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Flashcards in Neuro Deck (229)
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91

Pick Disease

  • causes dementia.
  • prominent frontal signs.
  • morphology: frontal and temporal lobe atrophy.  spares posterior 2/3 of superior temporal gyrus.  caudate and putamen can atrophy.
    • large ballooned neurons (Pick cells) and smooth agyrophilic inclusions made of straight and paired helical filaments (Pick bodies)

92

Progressive Supranuclear Palsy

  • men > 50yrs
  • from gene polymorphisms, MAPT haplotype
  • morphology: widespread neuronal loss and neurofibrillary tangles in globus pallidus, subthalamic nucleus, substantia nigra, colliculi, periaqueductal gray matter, dentate nucleus.
    • tau pathology in glial cells
  • presentation: loss of vertical gaze, truncal rigidity, dysequilibrium, loss of facial expression, mild progressive dementia.
  • death within 5-7 yrs

93

Corticobasal Degeneration

  • disease of elderly
  • same MAPT haplotype as progressive supranuclear palsy
  • morphology: motor, premotor, and anterior parietal cortex have neuronal loss, gliosis, ballooned neurons.
    • loss of pigmented neurons and argyrophilic inclusions in substantia nigra and locus ceruleus.
    • tufted astrocytes = tau immunoreactivity
    • coiled bodies = tau immunoreactivity in oligodendrocytes
  • presentation: extrapyramidal rigidity, asymmetric motor disturbances, sensory cortical dysfunction

94

Vascular Dementia

  • vascular injury ⇒ ↓ threshold for dementing effects of other disorders.
  • from multiple lacunar infarcts, HTN disease (Binswanger disease), specially located large infarcts (hippocampus, dorsomedial thalamus, frontal cortex), vasculitis.

95

Parkinsonism

  • causes: Parkinson disease, multiple system atrophy, postemcephalitic parkinsonism (1918 flu pandemic), frontotemporal dementias, dopamine antagonists or toxins.
  • presentation: diminished facial expression, stooped posture, slow voluntary movement, festinating gait (shortened and accelerated), rigidity, pill-rolling tremor (↓ function of nigrostriatal dopaminergic system)

96

Parkinson Disease

  • progressive L-DOPA responsive parkinsonism without toxic etiology.
  • morphology: pallor of substantia nigra and locus ceruleus with loss of pigmented catecholaminergic neurons and gliosis
    • remaining neurons have lewy bodies = intracytoplasmic eosinophilic inclusions with alpha-synuclein.
  • pathogenesis: autosomal dominant forms = overexpression of alpha-synuclein or gain of function in LRRK2 gene
    • juveninle recessive form = loss of function in parkin gene
    • recessive forms = mutated DJ-1 and PINK1 kinase
    • lose dopaminergic neurons in substantia nigra from alpha-synuclein aggregation, proteasome dysfunction, altered mitochondrial activity.
    • leads to striatal dopamine deficiency.
  • presentation: autonomic and cognitive dysfunction with diminished facial expression, stooped posture, slowed voluntary movement, festinated gait, rigidity, pill-rolling tremor.
    • L-DOPA improves it but become refractory.
  • tx: L-DOPA, neural transplantation, gene therapy, neurosurgical lesions in extrapyramidal system, deep brain stimulation.

97

Dementia with Lewy Bodies

  • dementia in 10-15% PD patients.
  • some have Alzheimers
  • most have alpha-synuclein-containing lewy bodies
  • flluctuating course with hallucinations and frontal signs.

98

Multiple System Atrophy

  • atrophy in CNS regions with glial tubular cytoplasmic inclusions made of alpha-synuclein, ubiquitin, and alpha-B crystallin
  • striatonigral degeneration = parkinsonism
    • atrophy of substantia nigra and striatum.
  • olivopontocerebellar atrophy = cerebellar ataxia, eye and somatic movement abnormalities, dysarthria, rigidity.
    • atrophy of cerebellar peduncles, basis pontis, inferior olives.
  • Shy-Drager syndrome = autonomic dysfunction with loss of sympathetic neurons of intermediolateral column in spinal cord.

99

Striatonigral Degeneration

  • parkinsonism
    • atrophy of substantia nigra and striatum.

