Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease
S. T. Grafton, J. C. Mazziotta, J. J. Pahl, P. St George-Hyslop, J. L. Haines, J. Gusella, J. M. Hoffman, L. R. Baxter and M. E. Phelps
Department of Neurology, University of Southern California, School of Medicine, Los Angeles 90033-4606.
OBJECTIVE--To determine the rate of change of glucose metabolism and
caudate size in persons at risk for Huntington's disease. DESIGN--Eighteen
persons at risk for Huntington's disease had two positron emission
tomographic glucose metabolic studies and two magnetic resonance imaging
scans separated by 42 (+/- 9) months. SETTING--Ambulatory research subjects
at a teaching hospital with magnetic resonance imaging and positron
emission tomographic technology. SUBJECTS--Seven of the individuals were
Huntington' disease gene negative by testing at the polymorphic DNA loci
D4S10, D4S43, and D4S125; the remainder were gene positive by genetic
testing or onset of chorea after study entry. INTERVENTIONS--None. OUTCOME
MEASURES--Onset of chorea and imaging results. RESULTS--The gene-positive
group demonstrated a significant 3.1% loss of glucose metabolic rate per
year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48)
compared with the gene-negative group. There was a 3.6% per year increase
in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a
linear measure of caudate atrophy. The rate of change in caudate size did
not correlate with the rate of change in caudate metabolism, suggesting
that metabolic loss and atrophy may develop independently. CONCLUSIONS--The
results suggest that a reduction in caudate glucose metabolism and atrophy
develop rapidly in Huntington's disease. The findings establish a strategy
for using serial positron emission tomographic imaging to monitor
experimental pharmacologic interventions in presymptomatic individuals who
have developed caudate hypometabolism.
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