambert-Eaton?

Back 153

Also involves ABs; often from small cell lung CA; ABs bind to Ca ch’s in presynaptic portion of nerve; prevents Ca from entering, prevents ACh release, presynaptic dz; weakness but briefly improves with exercise, then worse again; reflexes reduced but briefly improve with exercise

Front 154

What is the tx for NMJ defects?

Back 154

Immunosuppression (prednisone, azathioprine, cellcept), AChE inhibitors (mestinon), thymectomy, CA removal, plasma exchange/IVIG

Front 155

How do you evaluate NMJ defects?

Back 155

Tensilon test (inject IV, inhibits AChE so ACh lasts longer; must have crash cart and atropine nearby); NCS/EMG with repetitive stimulation to fatigue NMJ; ABs

Front 156

What are the examination findings in NMJ defects?

Back 156

FATIGABLE weakness anywhere (bulbar, ocular motility, appendicular), so, when m testing, must hold arms up for awhile first then test; have them look up to set off ptosis; reflexes NL except in LEMS, dysarthria, SOB, must take seriously all the time/may need urgent admission

Front 157

What are examples of pre and postsynaptic NMJ dz’s?

Back 157

Pre: botulism, Lambert-Eaton, congenital myasthenia; post: myasthenia gravis, congenital myasthenia

Front 158

What are common NMJ defects?

Back 158

More common in adults; fatigable weakness; diplopia, ptosis; more proximal than distal; painless/no sensory change; may be insidious; M. gravis most common.

Front 159

What is typical of presentation of myasthenia gravis?

Back 159

Affects young women and old men; see fatigable weakness

Front 160

How is ALS treated?

Back 160

LE is 3-5 years, can be extended 3 mos with riluzole, a glutamate antagonist; supportive care

Front 161

What characterizes myasthenia gravis?

Back 161

Body directs ABs against ACh rec’s & destroys them → when ACh is released, can’t bind to rec’s → weakness, a postsynaptic disease; weakness worsens with ex, reflexes NL, associated with other AI diseases

Front 162

What are the two main diseases of the NMJ?

Back 162

Myasthenia gravis & Lambert-Eaton S.

Front 163

What characterizes myopathies?

Back 163

Will see motor deficits only, NOT sensory loss; proximal is worse than distal weakness (opposite of neural problems which are length dependent); see atrophy, no sensory abNLs

Front 164

How are myopathies treated?

Back 164

Depends on dx – treat underlying problem or immunosuppression; supportive, counseling.

Front 165

How are myopathies evaluated?

Back 165

NCS/EMG with NL NCS and abNL motor unit APs; lab studies (CK), genetic testing, heart/lung testing, muscle bx.

Front 166

What are the clinical findings in myopathies?

Back 166

Proximal greater than distal weakness; pattern of weakness may help ID type of myopathy; can see associated skin rash, early respiratory problems, cardiomyopathy, or arrythmias; may first present to pulmonologist or after anesthesia trouble.

Front 167

What are the types of myopathies?

Back 167

Inflammatory (polymyositis, dermatomyositis, inclusion body myositis), metabolic (thyroid), toxic (cholesterol lowering agents, prednisone), mitochondrial, infectious, hereditary (Duchenne, Beckers, Limb-Girdle, Myotonic Dystrophy), congenital (central core, nemaline); the most common are inflammatory and hereditary.

Front 168

What is the risk of using Isotretinoin (Accutane) for cystic acne treatment?

Back 168

HIGHLY teratogenic, causing craniofacial and cardiovascular defects

Front 169

What is a premalignant precursor for Squamous Cell Carcinoma?

Back 169

Actinic keratosis

Front 170

What does “pearly papule” describe?

Back 170

Basal Cell Carcinoma, Malignant cells from the basal layer of the epidermis

Front 171

What are ABCDE’s of Malignant Melanoma?

Back 171

Asymmetry, Border irregularity, Color variegation, Diameter, Evolving

Front 172

What is the number one prognostic factor in Malignant Melanoma?

Back 172

Thickness

Front 173

Hepatitis C virus infection is associated with what type of skin disorder?

Back 173

Lichen Planus

Front 174

What characterizes anaplastic astrocytomas?

Back 174

aka “malignant” or “high-grade” astrocytoma, may arise de novo or from low-grade astrocytoma

Front 175

What is histologically seen in pilocytic astrocytomas?

Back 175

Pilocytic: cells appear “hair-like” and elongated – are biphasic in pattern (dense + loose patterns) – show Rosenthal fibers (one of the astrocytic responses to injury)

Front 176

What are the signs and symptoms of pilocytic astrocytoma?

Back 176

Optic nerve/chiasm --> visual defects; Hypothalamus --> diabetes insipidus; Cerebellum --> ataxia; Brainstem --> increased intracranial pressure (all occur in children, first 20 years of life)

Front 177

What characterizes pilocytic astrocytomas?

Back 177

WHO grade I, #1 glioma in children, may be seen with neurofibramotisis I
Common sites: cerebellum, optic nerve/chiasm, hypothalamus, brainstem (all below tentorium)
Present as discrete, contrast-enhancing cysts with mural nodule - can be excised (excellent prognosis)

Front 178

What are the genetic alterations implicated in astrocytomas?

Back 178

Primary glioblastoma: EGF-receptor amplication, loss of PTEN gene on chromosome 10
Secondary gliobastoma: p53 mutation
Note: Primary: 50yo comes in with ring-enhancing lesion of glioblastoma, no history of low-grade lesions
Note: Secondary: 30yo comes in with seizure, diagnosed as diffuse astrocytoma, excised as much as possible, comes back 4 years later with ring-enhancing lesion diagnosed as glioblastom

Front 179

What are the prognostic factors for various astrocytomas?

Back 179

Age (worse grade at higher age), proliferation markers (mitotic activity correlates with worse prognosis), extent of surgical resectability – all are non-curable

Front 180

What characterizes Glioblastoma?

Back 180

May arise de novo (primary glioblastoma) or from low-grade astrocytoma (secondary glioblastoma), short clinical history unless developed from low-grader astrocytoma, poorest prognosis (death in 1-2 years), histologic variants include gliosarcoma and giant cell glioblastoma

Front 181

What are different astrocytic tumors?

Back 181

Grade I: pilocytic astrocytoma (#1 glioma in children – cystic lesion with mural nodule - curable);
Grade II: diffuse (low-grade) astrocytoma (30-40yo – no contrast enhancement on CT);
Grade III: anaplastic astrocytoma (40+ yo – show enhancement on CT);
Grade IV: Glioblastoma (50+ yo – ring-like zone of contrast enhancement, #1 primary brain tumor)
Note: grade I, in all CNS tumors, means curable by neurosurgery (!)
Note: allastrocytomas are more common in males, higher grade lesions tend to occur in older patients (!)
Note: adult astrocytomas (Grade II, III, IV) occur supratentorially and are non-curable – children astrocytoma (pilocytic astrocytoma) occur below tentorium and is curable;
Grade I: subependymal giant cell astrocytoma (assc. tuberous sclerosis – located in lateral ventricle);
Grade II-III: pleomorphic xanthoastrocytoma (superficial location – cystic lesion with mural nodule);

Front 182

What characterizes diffuse (low-grade) astrocytoma?

Back 182

Represent 25% of tumors of cerebral hemispheres, are diffuse, spread progressively, and are difficult to excise due to diffuseness – mean survival 6-8 years, most are supratentorial (e.g. occur in hemispheres, not common in cerebellum), manifest often with new onset of seizures

Front 183

What is seen histologically with astrocytomas?

Back 183

Diffuse (low-grade): increase in astrocytic cells --> diffuse expansion of white matter
Anaplastic: same as above + mitotic activity (can stain with proliferation markers to detect)
Glioblastoma: same as above + mitotic activity + vascular (endothelial) proliferation + necrosis
Pleomorphic Xanthoastrocytoma: like glioblastoma but no mitotis, vascular proliferation, or necrosis

Front 184

What characterizes oligodendrogliomas?

Back 184

(chicken tumor)
WHO grade II, 5-18% of all intracranial gliomas, peak 40-50yo (3-5 year post-operative survival), presents with longer history of neurological s/s than astrocytomas, hallmark feature is “calcifications on CT”
Histology: “fried-egg” cells with perincular halo, braching blood vessels called “chicken-wire”
Note: Chicken tumor: egg-shell calcifications, fried-egg cells, chicken-wire blood vessels
Note: oligodendrogliomas are sensitive to chemotherapy, astrocytomas are not (!)

Front 185

What characterizes anaplastic ependymoma?

Back 185

WHO grade III - will show mitotis, vascular proliferation, necrosis; higher grade does not mean poorer prognosis than low-grade ependymoma (!)

Front 186

How can one distinguish between clear cell ependymoma (clear cells) and oligodendrogliomas?

Back 186

Both have clear cytoplasms around central nucles (fried-egg like), but clear cell ependymomas occur in the ventricles (!)

Front 187

What are various types of rossetes in CNS tumors?

Back 187

True (ependymal) rosettes: ependymal cells line up to form a true lumen – diagnostic of ependymomas
Perivascular pseudorosettes: ependymal cells line up againt central blood vessel – common in ependymoma
Homer-Wright rosettes: no true or pseudo lumen exists, fibrillary material fill up the center
Note: if see perivascular psuedorosettes --> think ependymomas

Front 188

What characterizes (low-grade) ependymoma?

Back 188

WHO grade II, 3-9% of all neuroepithelial tumors, #1 primary tumor of spinal cord – tumor of ependymal cells predominantly intraventricularly (with increased intracranial pressure); can also occur in ependymal cells of spinal cord central canal (more common in adults)

Front 189

What genetics is involved in oligodendrogliomas?

Back 189

Loss of chromosome 1p and 19q (except for anaplastic types: 9p loss --> worse prognosis)
Note: depending on which loss, treatment is chosen (1p, 19q --> better prognosis, 9p --> worse prognosis)

Front 190

What characterizes anaplastic oligodendrogliomas?

Back 190

Same as above, except will have mitosis, vascular proliferation, and necrosis, and loss of chromosome 9p (worse prognosis)

Front 191

What characteriezes pleomorphic xanthoastrocytoma?

Back 191

WHO grade II-III, less than 1% of astrocytomas, superficially located with easy excision – may look like glioblastomas (peak age 50+) but occur in young patients with long history of seizures (not new onset as in diffuse astrocytoma) – appear as cystic lesion with mural nodule – thought to originate from subpial astrocytes
Note: if hear cystic lesion with mural nodule --> think either pilocytic astrocytoma or this (!)

Front 192

What characterizes subependymal giant cell astrocytoma?

Back 192

WHO grade I, occur in children (0-20yo), associated with tuberous sclerosis – tumor is found in lateral ventricles (intraventricular tumor), when tumor develops in tuberous sclerosis patients (have epilepsy), the epilepsy gets much worse or intracranial pressure increases (due to obstruction in ventricles)
Note: tuberous sclerosis setting + astrocytic lesion --> think subependymal giant cell astrocytoma

Front 193

What characterizes the histology of pleomorphic xanthaastrocytomas?

Back 193

As ugly as glioblastoma but no mitosis, vascular proliferation, or necrosis – unique feature is “chronic inflammatory infiltrate” due to slow-growing of tumor (long history of seizures)

Front 194

What genetics are associated with ependymomas?

Back 194

Monosomy 22, associated with neurofibromatosis II (which also has mutation in chromosome 22)

Front 195

What should be suspected in a children with metastatic tumor of CNS origin?

Back 195

Choroid plexus carcinoma

Front 196

Is metastasis significant in CNS tumors?

Back 196

No – since the CNS effect of these tumors kill the patient before any significant metastasis presents
Exception: choroid plexus carcinomas in children metastasize and disseminate via meninges (!)

Front 197

What location is associated with choroid plexus tumors?

Back 197

Intraventricular: adults (4th ventricle), children (lateral ventricles), M>F, can cause obstructive hydrocephalus

Front 198

What are the various choroid plexus tumors?

Back 198

Most common are papillomas (5:1) - Choroid plexua papilloma (WHO grade I - curable), Choroid plexus carcinoma (WHO grade III – 80% occur in children – can metastasize)

Front 199

What is a curable form of ependymoma?

Back 199

Myxopapillary ependymoma (WHO grade I): occur in “filum terminale”, peak age 35yo, M>F
Subependymoma (WHO grade I): occur “intraventricular”, #1 site is 4th ventricle, incidental finding, M>F

Front 200

What characterizes Medulloblastoma/sPNET?

Back 200

(malignant)
Small, round, blue cells tumor of childhood (embryonal tumor) – can have neuronal and/or glial differentiation – uniquely have Homer-Wright pseudorosettes (no true lumen, fibrillar in center)
Medulloblastoma (always in cerebellum): good prognosis with chemotherapy, isochromosome 17q
sPNET (always in hemispheres): bad prognosis, incurable (s = supratentorial)

Front 201

What characterizes Hemangioblastoma?

Back 201

Sporadic or associated with VHL disease – #1 site is cerebellum – have cyst with mural nodule (--> Grade I)
Histology: composed of vessels (varying sizes) + neoplastic cells (lipidized/foamy stromal cells)

Front 202

What is the classification for a Meningioma that shows mitotic figures?

Back 202

Atypical meningioma (Grade II lesion)

Front 203

What is the only CNS tumor that is more common in females? ***********

Back 203

Meningioma: usually attached to dura, mostly benign + resectable (Grade I), show diffuse contrast enhancement – associated with chromosome 22 loss, various histologies possible – associated with NFII
Note: neurofibromatosis II is associated w/ chromosome 22 loss --> may have multiple meningiomas
Note: know meningiomas are F>M, associated with NFII, many histologic patterns

Front 204

What is the most common tumor of the pineal gland?*********

Back 204

**Germ cell tumor of pineal – pineocytoma (benign, in adults, composed of round/regular pineal ells + pineocytoma rosettes), pineoblastoma (malignant, in children - small, round, blue cell tumor)
Note: if show small, round, blue cell tumor in cerebellum --> medulloblastoma (curable)
Note: if show small, round, blue cell tumor in hemispheres --> sPNET (incurable)
Note: if show small, round, blue cell tumor in pineal --> pineoblastoma

Front 205

What CNS tumors are seen that resemble dysgerminoma/seminoma of genitals?

Back 205

Germ cell tumors: germinoma, teratoma, yolk sac tumor, embryonal carcinoma, choriocarcinoma, mixed germ cell tumors

Front 206

In what patients Primary CNS Lymphomas are seen?

Back 206

(most are diffuse B-cell lymphomas)
Immunosuppressed patients (HIV, transplant) – most are EBV-associated – most cases are diagnosed by CSF evaluation, poor prognosis despite therapy

Front 207

What characterizes Dysembryoplastic Neuroepithelial Tumors (DNT)?

Back 207

(mixed tumor)
Occur in young patient with medically intractable epilepsy and temporal lobe lesions, commonly associated with cortical dysplasia (also causes seizures); lesions are intracortical and superficial, mimic oligodendroglioma but have neurons – probably not true neoplasma (hamartomatous)
Histology: oligodendroglioma-like cells (perincular halo) + neuronal cells “floating” in the background of glioma
Case: 20yo patient with long history of seizures, unresponsive to all AEDs, scan shows superficial temporal lobe lesion, biopsy shows oligodendroglioma-like cells but also shows neurons

Front 208

What characterizes Central Neurocytoma?

Back 208

Occur in adults - composed exclusively of neuronal cells, resembles oligodendroglioma but neuronal markers (synaptophysin) show the exclusively neuronal composition – occurs in lateral ventricle, near foramen of Monro – good prognosis, surgically curable (Grade I)

Front 209

What characterizes Ganglioglioma?

Back 209

(mixed tumor)
Occur in young patient with medically intractable epilepsy, presents as cyst with mural nodule, contains glial + “dysplatic” neuronal components, surgically curable (Grade I)
Histology: shows perivascular chronic inflammation, neuronal cells in background of glioma
Note: when hear youn patient with medically intractable epilepsy --> usually low-grade, curable lesion
Note: when hear cyst with mural nodule --> usually low-grade, curable lesion
Case: 20yo patient with long history of medically intractable seizures, lesion is cystic with mural nodule

Front 210

What is von Hippel Lindau disease?

Back 210

AD, loss of tumor suppressor on 3p25 --> can lead to hemangioblastoma of brain/retina – at risk for renal cell carcinoma, pheochromocytoma
Case: child with hemangioblastoma --> think VHL and 3p25 loss --> check for RCC, pheochromocytoma
Note: most CNS tumor syndromes are AD and due to loss of tumor suppressor genes (!)

Front 211

What is the most common cause of excess production of anterior pituitary hormones?

Back 211

Pituitary adenomas – may get bitemporal hemianopsia, pituitary apoplexy (acute hemorrhage into adenoma) - microadenoma < 1cm, macroadenoma > 1cm – look like adenomas --> need evidence of metastasis to make a diagnosis of carcinoma

Front 212

What is the malignant counterpart of neurofibroma?

