H-1-NMR SPECTROSCOPY STUDIES OF HUNTINGTONS-DISEASE - CORRELATIONS WITH CAG REPEAT NUMBERS

Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progr essive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized H-1 spectroscopy. We h ave now extended these studies to show an almost threefold elevation i n occipital cortex lactate in 31 KD patients as compared with 17 norma l control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in co rtical regions, but three in eight showed elevated lactate in the stri atum. Similar to recently reported increases in task-related activatio n of the striatum in the dominant hemisphere, we found that striatal l actate levels in HD patients were markedly asymmetric (higher on the l eft side). Markers of neuronal degeneration, decreased N-acetylasparta te (NAA)/creatine and increased choline/creatine levels, were symmetri c. Both decreased NAA and increased lactate in the striatum significan tly correlated with duration of symptoms. When divided by his or her a ge, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with corre lation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat len gth. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD th at may extend to presymptomatic subjects.