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. 2025 May 8;20(1):221.
doi: 10.1186/s13023-025-03742-z.

The most bothersome symptoms in neuromuscular diseases: the ERN EURO NMD Survey

Michelangelo Mancuso  1   2 , Alessandro Colitta  3 , Manuela Lavorato  4 , Peter Van den Bergh  5 , Janbernd Kirschner  6 , Cornelia Kornblum  7 , Lorenzo Maggi  8 , Francois Lamy  9 , Hanns Lochmüller  6   10   11 , Marianne Nordstrøm  12   13 , Edoardo Malfatti  14 , Alessandra Ferlini  15 , Davide Pareyson  16 , Vincenzo Silani  17   18 , Kleopas A Kleopa  19 , Marianne de Visser  20 , Antonio Atalaia  21 , Teresinha Evangelista  22
Affiliations

The most bothersome symptoms in neuromuscular diseases: the ERN EURO NMD Survey

Michelangelo Mancuso et al. Orphanet J Rare Dis. .

Abstract

Background: Neuromuscular diseases (NMDs) comprise a range of genetic and acquired rare disorders that affect motor neurons, peripheral nerves, neuromuscular junctions and skeletal muscles, leading to significant impairments such as muscle weakness and fatigue resulting in functional limitations. This study aims to investigate the prevalence and severity of disease-related symptoms in adult patients with NMDs registered in the European Reference Network (ERN) EURO-NMD. A cross-sectional electronic survey was conducted with 1,253 participants who reported the severity of 28 symptoms, which were scored using multi-criteria decision analysis (MCDA).

Results: The results identified muscle fatigue, weakness and impaired physical function/activity as the most severe and prevalent symptoms in all NMD groups, followed by coordination and/or balance problems, muscle stiffness, mental fatigue, and pain. Notably, the analysis highlighted differences in symptom severity between disease subtypes and underlined the need for standardised patient-reported outcome measures (PROMs) to address the broad heterogeneity of NMDs.

Conclusions: The findings stress the critical importance of capturing patient perspectives to guide clinical care, research priorities and therapeutic development. This work argues for the development of uniform PROMs to better assess disease impact, natural history and treatment efficacy, contributing to improved patient-centred care across diverse NMD populations.

Keywords: Neuromuscular diseases; PROMs; Symptoms.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study did not require research ethics committee approval because it involves secondary analysis of anonymized aggregate data that adheres to recognized anonymization standards and does not contain sensitive information (e.g., clinical or genetic data). The study complies with all applicable ethical guidelines and data protection regulations. Additionally, it was conducted in accordance with the Helsinki Declaration of 1964, its subsequent amendments, and equivalent ethical standards where applicable. Consent for publication: Not applicable. Competing interests: MM has received honoraria for speaking, advisory boards and compensation for congress participation from Sanofi Genzyme, Khondrion, Biogen, UCB, Stealth and Precision Biosciences, outside the submitted work. LM has received honoraria for speaking, advisory boards and compensation for congress participation from Sanofi Genzyme, Roche, Biogen, Amicus Therapeutics, Alexion, Argenx, UCB, Janssen, Lupin, outside the submitted work. PV received honoraria, consultation fees, and compensation for advisory board participation from Pfizer, Sanofi Genzyme, CSL Behring, LFB, Natus, UCB Pharma, Janssen, Alnylam. VS received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, LiquidwebS.r.l., Novartis Pharma AG, Amylyx Pharmaceuticals, Biogen, and Zambon Biotech SA. MdV is a consultant to Novartis, Argenx and Astra Zeneca. CK acknowledges participation in Advisory Boards of Amicus Therapeutics, Chiesi, Fulcrum Therapeutics, Hormosan, Roche Pharma AG, Sanofi Genzyme, Stealth BioTherapeutics, and participation as local PI in clinical trials by Amicus Therapeutics, Fulcrum Therapeutics, Omeicos, Reneo Pharmaceuticals, Stealth Therapeutics, Scholar Rocks, and received travel grants and/or lecture fees from Amicus Therapeutics, Chiesi, Sanofi Genzyme, Argenx, Novartis, Santhera, Sarepta, UCB. DP acknowledges participation in Advisory Boards of Inflectis, Alnylam, Akcea, Arvinas, Augustine Tx, DTx, Novartis, participation as local PI in clinical trials sponsored by Alnylam, Ionis, AT Therapeutics, Nido-Biosciences. The remaining authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Distribution of age, sex, and nationality among recruited neuromuscular disease patients. On the y-axis: percentage of patients; above the bars: number of patients. Nations included in the ‘Other’ group: Finland, Austria, Croatia, Denmark, Romania, Czech Republic, Lituania
Fig. 2
Fig. 2
Patients’ severity scores of each symptom investigated by the EURO-NMD PRO Survey
Fig. 3
Fig. 3
Multi-Criteria Decision Analysis (MCDA) Severity Scores of symptoms
Fig. 4
Fig. 4
Multi-Criteria Decision Analysis (MCDA) Severity Scores of symptoms calculated excluding underrepresented neuromuscular diseases, the Other’ group, and the “I do not know my disease” group
See this image and copyright information in PMC

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