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Distinct Neurochemical Profiles of Spinocerebellar Ataxias 1, 2, 6, and Cerebellar Multiple System Atrophy

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Abstract

Hereditary and sporadic neurodegenerative ataxias are movement disorders that affect the cerebellum. Robust and objective biomarkers are critical for treatment trials of ataxias. In addition, such biomarkers may help discriminate between ataxia subtypes because these diseases display substantial overlap in clinical presentation and conventional MRI. Profiles of 10–13 neurochemical concentrations obtained in vivo by high field proton magnetic resonance spectroscopy (1H MRS) can potentially provide ataxia-type specific biomarkers. We compared cerebellar and brainstem neurochemical profiles measured at 4 T from 26 patients with spinocerebellar ataxias (SCA1, N = 9; SCA2, N = 7; SCA6, N = 5) or cerebellar multiple system atrophy (MSA-C, N = 5) and 15 age-matched healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA) was used to assess disease severity. The patterns of neurochemical alterations relative to controls differed between ataxia types. Myo-inositol levels in the vermis, myo-inositol, total N-acetylaspartate, total creatine, glutamate, glutamine in the cerebellar hemispheres and myo-inositol, total N-acetylaspartate, glutamate in the pons were significantly different between patient groups (Bonferroni corrected p < 0.05). The best MRS predictors were selected by a tree classification procedure and lead to 89% accurate classification of all subjects while the SARA scores overlapped considerably between patient groups. Therefore, this study demonstrated multiple neurochemical alterations in SCAs and MSA-C relative to controls and the potential for these neurochemical levels to differentiate ataxia types. Studies with higher numbers of patients and other ataxias are warranted to further investigate the clinical utility of neurochemical levels as measured by high-field MRS as ataxia biomarkers.

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Acknowledgements

This work was supported by the National Institute of Neurological Disorders and Stroke grant R21 NS056172 (GÖ) and Jay D. Schlueter Ataxia Research Fund. The 4-T TEM coil was built with a grant (3761-9236-07) from the Minnesota Medical Foundation (GÖ). The Center for MR Research is supported by National Center for Research Resources (NCRR) biotechnology research resource grant P41RR008079 and Neuroscience Center Core Blueprint Award P30 NS057091. The General Clinical Research Center is supported by NCRR grant M01RR00400. We thank the staff of the Center for MR Research for maintaining and supporting the NMR system.

Conflict of Interest

The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Center for MR Research, Department of Radiology, Medical School, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA

    Gülin Öz, Isabelle Iltis & Diane Hutter

  2. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    William Thomas

  3. University of Minnesota Ataxia Center, Department of Neurology, University of Minnesota, Minneapolis, MN, USA

    Khalaf O. Bushara

  4. Department of Neurology, University of Chicago, Chicago, IL, USA

    Christopher M. Gomez

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  1. Gülin Öz
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Correspondence to Gülin Öz.

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Öz, G., Iltis, I., Hutter, D. et al. Distinct Neurochemical Profiles of Spinocerebellar Ataxias 1, 2, 6, and Cerebellar Multiple System Atrophy. Cerebellum 10, 208–217 (2011). https://doi.org/10.1007/s12311-010-0213-6

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