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NS2 Test 2 > Chapter 28 part 5 > Flashcards

Chapter 28 part 5 Flashcards

1
Q

Atypical parkinsonism syndromes

A
  • minimally responsive to L-DOPA

- distinguished from PD through presence of additional signs and symptoms

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2
Q

PSP (progressive supranuclear palsy)–symptoms

onset? hallmark?

A

-taupathy
-trunkal rigidity, disequilibrium with frequent falls and difficulty with voluntary eye movements
-nuchal dystonia, pseudobulbar palsy, mild progressive dementia
-onset– 5th to 6th decade–males 2X
fatal–5-7 years of onset
-hallmark- presence of tau containing inclusions in neurons and glia

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3
Q

CBD (corticobasal degeneration)- clinical

A
  • progressive taupathy
  • extrapyramidal rigidity, asymmetric motor disturbances (jerkings movments of limbs), impaired higher cortical function
  • cognitive decline may occur later in illness
  • same tau variant linked to PSP
  • CBD- tau lesions more toward cerebral cortical involvement (In PSP- in brainstem and deep gray matter
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4
Q

MSA (multiple system atrophy)- different from other degenerative diseases why?

A

-hallmark is observed in glial cells and degeneration of white matter tracts

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5
Q

MSA (multiple system atrophy)– 3 distinct neuroanatomic circuits involved?

A
  • striatonigral circuit (parkinsonism)
  • olivopontocerebellar circuit (ataxia)
  • autonomic NS (autonomic dysfunction–orthostatic hypotension)
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6
Q

MSA pathogenesis

A
  • alpha-synuclein is major component of inclusions
  • sporadic disease
  • glial cytoplasmic inclusions- primary pathologic event
  • alpha-synuclein in onligodendrocytes–become more sensitive to oxidative stress
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7
Q

MSA diagnosis

A

-glial cytoplasmic inclusions (in oligodendrocytes)- contain alpha synuclein

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8
Q

HD (huntington disease)- characterized by?

A
  • autosomal dominant
  • progressive movement disorders and dementia caused by degeneration of strial neurons
  • jerky, hyperkinetic, dystonic movements (chorea)
  • later may develop bradykinesia and rigidity
  • fatal in 15 years
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9
Q

HD- prototype for?

A

-polyglutamine trinucleotide repeat expansion diseases

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10
Q

gene for HD

A
  • HTT-encodes huntingtin
  • CAG repeat–encodes polyglutamine region
  • normal HTT genes- 6-35 copies of CAG repeat
  • if above 35 copies=disease
  • longer repeats=earlier onset
  • polyglutamine region expansion–toxic gain of function on huntingtin-protein aggregation and intranuclear inclusions containing huntingtin
  • mutated huntingtin binds various transcriptional regulators
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11
Q

pathologic hallmarks of HD

A

-intranuclear inclusions containing huntingtin

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12
Q

HD morphology

A

atrophy of caudate nucleus, ventricular dilation

  • profound loss of striatal neurons (esp in caudate nucleus)
  • protein aggregates containing huntingtin in neurons
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13
Q

HD clinical features caused by?

A
  • loss of striatal neurons leads to dysregulation of basal ganglia circuitry that modulates motor output
  • these neurons normally function to dampen motor activity; their degeneration results in increased motor output (choreoathetosis)
  • 4-5 decade
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14
Q

HD clinical features

A
  • -movement disorder-choreiform, increased/involuntary jerky movements, writhing movements of extremities
  • early symptoms of higher cortical dysfunction–forgetfulness and though disorders–progress to dementia
  • intercurrent infection– most common cause of death
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15
Q

spinocerebellar degenerations–clinical

A

-cerebellar and sensory ataxia, spasticity, sensorimotor peripheral neuropathy

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16
Q

2 common autosomal recessive disorders characterized by spinocerebellar degeneration?

A
  • friedreich ataxia

- ataxia telangiectasia

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17
Q

SCA (spinocerebellar ataxia

A
  • autosomal dominant

- neuronal loss and secondary degeneration of white matter tracts

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18
Q

SCA (spinocerebellar ataxia) –3 mutations

A
  • polyglutamine diseases–expansion of CAG repeat
  • expansion of non-coding region repeats
  • point mutations
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19
Q

Friedreich Ataxia–characterized by? when?

