Module 7: CNS: Alzheimer's, Park, Hunt, ALS, MS, Wernicke Flashcards
First starting off this card deck will be Alzheimer’s disease, what is the etiology?
Elderly ppl
Down syndrome b/c APP is on Chr.21
80% sporadic
20% familial
Describe early vs late onset AD
Early:
APP (Ch.21), Presenilllin (Ch1 and 14), Clusterin (Ch.8) & Complement receptor (Ch1)
Late:
Apo E genotype (Ch19) and E4 increases risk of AD and E2 decreases risk
What is the pathogenesis for Alzheimer’s Disease?
Defective cleavage of transmembrane cellular proteins – atrophy of frontal, parietal and temporal lobes
–Occipital lobe is spared
Where does Alzheimer’s Disease begin?
Starts in temporal lobe aka hippocampus (which is why you have memory loss initially) the eventually generalized paralysis due to parietal lobe involvement
What is the presentation for Alzheimer’s Disease?
Slowly progressive dementia (impaired cognition) but motor and sensory systems are intact
again starts in temporal (memory loss) then paralysis and bed ridden (parietal and frontal)
For Alzheimer’s Disease, the dx is made on autopsy, what is seen?
Dx of exclusion (like rabies)
- Neurofibrillary tangles (TAU proteins): intracellular and hyperphosphorlyated
- Beta Amyloid Plaques, Abeta or Beta2: Extracellular, amyloid on H&E, localized (salmon pink on Congo red and apple green under polarized light)
What is seen on CT and histology and gross is Alzheimers patients?
CT: flattening of sulci and gyri with enlarged ventricles
Histology: neurofibrillary tangles + astrocyte proliferation
Gross: widening of cerebral sulci and narrowing of gyri
What complications are associated with Alzheimer’s Disease?
Hydrocephalus Ex Vaco: due to atrophy of the brain
Most common cause of death = Aspiration pneumonia (bed ridden, trouble swallowing and lung abscesses)
Bed Sores/Pressure Ulcers and DVTs – PE
Cerebral Amyloid Angiopathy: lobar hemorrhages (following a fall)
–deposition of amlyoid (homogeneous eosinophilic material) in the walls of cerebral vessels
The next topic will be Parkinson’s Disease, what is the etiology?
Several fold increase in incidence of Alzheimers disease
Etiology:
–usually no family history: most cases are sporadic
–mutation in the synuclein gene (synuclein is component of Lewy Bodies)
-non degenerative causes = medication and cocaine abuse
What is the pathogenesis for parkinsons disease?
Atrophy of substantia nigra (nucleus of dopaminergic neurons in the midbrain) and presence of Lewy Bodies
What is the pathogenesis for Parkinson’s disease?
Tremor, Rigidity, Akinesia and Shuffling Gait
Next is Huntington’s Disease, what is the etiology?
CAG repeats with genetic anticipation (Earlier onset in successive generations) – gain of function mutation that interferes with nucleic acid or protein regulations
–AD = male and females equal
What is the pathogenesis for Huntington’s Disease?
Marked atrophy of caudate and putamen
Lesser atrophy of globus pallidus and cerebral cortex
What is the presentation for Huntington’s Disease?
Choreiform movements
Motor Difficulties
Dementia
Next is ALS/Lou Gehrig’s/Motor Neuron Disease, what is the etiology?
Affects middle aged
Identified mutations:
–Ch.9 hexanucleotide repeat and SOD-1
Does not affect peripheral nerves (schwann cells)