Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.
OBJECTIVE
To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease.


METHODS
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.


METHODS
Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology.


METHODS
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.


METHODS
None.


METHODS
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.
Grafton
S T
ST
Department of Neurology, University of Southern California, School of Medicine, Los Angeles 90033-4606.
Mazziotta
J C
JC
Pahl
J J
JJ
St George-Hyslop
P
P
Haines
J L
JL
Gusella
J
J
Hoffman
J M
JM
Baxter
L R
LR
Phelps
M E
ME
D000328:Adult; D002421:Caudate Nucleus / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D005819:Genetic Markers; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014055:Tomography, Emission-Computed
D005819:Genetic Markers; D005947:Glucose