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Evaluation of corticospinal tracts in ALS with diffusion tensor MRI and brainstem stimulation

From the Department of Neurology, Division of Neuroscience (N.K.I., S.O., N.A., Y.T., S.K., I.K., S.T., Y.U.), and Department of Radiology and Bioengineering (S.A., O.A.), Graduate School of Medicine, University of Tokyo; National Institute of Neuroscience (I.K.), National Center of Neurology and Psychiatry, Tokyo, Japan; and Human Motor Control Section (N.K.I.), Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

Address correspondence and reprint requests to Dr. Nobue K. Iwata, Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N226, 10 Center Drive, Bethesda, MD 20892-1428 iwatan{at}ninds.nih.gov

Objective: To assess corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS) by correlating diffusion tensor imaging (DTI) measures with intra- and extracranial central motor conduction time (CMCT) and clinical features of the patients.

Methods: We investigated 31 patients with ALS and 31 normal volunteers by DTI and measured fractional anisotropy (FA) within the corticospinal tracts and in the extramotor white matter. We measured CMCT for the first dorsal interosseous muscle and segmented it into cortical-brainstem (CTX-BS CT) and brainstem-cervical root (BS-CV CT) conduction times by magnetic brainstem stimulation at the foramen magnum level. Clinical status of each patient was evaluated with the ALS Functional Rating Scale–Revised (ALSFRS-R) and upper motor neuron (UMN) score devised for this study.

Results: We found a significant decrease of mean FA in all regions of the corticospinal tracts in patients with ALS as compared with controls. We found that FA along the corticospinal tract decreased significantly with higher UMN scores. There was no significant correlation between FA and ALSFRS-R, to which both upper and lower motoneuron involvements contribute. FA showed a significant correlation with the intracranial part of the central motor conduction (CTX-BS CT) but not with the extracranial conduction time.

Conclusions: Fractional anisotropy reflects functional abnormality of intracranial corticospinal tracts and can be used for objective evaluation of upper motor neuron impairment in amyotrophic lateral sclerosis.

GLOSSARY: ALS = amyotrophic lateral sclerosis; ALSFRS-R = ALS Functional Rating Scale–Revised; BS-CV CT = brainstem-cervical root conduction time; CMCT = central motor conduction time; CTX-BS CT = cortical-brainstem conduction time; FA = fractional anisotropy; FDI = first dorsal interosseous; LMN = lower motor neuron; ROI = region of interest; UMN = upper motor neuron.

Supported by Research Project Grant-in-Aid for Scientific Research 16500194 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; Research Grant 15B-2 for Nervous and Mental Disorders from the Ministry of Health, Labor, and Welfare of Japan; a grant from the Committee of the Study of Human Exposure to EMF; the Ministry of Internal Affairs and Communications; grants from the Life Science Foundation of Japan and the Association of Radio-industry and Business; and the Nakabayashi Trust for ALS Research.

Disclosure: The authors report no conflicts of interest.

Received September 21, 2005. Accepted in final form August 8, 2007.

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