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.
Polyglutamine diseases: emerging concepts in pathogenesis and therapy
Shao and Diamond
Hum Mol Genet 2007;16:R115-R123.
ABSTRACT
| FULL TEXT
Huntingtin-deficient zebrafish exhibit defects in iron utilization and development
Lumsden et al.
Hum Mol Genet 2007;16:1905-1920.
ABSTRACT
| FULL TEXT
Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study
Kipps et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:650-655.
ABSTRACT
| FULL TEXT
Onset and rate of striatal atrophy in preclinical Huntington disease
Aylward et al.
Neurology 2004;63:66-72.
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| FULL TEXT
Striatal neural grafting improves cortical metabolism in Huntington's disease patients
Gaura et al.
Brain 2004;127:65-72.
ABSTRACT
| FULL TEXT
Expression of Full-length Polyglutamine-expanded Huntingtin Disrupts Growth Factor Receptor Signaling in Rat Pheochromocytoma (PC12) Cells
Song et al.
J. Biol. Chem. 2002;277:6703-6707.
ABSTRACT
| FULL TEXT
Clinical markers of early disease in persons near onset of Huntington's disease
Paulsen et al.
Neurology 2001;57:658-662.
ABSTRACT
| FULL TEXT
Huntington's disease progression: PET and clinical observations
Andrews et al.
Brain 1999;122:2353-2363.
ABSTRACT
| FULL TEXT
Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease
Harris et al.
Brain 1999;122:1667-1678.
ABSTRACT
| FULL TEXT
Clinical correlation of striatal 1H MRS changes in Huntington's disease
Sanchez-Pernaute et al.
Neurology 1999;53:806-806.
ABSTRACT
| FULL TEXT
Influence of lamotrigine on progression of early Huntington disease: A randomized clinical trial
Kremer et al.
Neurology 1999;53:1000-1000.
ABSTRACT
| FULL TEXT
Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the {epsilon}4 Allele for Apolipoprotein E
Reiman et al.
NEJM 1996;334:752-758.
ABSTRACT
| FULL TEXT
Protein:Protein Interactions in Alzheimer's Disease and the CAG Triplet Repeat Diseases
Strittmatter et al.
Cold Spring Harb Symp Quant Biol 1996;61:597-605.
ABSTRACT