Degenerative Diseases Of The NS

Question 1

What are the 3 microscopic changes that characterize Alzheimer’s disease

Answer 1

1. Neurofibrillary tangles - thick fiber-like strands of silver-staining loops/coils of hyperphosphorylated microtubular protein TAU in the cytoplasm
2. Neuritic plaques - spherical deposits of amorphous matl throughout cerebral cortex composed of AMYLOID core surrounded by degenerating nerve terminals
3. Granulovacuolar degeneration - of neurons in the pyramidal layer of the hippocampus

Question 2

The gene coding for APP (Amyloid Precursor Protein) is located on which chromosome? This links AD with what 2 other conditions which show Alzheimer changes?

Answer 2

Chromosome 21

Linking it to
Familial Alzheimer Disease
Down Syndrome

Question 3

Elevated levels of this protein that leads to aggregation of amyloid and then to neuronal toxicity

Answer 3

ABeta42

Question 4

These two endosomal proteins are thought to interact with or be a component of gamma secretase. Mutations in these also increase the relative levels of ABeta42 protein.

Answer 4

Presenilin 1& 2

Question 5

Neurotransmitter abnormalities in Alzheimer disease

Answer 5

Dec Choline acetyltransferase (ChAT) and ACh
Dec glutamate
Dec Substance P
Dec Somatostatin
Dec Cholecystokinin

Loss of monoaminergic neurons
Dec noradrenergic, gabaergic and serotonergic functions

Question 6

Apo E is a regulator of lipid metabolism with high affinity for ABeta in Alzheimer plaques. Which allele has been shown to be a susceptibility risk factor for AD tripling the risk of sporadic occurrence and accelerating its appearance by about 5years

Answer 6

Allele e4 on chromosome 19 coding for Apo E4

Question 7

Anticholinesterase inhibitor shown to be of benefit in reducing delusions, hallucinations, and anxiety in Lewy Body disease

Answer 7

Rivastigmine

Question 8

Triad of Huntington Disease

Answer 8

Dominant inheritance
Choreoathetosis
Dementia

Question 9

Characteristic pathologic abnormality of Huntington Disease

Answer 9

Bilateral gross atrophy of the head of the caudate and putamen

Question 10

Striatal degeneration in Huntington disease begins in the medial caudate nucleus but spares which structure

Answer 10

Nucleus accumbens

Question 11

Genetic mutation involved in the childhood onset Westphal or “rigid” variant of Huntington Disease.

Answer 11

HDL2 (Huntington disease-like-2) assoc with CATCG repeat expansion of the juntophilin-3 gene

Question 12

Oculomotor manifestations of Huntington disease

Answer 12

Impaired initiation and slowness of both pursuit and volitional saccadic movements
Inability to make a volitional saccad without movement of the head
Impaired upward gaze

Question 13

Manifestations of Dentatorubropallidoluydian atrophy

Answer 13

Chorea
Myoclonus
Rigidity

Question 14

Core features of Parkinson Disease

Answer 14

Bradykinesia
Resting Tremor
Postural instability
Rigidity

Question 15

Infrequency in blinking is an early sign of PD, in PD patients, no blinking may be reduced to:

Answer 15

5-10/min (from usual rate of 12-20/min)

Question 16

Tremors seen in PD

Answer 16

1. 4-per-sec “pill-rolling” tremor and tremor of repose
2. Essential type of tremor: fine 7 to 8-per-second, sl irregular action tremor which persists throughout voluntary movement

Question 17

Negro sign vs Froment sign

Answer 17

Both seen in PD
Negro sign = cogwheel phenomenon or tremor felt during passive movement of a rigid part

Froment sign = rigidity and cogwheeling elicited or enhanced by engaging opposite limb in a motor task requiring some degree of concentration

Question 18

Characteristics of arteriopathic or “arteriosclerotic” form of PD

Answer 18

Predominantly “lower half” parkinsonism
Shuffling gair, stickiness on turning, falling disproportionate to other features
No tremor
Little or no response to L-dopa

Question 19

Lewy bodies

Answer 19

Eosinophilic cytoplasmic inclusions, surrounded by a faint halo seen in remaining cells of pigmented nuclei seen in practically all cases of Idiopathic PD

Question 20

True or False

The finding of Lewy bodies in the Substantia nigra is pathognomonic of Idiopathic Parkinson Disease

Answer 20

False - although it is absent in postencephalitic parkinsonism and other inherited forms of PD, it appers occasionally in the Substantia nigra of aged, nonparkinsonian individuals

Question 21

Earliest changes in the brain among patients with PD occur in which areas?