A
  • autosomal recessive
  • progressive ataxia, spasticity, weakness, sensory neuropathy, cardiomyopathy!!
  • 1st decade of life–gait ataxia, followed by hand clumsiness and dysarthria
  • joint position and vibratory sense impaired
  • sometimes loss of pain and temperature
  • pes cavus, kyphoscoliosis
  • wheelchair bound within 5 years of onset
  • life expectancy- 40-50 age
  • cardiomyopathy!!
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20
Q

Friedreich Ataxia caused by?

A
  • expansion of GAA trinucleotide repeat in a gene that encodes frataxin- found in mitochondrial inner membrane where its involved in assembly of iron-sulfur cluster enzymes of complex I and II
  • reduced mitochondrial frataxin–decreased mitochondrial ox phos and increased free iron
  • free iron- ox stress!
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21
Q

Friedreich ataxia morphology

A
  • spinal cord- loss of axons and gliosis in posterior columns, CSTs, spinocerebellar tracts
  • degeneration of neurons in spinal cord, brainstem (CN7, 8, 9), cerebellum, motor cortex
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22
Q

Ataxia telangiectasia characterized by?

A
  • autosomal recessive
  • ataxic-dyskinetic syndrome early in childhood, with development of telangiectasias in conjuctiva, and skin along with immunodeficiency
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23
Q

Ataxia-Telangiectasia-gene?

A

-ATM (ataxia-telangiectasia mutated) gene–encodes a kinase- role in cellular response to double stranded DNA breaks

24
Q

Ataxia-Telangiectasia morphology

A
  • loss of purkinje and granule cells- cerebellum
  • degeneration of dorsal columns, spinocerebellat tracts, anterior horn cells, peripheral neuropathy
  • amphicytes–enlargement of nucleus 2-5X
  • LNs, thymus, gonads hypoplastic
25
Q

Ataxia-Telangiectasia clinical features

A
  • death in 2nd decade
  • initial-recurrent sinopulmonary infections, unsteadiness in walking
  • later- dysarthric speech, eye movement abnormalities
  • many develop lymphoid neoplasms, especially T-cell leukemias
26
Q

ALS–loss of?

A
  • loss of UMNs in cerebral cortex
  • loss of LMNs in spinal cord and brainstem
  • results in denervation of muscles–produces weakness
  • onset in 5th decade
  • sporadic ALS moree common than familial
27
Q

ALS genetics

A
  • autosomal dominant
  • 20% of cases–mutation in gene encoding SOD1
  • mutated SOD1-gain of function misfolds/forms aggregations-cell injury
  • aggregated SOD1 also in sporadic ALS
28
Q

most common mutation that gives rise to ALS and FTLD

A

-expansion of a hexanucleotide repeat-C90rf72

29
Q

ALS morphology

A
  • anterior roots of spinal cord are thin–loss of LMN fibers
  • reduction in anterior horn neurons throughout spinal cord, associated with reactive gliosis
  • skeletal muscles innervated by degenerated LMNs–show neurogenic atrophy
  • degeneration of corticospinal tracts
30
Q

ALS–clinincal symptoms–early, later

A
  • early–asymmetric weakness of hands, cramping, spasticity of arms/legs
  • later- m strength and bulk diminish, fasciculations
31
Q

progressive muscular atrophy

A

-LMN predominantly

32
Q

primary lateral sclerosis

A

-UMN predominantly

33
Q

progressive bulbar palsy (bulbar ALS)

A
  • degeneration of lower brainstem cranial motor nuclei

- deglutition, phonation abnormalities

34
Q

spinal and bulbar muscular atrophy (kennedy disease) characherized by?

A
  • X-linked polyglutamine repeat expansion disease
  • distal limb amyotrophy and bulbar signs (atrophy, fasciculations of tongue, dysphagia)–degeneration of LMNs
  • expanded repeat in androgen R–androgen insensitivity, gynecomastia, testicular atrophy, oligospermia
  • intranuclear inclusions
35
Q

SMA (spinal muscular atrophy)

A
  • childhood–marked loss of LMNs–weakness
  • most severe=SMA type 1
  • later onset–SMA type III
  • severity related to level of protein (SMN)
36
Q

genetic metabolic disease–3 classifications

A
  • neuronal storage diseases (autosomal recessive)–def in enzyme in catabolism of sphigolipids, mucopolysaccharides, or mucolipids
  • leukodystrophies (autosomal recessive)–deficincy in enzymes in myelin synthesis or catabolism
  • mitochondrial encephalomyopathies–ox phos
37
Q

Neuronal storage diseases

A
  • autosomal recessive
  • Tay-sachs, Niemann- Pick diseases, mucopolysaccharidoses
  • accumulation of substrate in neurons
38
Q

Leukodystrophies–different from demylinating disease because?

