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ADAMS > Degenerative Diseases > Flashcards

Degenerative Diseases Flashcards

1
Q

what has been established re: inheritance in Alzheimer disease

A

familial occurrence <1 percent there is a dominant inheritance pattern with a high degree of penetrance and appearance of disease at a younger age

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2
Q

T/F Women in general are at slightly higher risk for AD

A

True p1064

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3
Q

major symptom in AD

A

gradual development of forgetfulness

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4
Q

Ribot law of memory

A

Remote memories are preserved and recent ones lost. this is only relatively true.

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5
Q

repetition of every spoken phrase

A

echolalia

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6
Q

in AD, most prominent finding visible on MRI

A

extreme atrophy of hippocampus p1067

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7
Q

Microspcopic findings in AD

A

widespread loss of nerve cells

Early: most pronounced in layer II of entorhinal cortex marked neuronal loss in hippocampus, affected also are parahippocampal gyri, subiculum

other parts affected: anterior nuclei of thalamus, septal nuclei, diagonal band of Broca, amygdala, brainstem parts of the monoaminergic systems

cholinergic neurons of nucleus basalis of Meynert (substantia innominata) and locus ceruleus are reduced in number cerebral cortex:

cell loss affects pyramidal neurons

astrocytic hypertrophy which is compensatory prominent in layers III and V

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8
Q

3 Microscopic changes that make AD distinct

A
  1. neurofibrillary tangles - presence within the nerve cell cytoplasm of thick, fiber-like strands of silver-staining material, also in the form of loops, coils or tangled masses
  2. neuritic plaques - spherical deposits of amorphous material scattered through the cerebral cortex and easily seen with Periodic acid-Schiff

the core of aggregates is amyloiud, surrounded by degenerating nerve terminals

  1. Granulovacuolar degeneration of neurons most evident in the pyramidal layer of hippocampus
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9
Q

a discrete cytoskeletal protein, made of B2 transferrin, that promotoes assembly of microtubules, stabilizes their structure, and participates in synaptic plasticity

A

Tau

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10
Q

Conditions wherein there is aggregation of Tau

A

Alzheimer Disease

PSP

FTD

Picks

CBD

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11
Q

It is believed that the cleavage of the amyloid precursor protein by the B and gamma secretase results in 40- and 42-amino-acid by products. Which of these two forms is toxic?

A

AB42

the ratio of AB42 to AB40 is critical to neuronal toxicity of amyloid

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12
Q

True or False

The ratio of AB42 to AB40 is increased in Down syndrome.

A

True

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13
Q

genes encoding for endosomal proteins which are also implicated in Alzheimer

A

presenilin 1 and 2

the presenilins interact or maybe a component of gamma secretase, the enzyme that produces the AB42 fragment

Mutations of the APP and presenilin genes explain a very small proportion of Alzheimer cases

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14
Q

protein product from an inadequate functioning progranulin gener, deposited in neurons and may play a substantial role in the severity of expression of AD

this protein has been implicated in the pathogenesis of FTD and motor neuron disease

A

TDP-43

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15
Q

True or False

Studies showed that the presence of cerebral infarctions, small or large, and nondescript ischemic white matter disease accelerates the deposition of amyloid and the development of neurofibrillary tangles in the brains of AD patients.

A

True

p1069

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16
Q

Neurotransmitter abnormality in AD

A

reduction in choline acetyltransferase (ChAT) and acetycholine in the hippocampus and neocortex

loss of cholinergic synthetic capacity was attributed to a reduction in the number of cells in the basal forebrain nuclei (mainly the nucleus basalis of Meynert) from which the majorportion of neocortical cholinergic terminals originate

50% reduction in ChAT activity has been found in caudate nucleus

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17
Q

Mutations and Modulating factors associated with AD

A

APP - amyloid precursor protein bound to neuronal membranes

presenilin 1 and 2 - endosomal proteins

ApoE - regulator of lipid metabolism that has an affinity for AB alzheimer plaques; presence of E4 is associated with tripling the risk of developing sporadic AD (not a mendelian trait but a susceptibility risk

TREM2 - TREM2 polymorphism causes inadequate phagocytic clearance of amyloid

UBQLN1 - ubiquilin1 - interacts with PS1 and PS2 and participates in proteasomal degrradation

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18
Q

Coronal MRI, EEG in AD shows

A

disproportionate atrophy of hippocampi and corresponding enlargement of temporal horns of lateral ventricles