Answer 21

Dorsal glossopharyngeal-vagal and anterior olfactory nuclei

Question 22

Diagnostic criteria for Lewy-body dementia

Answer 22

2 of the following:

1. Parkinsonian syndrome usu symmetric
2. Fluctuations in behavior anf cognition
3. Recurrent hallucinations

Question 23

Pathology of Lewy-body dementia

Answer 23

Diffuse involvement of cortical neurons with Lewy-body inclusions (mainly composed of aggregated alpha synuclein)

Absence or inconspicuous number of neurofibrillary tangles and amyloid plaques

Question 24

Toxic metabolite of neurotoxin MPTP that produces irreversible signs of Parkinsonism and selective destruction of cells in the Substantia nigra.

Answer 24

Pyridinium MPP (1-methyl-4-phenylpyridinium)
- bound by melanin in the dopaminergic nigrl neurons sufficient concentrations to destroy the cells

Question 25

Mutation implicated in both sporadic and genetic forms of PD

Answer 25

LRRK2 (Leucine-rich repeat kinse 2) site coding for dardarin
AD with age related penetrance 85% at 70yrs
1% sporadic cases

Question 26

PD symptoms that responded least to ablative surgical therapy

Answer 26

Postural imbalance and instability
Paroxysmal akinesia
Bladder and bowel disturbances
Dystonia
Speech difficulties

Question 27

A mutation in this gene has been associated with multiple system atrophy

Answer 27

COQ2 gene

Question 28

MRI finding in the cerebellar form of MSA

Answer 28

Hot cross bun sign

- atrophy of pontocerebellar fibers that manifest high T2signal intensity in an atrophic pons

Question 29

Characteristic syndrome of PSP

Answer 29

Supranuclear ophthalmoplegia
Pseudobulbar palsy
Axial dystonia

Question 30

2 features of PSP that distinguishes it most conspicuously from other degenerative conditions

Answer 30

Abnormalities of eye movements

Pseudobulbar palsy

Question 31

Neuronal achromasia

Answer 31

Ballooned and chromatolytic neurons with eccentric nuclei seen in corticobasal degeneration

Question 32

Chromosomal location and protein product of DYT1 gene

Answer 32

DYT1 or TOR1A
Located at chromosome 9q
Codes for torsinA
- mutation in DYT1 causes glutamate deletion from torsin A peptide

Question 33

Juvenile onset dystonia-parkinsonism dramatically responsive to low doses of L-dopa

Answer 33

Segawa Syndrome

Question 34

Genetic susbstrate of Segawa syndrome and pattern of inheritance

Answer 34

GCH1 gene coding for GTP cyclohydrolase1 protein for the synthesis of tetrahydrobiopterin
Autosomal dominant inheritance

Question 35

Characteristic finding of dysmetric horizontal and vertical saccades even before ataxia is obvious is seen in this autosomal dominant hereditary form of ataxia

Answer 35

Machado-Joseph-Azorean Disease (SCA3)

Question 36

Characteristic foot deformity in Friedreich Ataxia

Answer 36

hammertoes
High plantar arch with retraction of the toes at the metatarsophalangeal joints and flexion at the interphalangeal joints

Question 37

Which 3 spinocerebellar ataxias are associated with an autosomal recessive genetic defect

Answer 37

1. Friedreich Ataxia FXN (frataxin)
2. VitE deficiency TTPA (Vitamin E transfer protein)
3. (AD, AR, sporadic) SCA8 ATXN8 (ataxin-8, CTG rpt noncoding)

Question 38

Characteristic ophthalmoscopic triad of retinitis pigmentosa

Answer 38

1. Pigmentary deposits that assume config of bone corpuscles
2. Attenuated vessels
3. Pallor of the optic discs