100

Olivopontocerebellar Atrophy

  • cerebellar ataxia, eye and somatic movement abnormalities, dysarthria, rigidity.
    • atrophy of cerebellar peduncles, basis pontis, inferior olives.

101

Shy-Drager Syndrome

  • autonomic dysfunction with loss of sympathetic neurons of intermediolateral column in spinal cord.

102

Huntington Disease

  • autosomal dominant movement disorder.
  • morphology: atrophy of caudate nucleus and putamen, loss of med-sized spiny striatal neurons that use GABA.
    • gliosis and intraneural huntingtin aggregates in striatum and cerebral cortex.
    • spares neurons with NO synthase and cholinesterase
  • pathogenesis: expansion of CAG repeat in huntingtin (>36 repeats) ⇒ toxic gain of function, aggregation, sequester transcriptional regulators, dysregulate transcription pathways for mitochondrial biogenesis or protection from oxidative injury.
    • anticipation = parental transmission ⇒ earlier expression in kids.
  • presentation: btw ages 20-50yrs, get chorea (jerky, hyperkinetic, dystonic movements) ⇒ parkinsonism
    • motor symptoms precede cognitive impairment ⇒ death in 15 yrs.

103

Friedreich Ataxia

  • autosomal recessive
  • expansion of intronic GAA repeat in gene for frataxin (mitochondrial membrane protein for iron regulation).
  • morphology: axonal loss and gliosis posterior columns of spinal cord, distal corticospinal and spinocerebellar tracts.
    • neuronal degredation of CN VIII, X, XII nuclei, dentate nucleus, Purkinje cells in superior vermis, and dorsal root ganglia.
  • presentation: gait ataxia, hand clumsiness, dyarthria, depressed tendon reflexes, sensory loss.
    • wheelchair bound in 5 yrs.
    • death from cardiac arrhythmias or pulmonary infections.

104

Ataxia-Telangiectasia

  • autosomal recessive
  • mutated ATM gene that repairs dsDNA breaks ⇒ ↑ risk malignancy and neurons more degradation prone.
  • morphology: cerebellar Purkinje and granule cells lost.  
    • degeneration of dorsal columns, spinocerebellar tracts, anterior horn cells
    • Schwann cell nuclei in dorsal root ganglia and peripheral nerves are 2-5x enlarged.
  • presentation: kids have cerebellar dysfunction, telangiectatic lesions in skin and conjunctiva, and immunodeficiency (lymph nodes and thymus hypoplastic).
    • death btw 10-20yrs old.

105

Amyotrophic Lateral Sclerosis (ALS)

  • aka Motor Neuron Disease
  • loss of lower and upper motor neurons.
  • pathogenesis: 5-10% familial and autosomal dominant.
    • 25% from gain of function in SOD1 gene for copper zinc superoxide dismutase ⇒ misfolded proteins that cause unfolded protein response.
    • may have abnormal axonal transport, protein accumulation, glutamate NT toxicity.
  • morphology: upper motor neuron degeneration ⇒ demyelination in corticospinal tracts and reactive gliosis.  can be atrophy of precentral gyrus.
    • remaining neurons have Bunina bodies = PAS-pos cytoplasmic inclusions.
    • affected skeletal muscles have neurogenic atrophy.
  • presentation: m>f, age>40yrs.  early clumsiness ⇒ muscle weakeness and fasciculations that ⇒ pneumonia when respiratory muscles involved
    • may have bulbar manifestations (involve motor CN) ⇒ problems with deglutition and phonation.
    • progressive, die from respiratory complications.

106

Bulbospinal Atrophy

  • aka Kennedy syndrome.
  • X-linked.
  • expansion of CAG/polyglutamine trinucleotide repeat in androgen receptor gene ⇒ intranuclear receptor aggregation.
  • lower motor neuron loss ⇒ androgen insensitivity (gynecomastia, testicular atrophy, oligospermia).

107

Neuronal Ceroid Lipofuscinoses

  • inherited lysosomal storage disorders ⇒ neuronal accumulation of lipofuscin.
  • can ⇒ blindness, mental and motor deterioration, and seizures.

