Malignant hyperthermia and rhabdomyolysis are phenotypes that have long been considered to occur only in response to external stimuli (trigger anaesthesia and physical exhaustion) show several features of a continuous disease manifestation. Previous studies showed prolonged bleeding time after injury, selective immunological advantages, axial muscle weakness and several social difficulties. A detailed study of the neuromuscular and multisystem features of patients with RYR1-related malignant hyperthermia or rhabdomyolysis is needed to provide clarification about the continuous and multisystem disease manifestations in these patients.
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To investigate the neuromuscular involvement of RYR1 related MH and rhabdomyolysis [ Time Frame: Directly after inclusion, a muscle MRI's and ultra sounds will be made of all subjects. ]
All subjects will have a total body muscle MRI and muscle ultra sound once
To investigate the multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: Directly after inclusion, subjects will fulfil a questionnaire study. ]
All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.
To investigate the multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: Six months after inclusion, subjects will fulfil a questionnaire study. ]
All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.
To investigate the multisystem features of RYR1 related MH and rhabdomyolysis [ Time Frame: Twelve months after inclusion, subjects will fulfil a questionnaire study. ]
All subject will fulfil a questionnaire study, it will focus on pain, activity and psychological aspects.
To investigate the immunological changes in subjects with RYR1 related MH and rhabdomyolysis. [ Time Frame: Directly after inclusion blood samples will be taken for immunological studies. ]
Peripheral mononuclear blood cells will be isolated and in vitro challenged using pathogens and stimulatia. The results of this part of the study will be compared to healthy controls.
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Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: Yes
Sampling Method: Probability Sample
A history of malignant hyperthermia susceptibility (MHS), confirmed by diagnostic RYR1 variant or IVCT, related to a RYR1 variant and/or a history of rhabdomyolysis related to a variant in RYR1
Minimum age 18 years old.
Patients diagnosed with a neuromuscular disease resulting in muscle weakness (apart from RYR1 related rhabdomyolysis and malignant hyperthermia).
Patients with symptoms of angina pectoris.
Patients with contra-indications for MRI-scan are excluded. Contra-indications for MRI-scan include metallic implants (vascular clips, foreign bodies like metallic splinters in the eye, coronary and peripheral artery stents, prosthetic heart valves, pacemakers and ICD's, cochlear implants, breast tissue expanders and some other electronic implants or devices and known claustrophobia.
Current malignancy
Pregnancy or lactating
Other health issues whereby patients are not able to fulfil the study protocol
No written informed consent by the patient
Exclusion criteria for immunological part of the study:
Diabetes mellitus
Patients currently using medicine affecting the immune system.
Patients with a compromised immunity (e.g. HIV)• Patients with a history of auto-immune disease (e.g. SLE, psoriasis, IBD)
Use of statins the past year
Use of systemic corticosteroids during more than two weeks in the past 5 years
Previous treatment with chemotherapy and/or radiation therapy
Age > 65 years old.
Exclusion criteria for healthy controls
History of malignant hyperthermia
Variant in RYR1
A RYR1 related myopathy
History of heat stroke
History of rhabdomyolysis
Family history of malignant hyperthermia or a RYR1 variant
Family history of inexplicable perioperative dead
Family history of a RYR1 related myopathy
Netherlands
RUniversity Recruiting
Nijmegen, Netherlands
Contact: Luuk van den Bersselaar, M.D. MSc +31 24 361 1111 luuk.vandenbersselaar@radboudumc.nl
Radboud University
Canisius-Wilhelmina Hospital
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