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October 2015; 2 (5) ArticleOpen Access

CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy

Takahiro Furukawa, Naoko Matsui, Koji Fujita, Hiroyuki Nodera, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Yuishin Izumi, Ryuji Kaji
First published August 6, 2015, DOI: https://doi.org/10.1212/NXI.0000000000000138
Takahiro Furukawa
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Naoko Matsui
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Koji Fujita
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Hiroyuki Nodera
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Fumitaka Shimizu
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Katsuichi Miyamoto
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Yukitoshi Takahashi
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Takashi Kanda
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Susumu Kusunoki
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Yuishin Izumi
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Ryuji Kaji
From the Department of Clinical Neuroscience (T.F., N.M., K.F., H.N., Y.I., R.K.), Institute of Health Biosciences, Tokushima University, Tokushima, Japan; Department of Neurology and Clinical Neuroscience (F.S., T.K.), Yamaguchi University Graduate School of Medicine, Ube, Japan; Department of Neurology (K.M., S.K.), Kinki University School of Medicine, Osaka, Japan; and National Epilepsy Center (Y.T.), Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
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Citation
CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy
Takahiro Furukawa, Naoko Matsui, Koji Fujita, Hiroyuki Nodera, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Yuishin Izumi, Ryuji Kaji
Neurol Neuroimmunol Neuroinflamm Oct 2015, 2 (5) e138; DOI: 10.1212/NXI.0000000000000138

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Abstract

Objective: We aimed to compare the cytokine and chemokine profiles of patients with multifocal motor neuropathy (MMN) with those of patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS) to investigate immunologic differences in the CNS.

Methods: CSF from 12 patients with MMN, 8 with PMA, 26 with sporadic ALS, and 10 with other noninflammatory neurologic disorders was analyzed for 27 cytokines and chemokines using the multiplex bead array assay. Cytokine titers of the 4 groups were compared, and correlations between the titers of relevant cytokines and clinical parameters were evaluated.

Results: There were no obvious intrathecal changes except for interleukin (IL)-1 receptor antagonist in patients with MMN. In contrast, IL-4, IL-7, IL-17, eotaxin/CCL11, fibroblast growth factor-2 (FGF-2), granulocyte colony-stimulating factor (G-CSF), and platelet-derived growth factor BB titers were significantly elevated in patients with PMA and ALS; of these, FGF-2 and G-CSF titers were elevated compared with those in patients with MMN. IL-4 and IL-10 titers were high in patients with ALS, particularly patients with possible ALS presenting with a slowly progressive course or mild symptoms.

Conclusions: The CSF cytokine profile of patients with MMN is distinct from that of patients with PMA and ALS. The similarity of the cytokine profiles between patients with PMA and ALS suggests that PMA shares common immunologic features with ALS in the CNS, even without clinical evidence of upper motor neuron involvement.

GLOSSARY

ALS=
amyotrophic lateral sclerosis;
ALSFRS-R=
revised ALS Functional Rating Scale;
CB=
conduction block;
FGF-2=
fibroblast growth factor-2;
G-CSF=
granulocyte colony-stimulating factor;
GM-CSF=
granulocyte-macrophage colony-stimulating factor;
IFN=
interferon;
IL=
interleukin;
IL-1ra=
IL-1 receptor antagonist;
IP-10=
IFN-γ–induced protein 10;
LMN=
lower motor neuron;
MCP-1=
monocyte chemotactic protein-1;
MIP=
macrophage inflammatory protein;
MMN=
multifocal motor neuropathy;
OND=
other noninflammatory neurologic disorder;
PDGF-BB=
platelet-derived growth factor BB;
PMA=
progressive muscular atrophy;
SOD1=
Cu/Zn superoxide dismutase;
TNF-α=
tumor necrosis factor α;
TNFR1=
TNF receptor;
UMN=
upper motor neuron;
VEGF=
vascular endothelial growth factor

Footnotes

  • Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by the authors.

  • Received February 9, 2015.
  • Accepted in final form June 15, 2015.
  • © 2015 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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