neurodegenerative dz Flashcards
primary risk factor=aging (>65yo)
genetic risk factor= ApoE4
-mutations in amyloid precursor protein or mutations in components of gamma-secretase
brain biopsy=senile plaques and neurofibrillary tangles found primarily in the hippocampus
beta-amyloid plaques
neurofibrillary tangles-tau protein
Alzheimer’s
personality and behavior change
echolailia (repitition)
subtype=pick’s dz
loss of personal/social awareness, disinhibition, loss of insight
frontotemporal lobar degeneration
tremors at rest, cogwheel rigidity, expressionless, postural instability
depigmentation of substanstia nigra
loss of neuromelanin containing neurons
lewy body inclusions
Parkinson’s
selective uptake through DA receptor
inhibits respiratory chain of mitochondria
acquired parkinsonnism with meperidine derivative MPTP intoxication
autosomal dominant
involuntary movements and deterioration of cognitive fxn
CAG repeats of huntintin gene on 4p->polyglutamine expansion
anticipation: increased number of repeats in subsequent generations
dementa, choreiform movements, family history
***cerebral atrophy
huntington dz
triplet expansions
> 20 genetically determined diseases
spinoverebellar ataxia
autosomal recessive, most common ataxia, GAA repeats->loss of farataxin fxn (iron regulator), presents early in childhood
progressive ataxia, kyphoscoliosis, progressive leg weakness, impaired sensation, loss of dtr in legs
death from hypertrophic cardiomyopathy
degeneration of dorsal column, DRG, spinocerebellar tracts/UMN
friedrich ataxia
degenerative disorder of umn/lmn
progressive wasting of extremities
eventual impairment of respiratory muscles
autosomal dominant=superoxide dismutase (sod-1)
-degeneration of spinocerebellar tracts
-degeneration of lateral corticospinal tracts
Amytrophic lateral sclerosis
-chronic/autoimmune
-demylination of brain/stem, cerebellum, cord
W>M
HLA-DR2, spares axons
multiple plaques, gradual accumulation of neurological deficits, vertigo, diplopia,
inc csf, IG levels, oligoclonal bands
multiphasic
multiple sclerosis
post infectious autoimmune rxn to myelin
- diffuse brain involvement
- monophasic with death/slow recovery
s/s: ha, v, f, meningismus
patchy myelin loss
acute disseminated encephalomyelitis ADEM
polyoma virus infection of oligodendroglia leads to demyelination
large, bizarre, atypical astrocytosis
large oligodendroglial cells
progressive multifocal leukoencephalopathy PML
nonimmune demyelinating disorder
-occurs after rapid correction of HYPOnatremia
-oligodendrocyte injury related to edema induced by sudden changes in osmotic pressure
central pontine myelinosis
rapidly progressive, acute immune-mediated demyelinating disorder of pns
-follows bacterial, viral, or fungal infection (UR or GI)
-most extensive injury in proximal motor nerve roots
guillain barre syndrome (acute inflammatory demyelinating polyradiculopathy)
deficiency of lysosomal enzyme arylsulfatase a
-sulfatides can’t be degraded
-cerebroside galactosyl sulfatide accumulates w/in schwann cell and oligo’cytes
autosomal recessive dysmyelinating dz
metachromatic leukodystrophy
deficiency of glactocerbroside beta-galactosidase
- appears in infancy
- globoid cells accumulate in perivascular areas of white matter
autosomal recessive dysmyelinating dz
krabbe dz
