6. PATH Demyelinating Degenerative Genetic Toxic Diseases

Question 1

Demyelinating disease are acquired conditions characterized by preferential damage to myelin with relative preservation of axons*, CNS has limited capacity to regenerate normal myelin and unmyelinated axons are susceptible to secondary damage such as immunologic and?

Answer 1

inherited DOs- leukodystrophies

Question 2

What autoimmune demyelinating disease more affects white and not grey- so severe cognitive impairment is not a feature, plaques occur in periventricular white matter, characterized by distinct episodes of neuro deficits separated in time due to white matter lesions that are separated in space, with relapsing and remitting episodes of variable duration?

Answer 2

Multiple Sclerosis- MC demyelinating disease

**More common in northern hemispehre

Question 3

Multiple Sclerosis lesions occur anywhere but some areas are more common, unilateral visual disturbances from damage to the optic nerve (optic neuritis)- frequently the initial symptoms (10-50% devel), brainstem signs include CN signs, internuclear opthalmoplegia (medial longitudinal fasciculus damage) and what two other main sx?

Answer 3

Ataxia and Nystagmus

SC: motor and sensory impariment of trunk and limbs, spasticity, bladder control loss

Question 4

Multiple Sclerosis is seen at any age though onset in childhood or >50 is rare, women twice as often as men, related to genetics and environment, 15fold higher in first degree relative, 150fold if monozyogtic twin, there is a strong linkage between IL2/7 and DR2, inflammation is chronic and is initiated by CD4Th1 and Th17 T cells that react against?

Answer 4

Self myelin antigens and secrete cytokines

Th1= secretes IFN gamma = activate mø
Th17= promote leukocytes

Note: plaque infiltrate are T cells mainly CD4+

Question 5

Multiple Sclerosis is a white matter dz, lesions are firmer than surrounding white matter (sclerosis) and contain well circumbscribed, depressed, glassy, grey-tan, irregularly shaped plaques commonly next to *lateral ventricles, optic nerves, brainstem, cerebellum and SC, the firm texture of the plaque is due to reactive?

Answer 5

astrocytosis

Note: commonly see thin corpus callosum and expansion ventricular system= hydrocephalus ex vacuo

Question 6

Multiple Sclerosis histo can be stained with luxol fast blue myelin stain to check for myelin and demyelinated areas, in areas without myelin- axons are preserved and swollen (if axons not preserved think infarction), what type of plaques are ongoing myelin breakdown with abundant mø containing lipid rich PAS* + debris with perivascular (small veins) inflammatory infiltrate at outer edge, with relative preservation of axons and only the oligodendrocyte is killed off?

Answer 6

Active Plaques

Question 7

A shadow plaque assoc w Multiple Sclerosis border between normal and affected white matter is not well defined- abnl thinned out myelin sheaths and partial/incomplete remyelination by surviving oligos, what plaques are quiescent, inflammation not present, no myelin/dec oligo nuclei, dec axons, mainly see astrocytic proliferation and gliosis?

Answer 7

Inactive plaques

Question 8

The CSF should be checked for Multiple Sclerosis, in wwhich one will see mildly elevated protein, moderate pleocytosis in 1/3 cases (elevated WBC count in CSF), IgG levels increased and what bands will be seen which are indicative of the presence of a small number of activated (self reactive) B cell clones?

Answer 8

Oligoclonal IgG Bands* on immunoelectrophoresis

Question 9

What demyelinating disease is assoc with synchronus bilateral optic neuritis and spinal cord demyelination, 10-50% developing MS, aka Devic disease, women greater then men, characterized by antibodies against aquaporin4 (maintain astrocyte foot process = BBB), see necrosis, neutrophils and vascular deposition of immuoglobulin and complement in white matter?

Answer 9

Neuromyelitis optica NMO

Question 10

Neuromyelitis optica NMO has CSF with commonly an abundance of WBC= neutrophils and an increased opening pressure which can be turbid (thick) treatment for this disease is an attempt to decrease antibody burden via?

Answer 10

Plasmapheresis***

Question 11

What demyelinating disease is an acute immunolgically mediated disease with features similar to MS but occurs in younger pts, abrupt onset and rapidly fatal, assoc with diffuse monophasic demyelinating disease that occurs after (1-2wks) viral infection or rarely viral immunization?

