Diagnostic Criteria and Management of MELAS and Stroke-Like Episodes: Consensus-Based Statements

Authors

• Michelangelo Mancuso
• Marcello Bellusci
• Valerio Carelli
• Irenaeus de Coo
• Daria Diodato
• Felix Distelmaier
• Omar Hikmat
• Michio Hirano
• Rita Horvath
• Amel Karaa
• Thomas Klopstock
• Mary Kay Koenig
• Cornelia Kornblum
• Chiara La Morgia
• Piervito Lopriore
• Mika Henrik Martikainen
• Robert McFarland
• Olimpia Musumeci
• Robert D S Pitceathly
• Guido Primiano
• Shamima Rahman
• Fernando Scaglia
• Andrew Schaefer
• Manuel Schiff
• Luisa Semmler
• Costanza Lamperti
• Serenella Servidei

Language

English

Publication Date

4-1-2026

Journal

European Journal of Neurology

DOI

10.1111/ene.70588

PMID

41999163

PMCID

PMC13090769

PubMedCentral® Posted Date

4-18-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background and purpose: Mitochondrial Encephalomyopathy, Lactic acidosis and Stroke-like episodes (MELAS) is a rare multisystem mitochondrial disorder with clinical heterogeneity. Diagnostic criteria and management strategies for MELAS and mitochondrial stroke-like episodes (SLE) remain inconsistent. This work provides international consensus recommendations on the definition, diagnosis, and management of MELAS and SLE in pediatric and adult populations.

Methods: An international Delphi consensus process was conducted within the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD), in collaboration with the US Mitochondrial Medicine Society, the ERN for Hereditary Metabolic Disorders (MetabERN), and patient representatives. Following a systematic literature review, 54 statements addressing diagnostic definitions and management of MELAS were evaluated. Statements not reaching consensus were revised and re-evaluated during a face-to-face meeting.

Results: Consensus supported defining MELAS as a clinical syndrome characterized by one or more SLE in the context of mitochondrial dysfunction caused by a pathogenic mitochondrial DNA variant, particularly m.3243A>G in MT-TL1. The use of terms such as "MELAS-like" or "MELAS spectrum" was discouraged. The panel agreed that the efficacy of L-arginine, L-taurine, L-citrulline, coenzyme Q10, vitamins, and other supplements remains unproven and requires validation in clinical trials. Antiseizure medications should be initiated promptly when seizures are suspected during SLE, and intravenous corticosteroids may be beneficial acutely. Multidisciplinary management of neurological, neuropsychiatric, and systemic complications was endorsed.

Conclusions: This international consensus provides updated definitions and practical guidance for the diagnosis and management of MELAS and SLE, aiming to harmonize clinical practice and inform future evidence-based research.

Keywords

Humans, MELAS Syndrome, Consensus, Delphi Technique, Stroke, Disease Management, consensus, diagnostic criteria, management, MELAS, primary mitochondrial diseases, recommendations

Published Open-Access

yes

Recommended Citation

Mancuso, Michelangelo; Bellusci, Marcello; Carelli, Valerio; et al., "Diagnostic Criteria and Management of MELAS and Stroke-Like Episodes: Consensus-Based Statements" (2026). Faculty, Staff and Student Publications. 4197.
https://digitalcommons.library.tmc.edu/uthmed_docs/4197