EEG: mild diffuse slowing (late in the illness)

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19
Q

SPECT and PET scan in AD

A

diminished activity in the parietal association regions and the medial temporal lobes

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20
Q

ratio of AB42 to tau in CSF in Alzheimer

A

Low

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21
Q

medications for Alzheimer

A

donepezil - acetylcholinesterase inhibitor for mild to moderately affected patients

SE: nausea, vomiting, insomnia, incraesed confusion

Memantine - NMDA glutaminergic antagonist- for use in the late-stage AD

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22
Q

True or False

The combination of memantine and donepezil in moderately to severely affected patients offered modest benefit over either drug alone.

A

FALSE

NO BENEFIT

p1073

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23
Q

a variant of lobar atrophy presenting with behavioral changes - apathy, disinhibition, perseveration, poor judgment, limited ability for abstraction, loss of empathy, bizarre affect, eating disorders

Insight is impaired, some subjects become euphoric or display repetitive compulsive behaviors

MRI: disproportionate atrophy and hypofunction in the frontal lobes usually asymmetric

a proportion presents with parkinsonian features

many cases shows deposition of progranulin consisting of ubiquitin neuronal inclusion consisting of TDP-43

A

Behavioral Variant of FTLD

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24
Q

Types of Primary Progressive Aphasia

A

progressive nonfluent - initially speaks less and has word finding difficulty, language stucture is intact

semantic - difficulty naming items, people and words followed by verbal perseveration; difficulty in generating lists of words of a given category

logophenic - shares most aspects of nonfluent aphasia but the meaning of words is retained

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25
Q

variant of lobar degenertaion with progressive loss of the ability to understand and use visual information

-progressive and ultimately severe visuospatial difficulty with a relative preservation of memory

Prosopagnosia, achromatopsia, dyslexia

difficulty with depth perception, reaching for objects and an inordinate sensitivity to bright light

A

Posterior Cortical Atrophy

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26
Q

defined by diffuse involvement of cortical neurons with Lewy-body inclusions and by an absence or inconspicuous number of neurofibrillary tangles and amyloid plaques

aggregated a-synuclein

typical form: parkinsonian features, dementia and a tendency to episodic delirium, especially nocturnally, rapid eye movement (REM) sleep behavior disorder

A

Lewy-body dementia

Diffuse Lewy-body Disease

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27
Q

Diagnostic Criteria for Lewy-body Dementia

A

requires 2 of 3 of the following:

  1. parkinsonian syndrome (usually symmetric)
  2. fluctuations in behavior and cognition
  3. recurrent hallucinations
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28
Q

psychotic features in LBD

A

episodic confusion, hallucinations, paranoid delusions

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29
Q

True or False

In LBD, the parkinsonian features may respond favorably to L-Dopa but only for a limited time and sometimes at the expense of causing an agitated delirum or hallucinations, uncharacteristic of early PD.

A

True

p1075

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30
Q

medication for LBD helps reduce delusions, hallucination and anxiety

A

Rivastigmine, anticholinesterase inhibitor

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31
Q

distinguished by the triad: dominant inheritance, choreoathetosis, dementia

A

Huntington Disease

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32
Q

True or False

The length of the nucleotide repeats CAG in Huntington determines not only the presence of the disease but also the age of onset wherein longer repeat length is associated with an earlier appearance of signs.

A

True

p 1077

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33
Q

CAG codon codes for what amino acid

A

glutamine

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34
Q

rare alternative mutation for Huntington

termed HDL2 (huntington diseae like-2) is associated with what repeat expansion of what gene

A

CATCG

juntophilin-3-gene

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35
Q

True or False

The first symptoms to appear in half the cases of Huntington are alterations in personality.

A

true

p 1077

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36
Q

True or False

The dementia in Hutington Disease is described as subcortical dementia, that is, the elements of aphasia, apraxia, and agnosia are observed only rarely and meomry loss is not profound.

A

true

p1077

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37
Q

Huntington

The abnormality of movement is subtle at first and most evident in the leg.

A

False

evident in the hands and face

Slowness of movementof the fingers and hands, reduced rate of finger tapping, difficulty in performing a sequence of hand movements are early signs.

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38
Q

True or False

As in parkinsonism, the frequency of blinking in Huntington is decreased.

