Format

Send to

Choose Destination
J Neurol. 2018 Dec;265(12):2861-2874. doi: 10.1007/s00415-018-9057-7. Epub 2018 Sep 29.

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

Author information

1
Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0001, Japan. yasukoga@med.kurume-u.ac.jp.
2
Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0001, Japan.
3
Institute of Fundamental Medicine and Biology, Open Lab Gene and Cell Technology, Kazan Federal University, Kazan, Russia.
4
Division of Medical Informatics, St. Marianna University School of Medicine, Kawasaki, Japan.
5
Center for Clinical Research and Development, National Center for Child Health and Development, Setagaya, Japan.
6
Department of Neurology, Tsukuba University School of Medicine, Tsukuba, Japan.
7
Department of Pediatric Neurology, Osaka Women's and Children's Hospital, Osaka, Japan.
8
Department of Neurology, Faculty of Nursing and Social Welfare Sciences, Fukui Prefectural University, Fukui, Japan.
9
Department of Neurology, Kobe University Hospital, Kobe, Japan.
10
Division of Neurology, National Center for Child Health and Development, Setagaya, Japan.
11
Department of Neurology, Nagoya Medical Center, Nagoya, Japan.
12
Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.

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.

KEYWORDS:

Ictus; L-Arginine; MELAS; Mitochondrial disease; Stroke-like episodes

PMID:
30269300
PMCID:
PMC6244654
DOI:
10.1007/s00415-018-9057-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center