Answer 11

Acute Disseminated Encephalomyelitis ADEM

Question 12

Acute Disseminated Encephalomyelitis ADEM usually present with headache, lethargy and coma, 20% die, rest recover completely, diffuse neuro deficits, (unlike MS which is focal), morph will see greyish decoloration of vessels in white matter, myelin loss w intact axons, early stages are associated with neutrophils and later stages with?

Answer 12

mononuclear cells

See accum of lipid laden mø- ALL LESIONS LOOK SAME = MONOPHASIC

Question 13

What demyelinating disease is aka acute hemorrhagic leukoencephalitis of weston hurst, has a sudden onset fulminating syndrome of CNS demyelination, seen in young adults and kids, always preceded by recent URI, mostly fatal? (can be though of more fulminant course of ADEM)

Answer 13

Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE) -uncommon

Question 14

What demyelinating disease is aka osmotic demyelination disorder where there is loss of myelin (preservation of axons/neuronal cell bodies) in a symmetric pattern involving the basis pontis and portions of the pontine tegmentum- sparing periventricular and subpial regions, WITHOUT inflammation, DUE TO OVERLY RAPID CORRECTION OF HYPONATREMIA?

Answer 14

Central Pontine Myelinolysis (2-6 days later)

Question 15

Central Pontine Myelinolysis presents with acute paralysis (quadraparesis), dysphagia, dysarthria, diplopia, and LOC, can also be assoc with severe electrolyte or osmolar imbalances which has a tropism for and damages oligodendrocytes but not anything else, pontine lesions present as rapid quadriplegia which may be fatal or lead to what syndrome in which people are fully conscious but cant respond?

Answer 15

Locked in Syndrome due to myelinosis of corticobulbar and corticospinal tract

Question 16

Neurogenerative disease are diseases of gray matter with progressive loss of neurons assoc with secondary changes in white matter tracts, presence of protein aggregates that are resistant to degradation through ubiquitin proteasome system….

Answer 16

MEOW

Question 17

Match the following disease with their corresponding aggregates recognized as inclusions…
Huntingtons
Alzheimers
Parkinsons
A-B-peptide derived from larger precursor protein
Expanded polyglutamine repeats from mutated protein
A-synuclein- unexplained alteration of NL cellular protein

Answer 17

Alzheimers = A-B-peptide derived from larger precursor protein
Huntingtons = Expanded polyglutamine repeats from mutated protein
Parkinsons = A-synuclein- unexplained alteration of NL cellular protein

Question 18

What Neurogenerative disease is the MCC of dementia in older adults which is not part of normal aging and always pathologic, there is insidious impairment of higher cognitive functions- disorientation, memory loss/aphasia, 5-10 yrs later see disabled/mute/immobile, incidence increases with age-doubles every 5 years, most cases are sporadic, 5-10% familial?

Answer 18

Alzheimer’s Disease AD

Question 19

Alzheimer’s Disease AD is caused by accum of AB and tau proteins that creates plaques, when APP is cleaved by a-secretase followed by gamma secretase is makes a soluble nontoxic fragment, but when it is cleaved by B-secretase and then gama, AB peptides that aggreagate and form amyloid cores that elicit a microglia and astrocytic response to form neuritic plaques = B=Bad, plaques are AB -APPprotein aggregates in EXTRA cellular neuropil while neurofibrillary tangles are aggregates of?

Answer 19

Tau (microtubule binding protein) which is found INTRAcellularly

AD might need AB first then tau, if tau alone will be another disease

Question 20

Alzheimer’s Disease AD may have a genetic defect in apolipoprotein E (ApoE) locus on chr19, especially in e4 allele, also seen w mut on chr21- in downs syndrome, biomarkers for AD include AB on imaging by using 18-f-labeled amyloid bindng compounds or looking for phosphorylated tau, there is cortical atrophy with widening of the sulci seen especially in the front, temporal (hippocampus/entorhinal cortex/amygdala) and?

