Head CT > Degenerative > Huntington's Disease > Pathophysiology

Huntington's Disease - Pathophysiology

Huntington's disease is one of many diseases resulting from an abnormal replication of a trinucleotide repeat. In the case of Huntington's disease, this trinucleotide repeat is found within the huntingtin gene located on chromosome 4. One postulated etiology of this disease is that the selective degeneration of medium sized spiny neurons of the striatum may be secondary to the expression of the huntingtin protein with its abnormally expanded trinucleotide repeats. These repeats may predispose the gene to undergo abnormal protein-protein interactions eliciting a novel, altered, or incomplete loss of protein function.

Given that the medium sized spiny neurons comprise roughly 90% of the striatal neurons, their loss severely disrupts critical interneuronal pathways to the globus pallidus and substantia nigra. Eventually corticostriatal pathways are affected as well, including pyramidal projection pathways to the frontal and parietal lobes.

Grossly these changes are initially manifested by striatal atrophy and reduction of cross-sectional area by 50-60%. Degeneration occurs most prominently in the caudate tail followed by the body, head, and eventually the putamen and nucleus accumbens. By the time the disease reaches its terminal phases, 20-30% of the total brain mass may be reduced.