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Journal of Neurology
Published in: Journal of Neurology 12/2018

Open Access 01-12-2018 | Original Communication

Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research

Authors: Yasutoshi Koga, Nataliya Povalko, Eisuke Inoue, Hidefumi Nakamura, Akiko Ishii, Yasuhiro Suzuki, Makoto Yoneda, Fumio Kanda, Masaya Kubota, Hisashi Okada, Katsunori Fujii

Published in: Journal of Neurology | Issue 12/2018

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Abstract

Objective

To examine the efficacy and safety of the therapeutic regimen using oral and intravenous l-arginine for pediatric and adult patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Methods

In the presence and absence of an ictus of stroke-like episodes within 6 h prior to efficacy assessment, we correspondingly conducted the systematic administration of oral and intravenous l-arginine to 15 and 10 patients with MELAS in two, 2-year, prospective, multicenter clinical trials at 10 medical institutions in Japan. Subsequently, patients were followed up for 7 years. The primary endpoint in the clinical trial of oral l-arginine was the MELAS scale, while that for intravenous l-arginine was the improvement rates of headache and nausea/vomiting at 2 h after completion of the initial intravenous administration. The relationships between the ictuses of stroke-like episodes and plasma arginine concentrations were examined.

Results

Oral l-arginine extended the interictal phase (p = 0.0625) and decreased the incidence and severity of ictuses. Intravenous l-arginine improved the rates of four major symptoms—headache, nausea/vomiting, impaired consciousness, and visual disturbance. The maximal plasma arginine concentration was 167 μmol/L when an ictus developed. Neither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. No treatment-related adverse events occurred, and the formulations of l-arginine were well tolerated.

Conclusions

The systematic administration of oral and intravenous l-arginine may be therapeutically beneficial and clinically useful for patients with MELAS.
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Metadata
Title
Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research
Authors
Yasutoshi Koga
Nataliya Povalko
Eisuke Inoue
Hidefumi Nakamura
Akiko Ishii
Yasuhiro Suzuki
Makoto Yoneda
Fumio Kanda
Masaya Kubota
Hisashi Okada
Katsunori Fujii
Publication date
01-12-2018
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 12/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-018-9057-7

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