Answer 20

Parietal Lobes which leads to hydrocephalus ex vacuo (compensatory ventricular enlargement due to dec brain volume)

Question 21

Alzheimer’s Disease AD on histo can see what type of plaques, with focal spherical collections of dilated tortuous neuritic processes (dystrophic neurites) around an amyloid core in hippocamp,amygdala, neocortex, the amyloid core stains CONGO RED and is AB derived from amyloid precursor protein APP, contain both AB40/42?

Answer 21

Neuritic Senile Plaques

Question 22

Alzheimer’s Disease AD along with neuritic senile plaques what other plaques occur when there is deposition of AB protein without surounding neuritic processes, mainly in cerebral cortex, basal ganglia, and cerebellar cortex, believed to be early stage of plaque development and down syndrome, NO AMYLOID CORE and predominantly AB42?

Answer 22

Diffuse Plaques

Question 23

Alzheimer’s Disease AD has neurofibrillary tangles which are bundles of filaments in the cytoplasm of neurons that displace or encircle the nucleus and is NOT specific to AD, often have elongated flame shape in pyramidal cells and are rounder (globose tangles) in rounder cells (basket weave fibers), commonly found in cortical neurons, entorhinal, pyramidal cells of hippo/amyg/basal forebrain and raphe nuclei, they are visible as basophilic fibrils with what silver stain?

Answer 23

Bielschowsky Stain

*resistance to clearance in vivo = ghost or tombstone tangles- last forever

Question 24

What is an abnormally hyperphosphorylated, axonal microtubule associated protein that enhances microtubule assembly seen in AD, contains MAP2 and ubiquitin?

Answer 24

Tau

Question 25

The fundamental abnl in AD is deposition of AB peptides which are derived through processing of APP, large burden of pplaques and tangles are highly associated with severe cognitive dysfunction, does the number of tangles or plaques correlate better with the degree of dementia?

Answer 25

*#of tangles inc = inc dementia

Question 26

AD histo is assoc with granulovacuolar degeneration where you see small clear intraneuronal cytoplasmic vacuoles which contain argyrophilic granules- normal aging finding- more abundant in AD hippo and olfactory bulb, what bodies are elongated glassy eosinophilic bodies - paracrystalline arrays of beaded filaments with actin as major component MC seen inside hippocampal pyramidal cells?

Answer 26

Hirano Bodies

Question 27

What angiopathy always found in AD pts, vasuclar amyloid is AB40 protein, instead of 42/40, bleeding occurs in peripheral cortex, remember amyloid is seen on congo red and when it is polarized is shows apple green birefringence? (Note: also seen in patients without AD)

Answer 27

Cerebral Amyloid Angiopathy CAA

Question 28

What neurogenerative disease are a heterogenous set of disorders associated with focal degeneration of front and or temporal lobes, share clinical features of progressive deterioration of language and changes in personality, have tau deposits without AB plaques?

Answer 28

Frontotemporal Lobar Degenerations FTLDs

Question 29

FTLD-tau is cortical degeneration and reactive gliosis with accumulations of tau AND NOT AB are characteristic, may look like tangles or smooth contoured inclusions (pick bodies), hyperphosphorylated tau is found in the plaques, there is atrophy of frontal and temporal lobes which are marked by neuronal loss, gliosis, presence of tau containing tangles but NOT AB, FTLD without Tau is vascular dementia, FTLD with tau pathology includes progressive supranuclear palsy and what disease?

Answer 29

Pick Disease

Question 30

What disease is the best known FTLD with tau-containing inclusions, clinical fts similar to AD although initially causes less memory loss and more behavioral changes, a rare -distinct progressive dementia, mostly sporadic, with early onset behavioral changes with alterations in personality (frontal lobe signs) and language disturbances (temporal lobe signs)?

Answer 30

Pick Disease

Question 31

Pick Disease is assoc with asymmetric atrophy of the front and temporal lobes that spares the posterior 2/3 of the superior temporal gyrus, some surviving neurons are swollen (pick cells) while others contain pick bodies which are cytoplasmic, round/oval, filamentous, stain well with silver* and weakly basophilic*, the atrophy can be so severe where the gyri become thin and look?