Back 212

(Schwanommas do not become malignant)
Malignant peripheral nerve sheath tumor – are sarcomas (spindle shaped cells with mitotis and necrosis), tend to be in patients with *** NF type I (why? the more neurofibromas, the more chance of developing malignancy) – cells may show divergent differentiation (e.g. peripheral nerve + skeletal muscle), poor prognosis
Note: Triton tumor = MPNST with rhabdomyoblastic differentiation

Front 213

What characterizes Neurofibromatosis type I?

Back 213

(aka von Recklinghausen (17 letters) disease) = benign
AD, loss of tumor suppressor gene 17q11.2 – have multiple neurofibromas (“plexiform” neurofibromas), café-au-lait spots, Lisch nodules (eye lesion), may have glioma of optic nerve/hypothalamus or pheochromocytomas

Front 214

What characterizes neurofibroma, in general?

Back 214

= benign
Occur in skin (SC tissue) at distal ends of peripheral nerves: closely associated with and expand the peripheral nerve – composed of mixed cells (Schwann cells, perineural cells, fibroblasts) – may be de novo or in association with NF type I
Note: Schwanomma hangs off the peripheral nerve – Neurofibroma is intimately associated with the peripheral nerve and diffusely expands it (!) ****

Front 215

What can cause bilateral CN8 Schwanommas?

Back 215

= benign
Neurofibromatosis type II – AD, loss of tumor suppressor 22q12, develops bilateral CN8 schwanommas, ependymomas, meningiomas (!)
Note: patient with bilateral CN8 schwanommas --> definitely NFII --> ID because at increased risk for other brain tumors (meningiomas, ependymomas)

Front 216

What is Schwannoma?

Back 216

= benign
Can occur centrally (cranial cavity) --> on the CN8 (vestibular branch = vestibular schwanomma) or on peripheral nerves – are well-separated from the nerve tissue – show Verocay bodies
Occur in two patterns: Antoni A (dense, compact), Antoni B (loose, myxoid)
Note: Schwanommas do not undergo malignant degeneration (!)

Front 217

What portion of CNS tumors are due to metastatis?

Back 217

50% - tend to be multiple, well-demarcated, located at gray-white junctions, usually ring-enhancing
Note: ring-enhancing lesion in brain: glioblastoma (old patients), metastasis (old patient) (!)*******
Note: when see multiple lesions --> think metastasis
Above = CNS tumors
Now = PNS tumors

Front 218

What are the opioids 4 major sites of action?

Back 218

Peripheral pain receptors and nerves (during inflammation); Spinal, midbrain, thalamic and cortical nociceptive synapses (pain relays from periphery to cortex); Limbic brain (affective reaction); Endogenous pain inhibitory processes descending from brainstem to spinal cord

Front 219

What are the Endogenous Opioid Peptides that Opioids act by mimicking?

Back 219

Enkephalins, beta-endorphin, Dynorphins, Endomorphins

Front 220

What are two ways Opioids regulate Ca2+ Flow?

Back 220

(1) direct effect of G protein on the Ca2+ channel (causes inhibition of Ca2+ entry on a nerve terminal membrane, Ca2+ doesn’t move in, & neurotransmitter release will↓);
(2) indirect effect through the underlying biochemical process through cAMP (opioids alter adenylate cyclase & cAMP is ↓, so phosphoproteins aren't formed to extent they normally would be, & these are one of the things that keeps the Ca2+ channel open, if ↓, the Ca2+ channel becomes a little ineffective)

Front 221

What type of opioid receptor produces analgesia, sedation (drowsy), euphoria & respiratory depression?

Back 221

Mu receptor (vs Kappa (): analgesia, sedation (sleep), dysphoria & limited respiratory depression)

Front 222

What is characteristic of the Kappa-receptors?

Back 222

Selective agonists for kappa & also interact as antagonists at the --> receptor** (Mixed receptor function --> mixed agonist/antagonist)

Front 223

What substitution and where must occur to provide optimal receptor interaction of opioids and opioid receptors?

Back 223

Simple alkyl substitution on 17-N and a non- substituted 3-OH (Bulky substitutions at 17 position create partial agonists or antagonists at Mu opioid receptor)

Front 224

What type of substitutions can improve the bioavailability of opioids?

Back 224

Alkyl groups on OH at positions 3 & 6 decreases charge and improves oral bioavailability. Also, reduces first pass metabolism (i.e. Codiene (OCH3 & OH in positions 3 & 6 respectively); Oxycodone & Hydrocodone (OCH3 & =O at 3 & 6 respectively); Heroin (OCOCH3 at both positions))

Front 225

How is the combination product of Pentazocine (agonist) & Naloxone (antagonist) effective?

Back 225

Helpful in pts who may abuse drugs, admin PO b/c Naloxone wont go across GI tract & Pentazocine does, get analgesic effect of Pentazocine not blocked by the antagonistic effect of Naloxone, but if injected, Pentazocine analgesic/rush effect won’t happen b/c blocked by Naloxone

Front 226

What are Orally active Opioids, Orally active, but w/ decreased bioavailability, and Poor oral bioavailability opioid drugs?

Back 226

Orally active: Hydromorphone (Dilaudid)*, Pentazocine, Naltrexone;
Orally active, but w/ decreased bioavailability: Morphine, Meperidine (Demerol);
Poor oral bioavailability: Naloxone (Narcan)

Front 227

What are different ways opioids can be administered to avoid the first pass effect?

Back 227

Buccal (fentanyl lollipop (esp. children));
Sublingual (buprenorphine);
Intranasal (butorphanol);
Rectal suppositories;
Dermal patch (fentanyl, esp. cancer)

Front 228

What is the effect of glucuronidation of 6-OH in morphine (not involved in receptor binding)?

Back 228

Creates a compound morphine 6-glucuronide (M6G) which is an effective & potent Opioid agonist, M6G accumulates slowly in CNS, & may play a role when morphine is taken chronically (act as an active metabolite)

Front 229

What is the effect of glucuronidation of 3-OH in morphine?

Back 229

Morphine & other phenathrenes can’t be substituted at 3 OH position or it wont fit into receptor, M3G, the metabolite formed is a CNS excitant and can cause seizures

Front 230

What are the commonly used opioid drugs?

Back 230

Morphine (classic compound remains the gold standard); Heroin (popular drug of abuse in the US ); Nalbuphine (sedation always occurs with analgesia, kappa-receptor drug); Meperidine (used in dentistry & medicine); Fentanyl (highly potent, used in cancer and anesthesia)

Front 231

What are the moderately effective opioid drugs used to block pain?

Back 231

Codiene, oxycodone, hydrocodone;
Partial Agonist (Mu receptor): Buprenorphine;
Mixed agonists (agonists at kappa, antagonists at Mu receptor): Pentazocine, Nalbuphine, Butorphanol

Front 232

What are the opioid antagonists?

Back 232

Naloxone, Naltrexone

Front 233

What are the highly effective opioid drugs used to block pain?

Back 233

Morphine, meperidine, methadone, hydromorphone, oxymorphone heroin, levorphanol, fentanyl & congeners,

Front 234

What is the Triad of Symptoms seen in an opioid overdose?

Back 234

Miosis, Respiratory depression, Unconsciousness

Front 235

How do opioids cause constipation & how do you treat it?

Back 235

They cause decrease in propulsive movement (muscle is contracted rather than being rhythmical) & sphincters are closed & decreased secretions,; Chronic opioid use requires treatment, Stool softeners Docusate Na+ (Colace), Milk of magnesia, Stimulants Bisacodyl (Dulcolax)

Front 236

What are Diphenoxylate, Loperamide, & Paregoric used for?

Back 236

Used to treat diarrhea; Diphenoxylate & loperamide synthetic opioids with low abuse potential & Paregoric – and alcohol extract (tincture) of opium

Front 237

What is the order of sensitivity of the opioids for inducing biliary colic?

Back 237

Morphine > Meperidine > Codiene

Front 238

What is the metabolite of Meperidine and what characterizes it?

Back 238

Normeperidine: chronic use complicated by accumulation of CNS excitatory and proconvulsant metabolite

Front 239

How is the prominent itching in the facial area that occurs w/ opioids treated?

Back 239

Titration using an opioid antagonist (Naloxone or Naltrexone), antihistamines, minimally effective because the itch is opioid-R regulated

Front 240

What class of opioid drugs causes skeletal muscle rigidity?

Back 240

Phenylpiperidines in high doses, Basal ganglia involved, causes chest wall rigidity during anesthesia requires reversal (Opioid antagonist or skeletal muscle relaxant)

Front 241

What characterizes Dextromethorphan?

Back 241

Compound currently seen in OTC cough preparations, it is the d-isomer of an opioid & does not produce analgesia (l-isomers)

Front 242

What class of opioid drugs has the lower incidence of histamine release?

Back 242

Phenylpiperidines

Front 243

By what two mechanisms does nausea occur with opioid use?

Back 243

Chemoreceptor trigger zone and vestibular effect

Front 244

What is the phenomena called when a patent who takes opioids for an extended period of time & the body adapts so that stopping the drug may result in physiological disruption?

Back 244

Dependence

Front 245

What is the phenomenon that is classified by craving and drug-seeking behavior, perhaps to continue the rewarding (e.g. euphoria) aspects of the drug?

Back 245

Psychological Dependence

Front 246

What drug is used for opioid abuse that reduces action of illicit opioids?

Back 246

Buprenorphine: partial Mu opioid agonist

Front 247

What drug can be given to reduces sympathetically-mediated opioid withdrawal symptoms?

Back 247

Clonidine

Front 248

What type of receptors have the highest abuse potential?

Back 248

Mu opioid agonists (due to euphoric effect and development of psychological dependence) vs Partial Mu and Kappa agonists which have lower abuse potential
(Kappa agonist’s dysphoric effect)

Front 249

What is the difference between intravenous and inhalational general anesthetics?

Back 249

Intravenous: rapid onset (<1min), short duration (due to redistribution), can be given by continuous infusion to extend anesthesia (recovery is slower and depends on metabolism, excretion, degree of tissue accumulation, and duration of infusion --> context sensitive half-time);
Inhalational: slow onset (>4min), duration dependent upon tissue solubility, used for maintenance of anesthesia

Front 250

What characterizes Sufentanil (and other fentanyls)?

Back 250

Induction: <1min; Anesthesia: incomplete amnesia; Eliminate reflex reaction to pain: yes;
Muscle paralysis: no; BP: minimal change (cardiac contractility is mostly maintained!); Ventilation: decrease; Note: anesthesia supplemented due to concern for partial awareness

Front 251

What characterizes Midazolam?

Back 251

Same as Thiopental except that there is only a minimal change in BP/ventilation, it is a water-soluble benzodiazepine, and it is most commonly employed for conscious sedation or preoperative anxiety

Front 252

What characterizes Ketamine?

Back 252

Induction: <1min; Anesthesia: dissociative (!); Eliminate reflex reaction to pain: yes (!);
Muscle paralysis: no; BP: slight decrease; Ventilation: minimal change;
Note: it blocks the NMDA receptor (MOA), may produce emergence delirium (patients wakes up crying, having delusions/bad dreams), it is a PCP derivative

Front 253

What characterizes Etomidate?

Back 253

Same as Thiopental except that there is only a minimal change in BP/ventilation, and there is a decrease in adrenocortical response to stress (patients may need to receive glucocorticoids post-anesthesia in order to maintain their stress response; especially the elderly)

Front 254

What characterizes Propofol?

Back 254

Same as Thiopental except that with its use there is a decrease in the opioid requirement, it is an antiemetic (reduces overall feeling of nausea upon recovery), there is rapid recovery with extrahepatic metabolism, and pain on injection (because the formulation is a viscous solution)

Front 255

What characterizes Thiopental?

Back 255

Induction: <1min; Anesthesia: yes; Eliminate reflex reaction to pain: no; Muscle paralysis: no;
BP: transient decrease; Ventilation: depressed; Note: given by IV bolus, travels rapidly to brain to cause unconsciousness, used for induction of anesthesia

Front 256

What defines general anesthesia?

Back 256

A drug-induced loss of consciousness where patients cannot be aroused, even by painful stimulation (excludes reflexive reactions to pain as these are not considered a purposeful reaction initiated by conscious perception)

Front 257

What is a common sequence of balanced anesthesia?

Back 257

Propofol (provides rapid anesthesia) --> Succinylcholine (neuromuscular blocker, for placing ventilation tube) --> N2O and halogenated hydrocarbon (general anesthetic) --> narcotic (block reflexive pain) --> non-depolarizing neuromuscular blocker (maintain skeletal muscle paralysis)

Front 258

What are the aspects of an ideal anesthetic management?

Back 258

Hypnosis and amnesia, block reflex reactions to pain, provide skeletal muscle paralysis, maintain vital functions, rapid induction of anesthesia, physical safety

Front 259

What characterizes N2O?

Back 259

Induction rate: 3-5min; Anesthesia: incomplete; Eliminate reflex reaction to pain: yes;
Muscle paralysis: no; BP/ventilation: no change; Note: laughing gas, MAC only achieved at hyperbaric conditions, at 20-50% N2O in inspired air analgesia is excellent but memory/response to commands may not be completely suppressed, at >50% dysphoria and nausea may occur with a risk of aspiration and subsequent pneumonitis (!)

Front 260

What characterizes Halothane?

Back 260

Rare liver dysfunction

Front 261

What characterizes Isoflurane?

Back 261

Commonly used, good cardiovascular safety, increased sympathetic outflow, maintains cardiac output (!)

Front 262

What characterizes Desflurane?

Back 262

Bad odor, airway irritation, increased sympathetic outflow, maintains cardiac output (!)

Front 263

What characterizes Sevoflurane?

Back 263

Pleasant smell, nephrotoxic by-product (not prominent), combative behavior, disorientation

Front 264

Which inhalational volatile liquid anesthetics are not used anymore and why?

Back 264

Methoxyflurane: causes excessive fluoride production which is toxic to the kidney;
Ether: flammable and explosive

Front 265

What characteristics do most inhalational volatile liquid anesthetics have in common?

Back 265

Induction: 3-5min (Sevoflurane/Desflurane), 10-30min (Isoflurane, Halothane, Enflurane), >60min (Methoxyflurane); Anesthesia: yes; Eliminate reflex reaction to pain: some;
Muscle paralysis: minimal-some; BP: decrease; Ventilation: decrease (marked, use ventilator)

Front 266

What characterizes the inhalational anesthetics?

Back 266

There are two physical forms: gases (--> supplied in gas tanks, currently only N2O) and volatile liquids (--> delivered by vaporizers, several halogenated hydrocarbon anesthetics exist) –
Minimum Alveolar Concentration (MAC): a measure of dose/potency of inhalational anesthetics

Front 267

What are the MAC values associated with Desflurane and Halothane?

Back 267

Desflurane: 6.0; Halothane: 0.75 (this means that 0.75% of inspired air will consist of Halothane when 50% of patients are not responding to surgical incision)

Front 268

How is the minimum alveolar concentration (MAC) measured?

Back 268

As a percentage of lung gases that are anesthetic gas, when 50% of patients are not responding to surgical incision

Front 269

What are some special characteristics of the shorter-acting general anesthetics?

Back 269

Propofol: extrahepatic metabolism; Sevoflurane/Desflurane: low tissue solubility; Short-acting narcotic, Remifentanil: metabolized by RBC/tissue esterases

Front 270

How does alveolar tension increase with each breathing cycle as new gases are delivered?

Back 270

At an exponential rate, up to the inspired tension

Front 271

What characterizes the uptake/distribution of inhalation anesthetics?

Back 271

Partial pressure gradients control equilibria of gases between various tissue compartments;
Alveolar partial pressure of the anesthetics is the driving for to establish brain partial pressure (i.e. the partial pressure in the brain can never be higher than that in the alveoli);
The rate at which the alveolar tension of an anesthetic gas approaches the inspired tension is influenced by the rate of gas delivery to the lung and tissue solubility of the drug

Front 272

Which general anesthetics have the most beneficial context sensitive half-times?

Back 272

Ketamine, Propofol, Etomidate (Midazolam less so; Thiopental/Diazepam are bad)

Front 273

What characterizes the distribution of an IV bolus of an IV anesthetic over time?

Back 273

Brain/heart/liver/kidney --> skeletal muscle/skin --> connective tissue/adipose tissue/bone

Front 274

What characterizes the pharmacokinetics of IV anesthetics when given as an IV infusion?

Back 274

Done primarily with drugs that are rapidly metabolized and/or excreted; Computer-assisted delivery for longer procedures

Front 275

What characterizes the pharmacokinetics of IV anesthetics when given as an IV bolus?

Back 275

Rapid initial distribution to the brain due to proportionally higher CO to tissues like brain, as well as lipid solubility of drug; Short action of single IV bolus since it is rapidly redistributed from brain to skeletal muscle and skin – Bolus is ideal for induction, very short procedures, and as a supplement to other anesthetic procedures

Front 276

What characterizes Enflurane?

Back 276

Myoclonus (contraindicated in patients with a history of seizures)

Front 277

What is the purpose of “conscious sedation” for minor operative procedures?

