Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease

Abstract

IMPORTANCE Brain hypometabolism is associated with the clinical consequences of the degenerative process, but little is known about regional hypermetabolism, sometimes observed in the brain of patients with clinically manifest Huntington disease (HD). Studying the role of regional hypermetabolism is needed to better understand its interaction with the motor symptoms of the disease.OBJECTIVE To investigate the association between brain hypometabolism and hypermetabolism with motor scores of patients with early HD. DESIGN, SETTING, AND PARTICIPANTSThis study started in 2001, and analysis was completed in 2016. Sixty symptomatic patients with HD and 15 healthy age-matched control individuals underwent positron emission tomography to measure cerebral metabolism in this cross-sectional study. They also underwent the Unified Huntington's Disease Rating Scale motor test, and 2 subscores were extracted: (1) a hyperkinetic score, combining dystonia and chorea, and (2) a hypokinetic score, combining bradykinesia and rigidity.MAIN OUTCOMES AND MEASURES Statistical parametric mapping software (SPM5) was used to identify all hypo-and hypermetabolic regions in patients with HD relative to control individuals. Correlation analyses (P < .001, uncorrected) between motor subscores and brain metabolic values were performed for regions with significant hypometabolism and hypermetabolism.RESULTS Among 60 patients with HD, 22 were women (36.7%), and the mean (SD) age was 44.6 (7.6) years. Of the 15 control individuals, 7 were women (46.7%), and the mean (SD) age was 42.2 (7.3) years. In statistical parametric mapping, striatal hypometabolism was significantly correlated with the severity of all motor scores. Hypermetabolism was negatively correlated only with hypokinetic scores in the cuneus (z score = 3.95, P < .001), the lingual gyrus (z score = 4.31, P < .001), and the crus I/II of the cerebellum (z score = 3.77, P < .001), a region connected to associative cortical areas. More severe motor scores were associated with higher metabolic values in the inferior parietal lobule, anterior cingulate, inferior temporal lobule, the dentate nucleus, and the cerebellar lobules IV/V, VI, and VIII bilaterally corresponding to the motor regions of the cerebellum (z score = 3.96 and 3.42 in right and left sides, respectively; P < .001). CONCLUSIONS AND RELEVANCEStriatal hypometabolism is associated with clinical disease severity. Conversely, hypermetabolism is likely compensatory in regions where it is associated with decreasing motor scores. Hypermetabolism might be detrimental in other structures in which it is associated with more severe motor symptoms. In the cerebellum, both compensatory and detrimental contributions seem to occur. This study helps to better understand the motor clinical relevance of hypermetabolic brain regions in HD.

Brain structure in juvenile-onset Huntington disease

“…In fact, a recent study looking at PET imaging in AOHD found that the cerebellum seemed to be playing both pathologic and compensatory roles at the same time. 28…”

The Neurodevelopmental Hypothesis of Huntington’s Disease

“…While somewhat overlooked in the past, the cerebellum has recently been described as both potentially pathologic, as well as compensatory in HD [49][50][51]. The cerebellum is often regarded as being 'spared' from neurodegeneration caused by HD.…”

The visual cortex and visual cognition in Huntington’s disease: An overview of current literature

“…45,46 A recent study reports similar findings of striatal hypometabolism in combination with hypermetabolism in the cerebellum, thalamus, and occipital cortex. 47 Here, hypermetabolism in the cuneus and lingual gyrus was negatively correlated with hypokinetic motor scores. These findings suggest that a decrease in glucose metabolism might be linked to clinical disease onset, whereas an increase in glucose metabolism indicates a compensatory mechanism for neuronal loss and/or motor disturbances.…”

“…These findings suggest that a decrease in glucose metabolism might be linked to clinical disease onset, whereas an increase in glucose metabolism indicates a compensatory mechanism for neuronal loss and/or motor disturbances. 46,47 As neuronal loss is indirectly measured using functional MRI, the reduced brain activity in the occipital cortex of HD patients found in previous fMRI studies might indeed explain the hypermetabolism found in these PET studies.…”