A

False

Blinking is increased!

p1077

and voluntary protrusion of the tongue, like other attempt at sustained posture is constantly interrupted by unwanted darting movements

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39
Q

In huntington, about how many years in which most patients deteriorate to a vegetative state

A

10-15 years of ymptoms

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40
Q

True or False

Suicidal rate in Huntington is high.

A

True

p1077

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41
Q

True or False

Huntington. The dementia is generally more severe in cases of early (15-40) onset and with correspondingly longer repeat lengths than in those of later onset (55-60).

A

True

p1077

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42
Q

Pathology in Huntington

A

gross atrophy of the bilateral caudate nuclei and putamen is characteristic

moderate degree of gyral atrophy in the frontal and temporal regions

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43
Q

PET findings in Huntington

A

low glucose metabolism in the caudate nuclei

which precedes the volumetric loss of tissue. The striatal degeneration begins in the medial part of the caudate nucleus and spreads, tending to spare the nucleus accumbens.

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44
Q

True or False

Huntington. The anterior parts of the putamen and caudate are more affected than the posterior parts.

A

True

p1078

in the cerebral cortex there is a slight neuronal loss in layers 3,5,6 with replacement gliosis

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45
Q

Anticipation is well described in huntington and is known to be attributable to increasing lengths of CAG repeat sequence. What is anticipation?

A

earlier onset of disease in successive generations

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46
Q

Huntington.

where does huntingtin protein accumulate

A

striatum and affected cortex

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47
Q

drugs that can occasionally cause chorea

A

amphetamines

cocaine

tricyclic antidepressants

lithium

isoniazid

linezolid

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48
Q

Treatment for huntington

A

haloperidol - dopamine antagonist - in dialy doses of 2-10mg

effective partially in suppressing movement disorder

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49
Q

other drugs that deplete dopamine or block dopamine receptors which suppress the chorea in huntington to some degree but their side effctes (drowsiness, akathisia, tardive dyskinesia) outweigh their desired effects

A

reserpine, clozapine, tetrabenazine

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50
Q

disease has been linked to chromosome 9q

there is mutation in gene encoding protein chorein - involved in cellular protein sorting and trafficking

atrophy and gliosis of caudate nuclei BUT NO NEURONAL LOSS

A

neuroacanthocytosis

2 categories

  1. defect in red cell lipid membrane (bassen-Kornzweig disease) and HARP hypobetalipoproteinemia, acanthocytosis, retinitis pigmentosa, pallidal degeneration
  2. second group that lacks lipid abnormality
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51
Q

disorder with acanthocytosis and gradual development of chorea in the middle to late life, degeneration of caudate and putamen

with myopathy (elevated CPK)

fewer facial tic and orofacial features

arise from mutations on the X-chromosome that encodes KX protein which binds to surface Kell antigens on red cells

diminished kell antigen expression on the red-cell surface

A

McLeod Disease

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52
Q

tetrad of hypo/bradykinesia, resting tremor, postural instability, rigidity

A

Parkinson Disease

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53
Q

True or False

Volitional movememt dampens the resting tremor momentarily.

A

True

p1083

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54
Q

True or False

Tremor in PD is aggravated by walking and excitement.

A

True

p1083

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55
Q

pill-rolling tremor frequency

A

4-per second

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56
Q

axial dystonia in PD

extreme forward flexion of the spine, severe stooping occurs

A

camptocormia

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57
Q

kinesis paradoxica

A

in PD, in the excitement of some unusual circumstance, e.g. escapinf from fire, the paient with all but advanced disease is capable of bried but remarkably effective movement

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58
Q

Myerson sign

A

inability to inhibit blinkingin response to a tap over the bridge of nose or glabella

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59
Q

dyskinesias after treatment with levodopa usually appears when?

A

3-5 years of treatmentwith levodopa

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60
Q

In parkinsons, how many fail to display the characteristic tremor? not responsive to L-dopa?

A

25% for tremor

10% do not respond to L-dopa

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61
Q

most constant and pertinent finding in idiopathic and postencephalitic PD

A

loss of pigmented cells in substantia nigra and other pigmented nuclei (locus ceruleus, dorsal motor nucleus of the vagus

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62
Q

Rate limiting enzyme for the synthesis of dopamine

A

Tyrosine hydroxylase

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63
Q

True or False

PD. The earliest changes in the brain occur in the dorsal glossopharyngeal-vagal and anterior olfactory nuclei.