Answer 31

Knife-Edge thin gyri***

marked reduction in size gyri with deep wide sulci

Question 32

What FTLD with tau pathology shows truncal rigidity with dysequilibrium and nuchal dystonia, pseudobulbar palsy, abnormal speech, ocular disturbances including vertical gaze palsy progressing to difficulty with all eye movements, mild progressive dementia, in 5-7th decade, fatal within 5-7 years of onset, widespread neuronal loss and globose neurofibrillary tangles: 4R TAU straight filaments seen?

Answer 32

Progressive supranuclear palsy

men 2x than women

Question 33

What dementia if due to vasculitis causes dementia that improves with treatment, it is a progressive cognitive disorder associated with vascular injury with widespread ares of infarction and diffuse white matter injury (HTN/CADASIL)?

Answer 33

Vascular Dementia

Question 34

Basal ganglia and brainstem are associated with movement disorders causing rigidity, abnormal posturing and chorea, in the basal ganglia especially what pathway, plays an important role of the +/- regulatory synapthic pathways that modulate feedback from the thalamus to motor cortex?

Answer 34

Nigrostriatal Dopaminergic Pathway

**PARKINSONS, Multiple System Atrophy, and Postencephalitic parkinsonism

Question 35

Clinical symptoms of parkinsons include stooped posture, slowness of voluntary movement, festinating gait (progressively shortened-accelerated steps), rigidity, pill rolling tremor and being withdrawn or?

Answer 35

diminished facial expression

NOTE: tremor dissipates when performing tasks with hands

Question 36

Parkinsons disease PD is a neurodegenerative disease with hypokinetic movement from loss of dopaminergic neurons from substantia nigra, involving nigrostriatal system, the diagnosis is made by looking at characteristic features (tremor, rigidity, bradykinesia) and the symptomatic response to what?

Answer 36

L-Dopa

Question 37

PD associated with protein accum and aggregation, mitochondrial abnls, and neuronal loss in substantia nigra (loss pigmentation), is autosomal dominant when there a-synuclein is mutated or amplified - chr4q21, a more common cause of AD PD is from mutated LRRK2 also found in sporadic cases, the juvenille autosomal recessive type is assoc with what mutation?

Answer 37

PARKIN

Question 38

PD has diagnostic hallmark of the Lewy body of which a-synuclein is a major component. Morphologically there is pallor of the substantia nigra and locus ceruleus from loss of pigmented catecholaminergic neurons in the region, what are found in remaining neurons (in basal nucleus of meynert/locus ceruleus/dorsal motor nucleus of vagus) and are single/multiple cytoplasmic, eosinophilic, round-elongated inclusions that have a dense core surrounded by a pale halo?

Answer 38

Lewy bodies- asynuclein densely packed at core, loose at edges

Question 39

PD can be accompanied by cog dysfunction, 10-15% of PD develop dementia, incidence increases with age, has fluctuating course where HALLUCINATIONS are present with prominent frontal signs, presence of lewy bodies in cortical locations, depigmentation of S nigra and L ceruleus w a relative preservation of cortex/hippo/amyg, What are abnormal neurites that stain positive for contain a-synuclein aggregated proteins?

Answer 39

Lewy Neurites

Question 40

What is another degenerative dz of basal ganglia and brainstem which is a sporadic disorder that affects a number of different systems in the brain, characterized by cytoplasmic inclusion of a-synuclein in oligodendrocytes- involving 3 systems: 1)Striatonigral Circuit (=parkinson) 2)Olivopontocerebellar circuit (ataxai) 3) autonomic nervous system (autonomic dysfunction = otho hypotension)?

Answer 40

Multiple System Atrophy MSA

Question 41

Multiple System Atrophy MSA hallmark is affected glial cells and is associated with the loss of white matter tracts because has tropism for oligodendrocytes, have diagnostic glial inclusions found in oligodendrocytes-what is the major component of the cytoplasmic inclusions?

Answer 41

α-synuclein is the major component of the inclusions

Question 42

What disease is an AD disorder characterized by progressive movement disorder and dementia that is caused by degeneration of striatal neurons, assoc with jerky, hyperkinetic sometimes dystonic movements involving all parts of the body = CHOREA, may later develop parkinsons with bradykinesia and rigidity, progressive-15 years dead?