Back 277

Minimizes drug-induced alterations of consciousness and vital functions

Front 278

What is the logic in using a combination of N2O with a halogenated hydrocarbon?

Back 278

Less of each drug will be needed, thus lowering the toxicity of the halogenated drug while preserving good anesthesia and analgesia

Front 279

Why does an inhaled drug with a greater solubility take longer to reach inspired tension?

Back 279

Because there is greater uptake into blood and tissues (large reservoir), thus reducing alveolar tension

Front 280

In what ways can the speed at which we attain an anesthetic concentration in the brain be increased, when agents of high solubility are being used?

Back 280

Increase MAC initially, then drop it down; Increase breathing rate

Front 281

What is the relationship between tissue solubility and anesthesia induction rate?

Back 281

The lower the tissue solubility, the faster the induction rate (i.e. if the drug is less absorbed into tissues, it will be more readily available in the plasma to cause induction of anesthesia in the brain)

Front 282

What does the Ostwald Solubility Coefficient express?

Back 282

The blood/gas partition coefficient (i.e. the concentration of the drug in blood divided by the concentration of the drug in the alveoli) – the higher the coefficient, the more soluble it is

Front 283

What head finding does indicate fracture of petrous portion of temporal bone?

Back 283

Mastoid ecchymosis (Battle sign): discoloration over mastoid area behind ear

Front 284

Where does contusion occur from a moving head that strikes a surface (e.g. falling to the floor)?

Back 284

At frontal and temporal regions of the brain: specifically at bony prominences of anterior and middle cranial fossae where brain moves against interior bones: called “contrecoup contusion” **** - location of contusion on the brain is stereotypical and does not indicate the location of blow to the head ****

Front 285

Where does contusion occur from a blow when head is stationary (e.g. beating of restrained head)?

Back 285

Directly beneath the site of impact: called “coup contusion”**

Front 286

If on autopsy, brain is shown to have hemorrhage on the superficial cortical layer, how can one justify a determination of contusion vs. hemorrhagic stroke?

Back 286

Superficial cortical layer receives some blood supply from meningeal vessels, and hence, is not affected with a cerebral vessel stroke; Contusion causes microscopic hemorrhage at the most superficial layer of cortex due to torn vessels

Front 287

What characterizes contusions?

Back 287

Wedge-shaped bruises of cortical surface due to hemorrhages from torn vessels – sub-pial layer is affected --> usually superficial, but can extend to subcortical white matter (“contusion hemorrhage”)

Front 288

What are various types of basilar fractures?

Back 288

Ring fracture: fall from great height causing spinal column moving up into foramen magnum
Hinge fracture

Front 289

What characterizes skull fractures?

Back 289

Linear fracture: simple fracture line that originates from point of impact – from broad-based forces
Basilar fracture: fracture at base of skull (thick) – from significant forces;
Depressed fracture: bone pushed inward into brain – from heavy force striking over a small surface area
Diastatic fracture (only in children): fracture that opens up a suture
Comminuted fracture: bone is fragmented; Compound fracture: overlying scalp is lacerated

Front 290

What characterizes CNS trauma?

Back 290

Head injury is #1 cause of death due to trauma, traffic/transport accidents are #1 cause of head injuries

Front 291

What head finding does indicate fracture of the orbital plate?

Back 291

Periorbital ecchymosis (“raccoon eyes”): swelling/discoloration of upper/lower eyelids – does not necessarily mean injury to the eye

Front 292

What are various types of blunt head trauma?

Back 292

Abrasion: superficial injury with scraping of skin; Contusion: bruise from trauma due to underlying vessel breakage; Laceration: splitting open/tearing of skin

Front 293

How is severity of diffuse axonal injury graded?

Back 293

Grade I: microscopic diffuse axonal damage in corpus callosum, white matter of hemispheres, brainstem
Grade II: focal hemorrhage in corpus callosum
Grade III: tissue tear hemorrhage in rostral brainstem
Note: survivors of diffuse axonal injury usually become PVS

Front 294

What can tearing of vertebral artery lead to?

Back 294

Traumatic basilar subarachnoid hemorrhage at the base of the brain

Front 295

What characterizes subarachnoid hemorrhage?

Back 295

Blood beneath the arachnoid membrane – may be non-traumatic (berry aneurysms), #1 cause is trauma – almost any type of brain injury can result in subarachnoid hemorrhage (e.g. all contusions, torn axons, etc) --> non-specific indicator of trauma – usually not at base of injury

Front 296

How are subdural hemorrhages dated?

Back 296

Acute, subacute, and remote – further out it gets, the harder it is to pinpoint the date - after 1 year, can get calcification/ossification of dura from subdural hemorrhage

Front 297

What characteriezes subdural hemorrhage?

Back 297

Bleeding between dura and arachnoid – venous in origin (#1: cortical bridging veins), no need for skull fractures – crescent-shaped, mostly in frontoparietal region; prognosis depends on rate of evolution and age
Note: tearing of bridging vein most common in the elderly with very minor degrees of trauma (no fractures needed) – subdural hematoma does not indicate foul play (!)
Case: dilated ventricle due to minor hydrocephalus, older patient, minor trauma --> minor subdural hemorrhage --> probably not clinically significant
Case: subdural hemorrhage --> brain pushed over on one side --> herniation --> blocking of foramen of Monro --> obstructive hydrocephalus --> dilated lateral ventricle on imaging --> clinically significant

Front 298

What characterizes epidural hemorrhage?

Back 298

Bleeding between skull and dura – arterial in origin (#1: middle meningeal artery), mostly associated with skull fractures – lens-shaped on imaging; prognosis depends on rate of evolution and volume

Front 299

What type of injury is seen when hitting hard in the face, causing twisting of head from the force?

Back 299

Brainstem avulsion: tearing of pons, cerebellum

Front 300

What contusion occurs when bone is driven into the brain?

Back 300

Fracture contusion

Front 301

What type of injury is seen in angular acceleration (e.g. sudden stopping of moving vehicle)?

Back 301

Diffuse axonal injury: shearing of axons – also occurs with shaken infants; can immediately lead to unconsciousness and death, but brain usually looks unremarkable on gross section
Note: if suspect shaken baby injury --> must look at microscopic sections of brain (gross is unremarkable)
Note: usually unremarkable on gross, but if see a lesion, they are hemorrhagic and involve the deep white matter such as corpus callosum, quadrants of rostral brainstem (as opposed to contusion, which involved superficial gray matter)

Front 302

What contusion occurs when a blow to the head causes rapid expansion of intracranial contents?

Back 302

Herination contusion – bullet shot to the head causing rapid expansion due to its high kinetic energy

Front 303

21. What are complications of CNS trauma – things to avoid from happening?

Back 303

Brain swelling and increased intracranial pressure --> may cause blockage of cerebral vessels --> may lead to hypoxic/ischemic brain damage
Note: small white matter lesions are associated with diffuse axonal injury
Note: intraventricular hemorrhage can be an extension of hypertensive hemorrhage or due to trauma (e.g. if see intraventricular hemorrhage and subdral hemorrhage --> trauma is the most likely cause)

Front 304

What are common types of peripheral nerve injuries?

Back 304

Segmental demyelination (10%), axonal degeneration (90%)*****

Front 305

What are inflammatory neuropathies?

Back 305

Guillain-Barre syndrome: “acute demyelinating polyradiculoneuropathy” --> acute demyelinating signs
CIDP: “chronic inflammatory demyelinating polyradiculoneuropathy” --> chronic demyelinating sign = “onion bulb”

Front 306

What characterizes the regeneration of axons after Wallerian degeneration due to transection?

Back 306

Multiple axonal sprouts will regenerate within the Schwann cell “tube”

Front 307

What is the response to axonal transaction in the nerve cell and in the axons?

Back 307

In nerve cells: central chromatolysis – In axons: Wallerian degeneration (degeneration of nerve fiber distal to site of transection) (!) ***

Front 308

What characterizes axonal degeneration?

Back 308

Axon destruction with 2’ demyelination --> if neuronal cell body and Schwann cells survive, axonal regeneration occurs; if motor nerve destroyed --> may get 2’ neurogenic atrophy of skeletal muscle

Front 309

What does repeated episodes of remyelination and demyelination result in?

Back 309

Onion bulb: concentric layers of Schwann cell cytoplasm and BM surround the thinly myelinated axon****
Note: onion bulb (know the EM picture) indicates a “chronic demyelinating disease” (!) ***************

Front 310

What characterizes segmental demyelination?

Back 310

Damage to Schwann cell or myelin sheath (axons spared), remyelination occurs but with shorter internodes/thinner myelin --> never as good as pre-injury; if repeated --> “onion bulb”

Front 311

What is the composition of normal peripheral nerves?

Back 311

Axon, its myelin sheath, and CT surrounding the entire nerve (epineurium), CT surrounding each fascicle and forming blood-nerve barrier (perineurium), and CT surrounding each nerve fiber (endoneurium) – thickness of myelin sheath and distance between nodes of Ranvier are directly proportional to the diameter and speed of conduction of axons

Front 312

What is the most common nerve biopsied?

Back 312

Sural nerve (pure sensory)

Front 313

What is used to visualize peripheral nerves?

Back 313

Myelinated: toluidine blue, Unmyelinated: electron microscopy (not used much anymore)

Front 314

What are causes of infectious neuropathy?

Back 314

Leprosy: due to Mycobacterium leprae, two forms: Tuberculoid (immune response, few M. leprae, granuloma formation), Lepromatous (no immune response, many M. leprae in Schwann cells)
Diphtheria (toxin-mediated demyelination), VZV (inflammation in ganglia), CMV (neuropathy in immunosuppressed)

Front 315

What can Lead poisoning do to peripheral nerves?

Back 315

Demyelination

Front 316

What characterizes malignancy-associated peripheral neuropathy?

Back 316

(less commonly) due to direct infiltration or compression from tumor
(more commonly) Paraneoplastic syndromes: small cell carcinoma of lung (anti-Hu antibodies againt CNS and PNS), plasma cell dyscrasias (e.g. multiple myeloma) --> MAG antibodies against myelin, light-chain amyloid deposition on peripheral nerves

Front 317

What can cause amyloid neuropathy?

Back 317

Plasma cell dyscrasias (e.g. multiple myeloma)

Front 318

What type of neuropathy is Diabetes Mellitus peripheral neuropathy?

Back 318

Axonal neuropathy (degenerating/regeneration axons) – may see thickening/hyalinization of endoneurial arterioles with BM reduplication (e.g. thickened blood vessels in biopsy)

Front 319

What pattern of neuropathy is seen in long-standing Diabetes Mellitus?

Back 319

“Stock-and-glove” pattern: distal symmetric sensori-motor neuropathy
Autonomic dysfunction (esp. vagus) --> can cause masking of angina in CV disease --> sudden death

Front 320

What is the most common hereditary neuropathy?

Back 320

Charcot-Marie-Tooth disease (HMSN I) – AD (17p duplication at Peripheral Myelin Protein 22 gene)****
Present in childhood/early adulthood with progressive atrophy of calf muscle (peroneal);
Is a progressive/chronic demyelinating disease --> “onion bulbs” seen
Note: most hereditary enzyme disorder --> AR since both gene copies of enzyme must be absent for disease
Note: most hereditary structural protein disorders --> AD since one fauly copy can cause disease
Note: know protein and gene for Charcot-Marie-Tooth disease ***********************************

Front 321

Why is nerve biopsy not helpful in diagnosis of GBS?

Back 321

Sural nerve is pure sensory – GBS is motor nerve disease (causes motor weakness)

Front 322

What characterizes CIDP?

Back 322

= chronic demyelination
Relapsing and remitting immune-mediated neuropathy --> “onion bulb” formation

Front 323

What is seen histologically in GBS?

Back 323

Segmental demyelination; inflammation around venules and endoneurium in spinal and cranial motor (anterior) nerve roots

Front 324

What characterizes Guillain-Barre syndrome?

Back 324

= acute demyelination - motor illness
Preceding flu-like illness --> distal weakness --> “ascending paralysis” to proximal weakness --> most recover, some die from respiratory failure; thought to be due to immune cross-reaction with myelin --> plasmapheresis may help

Front 325

What are traumatic neuropathies?

Back 325

Traumatic neuromas: composed of peripheral nerve + collage – is painful, may form a bump at amputation site (remove tumor instead of reamputation)
Compression neuropathies: carpal tunnel syndrome, “Saturday night palsy”, Morton neuroma (interdigital nerve foot, from wearing high heels)

Front 326

What characterizes Myasthenia Gravis pathology?

Back 326

Initially: extraocular muscle weakness (ptosis, diplopia), improve with anticholinesterases, associated with thymoma/thymic hyperplasia, on EM will see simplification of post-synaptic membrane with AchR loss

Front 327

What are the diseases of NMJ?

Back 327

Myasthenia Gravis – Ab againt Ach receptors, associated with thymomas/thymic hyperplasia
Lambert-Eaton myasthenic syndrome – Ab againt presynaptic Ca2+ channels, paraneoplastic process associated with small cell carcinoma of lung

Front 328

What is classically seen in neurogenic atrophy of skeletal muscles?******

Back 328

Angular, atrophic, esterase-positive myofibers
Fiber type grouping: type I fibers group together in one location, type II fibers group together elsewhere (instead of the alternating fiber distribution seen in normal muscle)
Target fiber (hole in muscle fiber): stained with NADH
Note: fiber type grouping is indicative of chronic denervation (!)

Front 329

To what form of the Na+ receptor do local anesthetics bind?

Back 329

Open/active state, and the inactive state (but not the channel at rest); this means that the block forms more quickly in rapidly conducting nerve (i.e. it is use dependent) – the binding site for the local anesthetic is located on the cytosolic surface of the Na+ channel

Front 330

What is responsible for hypersensitivity reactions with Ester-linked local anesthetics?

Back 330

They are derivatives of para-aminobenzoic acid (PABA); metabolism creates PABA or a PABA-like compound which can be allergenic in sensitive patients – formulations of either esters or amides may contain methylparaben or sulfite as preservatives which may also be allergenic

Front 331

What characterizes the clearance of local anesthetics?

Back 331

Most esters are metabolized by plasma pseudocholinesterase (rapidly hydrolyzed, caution in atypical pseudocholinesterase); Amides and Cocaine (an ester) are metabolized in the liver, most undergo N-dealkylation followed by hydrolysis, the Prilocaine metabolite o-toluidine causes methemoglobinemia; A slow rate of absorption into blood prolongs action (Lidocaine is a potent vasodilator, Epinephrine can be included in solution to retard absorption)

Front 332

How are Cocaine and Benzocaine different from other local anesthetics?

Back 332

Cocaine: vasoconstrictor (blocks the reuptake of NE), reduces bleeding when applied to thin mucosal membranes such as nasal mucosa, chronic use leads to ischemic necrosis of tissue, abuse leads to cardiovascular toxicity; Benzocaine: uncharged, possess solubility characteristics that allow it to penetrate the skin, used in ointment for sunburn and skin irritation

Front 333

What are the classes of local anesthetics?

Back 333

Divided up by the linkage between their lipophilic and hydrophilic portions: amide or ester linkage; Amide-linked: Lidocaine, Mepivacaine, Bupivacaine, Etidocaine, Prilocaine, Ropivacaine; Ester-linked: Procaine, Chloroprocaine, Tetracaine, Cocaine, Benzocaine

Front 334

Besides their anesthetics effects, what is the effect of local anesthetics on the heart?

Back 334

Blockade of Na+ channels, providing an antiarrhythmic effect; at higher doses they can cause a conduction block (toxic effect) – drugs incl. Lidocaine, Tocainide, Mexiletine

Front 335

By what mechanism of action does the non-ionized local anesthetic, Benzocaine, act?

Back 335

Dissolves into the membrane causing conformational changes in the membrane: lipid bilayer expands causing pressure that deforms the ion channels causing failure of ion conduction

Front 336

By what mechanism of action do local anesthetics work?

Back 336

They inhibit Na+ influx in neural tissue

Front 337

When local anesthetics are injected into inflamed tissue, what will happen to the potency of the drug?

Back 337

It will decrease due to an increase in acidity, causing more of the anesthetic to be in the ionized (less lipophilic) form

Front 338

What characterizes local anesthetics?

Back 338

They are weak bases with a pKa from 7..7-9.0; at physiological pH they exist largely in ionized form in equilibrium with a smaller non-ionized portion; the non-ionized portion is essential for diffusion to the site of action, whereas the ionized form is essential for channel binding

Front 339

What are the adverse cardiovascular effects from absorption of local anesthetics?

Back 339

Systemic vasodilation (leading to severe hypotension), depression of cardiac conduction leading to AV/ventricular conduction blocks (cardiac arrest may result)

Front 340

Why may anatomical position of fibers in a large nerve trunk create exceptions to the rules regarding differential nerve block?

Back 340

Since the local anesthetic diffuses from the outside of the large nerve trunk to the inside, the order of nerve block will be skeletal muscle innervation first, followed by a block of proximal sensory innervation, and finally a block of distal sensory innervation

Front 341

What is the general order of sensitivity regarding nerve fiber type and local anesthetics?