A

True

p1086

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64
Q

neurotoxin which produces irreversible signs of parkinsonism and selective destruction of cells in the subtantia nigra

analogue of meperidine

A

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine transformed by monoamine oxidase to a toxic metabolite pyridinium MPP

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65
Q

what protein/PARK gene accounts for 50% of earl-onset inherited PD, 20% of sporadic early-onset cases,

Autosomal recessive

A

PARK 2/parkin

66
Q

what protein/PARK gene resembles idiopathic PD

late onset, autosomal dominant

A

PARK 3

67
Q

what protein/PARK gene accounts for those seen in Ashkenazic Jews, protein also called dardarin, related to Gaucher disease

Autosomal dominant, late onset

A

Park8/ LRRK2

leucine rich repeat kinase 2

68
Q

the main component of Lewy bodies in both the sporadic and inherited forms of PD

A

a-synuclein

69
Q

CT scan and MRI finding in CBD

A

asymmetrical cerebral and pontine atrophy

70
Q

Elderly patients in whom the essential abnormality was a progressive asymmetrical extrapyramidal rigidity combined with signs of corticospinal disease with the ffg postmortem findings: cortical atrophy (mainly in the frontal motor-premotor, anterior parietal lobes) was associated with degeneration of the substantia nigra, and in one instance, of the dentatorubrothalamic fibers

A

Corticobasal degeneration

71
Q

Group of disorders characterized by neuronal degeneration mainly in the substantia nigra, striatum, autonomic nervous system, and cerebellum

A

multiple system atrophy

72
Q

orthostatic hypotension in Multiple System Atrophy has been attributed to

A

loss of intermediolateral horn cells and pigmented nuclei of brainstem

other autonomic changes aside from orthostatic hypotension

erectile dysfunction, loss of sweating, dry mouth, miosis, urinary retention, incontinence

73
Q

MRI finding in MSA

A

hot cross bun sign - reflects atrophy of the pontocerebellar fibers that manifest high T2 signal intensity in an atrophic pons

other findings: atrophied cerebellum and pons

Hypointense putamen, may have increased deposition of iron in the parkinsonian form

CT and MRI: atrophy of cerebellum and pons in those with cerebellar features

74
Q

Pathology in MSA

A

Abnormal staining material in the cytoplasm of astrocytes and oligodendrocytes and in some neurons call Glial cytoplasmic inclusions they contain a-synuclein

75
Q

prototype of all forms of progressive spinocerebellar ataxias

autosomal recessive, mutation is in the expansion of a GAA trinucleotide repeat with a gene that codes for the protein frataxin

  • reduction in the levels of frataxin and loss of its function
    features: ataxia of gait, hands become clumsy years after gait disorder, half of patients have cradiomyopathy (myocardial fibers are hypertrophic, contain iron-reactive granules, some die of CHF or arrhythmia), 10% have DM, gait abnormality is mized sensory and cerebellar, (+) Romberg sign, horizontal nystagmus may be present
A

Friedreich Ataxia

76
Q

Pathology in Friedreich Ataxia

A
  • spinal cord is thin
  • posterior columns and CST, spinocerebellar tracts are all depleted of myelin fibers
  • mild gliosis
  • nerve cells in the Clarke column, large neurons of the dorsal root ganglia esecially at the LS area are reduced in number
  • nuclei of cranial nerves VIII, X, XII all exhibit reduction of cells
  • moderate neuronal loss is seen also in the dentate nuclei, middle and superior cerebellar peduncles
  • some depletion of Purkinje cells in the superior vermis, inferior olivary nuclei
  • myocardial muscle fibers degenerate
77
Q

SCA3

A
  • Machado-Joseph
  • ATXN3 ataxin-3
  • age of onset: teens
  • 25% of dominant ataxias, spasticity, neuropathy, extrapyramidal symptoms
78
Q

Dentatorubropallidoluysian atrophy (DRPLA)

A
  • onset: childhood
  • gene ATN1
  • protein: atrophin1
  • presents with chorea, dystonia, seziures, dementia
79
Q
  • a special form of hereditary ataxia with brainstem and extrapyramidal signs
  • autosomal dominant
  • slowly progressive ataxia beginning in adolescence and early adult life
  • hyperreflexia, extrapyramidal features (rigidity and slowness), dystonia, bulbar signs, distal motor weakness, opthlamoplegia
  • no impairment of intellect
A