Answer 42

Huntington’s Disease HD

*MCC of death is infection

Question 43

Huntington’s Disease HD is caused by a polyglutamine trinucleotide repeat expansion disease (CAG REPEATS*) d/t HTT mutation on chr4p16.3 encoding Huntingtin, there is increased number of CAG repeats at N terminus (inverse relationship with age… more CAG = juvenile onset, less CAG = old onset), repeated expansions occur during spermatogenesis so that paternal transmission is associated with early onset in the next gen, this is aka?

Answer 43

Anticipation

***No sporadic form a dz

Question 44

Huntington’s Disease HD pathological hallmark is intranuclear inclusions of the mutated huntingtin and they may be prion like, shows loss of medium spiny striatal neurons that leads to dysreg of basal ganglia circuitry that modulates motor output, see cognitive changes, expansion produces toxic gain of function of huntingtin- protein forms intranuclear inclusions- brain is small and WHAT is strikingly atrophied?

Answer 44

CAUDATE NUCLEUS (striatal neuron loss) later the putamen, globus pallidus, corpus callosum frontal lobes*

Question 45

NOTE: PD = loss of initiation of movement
HD: loss of inhibition of movement

Answer 45

MEOW

Question 46

What degenerations involve the cerebellum and other components of the CNS and peripheral nerves, clinical symptoms include cerebellar and sensory ataxia, spasticity, and sensorimotor peripheral neuropathy, assoc w neuronal loss of affected areas and secondary degen of white matter tracts. Ex: friedreich ataxia and ataxia-telangiestasia?

Answer 46

Spinocerebellar

Question 47

What Spinocerebellar degeneration, is AR due to GAA trinucleotide repeat-chr 9q13; frataxin protein, begins in first decade of life with gait ataxia*, followed by hand clumsiness and dysarthria, DTRs depresses or absent but *extensor plantar reflex+, joint position and vibratory sense impaired, sometimes loss of pain and temp sensation and light touch, assoc w pes cavus (the sole of the foot is distinctly hollow when bearing weight; high instep) and kyphoscoliosis?

Answer 47

Friedreich Ataxia

Question 48

Friedreich Ataxia is assoc w progressive ataxia, spasticity, weakness, sensory neuropathy and cardiomyopathy, most patients wheelchair bound by 50, dont live past 50, the MC COD with this disease is intercurrent pulmonary disease and cardiomyopathy that leads to?

Answer 48

arrhythmias and CHF (cardiomyopathy) = DEATH MCC

DM see in 25% pts

Question 49

Freidreich Ataxia is expansion of GAA trinucleotide, there is loss of axons and gliosis in the posterior columns, corticospinal tracts, and the spinocerebellar tracts which account for loss of pain/temp and?

Answer 49

motor disturbances

Question 50

What spinocerebellar degerative dz is AR and is charactereized by an ataxic-dyskinetic syndrome that begins in early childhood, assoc with CNS/Conjuctiva/skin of face arms and neck telangiestasias, and immunodeficiency causing recurrent sinopulmonary infections, assoc w progressive death early in 2nd decade d/t lymphoid neoplasms, gliomas and carcinomas?

Answer 50

Ataxia-Telangiestasia

Question 51

Ataxia-Telangiestasia has a mutated ATM gene on chr 11q22-q23, which encodes a kinase that helps with orchestrating cellular response to double stranded DNA breaks, increased sensitivity to x-ray induce chromosome abnormalities and ultimatly fails to remove what?

Answer 51

cells with DNA damage

Question 52

Ataxia-Telangiestasia has immunodeficiency because the LN, thymus and gonads are hypoplastic….

Answer 52

MEOW

Question 53

What degenerative disease is progressive disease marked by loss of upper motor neurons in cerebral cortex and lower motor neurons of the SC and brainstem BOTH, it is rare, MC in M>F, occurs in 5th decade or later, 5-10% AD/familial, is a purely motor disease, SOD1 (superoxide dismutase) mutation on chr21**, causing adverse GOF, alanine to valine subs MC in US= rapid course without UMN signs?