108

Krabbe Disease

  • autosomal recessive
  • deficiency of galactocerebroside beta-galactosidase ⇒ ↑ ceramide
  • alternate pathway causes excess ⇒ galactosylsphingosine, toxic to oligodendrocytes.
  • morphology: diffuse loss of myelin and oligodendrocytes
    • aggregates of Globoid cells = glycolipid-engorged macrophages.
  • presentation: weakness and stiffness by age 3-6months.  die by age 2 yrs.

109

Metachromatic Leukodystrophy

  • autosomal recessive
  • deficiency of arylsulfatase ⇒ accumulate cerebroside sulfate.  may block oligodendrocyte differentiation.
  • morphology: myelin loss, gliosis, macrophages containing metachromatic material.

110

Adrenoleukodystrophy

  • progressive disorder from loss of myelin and adrenal insufficiency ⇒ inability to catabolize very long chain fatty acids

111

Pelizaeus-Merzbacher Disease

  • X-linked
  • mutation in gene encoding two alternatively-spliced myelin proteins (ex. PLP and DM20)

112

Mitochondrial Encephalopathy with Lactic Acidosis and Strokelike Episodes (MELAS)

  • most common neurologic syndrome with mitochondrial abnormalities.
  • involves mitochondrial tRNA.
  • presentation: muscle and metabolic findings, recurrent neurologic dysfunction and cognitive changes.
    • strokelike episodes have reversible deficits.

113

Leigh Syndrome

  • aka Subacute Necrotizing Encephalopathy
  • mutations in oxidative phosphorylation pathway.
  • morphology: bilateral brain damage with vascular proliferation and spongiform changes.
    • symmetrically involves midbrain periventricular gray matter, pontine tegmentum, thalamus, and hypothalamus.
  • presentation: 1-2yrs old with developmental arrest, feeding problems, seizures, extraocular palsies, hypotonia, and lactic acidemia.

114

Thiamine (Vitamin B1) Deficiency

  • ⇒ Beriberi, Wernicke encephalopathy, Korsakoff syndrome.
  • Beriberi = nutritional deficiency.  associated with cardiac failure
  • Wernicke encephalopathy = sudden onset psychosis and/or ophthalmoplegia
  • Korsakoff syndrome = progresses from Wernicke's to an irreversible memory disorder with conflabulation.
  • common in alcoholics
  • can come from gastric disease: carcinoma, chronic gastritis, persistent vomiting.
  • morphology: mammilary body (and 3rd and 4th ventricle) hemorrhage and necrosis.
    • thalamic dorsomedial nucleus lesions ⇒ memory disturbances.

115

Vitamin B12 Deficiency

  • anemia and nervous system injury.
  • morphology: vacuolar swelling of myelin affects both ascending and descending tracts starting at midthoracic cord.
  • presentation: slight ataxia and lower extremity paresthesias ⇒ lower extremity spastic weakness and paraplegia, may be permanent.

116

Hypoglycemia

  • affects large cerebral pyramidal cells, hippocampal pyramidal cells in CA1, and Purkinje cells.
  • prolonged, severe hypoglycemia ⇒ global neuronal injury.

117

Hyperglycemia

  • from poorly controlled DM.
  • can ⇒ ketoacidosis.
  • hyperosmolar state has dehydration ⇒ confusion, stupor, coma.
  • gradually correct fluid depletion to prevent cerebral edema.

118

Carbon Monoxide (Brain)

  • causes hypoxia from ↓ oxygen carrying capacity of hemoglobin.
  • injures neurons in layers III and V in cerebral cortex, hippocampal Sommer sector, and Purkinje cells.
  • bilateral necrosis of globus pallidus.

119

Methanol (Brain)

  • toxicity affects retina.
  • degeneration of ganglion cells ⇒ blindness.
  • may be from formic acid (metabolite of methanol)

120

Radiation (Brain)

  • causes acute CNS decompensation, can develop months to years later.
  • late radionecrosis associated with large zones of coagulative necrosis and edema in white matter.
  • blood vessels have thickened walls with intramural fibrin-like material.  proteinaceous spheroids in adjacent tissues.
  • can be synergistic with methotrexate.