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Levels of nitric oxide metabolites in cerebrospinal fluid correlate with cognitive impairment in early stage multiple sclerosis
  1. Kazumasa Okada1,
  2. Masako Kobata1,
  3. Yusuke Sennari1,
  4. Yukio Iwanaka1,
  5. Tomoyo Hashimoto1,
  6. Keiko Ohnari1,
  7. Masayuki Tahara2
  1. 1 Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Japan
  2. 2 Department of Neurology and Clinical Research Center, Utano National Hospital, Kyoto, Japan
  1. Correspondence to Dr Kazumasa Okada, Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, 8.07856e+006, Japan; gion{at}

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Cognitive impairment is an important clinical symptom of multiple sclerosis (MS) that often becomes an obstacle for employment, school attendance, and other activities of daily living and can occur in the early stage of disease, even in patients with clinically isolated syndrome or radiologically isolated syndrome.1

Recent studies have suggested both neuronal degeneration and central inflammation produce neuropathological damage to the central nervous system (CNS) in MS.2 Oxidative stress has been implicated in MS-related neurodegeneration.2 A previous study showed that nitrite and nitrate (NOx), which are oxidant metabolites of NO, are elevated in cerebrospinal fluid (CSF) from patients with MS.3 The excess production of NO may participate in MS-associated lesion formation and neuronal loss.

In order to better elucidate the relationship between NOx and CNS damage in the early stage of MS, we investigated the relationship between cognitive impairment and CSF NOx levels in patients with early stage disease.

Patients and methods

We enrolled a total of 23 patients who were newly diagnosed with relapsing-remitting MS in accordance with the 2010 McDonald criteria.4 Participants were within 2 years of clinical onset and in remission for more than 3 months since the time of their most recent corticosteroid therapy or acute exacerbation. No patients were receiving disease modifying therapy at the time of CSF sample collection. We excluded patients who had other autoimmune disease …

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  • Contributors KO* contributed to the conception and design of the study and drafted the manuscript. KO*, MK, YS, TH, KO and MT contributed to collection, analysis and interpretation of the data. KO* and KO performed the statistical analyses. KO* and MT edited the manuscript. KO* is corresponding author.

  • Funding This work was supported by Health and Labor Sciences Research Grants (grant number 201415033B).

  • Competing interests None declared.

  • Ethics approval The Ethical Committee of the University of Occupational and Environmental Health.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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