Back 341

First: C-fiber (dull pain, temp.), pre-/post-ganglionic autonomic fiber, Aδ-fiber (sharp pain, temp);
Second: Aγ-fiber (muscle tone), Aβ-fiber (pressure, touch); Third: Aα-fiber (proprioception, motor activity) – factors promoting high sensitivity to local anesthetic: small fibers, high firing frequency, longer AP duration (i.e. pain fibers), short internodal distance (2-3 nodes need to be blocked)

Front 342

What should be a concern regarding a spinal conduction block?

Back 342

Spinal headache due to loss of CSF and inflammation after puncturing the dura; should also be concerned about infection, and avoid the upward spread towards T1-4 (going to the heart) or brain

Front 343

What is meant by infiltration regarding local anesthetics?

Back 343

Any injection in which a specific cutaneous nerve is not targeted: subcutaneously (e.g. removal of warts and suturing), intravenously (Bier’s block, done with tourniquet applied, allows full block of an entire extremity)

Front 344

What local anesthetic is applied to the cornea?

Back 344

Proparacaine (ester-linked), has low antigenicity in eye since the amine group is in the meta rather than the para position on the benzene ring (i.e. won’t form PABA)

Front 345

What are the most common topical applications of local anesthetics?

Back 345

Benzocaine, Pramoxine, EMLA cream (eutectic mixture of lidocaine and prilocaine with adequate solubility for skin/mucosa)

Front 346

What characterizes the CNS toxicity of local anesthetics?

Back 346

Low plasma level: talkative, disoriented, drowsy; Higher level: restlessness, tremors, clonic seizures (administer oxygen, benzodiazepines, and perhaps succinylcholine); Higher yet: medullary paralysis leading to respiratory and cardiovascular collapse (supportive therapy)

Front 347

Which neuromuscular blockers have the fastest speed of onset?

Back 347

Succinylcholine<1min; Rocuronium<2min

Front 348

What is the association between the neuromuscular blockers and their effects on cardiac muscarinic receptors?

Back 348

None: Curare, Atracurium, cis-Atracurium, Vecuronium;
Slight: Rocuronium; Moderate: Pancuronium; Stimulation: Succinylcholine

Front 349

What is the association between the neuromuscular blockers and their effects on autonomic ganglia?

Back 349

None: Atracurium, cis-Atracurium, Pancuronium, Rocuronium, Vecuronium;
Weak block: Curare; Stimulation: Succinylcholine

Front 350

What characterizes the metabolism of steroidal neuromuscular blockers?

Back 350

Pancuronium, Vecuronium, and Rocuronium are partially metabolized to pharmacologically active compounds (i.e. their 3-OH, 17-OH, and 3,17-diOH metabolites): these accumulate in renal insufficiency, so with prolonged use caution since paralysis may persist

Front 351

Which neuromuscular blocking drug should be used in patients with liver/kidney disease?

Back 351

Atracurium – however, its metabolite Laudanosine may cause seizures and is inactivated in the liver (i.e. use low doses of Atracurium in liver disease or with prolonged use); less Laudanosine is formed from cis-Atracurium

Front 352

What drug is used for the pharmacological reversal of non-depolarizing blockers?

Back 352

Neostigmine

Front 353

What characterizes the elimination of neuromuscular blockers?

Back 353

Succinylcholine: eliminated in 5-10 min by butyrylcholinesterase (pseudocholinesterase); Atracurium: eliminated in 40 min by Hoffmann degradation and plasma pseudocholinesterase;
Others: eliminated by liver/kidney (generally slower and subject to alterations with diseased state)

Front 354

In what ways do neuromuscular blocking drugs produce skeletal muscle paralysis?

Back 354

By depolarizing the neuromuscular junction: Succinylcholine; By competitively antagonizing nicotinic receptors in the junction: isoquinoline derivatives (Curare, Atracurium, cis-Atracurium), steroid derivatives (Pancuronium, Vecuronium, Rocuronium)

Front 355

What structural characteristic do neuromuscular blockers have in common?

Back 355

They are quarternary ammonium compounds which act with anionic groups on skeletal muscle cholinergic receptors – they do not readily penetrate the BBB

Front 356

What are the therapeutic uses of neuromuscular blockers?

Back 356

Promote access to the operative field by removing muscle tone; Facilitates intubation by relaxing the jaw and by preventing reflex movement when tube touches trachea; Reduces the dosage of anesthetics required to eliminate movement (must be used with anesthetics!)

Front 357

What is used as a premedication to prevent bradycardia in a patient who is given Succinylcholine?

Back 357

Atropine

Front 358

How is the degree of neuromuscular blockade monitored (two methods)?

Back 358

Via a functional analysis based on the occurrence of a progressive dose-related paralysis: eyes/fingers > head/neck > limbs > respiratory musculature (recovery is in reverse order);
Via the use of a nerve stimulator to test the effectiveness of the neuromuscular blockade

Front 359

What are pharmacogenomic concerns with Succinylcholine?

Back 359

Plasma pseudocholinesterase deficiencies prolong action, so assisted ventilation may be required; Malignant hyperthermia can be initiated by Succinylcholine (antidote = Dantrolene: inhibits Ca2+ release from sarcoplasmic reticulum, can be used prophylactically in a hereditary condition)

Front 360

What are the adverse effects of Succinylcholine?

Back 360

Fasciculations cause muscle aches, particularly of the tongue; Stimulation of muscarinic receptor in the sinoatrial node may lead to arrhythmias with therapeutic doses; Stimulation of autonomic ganglia, particularly with high doses; Seriously injured patients may experience arrhythmias from K+ release from traumatized tissue

Front 361

What characterizes the pharmacology of Succinylcholine?

Back 361

Rapid onset, short duration; Two phases of blockade: Phase I --> persistent depolarization of end plate from repetitive agonistic interaction with receptors (initial muscle stimulation, sarcolemmal action potentials rapidly decline since Na+ entry is voltage gated and requires cyclical end plate potential), Phase II --> desensitization of cholinergic receptors when Succinylcholine persists within the neuromuscular junction – neither phase is reversible with Neostigmine

Front 362

By what mechanism can the pharmacological reversal of non-depolarizing neuromuscular blockers occur?

Back 362

By increasing ACh levels with Neostigmine (acetylcholinesterase inhibitor); must co-administer with Atropine in order to control the adverse effect of Neostigmine on the respiratory system, heart, GI tract, etc. without effecting skeletal muscle cholinergic receptors – concern for “recurarization” since Neostigmine has a shorter duration than most neuromuscular blockers

Front 363

What drug interactions are seen with the non-depolarizing neuromuscular blockers?

Back 363

Aminoglycosides enhance paralysis by reducing ACh release (blockade is not reversible with neostigmine, but may be partially reversed with calcium salts);
Calcium channel blockers potentiate the blockade; Synergistic interaction is seen with halogenated hydrocarbon anesthetics

Front 364

What is the association between the neuromuscular blockers and their effects on histamine release?

Back 364

None: cis-Atracurium, Pancuronium, Rocuronium, Vecuronium;
Slight: Atracurium, Succinylcholine; Moderate: Curare

Front 365

What will occur when Pancuronium interacts with its cardiac muscarinic receptor?

Back 365

Causes tachycardia and increased BP

Front 366

What is beta amyloid derived from?

Back 366

Amyloid precursor protein

Front 367

What off-label treatment strategies have been used for AD?

Back 367

Memantine, Statins (may be effective in reducing AD severity), antioxidants (Vit. E/C, Selegiline)

Front 368

What characterizes other NMDA antagonists?

Back 368

MK-801, Phencyclidine, Ketamine: they have slow off rates and are associated with coma, hallucinations, and anesthesia

Front 369

What characterizes Memantine?

Back 369

NMDA receptor antagonist: uncompetitive, channel must be active for Memantine to bind, the more active the channel the greater the blockade, results in some neuroprotection;
AEs: constipation, dizziness, HA, pain

Front 370

What are the AChE inhibitors and what are their associated adverse effects?

Back 370

Donepezil: nausea, diarrhea, HA, insomnia, generalized pain, dizziness;
Rivastigmine: n/v, diarrhea, HA, loss of appetite, abd. pain, accidental injury, tremor, dizziness;
Galantamine: n/v, diarrhea, HA, loss of appetite, UTI, dizziness

Front 371

What describes the formation and breakdown of ACh?

Back 371

Acetyl-CoA + Choline --> (via ChAT) ACh --> (via AChE) Choline + Acetate

Front 372

What differentiates between the non-amyloidogenic and amyloidogenic pathways?

Back 372

Non-amyloidogenic: α-secretase cleaves the pre-cursor leaving behind a water soluble molecule (α-sAPP) and another particle that is subsequently cleaved by γ-secretase to p3;
Amyloidogenic: β-secretase cleaves the precursor leaving behind β-sAPP and another particle that is subsequently cleaved by γ-secretase to β-amyloid

Front 373

What are possible causes of neuronal loss in neurodegenerative diseases?

Back 373

Apoptosis, necrosis, oxidative stress, inflammation

Front 374

What are risk factors for AD?

Back 374

High BP, high cholesterol, diabetes, smoking, family history (slight increase in risk

Front 375

Of the top 5 causes of death, which is the only one that is increasing in incidence?

Back 375

Alzheimer’s disease (AD)

Front 376

What describes the use of Lithium in ALS?

Back 376

When used in combination with Riluzole, a small study showed no progression of symptoms – Lithium promotes autophagy which induced neuroprotection; it may also suppress glial cell activation

Front 377

What neurons are lost in Huntington’s disease?

Back 377

GABA/enkephalin containing projection neurons from the striatum (specifically the D2 receptors) --> direct pathway becomes prominent causing excess movement

Front 378

What describes the indirect pathway of the basal ganglia?

Back 378

Glutamate is released from the neocortex onto the striatum --> GABA is released from the striatum, causing inhibition of the external pallidum --> less GABA is released from the external pallidum, meaning less inhibition of the subthalamic nucleus --> more glutamate is released by the subthalamic nucleus, causing stimulation of the internal pallidum --> more GABA is released from the internal pallidum, meaning inhibition of the thalamus --> less glutamate is released from the thalamus --> decreased stimulation of the neocortex – DA inhibits the excitatory effects of glutamate on the striatum (via D2), thus somewhat increasing thalamic output

Front 379

What describes the direct pathway of the basal ganglia?

Back 379

Glutamate is released from the neocortex onto the striatum --> GABA is released from the striatum, causing inhibition of the internal pallidum --> less GABA is released from the internal pallidum, meaning less inhibition of the thalamus --> more glutamate is released from the thalamus to the neocortex --> enhanced stimulation of the neocortex – DA enhances the excitatory effects of glutamate on the striatum (via D1), thus increasing thalamic output

Front 380

What is the end-result of activation of the direct and indirect pathways, respectively?

Back 380

Direct: increases movement (i.e. increases thalamic output);
Indirect: decrease movement (i.e. decreases thalamic output)

Front 381

What differentiates between D1 and D2 receptors in the striatum?

Back 381

D1: excitatory, GPCR, activates adenylyl cyclase which increases cAMP to induce APs;
D2: inhibitory, GPCR, inhibits adenylyl cyclase which reduces cAMP thus reducing excitability

Front 382

What substance may be involved with increased incidence of ALS?

Back 382

β-N-methylamino-L-alanine (found in Guam flying foxes and cyanobacteria)

Front 383

What describes the use of anti-psychotics for the treatment of psychiatric symptoms in AD?

Back 383

Short-term benefit, long-term may increase mortality – should be used to control violence, not for warehousing

Front 384

What drugs are used in the symptomatic treatment of ALS?

Back 384

Muscle cramping/twitching: Quinine, Carbamazepine, Phenytoin; Spasticity: Baclofen, Tizanidine, Memantine, Tetrazepam; Salivation: Amitriptyline, Glycopyrrolate, Atropine;
Laughing/crying: Amitriptyline, Fluvoxamine, Lithium, Levodopa

Front 385

What drug is used in the treatment of ALS?

Back 385

Riluzole: inhibits glutamate release, blocks postsynaptic glutamate receptors, inhibits voltage-dependent sodium channels – prolongs patient’s life, but does not provide symptomatic improvement

Front 386

What is the effect on the direct and indirect pathways with Parkinson’s disease (PD)?

Back 386

Direct pathway: lack of DA leads to a decreased inhibition of the internal pallidum which leads to an increase in thalamic inhibition, thus decreasing thalamic output to the cortex;
Indirect pathway: lack of DA leads to an increased inhibition of the external pallidum which via the subthalamic nucleus leads to an increased activation of the internal pallidum, thus causing an increase in thalamic inhibition, decreasing thalamic output to the cortex

Front 387

What are the Dopamine agonists used in PD?

Back 387

Bromocriptine mesylate (associated with heart valve damage), Pergolide mesylate (same as Bromocriptine), Pramipexole, Ropinirole, Rotigotine (transdermal), Amantadine

Front 388

What is the purpose of adding Carbidopa to a regimen of Levodopa?

Back 388

As a dopa decarboxylase inhibitor that does not cross the BBB, it reduces conversion of Levodopa to DA in the periphery, thus increasing availability of Levodopa in the brain and reducing peripheral side effects of DA

Front 389

What are the advantages and disadvantages of Levodopa?

Back 389

Advantages: most potent drug for PD, effective in early and advanced disease, well tolerated, low risk of cognitive disturbances; Disadvantages: short half-life, multiple dosing, wearing off, dyskinesias

Front 390

What are the advantages and disadvantages of Dopamine agonists?

Back 390

Advantages: effective in early and advanced disease, long half-life, low dosing frequency, well tolerated, low risk of wearing off or dyskinesia; Disadvantages: not as potent as Levodopa, risk of cognitive/behavioral problems, cardiovascular side effects for ergot agonists

Front 391

What are the advantages and disadvantages of MAO-B inhibitors?

Back 391

Advantages: effective in early and advanced disease, once-daily dosing, well tolerated, possible neuroprotection; Disadvantages: mild benefit, Selegiline metabolizes to amphetamine

Front 392

What drugs should be used depending on the severity of motor disability with PD?

Back 392

Mild: MAO-B inhibitor; Mild/moderate: Dopamine agonist; Moderate/Severe: Levodopa

Front 393

What drugs can be used in the treatment of Huntington’s disease?

Back 393

Dopamine receptor blockers: Haloperidol, Fluphenazine; Dopamine transporter blocker: Tetrabenazine; SSRIs: Fluoxetine, Paroxetine, Sertraline (used for psychiatric symptoms)

Front 394

What describes the metabolic pathway for Dopamine?

Back 394

Tyrosine --> (via tyrosine hydroxylase) DOPA --> (via aromatic L-amino acid decarboxylase) DA --> (via COMT) 3MT --> (via MAO) HVA; And, DA --> (via MAO) DOPAC --> (via COMT) HVA

Front 395

What does the treatment of Parkinson’s disease focus on?

Back 395

Neuroprotection: antioxidants, anti-inflammatory, block glutamate toxicity; Dopamine agonists: Ropinirole, Pramipexole; Levodopa

Front 396

What are the MAO-B inhibitors?

Back 396

Selegiline, Rasagiline

Front 397

What are the COMT inhibitors?

Back 397

Entacapone, Tolcapone (associated with hepatotoxicity)

Front 398

What is seen in the presentation of tonic-clonic seizures?

Back 398

An initial sequence of maximal tonic muscle spasms, followed by a period of synchronous clonic jerking of the limbs, followed by a period of prolonged depression (“postictal depression”)

Front 399

What is the treatment for complex partial seizures?

Back 399

Carbamazepine or Phenytoin (1st choice), Primidone, Valproic acid – partial seizures may be the most difficult to control

Front 400

What characterizes partial seizures?

Back 400

Psychomotor epilepsy, temporal lobe epilepsy; most difficult to treat effectively; Can see simple or focal cortical seizures with various manifestations, but without loss of consciousness; May involve only a single limb; May involve only a specific sensory system

Front 401

What is the treatment for absence seizures?

Back 401

Valproic acid, Ethosuximide, Clonazepam (sometimes useful, but tolerance develops to anticonvulsant effects) – seizures are made worse by Phenytoin or Carbamazepine

Front 402

What is the problem with seizures lasting longer than 5min?

Back 402

They can result in neurological damage

Front 403

What characterizes absence seizures?

Back 403

No warning (“aura”); Will see a brief loss of consciousness, a characteristic EEG pattern (3/sec spike and dome pattern), some clonic muscle movement (blinking of eyelid, jerking of entire body), no depression following seizure; Patient will remember little of seizure

Front 404

What is the treatment of tonic-clonic seizures?

Back 404

Phenytoin (first choice), Primidone, Carbamazepine, Valproic acid (effective in some patients)

Front 405

What characterizes the epilepsies?

Back 405

A collective designation for a group of CNS disorders; all have in common the spontaneous occurrence of brief involuntary dysfunction; disturbances are all associated with abnormal and excessive EEG discharges

Front 406

What characterizes tonic-clonic (grand mal) seizures?