SCA3

Machado-Joseph-Azorean Disease

80
Q

Pathologic findings in SCA3

Machado-Joseph-Azorean Disease

A

degeneration of dentate nuclei, spinocerebellar tracts, loss of anterior horn cells and neurons of the pons, substantia nigra, and oculomotor nuclei

81
Q
  • rare familial disorder, described mostly in Japan and some in Europe
  • cerebellar ataxia, choreoathetosis and dystonia
  • parkinsonisms, myoclonus, epilepsy or dementia
  • gene defect: unstable CAG repeat gene that codes for atrophin
  • autosomal dominant
  • anticipation
A

Dentatorubropallidoluysian atrophy (DRPLA)

82
Q

The earliest manifestation of the lower motor neuron component of ALS is sometimes

A

volitional cramping

83
Q

Prognosis in ALS

A

half the patients succumb within 3 years of onset

90 percent within 6 years

84
Q
  • lower motor neuron syndrome
  • more common in men
  • tends to progress at a lower pace, about 15 yrs or longer
  • younger patients had a more benign course
  • mutation in SOD1 gene
  • wasting of muscles, fascicular twitchings and crampings, tendon reflexes are diminished or absent
A

Progressive Muscular Atrophy

85
Q
  • first and dominant symptoms relate to weakness and laxity of muscles innervated by the motor nuclei of the lower brainstem
  • defective modulation
  • mastication and deglutition become impaired
  • jaw jerk may be exaggerated
  • pseudobulbar signs (pathologic laughing and crying)
  • progressive course
  • patient may die 2-3 years after onset from inanition and aspiration pneumonia
A

Progressive Bulbar Palsy

86
Q
  • With certainty: on average, the appearance of e4 allele acceerates the appearance of AD by about ____ years
    *
A

5 years

87
Q
  • the product of inadequate functionning of progranulin gene
  • deposited in neurons and may play a substantial role in teh severity of expression of AD
  • this protein has been implicated the pathogenesis of frontotemporal dementia and motor neuron disease
A

TDP-43

88
Q

major symptom in AD

A

gradual development of forgetfulness

89
Q

T/F

Alzheimer.

Occasionally, widespread myoclonic jerks or mild choreoathetotic movements are observed late in the illness.

A

True

p1065

90
Q

T/F

In Huntington Disease, memory is relatively spared.

A

True

p1077

91
Q

Alzheimer

Neuronal lass in the hippocampus specifically in

A

layer II of entorhinal cortes

92
Q

in Alzheimer:

astrocytic hypertrophy is an evidence of compensatory or reparative process most prominent in which layers

A

Layers III and V

93
Q

T/F

Neuritic plaques and neurofibrillary changes are found in all the association areas of the cerebral cortex.

A

True

p 1067

94
Q

Correlate best with the severity of dementia

A

Neurofibrillary tangles and quantitative neuronal loss

p1067

95
Q

define “subcortical dementia” as described in Huntington

A

elements of aphasia, apraxia, and agnosia are observed only rarely and memory loss is not profound

96
Q

T/F

in AD, PSP, FTD

tau is hyperphosphorylated and aggregates resultign in PAIRED HELICAL FILAMENTS that makeup the neurofibrillary tangles

A

True

p1068

97
Q

T/F

AD

Elevation of the levels of B42 leads to aggregation of amyloid and then to neuronal toxicity.

A

True

p 1068

98
Q

T/F

Huntington.

once the movement disorder is fully established, there is nearly always some degree of cognitive abnormality.

A

True

p 1077

99
Q

APP or amyloid precursor protein is located in chromosome

A

chrom 21

100
Q

T/F

low suicide rate in Huntington

A

False

High suicide rate

p1077

101
Q

T/F

In the westphal variant of Huntington, functional decline is much faster in children than it is in adults.

A

True

p 1077

102
Q

Loss of cholinergic capacity in AD was attributed to

A

a reduction in number of cells in the basal forebrain nuclei (mainly the nucleus basalis of Meynert)

from which the major portion of neocortical cholinergic terminals originate

103
Q

presenilin genes 1 and 2 are located in chromosome

A

chrom 14 and 1, respectively

104
Q

T/F

Huntington

Dementia is severe in cases of early onset and with correspondingly longer repeath lengths.

A

True

p1077

105
Q

T/F

Alzheimer

Possession of the e4 allele correlates with increased deposition of AB protein in the brain.

A

True

p1070

106
Q

The presence of e4 allele accelerated the appearance of Alzheimer disease by about ____ years.

