Neuropathology- Part VI- Degenerative + dementing disorders

Question 1

What is a neurodegenerative disease

Answer 1

have selectie neuronal loss w no inciting events

Question 2

What is parkinsons disease and what does it cause

Answer 2

loss of dopaminergic neurons in substantia nigra

=tremor, rigity, akinesia (overall loss of promotion of mvmt)

Question 3

What % of pop does parkinsons affect and age

Answer 3

2% of the pop

-5-8th decade

Question 4

What is one known cause of parkinsons

Answer 4

Acidental exposure to MPTP by ilicit synthesis of meperidine causes death of dopaminergic neurons in substantial nigra

Question 5

What is a major hisological aspect of parkinsons

Answer 5

lewy bodies ( intracytoplsmic round eosinoplhilic inclusions that contain a synuclein)

Question 6

What are the only 2 things you would see lewy bodies in

Answer 6

1. Parkinsons

2. Lewy body disease

Question 7

What pathway is lost in parkinsons

Answer 7

loss of extrapyramidal nigrostriatal pathway

Question 8

Major s/s of parkinsons

Answer 8

• Slowing of all voluntary mvmts
• tremor at rest that disappears w movemt
• rigidity of limbs and trunk accompanied by an inability to initiate voluntary movement

Question 9

What is the mc cause of dementia in elderly

Answer 9

Alzheimers (70% of causes)

>65

Question 10

2 forms of alzheimers disease

Answer 10

1. Sporadic

2. Hereditary (5-10%)= early onset or autosomal dominant trait

Question 11

What is the general pathogenesis of alzheimers

Answer 11

Due to defect in APP, a secretase cleaves it into large soluble fragment and smaller membrane anchored fragment

-clearence of these fragments is impaired in alzheimers

Question 12

What are the 3 possibe mutations that are known to cause AD

Answer 12

1. Amyloid precursor pro
2. Presenilin-1
3. Apoliproetin E

Question 13

Gross morphology of alzheimers

Answer 13

Cerebral atrophy w resultant hydrocephalus ex vacuo (compensatory expansion of ventricles)

Question 14

Microscopic morphology of alzheimers

Answer 14

Neurofibrillary tangles and senil plaques in hippocampus, cerebral neocortex

Question 15

2 major findings in alzheimers and what do they look like

Answer 15

Senile plaques- Swollen neuronal processes rich in hyperphosphorylated tau pro, usually surrounding b amyloid core

Neurofibllary tangles- intracellular aggregates of hyperphosphorylted tau pro

Question 16

S/s of alzheimers disease

Answer 16

-gradual decline in cognitive functions leading to severe cognitive dysfunction

Question 17

how to dx alzheimers

Answer 17

Made by the clinical diagnosis of dementia w/o another explanatuon

Question 18

What is diffuse lewy body disease and histo hallmark

Answer 18

Dementia w lewy bodies

-Lewy bodies in the neocortical neurons (limbic system/cingialte gyrus)

Question 19

s/s of lewy body disease (3)

Answer 19

1. Parkinsonism
2. Dementia
3. Visual hallucinations

Question 20

What is frontotemporal dementia/ Pick disease (gross morphology)

Answer 20

Frontotemporal dementia w parkinsonism linked to chromosome 17

-atrophy of frontal and temporal lobes

Question 21

Clinical pres of pick disease

Answer 21

Early onset behaviourl abnormalities w. alterations in personality and language

Question 22

What is vascular demenia and pathogenesis

Answer 22

Step wise decline in cog function

-Small microinfarcts in hippocampus and areas involved w mem

Question 23

What is normal pressue hydrocephalus and clinical pres triad

Answer 23

Excessive CSF in ventricles but normal pressure

triad of dementia, gait instability, urinry incontinence

Question 24

Epidimology of hunington chorea

Answer 24

Autosomal dominant disorder

mutation in HD gene located on chromosome 4

Question 25

Pathophysiology of hunington

Answer 25

Loss of caudate nucleaus GABA nergic neurone --loss of inhibitory influences on extra pyramidal tracts ---Leads to chorea (sporadic)

Question 26

Age of huningtons

Answer 26

20-40

Question 27

What is ALS

Answer 27

Degen + loss of upper and lower motor neurons that usually manifests in middle age

Question 28

pathophysiology of ALS and results

Answer 28

Loss of upper motor neurons (produces hyperreflexia/spas) Loss of lower mm neurons (weakness, atrophy, fasiculations)

Question 29

What type of disorder is friedreich ataxia and age1

Answer 29

autosomal recessive disorder | -early childhood onset

Question 30

Pathophysiology of friedreich ataxia

Answer 30

Expansion of an unstable triplit neucleotide reapeat in frataxin gene -frataxin key for mito reg and damage leads to dysfunction impacting sensory pathways

Question 31

Clinical manifistations of friedrich ataxia

Answer 31

Gait ataxia dysarthria hand clmbsiness loss of pos etc

Question 32

What is wilsons disease and what is it due to

Answer 32

autosomal recesive abnormality of wilson pro -Leads to defective synthesis of ceruloplasmin (copper accumulation)

Question 33

S/s of wilson disease

Answer 33

- Neuropsychiatric symptoms and ataxia (basal ganglia inv) in 20/30s - Kayser-fleiseer rings in the descent membrane of eye

Question 34

What is acute intermittent porphyria and major sign of it

Answer 34

Autosomal dom defect in porphyrin metabolism w deficit uroporphyrinogen syn --Urine is initially colorless but on exposure to light turns dark red

Question 35

What can vit B12 def cause (3)

Answer 35

1. Megaloblasic anemia 2. Demyelination of the spinal cord post column, lat corticospinal tracts 3. Vit b12 def also causes dementia and peripheral neuropathy