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May 2018; 5 (3) ArticleOpen Access

Normal brain imaging accompanies neuroimmunologically justified, autoimmune encephalomyelitis

Daiki Takewaki, Youwei Lin, Wakiro Sato, Hirohiko Ono, Masakazu Nakamura, Manabu Araki, Tomoko Okamoto, Yuji Takahashi, Yukio Kimura, Miho Ota, Noriko Sato, Takashi Yamamura
First published April 2, 2018, DOI: https://doi.org/10.1212/NXI.0000000000000456
Daiki Takewaki
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Youwei Lin
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Wakiro Sato
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Hirohiko Ono
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Masakazu Nakamura
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Manabu Araki
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Tomoko Okamoto
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Yuji Takahashi
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Yukio Kimura
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Miho Ota
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Noriko Sato
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
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Takashi Yamamura
From the Department of Immunology (D.T., Y.L., W.S., H.O., M.N., M.A., T.Y.) and Department of Mental Disorder Research (M.O.), National Institute of Neuroscience, National Center of Neurology and Psychiatry; Department of Neurology (D.T., Y.L., M.A., T.O., Y.T.) and Department of Radiology (Y.K., N.S.), National Center Hospital, National Center of Neurology and Psychiatry; Multiple Sclerosis Center (D.T., Y.L., W.S., H.O., M.N., M.A., T.O., N.S., T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan.
MD, PhD
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Full PDF
Citation
Normal brain imaging accompanies neuroimmunologically justified, autoimmune encephalomyelitis
Daiki Takewaki, Youwei Lin, Wakiro Sato, Hirohiko Ono, Masakazu Nakamura, Manabu Araki, Tomoko Okamoto, Yuji Takahashi, Yukio Kimura, Miho Ota, Noriko Sato, Takashi Yamamura
Neurol Neuroimmunol Neuroinflamm May 2018, 5 (3) e456; DOI: 10.1212/NXI.0000000000000456

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Abstract

Objective To examine cases with a clinical course, signs, and symptoms mimicking MS, but without abnormalities on conventional MRI.

Methods Among 550 people with a tentative diagnosis of MS or neuromyelitis optica spectrum disorder (NMOSD), we selected patients, who met the 2010 McDonald diagnosis criteria for MS, but did not show abnormal findings on conventional brain and spinal cord MRI. After evaluating their clinical data, we analyzed fractional anisotropy (FA) values in the brain white matter on diffusion tensor MRIs and the frequencies of B-cell subsets in the peripheral blood in the corresponding cases as compared to healthy controls.

Results Eleven patients (age: 41.1 ± 8.0 years, 9 women and 2 men) met the selection criteria. They were functionally disabled, with a median expanded disability status scale score of 6.0 (2.0–8.0). CSF oligoclonal bands were negative in all cases. IV methylprednisolone and plasmapheresis (PP) were found to be efficacious. Diffusion tensor MRI analysis revealed extensive white matter abnormalities characterized by significantly decreased FA values. The frequency of plasmablasts in the peripheral blood was significantly increased in these patients similar to NMOSD.

Conclusions The neurologic disabilities in these patients could be ascribed to brain white matter damage, as revealed by MRI analysis, whereas the efficacy of PP and B-cell abnormalities in the patients suggested an autoimmune-mediated pathogenesis. In the differential diagnosis of MS, we propose that this condition be referred to as, “Normal-appearing Imaging-associated, Neuroimmunologically Justified, Autoimmune encephalomyelitis.”

Glossary

AQP4=
aquaporin-4;
DTI=
diffusion tensor image;
EDSS=
Expanded Disability Status Scale;
FA=
fractional anisotropy;
FLAIR=
fluid-attenuated inversion recovery;
FOV=
field of view;
HC=
healthy control;
HTLV=
human T-cell leukemia virus;
IFN-β=
interferon-β;
IVMP=
IV methylprednisolone;
MOG=
myelin oligodendrocyte glycoprotein;
NCNP=
National Center of Neurology and Psychiatry;
NINJA=
Normal-appearing Imaging-associated, Neuroimmunologically Justified, Autoimmune encephalomyelitis;
NMOSD=
neuromyelitis optica spectrum disorder;
OB=
oligoclonal band;
PBMC=
peripheral blood mononuclear cell;
PP=
plasmapheresis;
SSEP=
somatosensory evoked potential;
TBSS=
tract-based spatial statistics;
VEP=
visual evoked potential

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

  • The Article Processing Charge was funded by the authors.

  • Received September 7, 2017.
  • Accepted in final form February 27, 2018.
  • Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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