Huntington disease pathology — MRCPsych Paper A MCQ

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ModerateNeuropathologyHuntington disease pathologyMRCPsych Paper A

A 41-year-old man has a 5-year history of progressive choreiform movements, irritability and executive decline. His father developed a similar illness in his 40s. MRI shows bilateral caudate atrophy. Which neuropathological finding is most characteristic?

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Correct answer: C — Preferential loss of striatal medium spiny GABAergic neurons

The correct answer is C. The progressive combination of chorea, behavioural change, cognitive decline, autosomal dominant family history and caudate atrophy indicates Huntington disease. Its characteristic pathology is preferential degeneration of medium spiny GABAergic projection neurons in the striatum, particularly the caudate and putamen, caused by toxic effects of mutant huntingtin. Cortical Lewy bodies are associated with dementia with Lewy bodies and Parkinson disease. Peripheral demyelination is not the substrate of this central neurodegenerative syndrome. Cerebral amyloid angiopathy involves beta-amyloid deposition in vessel walls and does not explain selective caudate atrophy. Prion disease produces spongiform change and usually causes a much more rapidly progressive neurological deterioration.

Reference: Jiang A, Handley RR, Lehnert K, Snell RG. From Pathogenesis to Therapeutics: A Review of 150 Years of Huntington's Disease Research. Abstract and neuropathology overview. International Journal of Molecular Sciences. 2023;24(16):13021. https://pubmed.ncbi.nlm.nih.gov/37629202/