NEUROLOGY
Degenerative Diseases
Alzheimer’s Disease
·
German
neurologist Alois Alzheimer described the case of his patient Auguste D, a
woman who developed dementia in her 50s and died in 1906.
·
An
estimated 25 million people worldwide have Alzheimer's disease.
·
Diagnosis:
Clinical. No comfirmatory tests exist.
·
Symptoms:
Memory loss, aphasia, apraxia.
·
Pathophysiology:
Decreased acetylcholine (Nucleus Basalis of Meynert), norepinephrine,
dopamine, & serotonin.
·
Apolipoprotein E4/E4 increases the number of plaques
of plaques, early onset.
·
Associated with Chromosome 21 (as in Down’s syndrome)
(also 14,19).
Pathology
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Cortical & hippocampal atrophy
·
Neurofibrillary
tangles: t protein. Neuritic plaques: bamyloid
protein. Both: cytoplasmic, silver
stained, paired helical filaments.
·
Granulovacular
degeneration: dark cytoplasmic granules w/clear halo in neurons.
·
No gliosis.
Treatment
·
Acetylcholinesterase inhibitors: donepezil, tacrine.
Slow progression.
·
Vitamin E
·
Selegiline: MAOI. Delays nursing home placement, but
not cognitive decline).
Huntington’s
Disease
·
Diagnosis: Chorea, demetia, family Hx.
·
Personality change occurs early, increased
blinking, abnormal eye movement.
·
Caudate/putamen atrophy > boxcar ventricles.
·
Genetics: AD, CAG repeat in protein huntingtin, chr
4.
·
dopamine,
NE, somatostatin (vs Alzheimers); ¯ GABA, Ach. L-dopa worsens.
·
Westphal variant: <20yo, more aggressive,
seizures, parkinsonism.
Subcortical
dementias
·
No aphasia, apraxia, or amnesia (memory OK). Seen in
Parkinsons & Huntingtons
Pick’s
disease
·
Frontal/
temporal atrophy
·
Path: Balloon
(“Picks”) cells (neurons, tau+). Neuron loss in cerebral cortex,
gliosis, cortical spongiosis.