The neuromuscular and multisystem features of RYR1-related malignant hyperthermia and rhabdomyolysis: A study protocol

Autor: Leonie Helder, Stan Buckens, Nicol C. Voermans, Ignacio Malagon, Nens van Alfen, Gert Jan Scheffer, Anna Greco, M.M.J. Snoeck, Baziel G.M. van Engelen, José A. E. Custers, Lucas T. van Eijk, Sheila Riazi, Luuk R van den Bersselaar, Nick Kruijt, Heinz Jungbluth, Susan Treves, Leo A. B. Joosten
Rok vydání: 2021
Předmět:
medicine.medical_specialty
Neuromuscular disease
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
malignant hyperthermia
Disease
calcium signaling
Rhabdomyolysis
Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Cohort Studies
Clinical Protocols
Study Protocol Clinical Trial
Surveys and Questionnaires
Internal medicine
RYR1
medicine
Humans
skeletal muscle cell
Prospective Studies
business.industry
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Malignant hyperthermia
Ryanodine Receptor Calcium Release Channel
Ryanodine receptor-1
General Medicine
medicine.disease
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
neuromuscular disorder
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
Cross-Sectional Studies
Cohort
Exertional rhabdomyolysis
Observational study
Animal studies
business
Research Article
myopathy
Zdroj: Medicine (Baltimore), 100, 33
Medicine (Baltimore), 100
Medicine
ISSN: 0025-7974
Popis: Contains fulltext : 238097.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Malignant hyperthermia (MH) and exertional rhabdomyolysis (ERM) have long been considered episodic phenotypes occurring in response to external triggers in otherwise healthy individuals with variants in RYR1. However, recent studies have demonstrated a clinical and histopathological continuum between patients with RYR1-related congenital myopathies and those with ERM or MH susceptibility. Furthermore, animal studies have shown non-neuromuscular features such as a mild bleeding disorder and an immunological gain-of-function associated with MH/ERM related RYR1 variants raising important questions for further research. Awareness of the neuromuscular disease spectrum and potential multisystem involvement in RYR1-related MH and ERM is essential to optimize the diagnostic work-up, improve counselling and and future treatment strategies for patients affected by these conditions. This study will examine in detail the nature and severity of continuous disease manifestations and their effect on daily life in patients with RYR1-related MH and ERM. METHODS: The study protocol consists of four parts; an online questionnaire study, a clinical observational study, muscle imaging, and specific immunological studies. Patients with RYR1-related MH susceptibility and ERM will be included. The imaging, immunological and clinical studies will have a cross-sectional design, while the questionnaire study will be performed three times during a year to assess disease impact, daily living activities, fatigue and pain. The imaging study consists of muscle ultrasound and whole-body magnetic resonance imaging studies. For the immunological studies, peripheral mononuclear blood cells will be isolated for in vitro stimulation with toll-like receptor ligands, to examine the role of the immune system in the pathophysiology of RYR1-related MH and ERM. DISCUSSION: This study will increase knowledge of the full spectrum of neuromuscular and multisystem features of RYR1-related MH and ERM and will establish a well-characterized baseline cohort for future studies on RYR1-related disorders. The results of this study are expected to improve recognition of RYR1-related symptoms, counselling and a more personalized approach to patients affected by these conditions. Furthermore, results will create new insights in the role of the immune system in the pathophysiology of MH and ERM. TRIAL REGISTRATION: This study was pre-registered at ClinicalTrials.gov (ID: NCT04610619).
Databáze: OpenAIRE
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