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February 02, 2016; 86 (5) Article

Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis

Tina Roostaei, Shokufeh Sadaghiani, Min Tae M. Park, Rahil Mashhadi, Aria Nazeri, Sina Noshad, Mohammad Javad Salehi, Maryam Naghibzadeh, Abdorreza Naser Moghadasi, Mahsa Owji, Rozita Doosti, Amir Pejman Hashemi Taheri, Ali Shakouri Rad, Amirreza Azimi, M. Mallar Chakravarty, Aristotle N. Voineskos, Arash Nazeri and Mohammad Ali Sahraian
First published January 6, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002326
Tina Roostaei
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Shokufeh Sadaghiani
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Min Tae M. Park
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Rahil Mashhadi
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Aria Nazeri
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Sina Noshad
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Mohammad Javad Salehi
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Maryam Naghibzadeh
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Abdorreza Naser Moghadasi
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Mahsa Owji
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Rozita Doosti
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Amir Pejman Hashemi Taheri
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Ali Shakouri Rad
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Amirreza Azimi
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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M. Mallar Chakravarty
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Aristotle N. Voineskos
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Arash Nazeri
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Mohammad Ali Sahraian
From the MS Research Center, Neuroscience Institute (T.R., S.S., Aria Nazeri, S.N., M.N., A.N.M., M.O., R.D., A.A., Arash Nazeri, M.A.S.), Interdisciplinary Neuroscience Research Program (T.R., S.S., M.N., Arash Nazeri), Urology Research Center (R.M.), Department of Neurology (A.N.M., M.A.S.), and Department of Radiology (A.P.H.T., A.S.R.), Tehran University of Medical Sciences, Iran; Kimel Family Translational Imaging-Genetics Laboratory (T.R., A.N.V., Arash Nazeri), Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto; Department of Psychiatry (T.R., A.N.V., Arash Nazeri), University of Toronto; Cerebral Imaging Centre (M.T.M.P., M.M.C.), Douglas Mental Health Institute, Verdun; Schulich School of Medicine and Dentistry (M.T.M.P.), Western University, London, Canada; Department of Electrical Engineering (M.J.S.), Sharif University of Technology, Tehran, Iran; Department of Neurology (A.A.), Thomas Jefferson University, Philadelphia, PA; and Departments of Psychiatry and Biomedical Engineering (M.M.C.), McGill University, Montreal, Canada.
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Citation
Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis
Tina Roostaei, Shokufeh Sadaghiani, Min Tae M. Park, Rahil Mashhadi, Aria Nazeri, Sina Noshad, Mohammad Javad Salehi, Maryam Naghibzadeh, Abdorreza Naser Moghadasi, Mahsa Owji, Rozita Doosti, Amir Pejman Hashemi Taheri, Ali Shakouri Rad, Amirreza Azimi, M. Mallar Chakravarty, Aristotle N. Voineskos, Arash Nazeri, Mohammad Ali Sahraian
Neurology Feb 2016, 86 (5) 410-417; DOI: 10.1212/WNL.0000000000002326

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Abstract

Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS).

Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms.

Results: Two SCN10A polymorphisms in high linkage disequilibrium (r2 = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10−4; rs6801957: p = 0.0025). Patients with MS with rs6795970AA genotype performed significantly worse than rs6795970G carriers in MSFC (p = 1.8 × 10−4) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970AA carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A–genotype effect was observed on MSFC performance in healthy participants.

Conclusions: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.

GLOSSARY

BOLD=
blood oxygenation level–dependent;
CRIMSON=
Cross-Modal Research Initiative for Multiple Sclerosis and Optic Neuritis;
EAE=
experimental autoimmune encephalomyelitis;
EDSS=
Expanded Disability Status Scale;
FWE=
familywise error;
MAF=
minor allele frequency;
MS=
multiple sclerosis;
MSFC=
Multiple Sclerosis Functional Composite;
PASAT=
Paced Auditory Serial Addition Test;
ROI=
region of interest;
SARA=
Scale for the Assessment and Rating of Ataxia;
SNP=
single nucleotide polymorphism

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 406

  • See page 473

  • Received December 26, 2014.
  • Accepted in final form July 27, 2015.
  • © 2016 American Academy of Neurology
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