Back 406

Often preceded by a “prodrome” (feeling of tenseness/depression, may precede seizure by several hours), an “aura” will immediately precede seizure, patient will remember little of actual seizure

Front 407

What are the major classifications of epilepsy?

Back 407

Generalized: tonic-clonic (grand mal), absence (petit mal); Partial: complex partial, simple partial

Front 408

What epilepsy drugs potentiate the effects of GABA at the GABA receptor?

Back 408

Benzodiazepines: limited use due to marked sedation and tolerance development (Diazepam is the drug of choice for status epilepticus); Barbiturates: Phenobarbital (too many adverse effects);
Deoxybarbiturates: Primidone (similar to Phenobarbital, used some in partial complex seizures);

Front 409

What drug interactions are seen with Phenytoin?

Back 409

Displaces other drugs from plasma protein binding sites: oral anticoagulants, salicylates, valproic acid, benzodiazepines; Can alter the metabolism of other drugs

Front 410

What toxicities are associated with Phenytoin?

Back 410

Dose dependent; When administered IV: cardiac arrhythmias, hypotension, CNS depression;
With acute oral overdose: cerebellar-vestibular disturbances; With chronic administration: gingival hyperplasia, hirsutism (can be minimized by reduction in dose)

Front 411

What characterizes Phenytoin?

Back 411

Oral absorption is slow and variable; rapidly distributed in total body water; extensively bound to plasma proteins; half-life is dose dependent; no active metabolites

Front 412

What epilepsy drugs block the Na+ channel?

Back 412

Hydantoins: Phenytoin, limits repetitive firing of action potentials by producing a sustained depolarization (slows rate of recovery of voltage-gated Na+ channels, effect is fairly selective at therapeutic doses); Carbamazepine: similar MOA to Phenytoin

Front 413

What epilepsy drugs increase GABA at the synapse?

Back 413

Tiagabine: blocks GABA uptake, adjunct therapy for partial complex seizures, adverse effects incl. confusion/dizziness/difficulty concentrating; Vigabatrin: irreversible inhibitor of GABA-transaminase, role in therapy uncertain, not approved in US

Front 414

What characterizes Primidone?

Back 414

Well absorbed orally, 60% of administered dose is metabolized (--> PEMA, Phenobarbital), half-life is 5-15hrs; Half-life of PEMA is 16hrs; Has similar MOA to Phenobarbital

Front 415

What characterizes febrile seizures?

Back 415

The more they occur in childhood, the more likely the child is to become epileptic later in life;
Start treatment after the second seizure: treat during times of elevated body temperature with phenobarbital

Front 416

What are the problems with therapy for epilepsy?

Back 416

Long-term treatment: costs, P450 induction, protein binding, minor toxicities (nausea, sedation)

Front 417

What characterizes status epilepticus?

Back 417

A series of recurrent seizures; represents a life-threatening emergency; treated with IV Diazepam, followed by administration of Phenytoin (longer duration of action)

Front 418

What characterizes the pharmacokinetics of Carbamazepine?

Back 418

Oral absorption is slow and erratic, widely distributed in total body water, induces P450 system, half-life following acute administration is ~36hrs (with chronic administration: 10-20hrs, in combination with phenobarbital: 10-12hrs); It has an active metabolite (the 10, 11-epoxide)

Front 419

What characterizes Valproic acid?

Back 419

Good oral absorption, over 90% plasma protein bound, distributed in extracellular water, half-life is 9-18hrs, no active metabolites

Front 420

What are epileptic drugs with an unknown or multiple mechanisms of action?

Back 420

Valproic acid: no effect on GABA systems, small reduction in low-threshold calcium currents, limits sustained repetitive firing and reduced T currents (may explain broader activity)

Front 421

What toxicities are associated with Ethosuximide?

Back 421

GI disturbances, fatigue, HA, dizziness – no significant drug interactions

Front 422

What characterizes Ethosuximide?

Back 422

Complete oral absorption, distributed in total body water, half-life of 40-50hrs in adults (30hrs in children), no active metabolites

Front 423

What are epilepsy drugs that block calcium T-currents?

Back 423

Succinimides: Ethosuximide, reduced low-threshold calcium currents in thalamic neurons, no effect on GABA systems, effective in absence epilepsy

Front 424

What characterizes Oxcarbazepine?

Back 424

Converted to active metabolite; very similar to Carbamazepine

Front 425

What toxicities are associated with Carbamazepine?

Back 425

Acute overdose: stupor, coma, hyperirritability, convulsions, respiratory depression;
Chronic administration: drowsiness, vertigo, ataxia, diplopia, blurred vision, water retention, hematological disorders (aplastic anemia, agranulocytosis) – can also see P450 induction

Front 426

What is the clinical use of Fosphenytoin?

Back 426

Pro-drug of Phenytoin that is rapidly converted to Phenytoin in the body – used parenterally in status epilepticus

Front 427

What are the uses of Carbamazepine?

Back 427

Tonic-clonic seizures and partial complex seizures – contraindicated in absence seizures

Front 428

What are the clinical indications for Valproic acid?

Back 428

Mainly used in absence seizures, but useful in all seizure disorders as adjunctive therapy; also effective in acute mania and migraine headaches

Front 429

What are the general principles in the treatment of epilepsy?

Back 429

Correct diagnosis is the key, may take weeks to establish correct dose, when at all possible use one drug, when seizure control is not adequate check compliance and consider an alternate drug, when altering the concentration of a drug taper it slowly, teratogenic potential in pregnancy is a significant concern (with Phenytoin, Carbamazepine, Valproic acid, Phenobarbital)

Front 430

What adverse effects are associated with Valproic acid?

Back 430

GI disturbances, and blah-blah-blah (sedation, ataxia, tremor, hepatic toxicity, acute pancreatitis, hyperammonemia, increased appetite, weight gain, rash, hair loss, thrombocytopenia) – drug interactions are related to high protein binding and competitive inhibition of drug metabolism with Phenobarbital

Front 431

What monitors are used during general anesthesia?

Back 431

Hypnosis: EEG analyzers, vapor concentrations; Analgesia: HR, BP; Amnesia: none;
Muscle relaxation: neuromuscular stimulators; Physiology: temp., O2 sat., CO2, ventilation, cardiac output, blood loss, urine output, evoked responses, ECG

Front 432

What are characteristics of non-depolarizing neuromuscular blockers?

Back 432

Decrease in twitch height (train-of-four fade), post-tetanic potentiation, absence of fasciculations, augmentation of other non-depolarizing neuromuscular blockers

Front 433

What drugs are used for the reversal of neuromuscular blockers?

Back 433

Acetylcholinesterase inhibitors: Neostigmine, Pyridostigmine, Edrophonium (minimize muscarinic stimulation with glycopyrrolate/atropine); Drug binding agents: Sugammadex
(binds Rocuronium, not yet approved)

Front 434

What side effects are associated with neuromuscular blockers?

Back 434

All: can mask awareness by preventing muscular response to stimulation; Succinylcholine: prolonged effect if pseudocholinesterase deficient, myalgia, hyperkalemia, bradycardia, increased IOP; Cisatracurium: histamine release, slow onset, ma require reversal; Rocuronium: slow onset, renal excretion, requires reversal, not associated with malignant hyperthermia

Front 435

Which neuromuscular blocker is used for quick intubation?

Back 435

Succinylcholine (depolarizing)

Front 436

What drugs are considered general anesthesia adjuvants?

Back 436

Lidocaine (anesthetized veins), Glycopyrrolate (decrease secretions), Phenylephrine/Ephedrine (sympathetic stimulation), Metoprolol/Labetalol (control cardiac function)

Front 437

What preoperative medications are used prior to general anesthesia?

Back 437

Anxiety relief: Diazepam; Sedation: Pentobarbital; Amnesia: Midazolam, Scopolamine; Analgesia: Morphine, Fentanyl; Anti-sialogogue effect: Glycopyrrolate;
Prevent ANS reflexes: Atropine, Esmolol

Front 438

What basic considerations is every anesthetic plan based on?

Back 438

Planned surgery, medical condition of patient, anesthetic history of patient, current drugs/allergies, patient requests/approvals – other consideration incl. patient’s physiologic status, post-op pain management, and skills of the anesthesiologist

Front 439

What are the steps in general anesthesia?

Back 439

Induction: Propofol, Thiopental, Etomidate, Ketamine; Maintenance: N2O, Desflurane, Sevoflurane; Emergence: reversal agents, oxygenation, pain relief; Recovery

Front 440

What are the major components of general anesthesia?

Back 440

Hypnosis: Propofol, Thiopental, inhalational anesthetics; Analgesia: opioids;
Amnesia: benzodiazepines; Muscle relaxation: Rocuronium, Succinylcholine –
halogenated inhalational anesthetics have all four properties

Front 441

What anesthetics can be used in a patient with major depression and HTN for electroconvulsive therapy?

Back 441

Requires general anesthesia for seizure induction (so that the patient doesn’t hurt himself): Labetalol (or Esmolol for HTN prophylaxis), Thiopental, Remifentanil, Succinylcholine, Ketorolac (NSIAD for symptoms after the procedure)

Front 442

What anesthetics can be used with a 30yo for appendectomy?

Back 442

Premedication: Fentanyl, Midazolam; Induction: Lidocaine (decreases consciousness), Propofol (induction agent), Rocuronium (paralyze vocal cords); Maintenance: Desflurane, Fentanyl; Adjuvants: Ondansetron (prophylaxis); Emergence: Neostigmine, Glycopyrrolate

Front 443

What anesthetics can be used with a 5yo for tonsillectomy?

Back 443

Midazolam syrup, Sevoflurane induction, Fentanyl, Ondansetron/Dexamethasone

Front 444

What anesthetics can be used in a patient for hysterectomy with a history of post-operative nausea/vomiting (PONV)?

Back 444

General anesthetic (long-lasting), muscle relaxant for abdominal surgery, infection and PONV prophylaxis: Cefazolin (abx), Ondansetron/Droperidol/Dexamethasone (n/v), Midazolam, Lidocaine, Propofol (induction and anti-nausea), Rocuronium, Fentanyl, Desflurane, Neostigmine, Glycopyrrolate

Front 445

What EEG pattern is seen with juvenile myoclonic epilepsy?

Back 445

4-6Hz spike and wave pattern

Front 446

What type of seizures can be seen in chronic alcoholics who suddenly stop drinking?

Back 446

ETOH withdrawal seizures – caused by the downregulation of GABA-mediated inhibition and the upregulation of NMDA receptors

Front 447

What is the drug of choice for temporal lobe seizures?

Back 447

1st choice: Carbamazepine, Oxcarbazepine, Phenytoin;
2nd choice: Lamotrigine, Valproate, Topiramate

Front 448

What type of seizures should be suspected in a patient who experiences strange smells and feelings prior to the onset of the seizure?

Back 448

Temporal lobe seizures

Front 449

Which seizures medications cause induction of CYP3A4?

Back 449

Carbamazepine, Phenytoin, Phenobarbital – they will decrease contraceptive effectiveness

Front 450

What describes the drug interaction between Lamotrigine and oral contraceptives?

Back 450

Lamotrigine is cleared by glucuronidation, and estrogens can induce glucuronosyltransferase causing a reduction in the plasma levels of Lamotrigine

Front 451

What is the drug of choice for juvenile myoclonic epilepsy?

Back 451

Valproic acid (can control all three types of seizures); watch for side effects: liver toxicity, weight gain; contraindicated in pregnancy – Lamotrigine may be effective to treat all seizure types as well (not FDA approved yet) – treatment is lifelong

Front 452

What are 3Hz spike and wave patterns on EEG indicative of?

Back 452

Absence seizures

Front 453

Which drug can make absence seizures worse?

Back 453

Carbamazepine (or phenytoin)

Front 454

What is the drug of choice for absence seizures?

Back 454

Ethosuximide (does not control tonic-clonic seizures); can also use Valproic acid (can cause hepatotoxicity and pancreatitis), Lamotrigine (can cause rash) – Valproic acid and Lamotrigine can treat absence and tonic-clonic seizures

Front 455

What should alcohol withdrawal seizures be treated with?

Back 455

Phenytoin and benzodiazepines – no need for long-term treatment

Front 456

What seizure state can be seen in patients undergoing benzodiazepine withdrawal?

Back 456

Nonconvulsive status epilepticus – treat accordingly

Front 457

With what AEDs is gingival hyperplasia seen?

Back 457

Phenytoin

Front 458

Which antiepileptic drugs (AED) are more commonly associated with Stevens-Johnson syndrome?

Back 458

Lamotrigine patients receiving valproate and/or aggressively titrated

Front 459

What are the two main types of seizures?

Back 459

Partial seizures and generalized seizures; seizures can progress simple partial → complex partial → generalized

Front 460

What are the causes of seizures?

Back 460

Idiopathic (68.7%), stroke, developmental, head trauma, brain tumor, infection, degenerative; most causes unknown; see a lot of mesotemporal sclerosis; a high fever can cause a seizure, basically ANYTHING that affects the brain can cause a seizure.

Front 461

What are more classifications of seizures?

Back 461

Partial: simple partial, complex partial, secondarily generalized; generalized: absence, myoclonic, tonic-clonic, tonic (stiffening), clonic (pattern of contraction/relaxation), atonic (lose all m tone)

Front 462

What characterizes generalized seizures?

Back 462

Initial involvement of BOTH hemispheres; almost always produces alteration/LOC and/or BL motor activity. Ex: fall to floor, stiffen, jerk

Front 463

What characterizes complex partial seizures?

Back 463

A partial seizure that involves some impairment of consciousness. Ex: impairment of consciousness with lip smacking, fiddling with hands

Front 464

What characterizes simple partial seizures?

Back 464

A partial seizure where there is NO impairment of consciousness. Ex: arm jerking, flashing lights, funny smells; may get auras.

Front 465

What characterizes partial seizures?

Back 465

It starts clinically/electrographically on ONE SIDE of the brain; usually the temporal lobe but can be anywhere; partial b/c starts in “part” of brain. There are two types of partial seizures, simple partial and complex partial.

Front 466

What is the definition of a seizure?

Back 466

Episode of sudden, relatively brief disturbance of mental, motor, sensory, or autonomic activity caused by anNL paroxysmal, electrical, or cerebral activity (gray matter)

Front 467

What percent of people have a seizure in their lifetime?

Back 467

1%; (epilepsy: 2 million Americans, up to 3% cumulative incidence by age 75)

Front 468

What is epilepsy?

Back 468

State of chronic, recurrent (2 or more) unprovoked seizures. Provoked seizures (such as via alcohol withdrawal, hyponatremia, etc) are NOT the cause of epilepsy b/c these can be easily prevented if the cause is reversed.

Front 469

What characterizes West Syndrome?

Back 469

Affects infants; triad of hypsarrythmia (chaotic EEG), infantile spasms, MR; poor px

Front 470

What is the WV law regarding driving after a seizure?

Back 470

Anyone who has a seizure with an impairment of consciousness cannot operate a motorized vehicle for ONE YEAR. But NOT required to report them by law. (Varies state to state.)

Front 471

What is the general tx for seizures?

Back 471

Time is the best test; after 1st unprovoked sz, chance of having 2nd unprovoked sz in 5 years is 35-50%, therefore, tx depends on pt, EEG/MRI findings, family hx, physical exam. But after 2nd unprovoked sz, the chance of a 3rd is 75% so everyone must be treated. Can depend some on patient after 1st, must discuss it.

Front 472

What characterizes Juvenile Myoclonic Epilepsy?

Back 472

Teenagers and young adults; see 4-6 Hz generalized spike and wave; pt’s often have morning jerks, generalized seizure; responds very well to meds, but need to always take meds or sz’s return

Front 473

What characterizes absence?

Back 473

School age children; see “staring spells”, 3Hz spike and wave; responds to ethosuximide

Front 474

What characterizes centrotemporal epilepsy?

Back 474

Affects kids 5-10 y/o; see centrotemporal spikes, drooling face, slurring words; often outgrow this

Front 475

What characterizes Lennox-Gestaut?

Back 475

Affects infants- young children; see slow spike and wave on EEG, multiple sz types, MR; poor px but not as bad as West S.

Front 476

What is the most important aspect of evaluating seizures?

Back 476

History. When, how often, how long, circumstances, aura, bowel/bladder, tongue biting, postictal state, sleep deprivation, video games, head trauma, meningitis/encephalitis, family hx, prenatal or postnatal problems, hx of sz’s/febrile sz’s as child; often confused, tired, stupified afterwards.

Front 477

What is epileptic syndrome?

Back 477

Term that describes certain seizure disorders, defined by a cluster of symptoms, signs, and findings on EEG and imaging studies. Depends on age, cause and type of sz’s, prognosis. Two particularly bad ones are West S and Lennox-Gestaut; others include centrotemporal epilepsy, absence, and juvenile myoclonic epilepsy

Front 478

What kind of tests are used to evaluate seizures?

Back 478

EEG: looking for spikes, sharp waves, spike and wave patterns; MRI especially checking the temporal lobe; also can look at spinal fluid, blood tests, genetic tests; MRI is like a picture, EEG tells you how it is “running”; if see squiggly’s all over at same time – it’s a generalized sz

Front 479

What are the principles of meds for seizures?

