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Original Investigation
July 3, 2017

Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease

Author Affiliations
  • 1Commissariat à l’Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d’Imagerie Biomédicale, MIRCen, Fontenay-aux-Roses, France
  • 2Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, Université Paris-Saclay, UMR 9199, Neurodegenerative Diseases Laboratory, Fontenay-aux-Roses, France
  • 3Department of Nuclear Medicine, CHU Tenon Hospital, Paris, France
  • 4ToNIC, Toulouse NeuroImaging Centre, Université de Toulouse, INSERM, UPS, Toulouse, France
  • 5Department of Nuclear Medicine, CHU Toulouse, Purpan University Hospital, Toulouse, France
  • 6Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
  • 7Centre National de Référence des Maladies Neurodégénératives Service de Neurologie and UMR CNRS 6214 INSERM U1083, CHU d’Angers, Angers, France
  • 8Neurology Department, CHU Amiens, Amiens, France
  • 9Neurology Department, CHRU de Nantes, Nantes, France
  • 10Université Pierre et Marie Curie, Paris, France
  • 11INSERM U955, Equipe 01, Neuropsychologie Interventionnelle, Créteil, France
  • 12NeurATRIS, Fontenay-aux-Roses, France
  • 13AP-HP, Hôpital Henri Mondor, Centre de Référence-Maladie de Huntington, Service de Neurologie, Créteil, France
  • 14Faculté de Médecine, Université Paris Est-Créteil, Créteil, France
  • 15Equipe Neuropsychologie Interventionnelle, Département d’Études Cognitives, École Normale Supérieure, PSL Research University, INSERM, Paris, France
  • 16Centre Expert Parkinson, CHU Henri Mondor, Créteil, France.
JAMA Neurol. Published online July 3, 2017. doi:10.1001/jamaneurol.2017.1200
Key Points

Question  What is the meaning of cerebral hypermetabolism in Huntington disease?

Findings  This cross-sectional study found that in 60 patients with early Huntington disease, less severe bradykinesia and rigidity were associated with hypermetabolism in the cuneus, lingual gyrus, and crus I/II of the cerebellum. Conversely, hypermetabolism in the inferior parietal and temporal lobules, anterior cingulate, dentate nucleus, and motor regions of the cerebellum was associated with more severe hyperkinetic symptoms (eg, dystonia and chorea).

Meaning  Brain regional hypermetabolism in early Huntington disease can either have a compensatory role or presumably reflect synaptic hyperactivity contributing to motor symptoms, although both roles could be found in the cerebellar associative or motor regions.


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 Participants  This 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 Relevance  Striatal 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.