A
  • insidious, progressive loss of cerebral function
  • younger ages
  • associated with diffuse, symmetric changes on imaging
39
Q

leukodystrophies–diseases

A
  • Krabbe disease
  • metachromatic leukodystrophy
  • adrenoleukodystrophy
40
Q

Krabbe disease–what is it?

A
  • autosomal recessive
  • deficiency of galactocerebroside-B galactosidase
  • galactocerebroside shunted to galactosylsphinosine–toxic at elevated levels
41
Q

Krabbe disease–clinincal symptoms

A
  • rapidly progressive
  • onset-ages 3-6 months; death by age 2
  • loss of myelin and oligodendrocytes in the CNS and in peripheral nerves
  • neurons and axons spared
42
Q

Krabbe disease–diagnostic features

A

-aggregation of engorged macrophages (globoid cells) in the brain parenchyma and around blood vessels

43
Q

metachromatic leukodystrophy–what is it?

A
  • autosomal recessive
  • deficiency of lysosomal enzyme arylsulfatase A (cleaves sulftate from sulfatides)
  • enzyme deficiency–accumulation of sulfatides, especially cerebroside sulfate
  • white matter injury, inhibiting differentiation of oligodendrocytes, proinflammatory response
44
Q

metachromatic leukodystrophy-diagnosis

A

-urine-metachromasia–sulfatides shift the absorbance spectrum dye

45
Q

adrenoleukodystrophy–what is it?

A
  • x-linked recessive disease
  • mutations in ABCD1 (ATP binding cassette transporter proteins)-involves in transport of molecules into peroxisomes
  • inability to catabolize VLCFAs (very long chain FAs) within peroxisomes–results in VLCFAs in serum
  • progressive loss of myelin in CNS and peripheral nerves, adrenal insufficiency
46
Q

Pelizaeus–Merzbacher disease

A

mutations in genes that encode proteins required for myelin formation

47
Q

alexander disease

A

-mutations in genes that encode proteins for GFAP (intermediate filament proteins)

48
Q

vanishing white matter leukoencephalopathy

A

-mutations in genes that encod proteins required for subunits of translation initiation factor eIF2B

49
Q

mitochondrial encephalomyopathies–characteristics, selectively target?

A
  • present as m diseases
  • heteroplasmy–cells have a mix of normal and abnormal mitochondria
  • selectively target neurons, gray matter
  • elevated tissue lactate levels
50
Q

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes)–characteristics, gene?

A
  • recurrent episodes of acute neurologic dysfunction, cognitive changes, m weakness, lactic acidosis
  • stroke-like episodes–reversible deficits (dont correspond to specific vascular areas)
  • infarction areas
  • altered expression of cytochrome c oxidase
  • most common mutation–MTTL1 (mitochondrial tRNA-leucine)
51
Q

MERRF (myoclonic epilepsy and ragged red fibers)

A
  • maternally transmitted
  • myoclonus, seizure disorder, myopathy
  • myopathy–ragged red fibers
  • ataxia–neuronal loss from cerebellar system
  • mutations in tRNAs often
52
Q

Leigh syndrome characterized by?

A
  • disease of infancy
  • lactic acidemia, arrest of psychomotor development, feeding problems, seizures, extraocular palsies, weakness with hypotonia
  • death 1-2 years
  • regions of destruction of brain tissue associated with spongiform appearance, proliferation of blood vessels
53
Q

Thiamine deficiency causes

A
  • Wernicke encephalopathy–acute appearance of psychotic symptoms and opthalmoplegia
  • symptoms reversible if treated
54
Q

korsakoff syndrome

A
  • thiamine (B1) deficiency–can be due to gastric disorders
  • disturbances of short term memory, confabulation (dosomedial nucleus of thalamus)
  • chronic alcoholism
55
Q

wernicke encephalopathy–morphology–early, later lesions

A
  • foci of hemorrhage and necrosis in mamillary bodies and walls of 3/4 ventricles
  • early–dilated capillaries–leaky hemorrhages
  • later–macrophages, cystic space
56
Q

vitamin B12 deficiency causes? symptoms?

A
  • subacute combined degeneration of spinal cord–degeneration of asc and desc spinal tracts
  • defect in myelin formation
  • early-bilateral symmetrical numbness, tingling, ataxia in LE
  • complete paraplegia may occur
  • axons degenerate
57
Q

Adrenoleukodystrophy–clinical

A

–young males, behavioral changes, adrenal insufficiency

NS2 Test 2 (16 decks)

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