A

5 years

107
Q

Mutations and Modulating factors associated with Alzheimer

A

APP

Presenilin 1 nd 2

UBQLN1

TREM2

ApoE

108
Q

T/F

A form of motor neuron disease is also linked to frontotemporal dementia in a small number of cases.

A

true

p1074

109
Q

huntington gene is localized in chromosome

A

chromosome 4

110
Q

T/F

The pathologic change in lobar atrophy is circumcscribed and often asymmetrical. The parietal lobes are involved less frequently than the frontal and temporal lobes.

A

True

p1073

111
Q

T/F

Huntington

In adult patients with early onset, the chorea and intellectual loss tend to be more prominent initially.

In the patients with older age of onset, the emotional disturbance is more often the initial complaint.

A

False

early onset: emotional disturbance precedes chorea

older oage of onset: chorea is more prominent initially

112
Q

T/F

In Huntington, levodopa and other dopamin agonists may improve chorea.

A

False

p1079

LD and other dopa agonists make the chorea worse, and in the rigid form of the disease, evoke chorea.

Drugs that deplete dopamin or block dopamine receptors - clozapine, reserpine, tetrabenazine suppress the chorea to some degree, but their side effects usually outweigh their desired effects. (drowsiness, akathisia, tardive dyskinesia)

113
Q

T/F

PD

The 4-per-second “pill-rolling” tremor of the thumb and fingers, although most characteristic, is seen in only about half the patients.

A

True

p1082

114
Q

indicate the gene/protein and notation:

Two main mutations A53T, A30P

promote oligomerization of a-synuclein

A

Park1 and 4

SCNA (a-synuclein)

115
Q

indicate the gene/protein and notation:

Accounts for 50% of early-onset inherited PD; 20% of sporadic early onset cases

A

Park 2

parkin

116
Q

indicate the gene/protein and notation:

rese,bles idiopathic PD

A

Park3

117
Q

indicate the gene/protein and notation:

PD

mitochondrial gene

A

PINK1

PTEN-induced putative kinase 1

118
Q

indicate the gene/protein and notation:

gene is implicated in the formation and identity of dopaminergic neurons

A

NR4A2

NURR1

nuclear-receptor related protein 1

119
Q

PD

Dopamine Agonists

A

Ropinirole

Pramipexole

120
Q

PD

Glutamate antagonist

A

Amantadine

121
Q

PD

Anticholinergics

A

Benztropine

Trihexyphenidyl

122
Q

COMT inhibitors

A

Entacapone

123
Q

MAO-inhibitors

A

Rasagiline

Selegiline

124
Q

Symptoms in PD that responded least well to surgical therapy

A

postural imbalance and instability

aproxysmal akinesia

bladder and bowek disturbances

dystonia and speech difficulties

125
Q

T/F

in PD

The anticholinergic drugs have limited effect on postural, hypokinetic, and other manifestations of diseas.

A

True

p1092

126
Q

DBS in Parkinson disease

the electrodes are placed in:

A

posterior and ventral (medial) parts of the subthalamic nucleus

OR

internal segment of gobus pallidus

127
Q

PET findings in MSA

A

impairment of glucose metabolism in striatum and to a lesser extent in the frontal cortex

due to loss of functioning neuronal elements in the said parts

128
Q

onset 6th decade

combination of difficulty of balance, abrupt falls, visual and ocular disturbances, slurred speech, dysphagia and sometimes vague changes in personality, apprehensiveniess, fretfulness,

difficulty in voluntary verticla movement of the eyes, often downward but sometimes only upward, and later impairment of voluntary saccades in all directions

A

Progressive Supranuclear Palsy

129
Q

in PSP

most common early complaint

A

unsteadiness of gait and unexplained falling without loss of consciousness

130
Q

other degenerative conditions that can manifest with a supranuclear vertical gaze disorder although never to the extent in PSP

A

CBD

LBD

PD

whipple disease

131
Q

MRI findings in PSP

A

atrophy of the dorsal mesencephalon

(superior colliculi, red nuclei)

giving rise to “mouse ears” configuration

132
Q

pathology in PSP

A

Postmortem examinations have disclosed a bilateral loss of neurons and gliosis in the periaqueductal gray matter, superior colliculus, subthalamic nucleus, red nucleus, pallidurn, dentate nucleus, and pretectal and vestibular nuclei, and to some extent in the oculomotor nucleus