Back 479

There are many different seizure meds with different SEs and different efficacies against the different sz types. There is no single best drug.

Front 480

What is the tx for status epilepticus?

Back 480

ABCs, ativan .1mg/kg, dilantin 20mg/kg, head scan, AED levels.

Front 481

What are the causes of status epilepticus?

Back 481

Kids: fevers, CNS infections, electrolyte disturbances, hypoxia, previous epilepsy, low AEDs; adults: fevers, CNS infections, tumors, trauma, previous epilepsy, low AEDs.

Front 482

What is status epilepticus?

Back 482

Recurrence of sz episodes at intervals too short to allow recovery to pre-seizure condition, or any seizure lasting longer than 5-10 minutes. (CAN be in this state for months!)

Front 483

What other treatments are used to treat seizures?

Back 483

Ketogenic diet, vagal nerve stimulator, surgery for “lesional epilepsy” (invasive)

Front 484

What are some of the common meds and related SEs used to tx seizures?

Back 484

Dilantin (rash, purple glove syndrome, nystagmus), tegretol (hyponatremia), depakote (wt gain), lamictal (rash), keppra (cognitive), topamax (wt loss). The first 3 are the old standards and are cheaper; last 3 are newer. Difference is in SEs.

Front 485

What are the rules for efficacy?

Back 485

1st drug: 60%, 2nd drug: 75%, 3rd drug 80%, and so on. No drug will stop ALL seizures.

Front 486

What nerve mediates migraine pain?

Back 486

Trigeminal nerve which inn’s bld vessels and dura

Front 487

What stx appears to be involved in cluster h/a?

Back 487

Hypothalamus; seems to be triggered by REM sleep. There is ↑ parasympathetic outflow. Signal is sent from hypothalamus down to trigeminal nerve then to superior salivatory nucleus which regulates pain and sympathetic outflow.

Front 488

What characterizes cluster h/a?

Back 488

Very severe; can lead to suicide; occurs in groups for weeks-mos then may disappear for mos/years; often around the eye; occurs at night and can wake person, M > F; associated with eye redness, tearing, rhinorrhea, Horner’s S. alcohol and cigg’s can be a trigger.

Front 489

What is a tension h/a?

Back 489

Can occur daily; can last hours or all day; BL; squeezing or pressure-like; no aura and no significant neuro sx’s; can be triggered by stress; take Tylenol/aspirin and it goes away.

Front 490

What is a complicated migraine?

Back 490

Symptoms last longer than 24 hours, h/a may be secondary. Looks like a stroke.

Front 491

What is a migraine equivalent?

Back 491

When have aura but not followed by a h/a; could have scotomas, confusion

Front 492

What is an aura?

Back 492

Occurs in 25% of migraines; area of brain becomes hyper then hypoexcitable; “spreading corticodepression” that does NOT occur in vascular distribution, rather, thought to be a neuronal thing. Pain is the response of blood vessels TO that neuronal event.

Front 493

What important things need to be asked in history?

Back 493

Date of onset, duration, timing of attacks, frequency, severity, triggers, quality, factors that ↑ or ↓ h/a, meds including OTC, previous/current, trauma, drug abuse.

Front 494

What characterizes a migraine h/a?

Back 494

Usually <3x/wk, begins UL, may alternate sides, throbbing/pulsating, +/- photophobia, N/V. Can be triggered by stress, lack of sleep or food, menses, a food trigger. May have + family hx.

Front 495

What are the most common type of h/a?

Back 495

Tension h/a, but most commonly seen in clinic is migraine b/c people seek help for migraines

Front 496

What are CIs for performing a LP?

Back 496

Anticoagulants, platelets <50,000, signs of ↑ ICP; don’t want to cause herniation!

Front 497

Besides meningitis/encephalitis, what other condition commonly has neck pain?

Back 497

Carotid or vertebral artery dissection

Front 498

What characterizes carotid or vertebral artery dissection?

Back 498

May happen spontaneously or following trauma; h/a with some neck pain, neuro deficits that may wax/wane, may see BS signs with vertebral A dissection. Need neuroimaging.

Front 499

What characterizes meningitis/encephalitis?

Back 499

H/a common, associated fever, neuro deficits esp MS change, loss of smell (HSV), may/may not have stiff neck, sz’s may occur, neuroimaging if focal deficit, then LP. CT can look NL – if suspicious STILL do LP!

Front 500

What condition predisposes to aneurysms?

Back 500

CN palsies: MUST check CNs and LOOK for aneurysms. 20% of pt’s have multiple aneurysms.

Front 501

What is xanthochromia?

Back 501

Helps distinguish true bleeds from trauma from tap; if see xanthochromia (yellowish discoloration), you know bleed has been there a/l 12 hours (RBCs have had chance to break down bilirubin)

Front 502

What characterizes an aneurysm/hemorrhage?

Back 502

Pt describes as “worse h/a of my life”; acute, explosive onset, meningeal irritation/stiff neck if SAH, may/may not have neuro deficit/HTN; need stat CT scan without contrast and if no bleed seen, then do LP; if LP +, then need angiogram

Front 503

What are some causes of secondary headaches?

Back 503

Aneurysm/hemorrhage, meningitis/encephalitis, carotid or vertebral A dissection, cerebral venous thrombosis (DVT of head)

Front 504

What is CT/MRI better at dectecting?

Back 504

CT: blood and bone, so better if suspect acute bleed, fx, or sinus problems. MRI: more sensitive for little lesions in parenchyma like posterior fossa lesions, ischemia, subdural and epidural hematomas, meningeal disease. So MRI is good if suspect stroke. NOT every h/a pt needs neuroimaging.

Front 505

What additional testing may be needed?

Back 505

In primary h/a, usually none. But in secondary h/a: neuroimaging (CT or MRI), blood work (SED rate if suspect temporal arteritis), LP (esp if personality changes present), angiography (stenosis, aneurysms)

Front 506

What characterizes Giant Cell Arteritis?

Back 506

55 and older, pain in temple or around eye, pain brushing hair, tender scalp, jaw claudication, episodes of vision loss. Anorexia, fever, joint pains. ↑ SED rate (esp if over 40). Must start steroids NOW to avoid blindness THEN get temporal artery bx.

Front 507

What characterizes cough/exertional h/a?

Back 507

Might also reflect aneurysm leak, Arnold-Chiari malformation type 1. Usually benign but must be SURE they are benign.

Front 508

What drugs can lead to medication overuse h/a?

Back 508

Narcotics/opioids, NSAIDS, triptans, acetaminophen, butalbital, caffeine; duration of use also important. May need steroids or medrol dose packs

Front 509

What is the mechanism for h/a to be worse in am?

Back 509

After laying down at night and CO2 levels ↑, get dilation of blood vessels making h/a worse.

Front 510

What characterizes AVM, tumor, or intracranial mass?

Back 510

H/a with cough/exertion, esp if posterior fossa lesion, may be worse in am, neuro s/s reflect location of mass, may have N/V; if fever, suspect abscess, if antecedent head trauma, suspect hematoma. Neuroimaging: CT with and without contrast or MRI. Note that NOT everyone with a brain tumor has a h/a.

Front 511

What drugs are associated with pseudotumor cerebri?

Back 511

Tetracyclines, Vit A stuff, nitrofurantoin, sulfonamides, bactrim. Also hypercapnia.

Front 512

What characterizes pseudotumor cerebri?

Back 512

Diffuse h/a, blurred vision or seconds of obscured vision; most seen in obese F, NL neuro exam except DO have papilledema (disc margins look funny), +/- CN6 nerve palsy and visual field deficits. CT and MRI NL. LP also NL but ↑ opening pressure. (anything over 20). Rarely seen in men, but if do, usually have sleep apnea/hypercapnea.

Front 513

What characterizes CVT?

Back 513

H/a as first symptom, neuro deficit depending on location of thrombosis, sz’s may occur, predisposing conditions: pregnancy, postpartum, dehydration, CA, coagulopathy, trauma (hypercoagulable conditions). Neuroimaging including CT with contrast, MRV and arteriogram.

Front 514

What are some causes of recurrent secondary h/a?

Back 514

Giant cell arteritis (temporal arteritis), pseudotumor cerebri (benign intracranial HTN), AVM, tumor, intracranial mass, medication overuse, cough/exertional, CNS vasculitis.

Front 515

What happens if a CVT affects the brain around the superior sagittal sinus?

Back 515

BL LE weakness. (the part of the brain taking care of the legs is over medial aspect)

Front 516

What characterizes CNS vasculitis?

Back 516

Neuro deficits represent different sites of ischemia; MRI abNL.

Front 517

What is the mechanism of the Valsalva?

Back 517

Cough → ↑ pressure around SC/CSF → transmitted up → causes descent of cerebellum thru f. magnum → h/a

Front 518

What Serotonin receptor family is not a GPCR, but rather a 5-HT-gated ion channel?

Back 518

The 5-HT3 family

Front 519

What Serotonin drug class is used in the treatment of GI disorders (IBS, GERD)?

Back 519

5-HT4 agonists: increase gut contractile activity, increase colonic transit/emptying;
5-HT3 antagonists: decrease visceral perception, slow colonic transit

Front 520

What Serotonin drug class is used in the treatment of emesis?

Back 520

5-HT3 antagonists: Ondansetron, Granisetron, Dolasetron (and other –setrons); MOA: block the effects of Serotonin released from enterochromaffin cells by cytotoxic agents (e.g. those used in the treatment of cancer); AE: HA, enhanced effects of alcohol, cardiovascular effects (esp. with Dola-, Palono-, and Tropisetron); DI: all are metabolized by P450 (all drugs, except Granisetron, are metabolized by a CYP isoform that exhibits polymorphisms, significantly affecting activity)

Front 521

What characterizes Serotonin syndrome?

Back 521

Can be caused by many different drugs; produces mental status changes, autonomic hyperactivity, and neuromuscular abnormalities – difficult to diagnose; in severe cases, can see delirium, neuromuscular rigidity, hyperthermia

Front 522

What agents are associated with the pharmacological modulation of Serotonin?

Back 522

Tryptophan/tryptophan hydroxylase, MAOIs, SRIs (selective/non-selective), releasing agents (amphetamine), depleting agents (reserpine), receptor agonists/antagonists

Front 523

What diseased states are associated with Serotonin?

Back 523

Carcinoid tumors, anxiety/depression/psychosis, GI disorders, emesis, migraine, obesity

Front 524

What are the physiological roles of endogenous Serotonin?

Back 524

CNS neurotransmitter, stimulant of pain/itch, activates chemoreceptor reflex, smooth muscle constriction (direct action), smooth muscle dilation (via NO), modulation of GI function (!), modulation of platelet function, role in cardiovascular function, probable role in bone metabolism, possible role in glucose regulation

Front 525

What describes the synthesis of Serotonin?

Back 525

L-tryptophan --> (via tryptophan hydroxylase --> rate-limiting step) L-5-hydroxy-tryptophan -->
(via dopa decarboxylase) 5-hydroxy-tryptamine (5-HT, Serotonin)

Front 526

What characterizes the metabolism of Serotonin?

Back 526

5-HT --> (via MAO) 5-hydroxyindole acetaldehyde --> (via aldehyde dehydrogenase) 5-HIAA and (via aldehyde reductase) 5-hydroxy-tryptophol

Front 527

What are examples of derivatives of Serotonin?

Back 527

Melatonin, Dimethyltryptamine, LSD

Front 528

What characterizes Cilansetron?

Back 528

Being tested for use in diarrhea-predominant IBS

Front 529

What are the most important Serotonin receptors, drugs, and their associated functions?

Back 529

5-HT1D agonists: Sumatriptan (and others), used in the treatment of migraines;
5-HT3 antagonists: Ondansetron (and others), used for chemotherapy induced emesis;
5-HT4 agonists: Cisapride, used for GI disorders

Front 530

Which Serotonin receptor subtype is involved in the modulation of satiety, and what drugs affect this receptor?

Back 530

5-HT2C: Sibutramine (controlled substance, inhibits reuptake of 5-HT, NE, DA),
Fenfluramine/Dexfenfluramine (stimulates release/inhibits uptake, associated with heart valve hypertrophy via 5-HT2A/2B and pulmonary side effects)

Front 531

What drugs are used in the prophylaxis of migraine?

Back 531

Beta blockers (first choice) and other hypertensives (CCBs, ATII blockers);
Tricyclic antidepressants (amitriptyline, nortriptyline – not safe from cardiovascular standpoint); antiepileptic drugs (valproate, topiramate, gabapentin – reduce migraine frequency)

Front 532

What Serotonin drug classes are used in the treatment of migraine?

Back 532

5-HT1D/1B agonists: Sumatriptan, Naratriptan, Rizatriptan (and other –triptans); used for acute migraine and cluster headaches (not useful for prophylaxis); CI: cardiovascular disease;
PK: metabolized by MAO – Serotonin syndrome can develop with concurrent use of SSRIs/SNRIs

Front 533

What are the major regions of drug action associated with various Serotonin modulators?

Back 533

5-HT3 antagonists: act at the vagus nerve to inhibit emesis; SSRIs: stimulate intestinal motility and cause nausea; Alosetron: slows colonic propulsion and might reduce intestinal sensation;
Sumatriptan/Buspirone: relax gastric fundus; Metoclopramide/Tegaserod: increase GI propulsion

Front 534

What characterizes Sumatriptan?

Back 534

5-HT1B agonist: useful in dyspepsia; decreases GI tone with NO release from neuron in the gut

Front 535

What characterizes Tegaserod?

Back 535

5-HT4 partial agonist: used for constipation predominant IBS; withdrawn due to increased risk of cardiovascular events (still available through age/gender restricted IND protocol)

Front 536

What characterizes Alosetron and Cisapride?

Back 536

5-HT3 antagonists (Cisapride also has 5-HT4 agonist activity): restricted usage due to ischemic colitis (Alosetron) and cardiovascular events (Cisapride)

Front 537

What are common myths about opioids?

Back 537

Respiratory depression is a common side effect;
Opioid addiction is a common problem (not addiction, but dependence);
Opioid tolerance develops rapidly;
Adequate dosing causes unmanageable constipation;
A majority of patients require prophylactic anti-emetics (not much of an issue when given PO);
Short-acting opioids are preferred for moderate/severe pain;
Unacceptable sedation and confusion occur frequently;
Controlled release opioids should only be used for cancer pain;
Dosage titration is difficult to achieve with controlled release opioids;
Severe cancer pain requires parenteral opioids;
Plasma opioid concentrations correlate directly with analgesia

Front 538

What is the benefit of pain control in a patient suffering from extreme pain, who also has a high risk of suffering an MI?

Back 538

Extreme pain causes stress which produces an elevation in NE; NE increases cardiac function which can lead to MI

Front 539

What is the relationship between hydrocodone and hydromorphone?

Back 539

Hydromorphone is a metabolite of hydrocodone

Front 540

What is given to treat neuropathic pain?

Back 540

Tricyclic antidepressants: Amitriptyline – can also give an SNRI, or Pregabalin/Gabapentin (potency = 6:1)

Front 541

What can occur in a patient taking chronic oxycodone, when nalbuphine is administered?

Back 541

Iatrogenic withdrawal (since nalbuphine is a mixed agonist/antagonist) – treat by giving morphine

Front 542

What are the acquired NMJ disorders?

Back 542

Botulism: cleaves ACh release-needed proteins; Lambert-Eaton syndrome: antibodies against presynaptic calcium channels; Myasthenia Gravis: antibodies against postsynaptic ACh receptor or MuSK (receptor tyrosine kinase); Carbamates/organophosphates: postsynaptic AChE inhibition

Front 543

What is the difference between Edrophonium and Pyridostigmine?

Back 543

Edrophonium has a very short duration of action whereas Pyridostigmine lasts longer

Front 544

What will be seen with repetitive nerve stimulation in a patient with MG?

Back 544

A decrement in neuromuscular transmission (with 2Hz nerve stimulation)

Front 545

What tests are available for MG?

Back 545

Tensilon test: give patient Edrophonium (AChE inhibitor) and watch weakness disappear; can also do repetitive nerve stimulation, look for abnormal antibodies to AChR/MuSK, or do a chest CT (some patients will have a tumor of the thymus gland) – MuSK antibodies are more so associated with bulbar weakness: tongue, swallowing, facial muscles, muscles of the eyes (this subclass is highly sensitive to immunosuppressive therapy)

Front 546

What is the hallmark of Myasthenia Gravis (MG)?

Back 546

History of fatigable weakness: mainly affects cranial nerves (ptosis, tongue weakness, problems swallowing) and proximal musculature – respiratory function should be monitored since disease can affect respiratory musculature

Front 547

What are the treatment options for MG?

Back 547

Anticholinesterase drugs (Mestinon = Pyridostigmine); Airway/respiratory support (essential); Thymectomy; Immunosuppressive therapy (Prednisone, Azathioprine); Plasmapheresis and IVIG

Front 548

What characterizes the use of plasmapheresis and IVIG with MG?