Answer 53

Amyotrophic Lateral Sclerosis ALS

TDP43 also associated with ALS (along with SOD-1 familial)

Question 54

Amyotrophic Lateral Sclerosis ALS anterior roots of the spinal cord are thin from loss of LMN fibers, loss of anterior horn neurons and reactive gliosis, precentral gyrus may be atrophic (primary motor cortex), Neurons contain PAS+ cytoplasmic inclusions which are called what- which are remnants of autophagic vacuoles - dark pink?

Answer 54

Bunina Bodies

Question 55

Amyotrophic Lateral Sclerosis ALS has skeletal msucles with neurogenic atrophy* d/t loss of LMN innervation causing hyporeflexia, hypotonia and atrophy, loss of UMNs leads to degeneration of corticospinal tracts, loss of volume and absence of myelinated fibers, early symptoms include asymmetric weakness of hands, cramping, problems w fine motor, and?

Answer 55

Dropping Objects

Question 56

Amyotrophic Lateral Sclerosis ALS with time muscle strength and bulk decreases and fasciculations begin which are involuntary muscle contractions, respiratory infections are common due to respiratory muscle involvement, progressive muscluar atropy= uncommon cases in which LMN involvement predominates, and what is degeneration of lower BS cranial motor nuclei occuring early and **PROGRESS RAPIDLY- Deglutination and phonation difficiulties?

Answer 56

Progressive Bulbar Palsy (BULBAR ALS)

speaking and swallowing difficulties

Question 57

A subset of genetic metabolic disease affects the nervous system preferentially, many express themselves in children who are normal at birth but begin to miss developmental milestones… Neuronal storage disease are mostly AR caused by defect in catabolism of sphingolipids, mucopolysaccharides, or mucolipids, accumulation of substrate of enzymes in lysosomes leads to neuronal death, loss of cognitive function, and?

Answer 57

SEIZURES

Question 58

What genetic metabolic diseases is mostly AR, (adrenoleukodystrophy is Xlinked), assoc with myelin abnormalities and generally lack neuronal storage defects, due to lysosomal or peroxisomal enzymes, *diffuse involvement of WHITE MATTER, deterioration of motor skills, spasticity, hypotonia or ataxia?

Answer 58

Leukodystrophies

Question 59

What genetic metabolic diseases more commonly involve GRAY matter and skeletal muscle, due to mutations in mitochondiral genome or oxidative phosphorylation disorders?

Answer 59

Mitochondrial Encephalomyopathies

Question 60

What disease is due to HEXA gene on chr 15, and enzyme hexosaminidase A, associated with GM2 gangliosides which never go away, tragic presentation, kids are fine at birth and until 1 year, causes death at 2-3years, see cherry red spots in macule (normal choroid against swollen, pale, ganglioside stuffed retina)?

Answer 60

Tay-Sachs

Question 61

Mitochondrial Encephalomyopathies are many inherited disorders of mitochondrial oxidative phosphorylation which present as muscle disease, CNS is second MC affected tissue, freidreich ataxia is also a mitochondrial disorder, what is important to remember about mitochondrial inheritance?

Answer 61

ONLY inherited through maternal lines

Question 62

What Mitochondrial Encephalomyopathies is due to mutation in tRNAs leucine -MTTL1, and is the MC neurologic syndrome caused by mitochondrial abnormalities, assoc w recurrent episodes of acute neurologic dysfunction, cognitive changes, and evidence of muscle involvement with weakness and lactic acidosis*, stroke like episodes are reversible that do NOT correspond well to specific vascular territories?

Answer 62

Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke Like Episodes MELAS

Question 63

What is a maternally transmitted disease assoc with myoclonus, a seizure disorder, myopathy, ragged red ribers in the muscle* and ataxia, most cases are associated with tRNAs (same as MELAS)?

Answer 63

Myoclonic Epilepsy and Ragged Red Fibers MERRF

Question 64

What syndrome is aka opthalmoplegia plus, sx of ataxia, pigmentary retinopathy and cardiac conduction defects, histo: spongiform change in gray and white matter and neuronal loss most evident in cerebellum? (***progressive inability to move eyes and eyebrows)

Answer 64

Kearn-Sayre Syndrome

Question 65

What syndrome is aka subacte necrotizing encephalopathy, seen as lactic acidemia in childhood with seizures and weakness with hypotonia, histo shows spongiform appearance and vascular proliferation- dark areas of degeneration of neural tissue around the aqueduct?

