Reduced Cerebral Glucose Metabolism in Asymptomatic Subjects at Risk for Huntington's Disease

Abstract

Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder.

How reliable is 18FDG PET for predicting the onset of Huntington’s disease?

“…This study showed significant hypometabolism in the caudate nucleus of gene mutation carriers as compared with mutation-negative subjects [9]. These first discoveries were followed by several years of relevant scientific research activity on HD which confirmed the preliminary reports and showed a significant relationship between striatal and cortical hypometabolism and motor impairment progression and cognitive changes [10][11][12]. Hayden et al found significant caudate nucleus hypometabolism in a cohort of mutation-positive subjects with no signs of cortical or striatal atrophy [13], and later Ciarmiello et al found that striatal hypometabolism is significantly correlated with the estimated age at onset [14].…”

Imaging in cell-based therapy for neurodegenerative diseases

“…These initial observations were confirmed by a number of other studies where alterations in striatal glucose metabolism were seen in early or presymptomatic HD patients [97,98]. However, a decrease in striatal glucose consumption in at-risk patients was not always observed [99]. Moreover, it is worth noting that for several reasons mainly associated with ethical considerations, such studies may be confounded by the fact that the patients may have to take medications that most of the time compete competitively with the radiotracer used (for a review, see [100]).…”

The Use of Technetium-99m-HM-PAO in the Assessment of Patients with Dementia and other Neuropsychiatric Conditions

“…While this patient, who is "at risk" of developing Huntington's disease, cannot strictly be considered to be pre symptomatic be cause she exhibits some affective symptoms, it is of A 8 interest to note that she shows similar appearance to that seen in established Huntington's disease. It is likely that HM-PAO is able to demonstrate pre symptomatic involvement of the caudate nucleus before any structural change is evident with X-ray CT or MRI, in a similar way that PET scanning using fluorodeoxyglucose has been shown to (Mazziotta et al, 1987).…”