title: In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7.
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 ((1) H 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.
authors.affiliation: INSERM U 1127, Sorbonne Universités, UPMC Univ Paris Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Adanyeguh
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Henry
authors.forename: Tra M
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Daisy
authors.initials: D
authors.lastname: Rinaldi
authors.forename: Celine
authors.initials: C
authors.lastname: Jauffret
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.forename: Uzay E
authors.initials: UE
authors.lastname: Emir
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Deelchand
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000067528:Ataxins / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D017827:Machado-Joseph Disease; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D011522:Protons; D020754:Spinocerebellar Ataxias / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D000067528:Ataxins; D011522:Protons; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: NMR spectroscopy; biomarker; movement disorders; neurochemical profile; spinocerebellar ataxia