The striatum is a well-known region affected in Huntington disease (HD). However, other regions, including the visual cortex, are implicated. We have identified previously an abnormal energy response in the visual cortex of patients at an early stage of HD using 31P magnetic resonance spectroscopy (31P MRS). We therefore sought to further characterize these metabolic alterations with 1H MRS using a well-validated semi-localized by adiabatic selective refocusing (semi-LASER) sequence that allows the measurement of an expanded number of neurometabolites. Ten early affected patients [Unified Huntington Disease Rating Scale (UHDRS), total motor score = 13.6 ± 10.8] and 10 healthy volunteers of similar age and body mass index (BMI) were recruited for the study. We performed 1H MRS in the striatum – the region that is primarily affected in HD – and the visual cortex. The protocol allowed a reliable quantification of 10 metabolites in the visual cortex and eight in the striatum, compared with three to five metabolites in previous 1H MRS studies performed in HD. We identified higher total creatine (p < 0.05) in the visual cortex and lower glutamate (p < 0.001) and total creatine (p < 0.05) in the striatum of patients with HD compared with controls. Less abundant neurometabolites [glutamine, γ-aminobutyric acid (GABA), glutathione, aspartate] showed similar concentrations in both groups. The protocol allowed the measurement of several additional metabolites compared with standard vendor protocols. Our study points to early changes in metabolites involved in energy metabolism in the visual cortex and striatum of patients with HD. Decreased striatal glutamate could reflect early neuronal dysfunction or impaired glutamatergic neurotransmission.
Bibliographical noteFunding Information:
I.M.A., M.‐L.M. and D.R. have no conflicts of interest to disclose. L.F. received grant support from the National Multiple Sclerosis Society. A.D. received grant support from the French Agency for Research, Fondation pour la recherche médicale (FRM) and Pfizer Inc. S.L. received grants from Agence Nationale de la Recherche (ANRMNP 2009, Nucleipark), DHOS‐Inserm (2010, Nucleipark), France Parkinson (2008) and Ecole Neuroscience de Paris, ‘Investissements d'avenir’ (grant numbers ANR‐10‐IAIHU‐06 and ANR‐11‐INBS‐0006) during the course of the study. Outside of this study, he received commercial research support from Servier and Pfizer, funding for travel from Siemens and General Electric, and honoraria from Pileje, Lundbeck and Roche. P.‐G.H. received grant support from the National Institutes of Health (NIH) (P41 EB015894, P30 NS076408), Friedreich's Ataxia Research Alliance and the CureFA Foundation. F.M. received grant support from INSERM, Carnot Institutes, ASL Foundation and Ultragenyx Pharmaceutical.
The authors wish to thank warmly the patients and volunteers who participated in this study. The authors are also grateful to collaborators from the Center for Neuroimaging Research, France, and the Center for Magnetic Resonance Research, USA. This study was funded by National Institutes of Health (NIH) grants (P41EB015894 and P30NS076408) and the Ecole des Neurosciences de Paris. The study also received funding from Ipsen (NCT01696708) and the program ?Investissements d'avenir? ANR-10-IAIHU-06 and ANR-11-INBS-0006.
This study was funded by National Institutes of Health (NIH) grants (P41EB015894 and P30NS076408) and the Ecole des Neurosciences de Paris. The study also received funding from Ipsen (NCT01696708) and the program ‘Investissements d'avenir’ ANR‐10‐IAIHU‐06 and ANR‐11‐ INBS‐0006.
Copyright © 2018 John Wiley & Sons, Ltd.
- H MRS
- Huntington disease
- movement disorders
- neurochemical profile