@article{oai:tsukuba.repo.nii.ac.jp:00048626,
 author = {石井, 亜紀子 and ISHII, Akiko and Koga, Yasutoshi and Povalko, Nataliya and Inoue, Eisuke and Nakamura, Hidefumi and Suzuki, Yasuhiro and Yoneda, Makoto and Kanda, Fumio and Kubota, Masaya and Okada, Hisashi and Fujii, Katsunori},
 issue = {12},
 journal = {Journal of neurology},
 month = {Dec},
 note = {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.},
 pages = {2861--2874},
 title = {Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research},
 volume = {265},
 year = {2018},
 yomi = {イシイ, アキコ}
}