133
Q

this drug has been reported to ameliorate the akinesia and rigidity of PSP

A

zolpidem

134
Q

described mostly in Japan

symptoms of cerebellar ataxia coupled with choreoathetosis, dystonia, parkinsonism, myoclonus, dementia

unstable CAG repeat in the gene that codes for atrophin

A

Machado-Joseph-Azorean Disease

135
Q

The most common early symptom was an asymmetrical clumsiness of the limbs, in half of the patients, with rigidity and, in one-fifth, with tremor

asymmetric or unilateral akinetic-rigid syndrome, which may be considered the essential motor disorder of this disease and various forms of gait disorder and dysarthria

cannot effectively direct their voluntary actions. Attempts to move a limb to accomplish some purposeful act might result in a totally inappropriate movement, always with great enhancement of rigidity in the limb and in other affected parts, or the limb may drift off and assume an odd posture, such as a persistent elevation of the arm without the patient’s awareness-a kind of catalepsy

“alien hand”

A

Corticobasal degeneration

136
Q

pathology in CBD

A

cortical atrophy - mainly frontal motor-premotor and anterior parietal lobes

degeneration of substantia nigra

dentatorubrothalamic fibers

137
Q

CT and MRI in CBD

A

cerebral and pontine atrophy

138
Q

gene that codes for torsine A which is found in most cases of dystonia musculorum deformans

A

DYT1

139
Q

T/F

in Torsion Dystonia

recumbency initially relieves the spasms but later on position has no influence.

A

True

p1100

140
Q

dystonia that is responsive to L-dopa

found a linkage to the gene on chromosome 14q for the protein GTP cyclohydrolase 1 (GCH1 gene) that is implicated in the synthesis of tetrahydrobiopterin, a cofactor for tyrosine hydroxylase

mutation impairs the generation of dopamine

no cell loss in substantia nigra

A remarkable feature is the disappearance or marked subsidence of the symptoms after a period of sleep and worsening as the day progresses.

A

Hereditary Dystonia-Parkinsonism

(Segawa syndrome, Juvenile Dopa-Responsive Dystonia)

141
Q

men are affected twice as often as women

pts older than 45 at onset of symptoms

weakness in a distal part of one limb

unexplained tripping from slight foot-drop, awkwardness in tasks reuiring fine finger movements

stiffness of the fingers

slight weakness or wasting of hand muscles on one side

cramping beyond what is natural, fasciculations of muscles of the upper arm, shoulder girdle

atrophic weakness, fasciculations, slight spasticity of arms and legs, generalized hyperreflexia

A

ALS

142
Q

GAA trinucleotide repeat in Friedreich ataxia codes for what protein

A

frataxin

mutation is a missense, reduction in levels of frataxin and loss of its function

143
Q

nearly always the initial symptom in Friedreich ataxia

A

ataxia of gait

144
Q

T/F

Tendon reflexes are abolished in almost all cases of Friedreich ataxia.

A

True

p1104

may be obtainable when the patient is examined early in teh illness

Plantar reflexes are extensor and flexor spasms may occur even with complete absence of tendon reflexes.

145
Q

Diagnostic tests in Friedreich ataxia

NCV

ECG/Echo

CT/MR

CSF

genetic testing

A

sensory nerve conduction velocities and amplitudes - normal because peripheral neuropathy is not a component

ECG/Echo - heart block and ventricular hypertrophy

CT and MRI - seldom reveal a significant degree of cerebellar atrophy but the spinal cord is small

CSF and blood - no consistent abnormality

genetic testing for the length of GAA is available

146
Q

first and dominant manifestations of motor neuron disease may be

A

spastic weakness of legs

147
Q

friedreich ataxia

serum may be submitted for an assay of which vitamin?

deficiency of a certain vitamin transport protein can cause a similar spinocerebellar syndrome

A

vitamin E

148
Q
  • progressive, degenerative disease of upper motor neurons characterized by progressive spasticity
  • 5th or 6th decade
  • stiffness of one leg then in the other
  • slowing of gait with spasticity predominating over weakness
  • over the years finger movements become slower, arms become more spastic
  • no sensory symptoms or signs
  • half the patients acquire spasticity of the bladdder
  • diagnostic criterion: progression for 3 years without evidence of LMN dysfunction
A