Answer 65

Leigh Syndrome

Question 66

What vitamin deficiency is aka wernicke encephalopathy which is acute psychotic symptoms and opthalmoplegia which is REVERSIBLE, also associated with korsakoff syndrome that is IRREVERSIBLE memory disturbances and confabulation, MC due to chronic alcoholism?

Answer 66

Thiamine B1 Deficiency

Question 67

Thiamine B1 Deficiency or wernicke encephalopathy is associated with early lesions with dilated capillaries that become leaky to hemorrhage, eventually mø come in and create cytic space with hemosiderin mø- spaces are chronic and lead to problems in dorsomedial nucleus of thalamus (memory/confabulation = korsakoff), what is MC seen on histo***?

Answer 67

foci of hemorrhage and necrosis in the mammillary bodies and the walls of the 3rd/4th ventricles

Question 68

What vitamin deficiency can cause anemia and or neurologic issues, first few weeks see numbness, tingling and slight ataxia in LE, rapid progresion to spastic weakness of LE, c to complete paraplegia, can reverse symptoms only if paraplegia hasnt occured yet?

Answer 68

Vitamin B12 Def

Question 69

Vitamin B12 Def on histo shows swelling of myelin layers = vacuoles, begins segmentatlly at midthoracic level of SPC, HALLMARK= axons of BOTH the ascending tract of posterior column and DESCENDING pyramidal tracts degenerate causeing what of the spinal cord due to loss of neurons by macrophages?

Answer 69

Subacute Combined Degeneration of the Spinal Cord due to B12 deficiency

Question 70

What metabolic disturbance affects the same areas of hypoxia would, initially there is selective injury to large pyramidal neurons of the cerebral cortex that lead to pseudolaminar necrosis, also damage to sommer sector CA1 of hippo and loss purkinje cells of cerebellum, if there is enough loss there could be widespread damage to brain?

Answer 70

Hypoglycemia

Question 71

What metabolic disturbance is usually due to inadequately controlled diabetes associated with either keotacidosis or hyperosmolar coma, usually patient becomes dehydrated and develops confusion, stupor, and coma, *fluid repletion GRADUALLY corrected to avoid sever cerebral edema?

Answer 71

Hyperglycemia

Question 72

What metabolic disturbance is a primarily glial cellular response in CNS due to impaired liver function, can see alzheimer type II cells in the cortex, basal ganglia, and other subcortical gray matter regions, seen as hyperintensity in globus pallidus and other areas on MRI?

Answer 72

Hepatic Encephalopathy

Question 73

What toxin have pathological findings following hypoxia due to altered oxygen carrying capacity, *layers II and V of the cerebral cortex, sommer’s sector (ca1 hippo), and purkinje cells are most sensitive, see bilateral necrosis of globus pallidi more common?

Answer 73

Carbon Monoxide

Question 74

What toxin preferentially attacks the retina*, by degeneration of retinal ganglion cells that leads to blindness, also see bilateral putamenal necrosis and focal white matter necrosis, formate is the metabolite and causes the retinal toxicity?

Answer 74

Methanol –> formic acid + formaldehyde

Question 75

What toxin can be directly toxic or secondary to nutritional deficits, 1% of chronic alcoholics have cerebellar dysfunction assoc w truncal ataxia, unsteady gait and nystagmus, there is atrophy and loss of granule cells in the anterior vermis, in advanced cases see loss of purkinje cells and proliferation of adjacent astrocytes = BERGMAN GLIOSIS between depleted granular cell layer and molecular layer?

Answer 75

ETHANOL

*anterior cerebellar degen = ataxia

Question 76

What toxin exposure in high doses causes intractable nausea, confusoin, convulsions, and rapid onset of coma followed by death, delayed effects can also present with rapidly evolving sx like HA, nausea, vomiting, papilledema, it can induce tumors like sarcoma, gliomas and meningiomas***, and on histo see large areas of coagulative necrosis with edema in white matter, vessels have thickened walls with intramural fibrin like material?

Answer 76

Radiation