Language

English

Publication Date

10-27-2025

Journal

Journal of Patient-Reported Outcomes

DOI

10.1186/s41687-025-00962-6

PMID

41144106

PMCID

PMC12559487

PubMedCentral® Posted Date

10-27-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background and objectives: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare genetic syndrome mostly associated with pathogenic variants in mitochondrial DNA. As there is limited research on the life experience of patients with MELAS, this study aimed to develop an understanding of the patient experience of MELAS through qualitative interviews to identify, describe, and substantiate important and relevant signs, symptoms, and health-related quality-of-life (HRQoL) impact (S/S/I) concepts.

Methods: Clinician and patient interviews were conducted virtually using semi-structured interview guides. During 60-minute interviews with five experts in the United States, clinicians were asked for their perspective on S/S/I of patients with MELAS, patient experience of fatigue and cognitive impairment, and whether patients would be able to accurately report and rate their symptoms and complete a 90-minute patient experience interview. During a 45-minute interview conducted with 16 adults with confirmed pathogenic variant and clinical diagnosis of MELAS, patients were asked about S/S/I. Interviews were recorded, transcribed, anonymized, coded, and analyzed for saturation and concept frequency and clarification (e.g., severity, frequency, duration).

Results: Experts reported 44 distinct S/S and 36 HRQoL impact concepts. All five experts confirmed that cognitive impairment would not inhibit a typical patient's ability to report on their own experiences; three reported that patients with MELAS would not be able to complete a 90-minute interview. Sixteen patient interviews (mean age: 42.3 [11.1], n = 10 women) were conducted. Interviews with patients with MELAS achieved saturation of concept and yielded 35 S/S concepts and 68 HRQoL impacts across 15 domains. The most frequently reported S/S concepts were physical fatigue (n = 15, 93.8%), hearing loss (n = 13, 81.3%), mental fatigue (n = 12, 75.0%), and exercise intolerance and memory problems (n = 11, 68.8% each). The most frequently reported impact domains were adaptive behaviors and work impacts (n = 14, 87.5% each) and emotional function (n = 13, 81.3%).

Discussion: Patients with MELAS can self-report on S/S/I. Results from both patient and clinician interviews demonstrate that symptoms related to fatigue and cognitive impairment are frequent, bothersome, and important to improve. Assessments of fatigue and cognitive function should therefore be considered key outcome measures in clinical trials enrolling patients with MELAS.

Keywords

Humans, MELAS Syndrome, Quality of Life, Female, Adult, Male, Middle Aged, Qualitative Research, Interviews as Topic, Fatigue, Cognitive Dysfunction, Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MELAS; Mitochondrial disease; Concept elicitation; Qualitative interviews; Patient-centered outcomes

Published Open-Access

yes

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