13: HD Clinical

Question 1

HD motor dysfunction examples

Answer 1

motor impersistence (can’t maintain sustained muscular contraction). eye movement abnormalities. dystonia, parkinsonism. incoordination, unsteadiness, immobility, dysarthria, dysphagia

Question 2

HD: pathology - 3 main things? degree of pathology related to?

Answer 2

striatal atrophy. neuronal loss + gliosis. diffuse cortical changes, primarily frontal. degree of pathology realted to duration of symptomatic HD

Question 3

selective neuronal loss in HD?

Answer 3

striatal PROJECTIOn neurons affected aka medium spiny neurons that are GABAergic. ones projecting to GPe and SN are most vulnerable while those to GPi degenerate more gradually. interneurons spared

Question 4

experimental HD treatment?

Answer 4

ACR16 - DA modulating drug

Question 5

goal in HD treatment

Answer 5

delay/prevent onset of symptomatic HD in the asymptomatic individual

Question 6

2 animal models

Answer 6

intrastriatal kainic acid or quinolic acid

Question 7

excitotoxic hypothesis?

Answer 7

intrastriatal injection of excitotoxic amino acids mimics characteristic pathology of HD; toxicity can be prevented by NMDA antagonists BUT acute striatal lesion unlike slow cell loss associated with NDDs.

Question 8

2 NPA

Answer 8

inhibits mitochondrial succinate dehydrogenase, blocked by NMDA-antagonists. associated with striatal pathology similar to HD

Question 9

HD: impaired mito. energy metabolism = ?

Answer 9

increased neuronal sensitivity to endogenous glutamate = excitotoxicity and loss of neurons