In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7 |
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| Authors: | Isaac M. Adanyeguh MS Pierre‐Gilles Henry PhD Tra M. Nguyen MS Daisy Rinaldi PhD Celine Jauffret MS Romain Valabregue PhD Uzay E. Emir PhD Dinesh K. Deelchand PhD Alexis Brice MD PhD Lynn E. Eberly PhD Gülin Öz PhD Alexandra Durr MD PhD Fanny Mochel MD PhD |
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| Affiliation: | 1. INSERM U 1127, Sorbonne Universités, UPMC Univ Paris Institut du Cerveau et de la Moelle épinière, ICM, Paris, France;2. Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States;3. Center for NeuroImaging Research, Institut du Cerveau et de la Moelle épinière, Paris, France;4. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA;5. Assistance Publique‐H?pitaux de Paris, Fédération de Génétique, La Pitié‐Salpêtrière University Hospital, Paris, France |
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| Abstract: | Spinocerebellar ataxias (SCAs) belong to polyglutamine repeat disorders and are characterized by a predominant atrophy of the cerebellum and the pons. Proton magnetic resonance spectroscopy (1H MRS) using an optimized semiadiabatic localization by adiabatic selective refocusing (semi‐LASER) protocol was performed at 3 T to determine metabolite concentrations in the cerebellar vermis and pons of a cohort of patients with SCA1 (n = 16), SCA2 (n = 12), SCA3 (n = 21), and SCA7 (n = 12) and healthy controls (n = 33). Compared with controls, patients displayed lower total N‐acetylaspartate and, to a lesser extent, lower glutamate, reflecting neuronal loss/dysfunction, whereas the glial marker, myoinositol (myo‐Ins), was elevated. Patients also showed higher total creatine as reported in Huntington's disease, another polyglutamine repeat disorder. A strong correlation was found between the Scale for the Assessment and Rating of Ataxia and the neurometabolites in both affected regions of patients. Principal component analyses confirmed that neuronal metabolites (total N‐acetylaspartate and glutamate) were inversely correlated in the vermis and the pons to glial (myo‐Ins) and energetic (total creatine) metabolites, as well as to disease severity (motor scales). Neurochemical plots with selected metabolites also allowed the separation of SCA2 and SCA3 from controls. The neurometabolic profiles detected in patients underlie cell‐specific changes in neuronal and astrocytic compartments that cannot be assessed by other neuroimaging modalities. The inverse correlation between metabolites from these two compartments suggests a metabolic attempt to compensate for neuronal damage in SCAs. Because these biomarkers reflect dynamic aspects of cellular metabolism, they are good candidates for proof‐of‐concept therapeutic trials. © 2015 International Parkinson and Movement Disorder Society |
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| Keywords: | spinocerebellar ataxia biomarker movement disorders NMR spectroscopy neurochemical profile |
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