Neuropathology- Part VI- Degenerative + dementing disorders Flashcards
What is a neurodegenerative disease
have selectie neuronal loss w no inciting events
What is parkinsons disease and what does it cause
loss of dopaminergic neurons in substantia nigra
=tremor, rigity, akinesia (overall loss of promotion of mvmt)
What % of pop does parkinsons affect and age
2% of the pop
-5-8th decade
What is one known cause of parkinsons
Acidental exposure to MPTP by ilicit synthesis of meperidine causes death of dopaminergic neurons in substantial nigra
What is a major hisological aspect of parkinsons
lewy bodies ( intracytoplsmic round eosinoplhilic inclusions that contain a synuclein)
What are the only 2 things you would see lewy bodies in
- Parkinsons
2. Lewy body disease
What pathway is lost in parkinsons
loss of extrapyramidal nigrostriatal pathway
Major s/s of parkinsons
- 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
What is the mc cause of dementia in elderly
Alzheimers (70% of causes)
>65
2 forms of alzheimers disease
- Sporadic
2. Hereditary (5-10%)= early onset or autosomal dominant trait
What is the general pathogenesis of alzheimers
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
What are the 3 possibe mutations that are known to cause AD
- Amyloid precursor pro
- Presenilin-1
- Apoliproetin E
Gross morphology of alzheimers
Cerebral atrophy w resultant hydrocephalus ex vacuo (compensatory expansion of ventricles)
Microscopic morphology of alzheimers
Neurofibrillary tangles and senil plaques in hippocampus, cerebral neocortex
2 major findings in alzheimers and what do they look like
Senile plaques- Swollen neuronal processes rich in hyperphosphorylated tau pro, usually surrounding b amyloid core
Neurofibllary tangles- intracellular aggregates of hyperphosphorylted tau pro
S/s of alzheimers disease
-gradual decline in cognitive functions leading to severe cognitive dysfunction
how to dx alzheimers
Made by the clinical diagnosis of dementia w/o another explanatuon
What is diffuse lewy body disease and histo hallmark
Dementia w lewy bodies
-Lewy bodies in the neocortical neurons (limbic system/cingialte gyrus)
s/s of lewy body disease (3)
- Parkinsonism
- Dementia
- Visual hallucinations
What is frontotemporal dementia/ Pick disease (gross morphology)
Frontotemporal dementia w parkinsonism linked to chromosome 17
-atrophy of frontal and temporal lobes
Clinical pres of pick disease
Early onset behaviourl abnormalities w. alterations in personality and language
What is vascular demenia and pathogenesis
Step wise decline in cog function
-Small microinfarcts in hippocampus and areas involved w mem
What is normal pressue hydrocephalus and clinical pres triad
Excessive CSF in ventricles but normal pressure
triad of dementia, gait instability, urinry incontinence
Epidimology of hunington chorea
Autosomal dominant disorder
mutation in HD gene located on chromosome 4
Pathophysiology of hunington
Loss of caudate nucleaus GABA nergic neurone
–loss of inhibitory influences on extra pyramidal tracts
—Leads to chorea (sporadic)
Age of huningtons
20-40
What is ALS
Degen + loss of upper and lower motor neurons that usually manifests in middle age
pathophysiology of ALS and results
Loss of upper motor neurons (produces hyperreflexia/spas)
Loss of lower mm neurons (weakness, atrophy, fasiculations)
What type of disorder is friedreich ataxia and age1
autosomal recessive disorder
-early childhood onset
Pathophysiology of friedreich ataxia
Expansion of an unstable triplit neucleotide reapeat in frataxin gene
-frataxin key for mito reg and damage leads to dysfunction impacting sensory pathways
Clinical manifistations of friedrich ataxia
Gait ataxia
dysarthria
hand clmbsiness
loss of pos etc
What is wilsons disease and what is it due to
autosomal recesive abnormality of wilson pro
-Leads to defective synthesis of ceruloplasmin (copper accumulation)
S/s of wilson disease
- Neuropsychiatric symptoms and ataxia (basal ganglia inv) in 20/30s
- Kayser-fleiseer rings in the descent membrane of eye
What is acute intermittent porphyria and major sign of it
Autosomal dom defect in porphyrin metabolism w deficit uroporphyrinogen syn
–Urine is initially colorless but on exposure to light turns dark red
What can vit B12 def cause (3)
- Megaloblasic anemia
- Demyelination of the spinal cord post column, lat corticospinal tracts
- Vit b12 def also causes dementia and peripheral neuropathy