Primary Lateral Sclerosis

149
Q

Laboratory Features of Motor Neuron Disease

EMG

CSF

Motor Evoked Potentials

MRI

A
  • EMG - widespread fibrillations (evidence of activer denervation) and fasciculations and enlarged motor units (denoting reinnervation)
  • motor nerve conduction studies reveal only slight slowing
  • WITHOUT FOCAL motor conduction block
  • SNAPs are normal
  • CSF protein usually normal or marginally elevated
  • motor evoked potentials are prolonged
  • slight atrophy of the motor cortices
150
Q

pathology: principal finding in ALS

A

loss of nerve cells in the anterior horn cells in the Spinal Cord and motor nuclei of the brainstem

Large alpha motor neurons tend to be affected before small ones

slight gliosis and proliferation of microglia cells

151
Q

noted a finding of a cytoplasmic inclusion in ALS

most studies indicate that these are made up of

A

TDP-43 and ubiquitin

152
Q

most frequent form og spinal muscular atrophies, the severe infantile type

occur once in every 20,000 live births

A

Werdnig-Hofmman SMA type I

153
Q

Spinal Muscular Atrophy

genetic aspects

A
  • autosomal recessive
  • mutations affect the gene at the “survival of motor neuron”
154
Q

function of SMN gene

how does the presence/absence correlate with the severity of the disease in SMA?

A
  • SMN protein participates in forming protein-RNA complexes (small nuclear ribonucleoproteins and RNA) that are essential for gene splicing
  • 2 alleles in SMN locus
  • SMN1 - generates a full-length fully functional form of SMN
  • SMN2 - tuncated partially functional SMN

latter can partially compensate for loss of SMN1

disease due to loss of both copies of SMN1 causes very severe SMA in individuals who carry only one copy of SMN2 while those with multiple copies of SMN 2 have milder disease

155
Q

Characteristics of SMA type I

Werdnig-Hoffman Disease

A
  • at birth, weakn and limp, floppy
  • fetal movement in utero are less than expected
  • arthrogryposis at the ankles and wrists or dislocation of the hips
  • muscle weakness in these children is generalized form the beginning, death comes early usually in the first yr
  • hypotonic
  • tendon reflexes unobtainable
  • respiratory movements become paradoxical - abdominal protrusion, chest retraction
  • legs in “frog position”
156
Q

EMG findings in SMA type I

A
  • fibrillations - denervation process
  • MUP are diminished in number, some are larger than normal (giant or polyphasic potentisls reflecting reinnervation)
  • Motor nerve conduction velocities are normal or fall in the low normal range
157
Q
  • age of onset 1 yera to adolescence
  • weakness and atrophy of the pelvic girdle and proximal leg muscles, followed by involvement of the shoulder girdle and upper arm muscles
  • Bulbar musculature and corticospinal tracts are spared
A

Chronic Childhood and Juvenila Proximal Spinal Muscular Atrophy

Wohlfart-Kugelberg-Welander Syndrome

158
Q

Type of SMA s

Number of SMNs

Age of onset

A
  • SMA I - infantile, Werdnig-Hoffman, auotosomal recessive, Two copies of SMN2, preterm to 6 months
  • SMA II - intermediate type, Dubowitz Disease, autosomal recessive, at least 3 copies of SMN2, 6-16 months
  • SMA III - Wohlfart-Kugelber-Welander, AR, or dominants, at least 3 copies of SMN2, 1 year to adolescence
  • SMA IV - AR, at least 4 copies of SMN2, after age 3
159
Q
  • distal muscualr atrophy with prominent bulbar signs
  • onset: childhood to adult age
  • symptoms on 3rd decade
  • X-linked pattern
  • dysarthria, dysphagia
  • tendon reflexes become depressed
  • 2/3 gynecomastia, oligospermia, diabetes
  • Ck is leevated
  • genetic defect: CAG expansion, that codes for androgen receptor on the X-chromosome
A

Kennedy syndrome

X-linked Bulbospinal Muscular Atrophy

160
Q
  • progressive paralysis of the facial, lingual, pharyngeal, laryngeal and sometimes ocular muscle
  • stridor and respiratory symptoms, followed by facial diplegia, dysarthria, dysphagia, and dysphonia
  • mutation in SLC52A3, a riboflavin trasnporter, and some beneficial effect is derived from administration of riboflavin (vitamin B2)
A

Progressive Bulbar Palsy of Childhood

(Fazio-Londe Syndrome)

161
Q
A

ADAMS (29 decks)

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