A Case of "Prodromal" Huntington's Disease with Neuropathology (P5.296)

OBJECTIVE: To present the first case of neuropathologically confirmed “prodromal” Huntington’s disease (HD). BACKGROUND: HD is neurodegenerative disorder inherited in an autosomal dominant manner. The current diagnostic criteria based exclusively on motor signs have been questioned recently by Reilmann et al., who proposed new criteria that incorporate historical information including behavioral and cognitive changes, and drew a distinction between presymptomatic and prodromal cases. Perhaps biased by current definitions, clinicopathologic studies to date have examined either asymptomatic (presymptomatic) HD or manifest HD of several years duration, of which relatively few have grade 1 neuropathology (16 cases in total; Gomez-Tortosa et al, Myers et al, Pillai et al), but to our knowledge, no cases of “prodromal” HD have been published with neuropathology. DESIGN/METHODS: The patient was a brain donor to the New York Brain Bank at Columbia University. History was obtained post-mortem through family members. Neuropathologic grade was assigned according to the Vonsattel HD grading scale. RESULTS: A 29-year old male with a maternal history of HD presented to autopsy after suffering lethal gunshot wounds in an altercation. Two weeks prior to death a family member familiar with HD noted an unsteady gait, dropping of objects, and apathy. The patient had become unemployed several months prior. He was not aware of deficits, did not present to a neurologist, and was not tested for CAG-repeat length. Neuropathology revealed grade 1 HD. The head and body of the caudate nucleus were atrophic; there was mild atrophy in the putamen and external segment of the globus pallidus. CONCLUSIONS: 1) Brain donation pre-plans are essential to capturing unexpected deaths associated with early HD. 2) The clinical course presented here is consistent with our current understanding of HD, and supports the use of a “prodromal” diagnostic category 3) Prodromal HD may correlate with grade 1 disease neuropathologically. Disclosure: Dr. Robakis has nothing to disclose. Dr. Vonsattel has nothing to disclose. Dr. Marder has received personal compensation in an editorial capacity for Current Neuroscience.