Term
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Definition
1. idiopathic (Parkinson's Disease)
2. Hereditary
3. Postencephalitic
4. Toxic: MPTP, Cycad beans, pesticides/herbicides
5. head trauma (boxers) |
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Term
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Definition
Park 1
1. chromosome 4
2. affects phosphoprotein involved in synaptic vessel transport
3. early onset, autosomal dominant |
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Term
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Definition
Park 2
1. chromosome 6
2. normal parkin is a ubiquitin ligase
3. juvenile, autosomal recessive |
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Term
| Parkinsonism as a mitochondrial disease |
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Definition
1. increased reactive oxygen species in mitochondria (mechanism of MPTP)
2. ROS lead to free radical formation, resulting in increased Mt membrane permeability and apoptosis
3. ROS inhibit ubiquitin-proteolysis system, increasing misfolded proteins |
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Term
| misfolded protein response in Parkinsonism |
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Definition
1. mutations in chaperone proteins that assist in folding or free radicals cause misfolding
2. misfolded proteins are dysfunctional or may aggregate
3. this may lead to degradation or apoptosis |
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Term
| role of reactive oxygen species in parkinsonism |
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Definition
1. urate is a natural antioxidant
2. pts with higher serum and CSF urates have lower risk for PD |
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Term
| clinical features of parkinson's disease |
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Definition
1. onset 50-70 yrs
2. resting tremor, especially pill rolling
3. rigidity
4. bradykinesia
5. dementia sometimes late in course
6. disability in 10-15 yrs |
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Term
| pathologic changes in parkinson's disease |
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Definition
1. loss of pigment in substantia nigra
2. injury to dopaminergic system - this loss of neurons causes the depigmentation
3. affects many nuclei that contain neuromelanin
4. Lewy bodies from inhibition of ubiquitin-proteolysis system |
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Term
| neuroimaging findings in Parkinson's Disease |
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Definition
1. PET scanning used
2. signal loss in putamen - loss of substantia nigra projections to corpus striatum |
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Term
| treatment strategies for Parkinson's Disease |
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Definition
1. antioxidants to combat ROS
2. co-enzyme Q to promote Mt integrity
3. dopamine agonists to stop apoptosis
->pramipexole works on D2 receptors |
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Term
| Diffuse Lewy Body Disease |
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Definition
1. Dementia
2. Parkinsonian features
3. more rapid course than classic PD
4. Lewy bodies in cerebral cortex and brainstem |
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Term
| clinical features of Progressive supranuclear palsy |
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Definition
1. sporadic disease aka atypical PD
2. onset 40-60 yrs, more common in men
3. wide-eyed vacant stare with a vertical gaze palsy (can't look up)
4. rigid, weak, spastic
5. dysarthria, dysphagia
6. dementia
7. progressive, fatal in 5 yrs |
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Term
| pathology of Progressive supranuclear palsy |
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Definition
1. widespread loss of neurons in the cerebral cortex, globus pallidus, substantia nigra, colliculi, periaqueductal grey, and brainstem nuclei
2. Neurofibrillary tangles in neurons and glia - huge and round
3. globose NFTs found on silver stain and tau stain - large and bulbous |
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Term
| genetics of Huntington's disease |
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Definition
1. autosomal dominant
2. chromosome 4
3. gene product is huntingtin (polyglutamate region)- increased CAG repeats (trinucleotide repeats)
4. increased glutamine segments causes abnormally shaped protein that is dysfunctional
5. normal protein prevents apoptosis of neurons (mutation = accelerated death) |
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Term
| clinical features of Huntington's Disease |
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Definition
1. age of onset 30-50 yrs
2. choreiform movements
3. personality changes
4. dementia late stages
5. 15 yrs survival after diagnosis |
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Term
| pathologic features of Huntington's Disease |
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Definition
1. atrophy of caudate nucleus and putamen as well as cortex
2. atrophy of small GABA-ergic neurons
3. Huntingtin inclusions - intranuclear inclusions within neurons that contain the mutant protein - not seen with H&E, need immunostain |
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Term
| clinical features of Friedreich's ataxia |
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Definition
1. onset in older children and young adults
2. staggering ataxic gait
3. dysarthria, nystagmus
4. decreased vibratory sensation and proprioception
5. Babinski responses and weakness
6. increased incidence of diabetes (30% of pts)
7. 15 yr survival after diagnosis |
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Term
| genetics of Friedreich's ataxia |
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Definition
1. possibly due to impaired Mt function
2. Chromosome 9
3. gene product is frataxin - increased GAA repeats
4. regulation of protein synthesis is altered and there is a shortage of frataxin
5. normal protein located on inner Membrane, maintenance of Mt genome |
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Term
| pathologic features of Friedreich's ataxia |
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Definition
1. cerebellar cortical atrophy
2. damage to posterior and lateral columns
3. cardiomyopathy, myocarditis giving rise to CHF and arrhythmias |
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Term
| Spinocerebellar degenerations |
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Definition
1. several types
2. autosomal dominant
3. usually caused by increased CAG repeats (polyglutamate regions) |
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Term
| genetics of Amyotrophic Lateral Sclerosis |
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Definition
1. 90% idiopathic
2. familial cases have dominant inheritance - juvenile onset
3. Super Oxide Dismutase (SOD) disease locus on chromosome 21 - neruons killed by free radicals normally eliminated by SOD |
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Term
| pathogenesis of sporadic ALS |
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Definition
1. intracytoplasmic inclusions of TDP-42 (DNA binding protein)
2. TDP-43 normally prevents apoptosis |
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Term
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Definition
1. onset age 30-60 yrs
2. UMN/LMN disease
3. muscular weakness, begins distally - facial muscles spared
4. atrophy and fasciculations
5. hyperactive reflexes
6. Babinski responses
7. progressive course with 3-5 year survival |
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Term
| pathologic features of ALS |
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Definition
1. small atrophic anterior roots
2. Wallerian degeneration of pyramidal tracts
3. loss of motor neurons with central chromatolysis
4. Bunina bodies in cytoplasm of motor nuerons - round, red, autophagic vacuoles - suggests accelerated neuron death |
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Term
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Definition
1. due to picornavirus
2. onset in older children adn young adults, when virus is neurotropic
3. acute paralysis: legs>arms, sometimes bulbar or respiratory muscles
4. most pts recover in 6 months |
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Term
| pathologic features of polio |
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Definition
neuronophagia, lymphocytic cuffing
old polio: loss of anterior horn cells and gliosis |
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