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

Abstract

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. 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. 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. 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.