Back 548

Used with non-compliant patients in the ICU in order to rapidly remove the offending antibodies – treatment is very expensive and doesn’t last very long

Front 549

What are the major side effects of Azathioprine?

Back 549

Bone marrow and liver involvement – must monitor closely

Front 550

What is the major issue with Prednisone treatment for MG?

Back 550

It has a terrible side effect profile – but it is very effective

Front 551

What are the rules for doing a thymectomy in a patient with MG?

Back 551

Teens/twenties: must clear out entire anterior mediastinum to remove all fragments of the thymus;
30+: still perform thymectomy, but need double-blind study to determine whether appropriate;
50+: no thymectomy needed – only major side effect of thymectomy is the surgery itself

Front 552

What side effect is associated with Pyridostigmine?

Back 552

Diarrhea, treated with Atropine

Front 553

In what type of autopsy must the family request an autopsy?

Back 553

Hospital Autopsy

Front 554

What is involved in the external examination?

Back 554

Identification, Identifying characteristics (body type, clothing, age, weight), Head to Toe Examination (skin, hair color, chest, abdomen, back, extremities), Toxicology

Front 555

Under what circumstances do cases full under the medical examiner authority?

Back 555

Criminal Violence, Suicide, Accident, Sudden death when in good health, Death unattended by practicing physician, Death under suspicious or unusual circumstances, Abortion, Poisoning, Disease constituting a threat to public health, Disease, injury or toxic agent resulting from employment, associated w/ diagnostic or therapeutic procedures, any prison or penal institution, in legal custody, cremation, dissected or buried at sea, Unclaimed bodies, Body brought into a new medicolegal jurisdiction w/o proper medical certification

Front 556

What are the components of an autopsy?

Back 556

External Examination, Internal Examination, Inspection

Front 557

What are the characteristics of Livor Mortis?

Back 557

Lividity, postmortem hypostasis, Reddish purple coloration, Accumulation of blood in the small vessels, Evident 30 min-2 hrs after death, Can appear antemortem, Maximum coloration at 8-12 hrs --> Fixed

Front 558

What are the characteristics of Rigor Mortis?

Back 558

Stiffening of the body after death, Cessation of ATP generation, Develops in all muscles at the same time, Cold-delay onset and prolong presence, Heat-speed up onset, Disappears with decomposition

Front 559

What are Rigor Mortis and Livor Mortis used for?

Back 559

Not very important in determining the time of death. It is important in determining whether the body has been moved

Front 560

What is the most method for determining time of death?

Back 560

When was the person last seen? (i.e. 10:00 pm), When was the person found? (i.e. 9:00 am); The person died sometime between 10:00 pm and 9:00 am

Front 561

What are the components of toxicology?

Back 561

Blood (most important), Vitreous Humor, Urine, Bile, Gastric contents

Front 562

What is involved in the external examination?

Back 562

Identification, Identifying characteristics (body type, clothing, age, weight), Head to Toe Examination (skin, hair color, chest, abdomen, back, extremities), Toxicology

Front 563

What are the types of blunt force wounds?

Back 563

Contusion (Bruise), Abrasions, Laceration

Front 564

What is the difference between a recent and old bruise?

Back 564

Recent is purple or red; Old is yellow or brown

Front 565

How can you tell a laceration from a stab wound?

Back 565

Skin bridging, there is tissue that is still connected where the skin was town, laceration has rough edges (stab wound is smooth)

Front 566

What is seen in a Basilar Skull Fx?

Back 566

Have a battle sign (bruising behind the ears) & raccoon eyes

Front 567

What are the types of sharp force wounds and what differentiates them?

Back 567

Incised wounds (Length > depth, No Abrasion, No Contusion, No Bridging) and Stab wounds (Pointed instruments, Homicidal, Depth exceeds length, Sharp edges)

Front 568

What is the most important thing about GSW?

Back 568

Determining if it is an entrance or exit wound

Front 569

How can you tell if a GSW is an Entrance wound & what types of entrance wound exist?

Back 569

If there is injury to the skin present, reddening & abrasions of the superficial skin, there is tissue lost;
Contact Entrance Wound (muzzle imprint);
Intermediate Entrance Wounds (Powder Tattooing: abrasions created by powder);
Distance Entrance Wounds: no muzzle imprint, no powder tattooing, just skin abrasion & tissue lost of skin around it

Front 570

What is included in the Internal Examination?

Back 570

Organs in anatomical Position, Gross examination of each organ, Documentation of injury to organs, Microscopic sections if needed

Front 571

What are the most common natural disease processes that cause death?

Back 571

Heart disease, Lung Disease (COPD, asthma), Cancer, Liver Disease

Front 572

What organism can affect normal valves and cause Acute IE?

Back 572

Staphylococcus aureus

Front 573

What is the most important thing for a pathologist to figure out for MVA?

Back 573

Who was driving?

Front 574

What is dicing?

Back 574

The side paneling on glass windows breaks into cubes and causes this characteristic abrasions and lacerations to the arm in MVAs

Front 575

What is the protocol for thermal injuries?

Back 575

Complete X-Rays due to their Pugilistic position (Arms and legs will be contracted (i.e. like a boxer), Toxicology

Front 576

What are the characteristic findings in thermal injuries?

Back 576

Skin splitting (expose muscle); Ruptured muscle; Unburned skin (seared leathery appearance); Burned bone (grey/white with fine superficial fractures (curved))

Front 577

When is it protocol to perform complete X-Rays?

Back 577

Gunshot wounds, Sharp force deaths, Fire deaths

Front 578

What is a defensive type wound?

Back 578

Shows whether the person tried to fight back or not, usually on the fingers (person grabs knife), back of the hands, back of the arm

Front 579

What is important in Infants and Childhood Deaths?

Back 579

Complete X-Rays (Battered babies and abused children often have old, healing fractures), Possible cultures, Heart very important, CPS reports (old Hx of abuse), SUID (Sudden Undetermined Infant Death), Doll reenactment

Front 580

What classifies Drowning?

Back 580

Dx of exclusion, wrinkled skin, possible pulmonary edema

Front 581

What is a Nasal Plume?

Back 581

Due to pulmonary edema, seen w/ asphyxiated death (i.e. drowning, drug overdose)

Front 582

What are the types of Asphyxia deaths?

Back 582

Hanging, Smothering, Strangulation, Chemical Asphyxia

Front 583

What classifies how autoerotic asphyxia?

Back 583

Asphyxial Deaths, Anoxia induced to enhance sexual arousement produced by masturbation

Front 584

What is the primary lesion seen in Multiple Sclerosis?

Back 584

Plaques of demyelination: periventricular white matter (classical site), gray-white matter junctions, optic nerves/chiasm/tracts, brainstem ascending/descending tracts, subpial region of spinal cord
Note: on actual gross sections, areas of white matter afflicted with MS look discolored and grayish

Front 585

What disease is similar to ADEM in pathology but is usually fatal?

Back 585

Acute Hemorrhagic Leuko-Encephalitis (AHLE) aka Weston-Hurst disease: acute, monophasic (following a viral illness or immunization), causes perivenous demyelination (like ADEM) as well as petechial hemorrhage in the demyelinated white matter, and possibly neutrophilic infiltrate
Note: AHLE is usually fatal due to petechial hemorrhages, whereas ADEM patients recover (!)

Front 586

What is found grossly and microscopically in ADEM?

Back 586

Grossly: normal brain – Microscopically: perivascular pattern of demyelination (no hemorrhage)

Front 587

What characterizes Acute Disseminated Encephalo-Myelitis (ADEM)?

Back 587

Perivenous encephalomyelitis: acute, monophasic demyelination in children (following a viral illness or immunization), usually recovers with supportive therapy

Front 588

What are clinical variants of Multiple Sclerosis?

Back 588

Classic or Charcot type: relapsing/remitting form
Acute or Marburg type: first lesion can rapidly progress, cause extensive demyelination, and be fatal acutely (!)
Devic disease: affects only optic pathway and/or spinal cord (aka neuromyelitis optica)
Balo concentric sclerosis: only concentric areas of demyelination
Schilder disease: all MS variants that do not fit elsewhere

Front 589

What morphological variant of macrophages are seen in demyelinating diseases?

Back 589

Crutzfeldt cells: macrophages with mitotic figures (not unique to MS, may be seen in all demyelinating disease)

Front 590

What is seen microscopically with Multiple Sclerosis?

Back 590

Acitve plaques (demyelination): loss of myelin, macrophages (sometimes Crutzfeldt cells), **relative sparing of axons and neurons, **perivascular mononuclear T cell infiltrates, reactive astrocytosis, edema
Remyelination: “Shadow plaques” showing some remyelination, Schwann cell migration to spinal cord --> remyelination from Schwann cells in spinal cord
Inactive plaques: demarcated/acellular/inactive areas of previous demyelination with little inflammatory infiltrate
Note: axons are less involved than the white matter in Multiple Sclerosis ****
Note: remyelination never produces equally good myelin as original (!)

Front 591

What characterizes Multiple Sclerosis?

Back 591

F > M, linkage to HLA-DR2, 15-fold greater risk when 1st relative has MS, 25% concordance rate in monozygotic twins, increased incidence with distance away from the equator – pathogenesis is thought to involve genetic predisposition, immune factors, and possibly environmental antigens (virus?)

Front 592

What is a screening test for Multiple Sclerosis?

Back 592

CSF evaluation: looking for oligoclonal bands in CSF

Front 593

How does Multiple Sclerosis present clinically?

Back 593

Most common presentation: relapsing/remitting neurological deficits
Other signs: optic neuritis, brainstem involvement (CN signs, ataxia, nystagmus, ophthalmoplegia), spinal cord involvement (motor/sensory abnormalities, bladder dysfunction), oligoclonal bands in CSF

Front 594

What characterizes Krabbe Disease (Globoid Cell Leukodystrophy)?

Back 594

Galactocerebroside b-galactosidase deficiency (AR) --> psychosine accumulation, demyelination with multinucleated globoid cells, curved tubular inclusions in macrophages/Schwann cells (EM)
Note: globoid cells are multinucleated marcophages (!)

Front 595

What leukodystrophies can cause demyelination of PNS?

Back 595

Metachromatic leukodystrophy, Krabbe disease

Front 596

What are some demyelinating diseases of PNS?

Back 596

Guillain-Barre syndrome, Chronic Inflammatory Demyelinative Polyradiculoneuropahy (CIDP)

Front 597

What characterizes Canavan Disease?

Back 597

Aspartoacylase enzyme deficiency (AR) --> “spongy” degeneration of white matter, Alzheimer type 2 astrocytes
Note: Alzheimer type 2 astrocytes are seen in Canavan disease and Hepatic Encephalopathy (!)

Front 598

What characterizes Pelizaeus-Merzbacher Disease?

Back 598

Proteolipid protein synthesis defect (X-linked, M>F) --> widespread demyelination + perivascular myelin sparing (“tigroid” demyelination)
Note: proteolipid protein is the precursor for CNS myelin

Front 599

What characterizes Alexander Disease?

Back 599

Sporadic pattern of inheritance (most patients have new mutations), patients present with macrocephaly, demyelination, and large numbers of Rosenthal fibers (astrocytic inclusions)
Note: demyelination + lots of Rosenthal fibers --> think Alexander Disease

Front 600

What characterizes Adrenoleukodystrophy?

Back 600

ATP-binding cassette transporter deficiency in Perixosomes (X-linked, M>F) --> very long chain fatty acid accumulation (from peroxisomal dysfunction), adrenal dysfunction (enzyme has role in adrenals)
Demyelination is more prominent posteriorly, with **perivascular lymphocytes (mimicking MS) and cleftlike inclusions in macrophages
Note: case wording may be: adrenal cortex thinning, posterior brain demyelination, demyelination with macrophages + perivascular lymphocytes, cleftlike inclusions in macrophages

Front 601

What are the infectious demyelinating diseases?

Back 601

Progressive multifocal leukoencephalopathy (PML): due to JC virus, primarily affects oligodendrocytes (leading to demyelination), oligodendrocytes appear with intranuclear viral inclusion (glassy appearance, chromatin pushed to the side), JC viruses (under EM) look like spaghetti and meatballs (!)
Others include subactue sclerosing panencephalitis, Rubella, HIV leukoencephalopathy

Front 602

What characterizes Metachromatic Leukodystrophy?

Back 602

Arylsulfutase A deficiency (AR) --> metachromatic accumulation in macrophages/Schwann cells, prismatic/tuffstone inclusions (EM)
Note: metachromasia refers to staining that produces a different color from what’s expected of the stain (!)

Front 603

What are leukodystrophies?

Back 603

Hereditary disorders of myelin – most are due to enzyme deficiency (AR) – in all, demyelination is seen as “confluent areas of discolored, gelatinous white matter” - diseases are listed below …
Note: leukodystrophies spare the subcortical arcuate fibers, whereas in MS, they are affected (!)

Front 604

What are vascular disorders that can cause demyelination of white matter?

Back 604

Binswanger disease, Chronic edema

Front 605

What can Thiamine deficiency lead to in the CNS?

Back 605

Wernicke encephalopathy + Korsakoff psychosis + (possible) beriberi (involvement of PNS, CV)
Wernicke encephalopathy: eye problems + nystagmus/ataxia + global confusion + disorientation
Korsakaoff psychosis: cannot form new memories (retrograde amnesia), confabulation

Front 606

What characterizes methanol poisoning?

Back 606

Metabolic acidosis (systemically), blindness, respiratory depression – causes **** bilateral necrosis of putamen, degeneration of retinal ganglions – treated with ethanol
Note: if see “bilaterally symmetric” lesion of putamen --> think methanol poisoning ****

Front 607

What lesions are seen in CO poisoning?

Back 607

Acute lesion: cherry-red discoloration
Chronic lesion: **** bilateral necrosis of globus pallidus, demyelination of white matter tracts
Note: most hypoxic, stroke-type damages are not bilaterally symmetric (!)
Note: if see “bilaterally symmetric” lesion of globus pallidus --> think CO poisoning (Slide 21 – KNOW)

Front 608

What characterizes CO poisoning?

Back 608

Acutely leads to hypoxic damage to brain --> in surviving patients, leads to delayed encephalopathy and Parkinsonism – seen in accidental or suicidal settings

Front 609

What characterizes Marchiafava-Bignami disease?

Back 609

Demyelination/necrosis of Corpus Callosum --> symptoms of interhemispheric disconnection (Neuropsychiatric disorders), dysarthia, impaired consciousness – 1st described in Italian red wine drinkers (but can occur in anyone, with any type of drink)

Front 610

What characterizes Central Pontine Myelinolysis? ****

Back 610

Iatrogenic disorder seen most commonly in setting of alcoholism: too rapid correction of hyponatremia --> diamond-shaped demyelination in basis pontis --> rapidly evolving quadriplegia

Front 611

What lesions are seen in Wernicke-Korsakoff syndrome?

Back 611

Mamillary body lesions (acute: edema, hemorrhage, capillary proliferation – chronic: shrunken, brown mamillary bodies with gliosis) – other periventricular area lesions may be seen (!)

Front 612

What are CNS lesions in alcoholism?

Back 612

Trauma, cerebellar degeneration, Wernicke-Korsakoff syndrome, Central Pontine Myelinolysis, Marchiafava-Bignami disease, Fetal Alcohol Syndrome

Front 613

What are other causes of cerebellar vermis atrophy?

Back 613

Ethanol, phenytoin, heavy metals (Mercury), spinocerebellar ataxias

Front 614

What characterizes Alcoholic Cerebellar Degeneration?

Back 614

Atrophy of anterior, superior vermis (midline cerebellum) --> truncal ataxia, unsteady gait, nystagmus – affects 1% of chronic alcoholics – histology shows loss of Purkinje cells with Bergmann gliosis

Front 615

What chemotherapeutic agent can cause brain damage?

Back 615

Methotrexate --> white matter damage with swollen axons

Front 616

What are lysosomal storage diseases of CNS?

Back 616

Sphingolipidoses: enzyme deficiency (AR), affect either gray or white matter
Mucopolysaccharidoses
Neuronal ceroid lipofuscinosis

Front 617

What characterizes the CNS pathology of Vitamin B12 deficiency?

Back 617

Subacute combined degeneration of the spinal cord (combined posterior + lateral column degeneration)***

Front 618

What characterizes the pathology of Vitamin B12 deficiency in CNS?

Back 618

(all insidious, progressive)
Spinal cord problems: spastic paraparesis, sensory ataxia, severe paresthesias in lower limbs
Megaloblastic anemia, increased methylmalonic acid in urine, improvement with IV B12

Front 619

What are the etiologies for Vitamin B12 deficiency in CNS?

Back 619

#1 cause is Intrinsic Factor deficiency (from pernicious anemia or gastrectomy), other causes include dietary deficiency, malabsorption (Crohn’s disease), fish tapeworm infection, or increased metabolism of Vitamin B12 (pregnancy, hyperthyroidism, cancer)

Front 620

What is seen microscopically with Solvent Abuse Leukoencephalopathy?

Back 620

Brain atrophy with discoloration of white matter (more subtle than leukodystrophies)
Loss of myelin, ** characteristic PAS-positive macrophages around blood vessels (!)
Note: all changes are extremely subtle in this disease, except PAS-positive macrophages around vessels (!)

Front 621

What occurs with inhalant abuse of toluene-containing solvents (e.g. glue sniffing)?

Back 621

Solvent Abuse Leukoencephalopathy: volume loss of white matter, loss of gray-white matter demarcation, increased white matter signal on MRI - Mimic leukodystrophies, but have more subtle discoloration of white matter

Front 622

What characterizes Lead poisoning?

Back 622

Mimic of meningitis (encephalopathy, increased intracranial pressure, nuchal rigidity), characteristic peripheral neuropathy (demyelinating, with wrist/foot drop), epigastric pain/vomiting/constipation, anemia, chronic tubulointerstitial nephritis

Front 623

What occurs to the brain as a result of cranial irradiation?

Back 623

Acute: patchy edema of white matter – Delayed: white matter damage, fibrinoid changes in blood vessels
Secondary tumors can appear (#1: meningioma)
Histologically: typical change is appearance of atypical cells with big nucleus AND big cytoplasm

Front 624

Given the major function and G-protein class name the receptor

↑ H2O permeability and reabsorption in the collecting tubules of the kidney

What mechanims does it use?

Back 624

V2

Receptor --(Gs)--> adenylyl cyclase...

Lipids --(adenylyl cyclase)--> ↑ cAMP --> protein kinase A

Front 625

How is Gaucher disease diagnosed?

Back 625

CNS findings are subtle: Gaucher cells in perivascular spaces – not usually tested for diagnosis
Diagnosis is done by looking for Gaucher cells in liver or BM

Front 626

What findings are seen in CLN disorders?

Back 626

CLN1 (infantile) – Granular bodies on EM;
CLN2 (late-infantile) – Curvilinear bodies on EM;
CLN3 (juvenile) – Fingerprint profiles on EM

Front 627

What disease causes accumulation of Lipofuscin-like material in neurons?

Back 627

Neuronal Ceroid Lipofuscinosis (CLN) aka Batten disease – unknown enzyme defect --> progressive neurologic illness with blindness

Front 628

Which Mucopolysaccharidoses is X-linked?

Back 628

Hunter syndrome

Front 629

What are the most common findings in Mucopolysaccharidoses?

Back 629

Common findings: involvement of soft tissue/bone of face --> coarse facial features, corneal clouding (cataracts), joint stiffness, mental retardation

Front 630

What characterizes Mucopolysaccharidoses?

Back 630

Glycosaminoglycan degradative enzyme deficiency (most are AR) --> systemic involvement – storage material in cells are called “zebra bodies” - can be diagnosed by urine monitoring for accumulated mucopolysaccharides

Front 631

What characterizes Niemann-Pick disease?

Back 631

Sphingomyelinase deficiency (AR) --> visceral storage mainly in macrophages (hepatosplenomegaly, lymphadenopathy), CNS storage mainly in neurons and macrophages (progressive psychomotor deterioration)

Front 632

What are lysosomal storage diseases of CNS that predominantly affect the white matter?

Back 632

Leukodystrophies: Metachromatic leukodystrophy (Arylsulfatase A), Krabbe disease (Galactocerebroside -->-galactosidase, Globoid cells)

Front 633

What characterizes Gaucher disease?

Back 633

Glucocerebroside deficiency (AR) --> systemic disease --> distended, PAS-positive phagocytes (Gaucher cells) systemically, in CNS found in perivascular spaces
Note: know that Gaucher disease is a systemic sphingolipidoses and enzyme replacement therapy is available for it (!)
Note: Gaucher cells are supposed to look like “wrinkled tissue paper” (!)

Front 634

What characterizes Tay-Sachs disease (GM2 Gangliosidoses)?

Back 634

(more common in Ashkenazi Jews)
Hexosaminidase A deficiency (AR) --> progressive motor/mental deterioration beginning in infancy
Characteristic but not pathognomonic finding is “macular cherry-red spots”
Storage material accumulates exclusively in the gray matter (neurons) – not a systemic disease (!)
Case: 6-month old child with cherry-red spot on retinal exam, know what enzyme is missing (!)
Note: this is on the test (99% chance)

Front 635

What peroxisomal disorder presents as a combination of leukodystrophy and abnormal neuronal migration? ********

Back 635

Zellweger syndrome: is a generalized peroxisomal dysfunction --> accumulation of very long chain fatty acids --> abnormal neuronal migration and/or myelination disturbances

Front 636

Which mitochondrial disease is due to large deletions in mitochondrial DNA?

Back 636

Kearns-Sayre syndrome (sporadic)

Front 637

What mitochondrial encephalomyopathies are due to mutations in mitochondrial tRNA (and maternally transmitted)?

Back 637

MERRF: myoclonus, myopathy, ataxia – neuronal loss in inferior olives, cerebellar cortex, cerebellar outflow nuclei
MELAS: neurologic dysfunction, weakness, lactic acidosis – patients will have strokes in white/gray matter
Note: see a child with stroke-like lesion --> think MELAS (!) *********

Front 638

What characterizes Leigh syndrome?

Back 638

Due to decreased cytochrome c oxidase activity - lesions look like Wernicke-Korsakoff, but occurs in children: spongiform degeneration and proliferation of blood vessels in periventricular gray matter

Front 639

What characterizes Mitochondrial Encephalomyopathies?

Back 639

Mutations can be either in the mitochondrial DNA (maternal transmission) or in nuclear DNA – common finding in all disorders are “ragged red fibers”, lactic acidosis, weakness with hypotonia

Front 640

Which Glycogen Storage Disease involves CNS?

Back 640

Pompe disease due to Acid Maltase deficiency --> systemic involvement of muscle, liver, CNS (!) --> MORE SEVERE than McArdle’s

Front 641

What are common findings in Glycogen Storage Disorders?

Back 641

Hepatic enlargement, hypoglycemia, muscle cramps after exercise – only know the following …
McArdle’s disease due to Myophosphorylase deficiency --> only involves muscles (!) --> LESS SEVERE

Front 642

What are the routes of entry for CNS infections?

Back 642

Hematogenous spread (most common);
Direct implantation (traumatic, iatrogenic);
Local extension (sinuses, cranial bones);
Via the peripheral nervous system (rabies)

Front 643

What are the causative organisms for community acquired acute pyogenic meningitis?

Back 643

Streptococcus pneumoniae (most common), Neisseria meningitidis (i.e. outbreak on college campus, military groups), group B streptococcus, Listeria monocytogenes

Front 644

What are the causative organisms for acquired acute pyogenic meningitis?

Back 644

S. pneumoniae, Staphylococcus species, gram-negative bacilli

Front 645

What are the causative organisms for immunocompromised patients w/ acute pyogenic meningitis?

Back 645

L. monocytogenes, gram-negative bacilli

Front 646

What are the symptoms associated with acute pyogenic meningitis?

Back 646

headache, photophobia, irritability, clouding of consciousness, neck stiffness

Front 647

What is the pathology & what found in the CSF of a pt w/ acute pyogenic meningitis?

Back 647

Path: Prominent meningeal vessels, Neutrophils in subarachnoid space, Phlebitis with hemorrhagic infarction, Chronic adhesive arachnoiditis;
CSF: Cloudy/purulent, increased pressure, increased neutrophils, increased protein, decreased glucose

Front 648

What are the Predisposing conditions for brain abscess?

Back 648

Bacterial endocarditis, cyanotic congenital heart disease, & chronic, pulmonary sepsis

Front 649

What are the primary causative organisms for brain abscess & how do patients present?

Back 649

Streptococci & staphylococci;
Present with focal deficits & increased intracranial pressure

Front 650

What types of CNS lesions are discrete with central necrosis surrounded by a fibrous collagen capsule & edema and can be treated with surgery and antibiotics?

Back 650

Brain Abscess

Front 651

What are the causes of chronic bacterial meningoencephalitis?

Back 651

Tuberculosis, Neurosyphilis, Lyme disease (neuroborreliosis)

Front 652

What are describes Tuberculous Meningitis?

Back 652

Symptoms: headache, malaise, mental confusion, vomiting;
CSF: mononuclear cells, increased protein, normal or moderately decreased glucose (less severe extent that in acute bacterial meningitis);

Front 653

What is a Tuberculoma?

Back 653

Well-circumscribed intraparenchymal mass (mass lesion)

Front 654

How does TB meningitis present pathologically?

Back 654

Gross: Gelatinous or fibrinous, basally located exudate
Histo: Granulomatous inflammation (like it is w/ TB in other organs) with caseous necrosis & obliterative endarteritis

Front 655

What is vertebral involvement in TB meningitis called?

Back 655

Pott disease (can cause the bones to collapse and compress the spinal cord)

Front 656

What are the 3 types of neurosyphilis?

Back 656

Meningovascular neurosyphilis - chronic meningitis with obliterative endarteritis & a perivascular plasma cell infiltrate;
Paretic neurosyphilis - invasion of the brain by treponemal organisms with brain atrophy & resultant severe dementia;
Tabes dorsalis - damage to dorsal root sensory nerves with impaired sensation & absence of deep tendon reflexes

Front 657

What causes Lyme disease and what are the neurologic findings?

Back 657

Spirochete Borrelia burgdorferi; Neurologic findings are non-specific & include aseptic meningitis, facial nerve palsies, mild encephalopathy, & polyneuropathies

Front 658

What is the most common cause of aseptic meningitis?

Back 658

Enteroviruses, can be viral or chemical

Front 659

What is seen in the CSF of Aseptic meningitis?

Back 659

Lymphocytic pleocytosis with moderate protein elevation & normal glucose (vs Bacteria meningitis which has decreased glucose)

Front 660

What is the difference between Aseptic meningitis and Bacterial meningitis?

Back 660

Aseptic meningitis is usually self-limited (vs bacterial which needs surgery or ABX treatment)

Front 661

What is viral meningoencephalitis?

Back 661

Parenchymal infection of the brain associated with meningeal inflammation

Front 662

What histological features are always seen in all viral CNS infections?

Back 662

Perivascular & parenchymal mononuclear cell infiltrates, glial nodules, Neuronophagia

Front 663

What are responsible for epidemic viral encephalitis (Arthropod-Borne viral encephalitis)?

Back 663

Include Eastern, Western, & Venezuelan equine, St. Louis, Japanese B, California, Murray Valley, West Nile, and tick-borne encephalitis viruses; Animal hosts & mosquito or tick vectors, they present with Generalized or focal neurologic deficits

Front 664

What is the most common cause of sporadic encephalitis?

Back 664

HSV-1 (hemorrhagic encephalitis involving the temporal lobes & orbital gyri of the frontal lobes) (vs HSV-2: severe generalized encephalitis in neonates & immunocompromised patients)

Front 665

What CNS virus are Cowdry A nuclear inclusions present in?

Back 665

Herpes Simplex Virus

Front 666

What type of CNS manifestation can VZV cause in immunocompromised patients?

Back 666

Acute meningoencephalitis

Front 667

What characterizes CMV in the CNS?

Back 667

Infections occur in fetuses & immunocompromised patients; Periventricular necrosis & calcification; Prominent cytomegalic cells with intranuclear & intracytoplasmic inclusions

Front 668

What classified the poliovirus?

Back 668

Enterovirus that has been controlled by immunization; Specifically attacks lower motor neurons producing a flaccid paralysis with muscle wasting & hyporeflexia

Front 669

What is syndrome presents as late neurologic syndrome characterized by progressive weakness associated with decreased muscle bulk & pain?

Back 669

Postpolio syndrome

Front 670

What are Negri bodies?

Back 670

Cytoplasmic eosinophilic inclusions in pyramidal neurons of the hippocampus & cerebellar Purkinje cells, found in Rabies

Front 671

What is characteristic presentation of rabies?

Back 671

Patients exhibit CNS excitability (sensitivity of light and fear of water)

Front 672

How does Rabies enter the CNS?

Back 672

Virus enters CNS by ascending along the peripheral nerves from the wound site

Front 673

What are the CNS manifestations of HIV?

Back 673

Aseptic meningitis (early HIV); Meningoencephalitis with microglial nodules & multinucleated giant cells (AIDS); Vacuolar myelopathy (myelin damage); Cranial & peripheral neuropathies; Myopathies (inflammatory and drug-related); Opportunistic infections

Front 674

What does the JC virus cause?

Back 674

Progressive Multifocal Leukoencephalopathy, infects & kills oligodendrocytes, Demyelination with lipid-laden macrophages, Nuclear viral inclusions in oligodendrocytes, Bizarre giant astrocytes

Front 675

What can a defective form of the measles virus cause?

Back 675

Subacute Sclerosing Panencephalitis: Cognitive decline, spasticity of the limbs, and seizures; Loss of myelin and gliosis (predominantly a white matter disorder); Nuclear and cytoplasmic viral inclusions

Front 676

What are the manifestations of the CNS of fungal infections?

Back 676

Cause chronic meningitis, vasculitis, & parenchymal invasion; Usually result from hematogenous dissemination from a primary infection elsewhere; Encountered primarily in immunocompromised patients

Front 677

What Encapsulated yeast causes meningitis or parenchymal lesions with Sparse inflammatory cell infiltrate?

Back 677

Cryptococcus neoformans causes Cryptococcus (5-10 micrometer yeasts with wide capsular halo; narrow-based unequal budding)

Front 678

What fungus produces microabscesses in the CNS?

Back 678

Candidiasis (Candida albicans, Hyphal and yeast forms, Nonbranching pseudohyphae + Blastocondia)

Front 679

What fungus has a predilection for vessel walls leading to hemorrhagic abscesses in the CNS?

Back 679

Aspergillosis (Aspergillus fumigatus or A. flavus most common; Septate, branching hyphae (45 degree angle; Acute angle = Aspergillosis), rare fruiting bodies)

Front 680

What fungus causes Rhinocerebral infection in patients with diabetes and ketoacidosis and is angioinvasive?

Back 680

Mucormycosis (Mucor, Rhizopus, and Absidia, Irregular, Irregular broad (empty-looking) non-septate hyphae that branch at right angles [wide-angle])

Front 681

mandón/mandona

Back 681

bossy

Front 682

What characterizes histoplasmosis, coccidioidomycosis, and blastomycosis?

Back 682

Histoplasmosis (Tiny (2-5 micrometers) yeasts, occasional unequal budding;
Coccidioidomycosis (20-60 micrometer spheres with endospores);
Blastomycosis (Larger (up to 25 micrometers) yeasts, double-contoured, broad-based budding)

Front 683

What parasitic infection must be clinically distinguished from primary CNS lymphoma?

Back 683

Toxoplasmosis

Front 684

What characterizes Toxoplasmosis?

Back 684

Toxoplasma gondii, Infects immunosuppressed patients and fetuses, Necrotic lesions surrounded by inflammation; Free tachyzoites and encysted bradyzoites

Front 685

What are the types of Amebias that can infect the CNS?

Back 685

Naegleria: Rapidly fatal meningoencephalitis;
Acanthamoeba and Balamuthia: Chronic granulomatous encephalitis, Keratitis in contact lens wearers

Front 686

What classifies cysts containing larval forms of the organism that are commonly found in the CNS?

Back 686

Cysticercosis (Taenia solium (pork tapeworm))

Front 687

What are the different types of Spongiform Encephalopathies?

Back 687

Creutzfeldt-Jakob disease; Kuru; Gerstmann-Straüssler-Scheinker syndrome; Fatal familial insomnia; Variant Creutzfeldt-Jakob disease

Front 688

What is the cause of spongiform encephalopathies & what are the manifestations?

Back 688

Caused by prion proteins: normal cellular prion protein (PrP) undergoes a conformational change to an abnormal beta-pleated sheet isoform which resists digestion and accumulates in neural tissue; Rapidly progressive dementia, Spongiform change, neuronal loss, & reactive astrocytosis

Front 689

What type of spongiform encephalopathy can be iatrogenic transmission?

Back 689

Creutzfeldt-Jakob disease (Rapidly progressive dementia with myoclonus; Uniformly fatal; Spongiform change, neuronal loss, and gliosis)

Front 690

What spongiform encephalopathy is an inherited disorder that causes cerebellar ataxia & is characterized by Large amyloid plaques in cerebellum?

Back 690

Gerstman-Straussler-Scheinker Syndrome

Front 691

What classifies Fatal Familial Insomnia?

Back 691

Spongiform encephalopathy, Inherited, Sleep disturbances, ataxia, and autonomic problems, Pathologic changes in thalamus

Front 692

What spongiform encephalopathy has characteristic florid plaques pathologically?

Back 692

Variant CJD (United Kingdom, Younger age of onset, more prominent behavioral disturbances, and a longer clinical course than typical CJD cases, Linked to bovine spongiform encephalopathy)

Front 693

What are the two main types of Infections that bacteria can cause?

Back 693

(1) Inflammation of the Meninges (Meningitis)
(2) Localized infections due to bacteria (Abscesses)