PracticeUpdate

SomeNeuromuscular Diseases Linked toMalignant Hyperthermia or Similar Reactions Neurologists may need to take or advise perioperative precautions in patients with diverse muscular diseases C ertain muscular disorders may be linked with malignant hyperthermia or malignant hyperthermia-like reac- tions, concluded a systematic literature review presented at ICNMD 2018. Muscular dystrophies such as Duchenne and Becker muscular dystrophies can also be associated with a malignant hyperther- mia-like reaction to succinylcholine. hyperthermia. Such case reports can cause neurologists to feel uncertain, and can lead to excessive presumption of individuals as being susceptible to malignant hyperthermia, or even worse, missed diagnosis.

Dr. Claeys explained that malignant hyperthermia is a life-threatening hypermetabolic reaction that attacks susceptible individuals. It is caused by excessive calcium release from the sar- coplasmic reticulum in skeletal muscles in response to primarily volatile halogenated anesthetics and the depolarizing muscle relaxant succinylcholine. Mutations in the gene encoding the ryanodine receptor 1 (RYR1) are the most frequently identified underlying genetic defects. Mutations in other genes have also been described, such as CACNA1S, STAC3, SCN4A, and CACNL2A. In susceptible individuals, medications induce the release of stored calcium ions within muscle cells. The resulting increase in calcium concentrations within the cells causes the muscle fibers to contract. This generates excessive heat and results in metabolic acidosis. Although, various laboratory investiga- tions may prove confirmatory, diagnosis is primarily based on symptoms. These include a raised creatine kinase level, elevated potassium, increased phosphate (leading to decreased calcium) and – if determined – raised myoglobin resulting from damage to muscle cells. Severe rhabdomyolysis may lead to acute kidney failure, so kidney function is measured frequently. Individuals may also develop premature ventricular contractions due to increased levels of potassium released from the muscles during the episode. Typical signs of malignant hyperthermia are due to a hypercatabolic state, which presents as a very high temperature, increased heart rate, and abnormally rapid breathing, increased carbon dioxide production, increased oxygen consump- tion, mixed acidosis, rigid muscles, and rhabdomyolysis. These signs can develop at any time during the administration of the anesthetic agents. Over the years, case reports have linked an increasing number of muscular phe- notypes with a susceptibility to malignant

Bram De Wel, MD, and Kristl G. Claeys, MD, PhD, of University Hospitals Leuven in Belgium, explored muscular disorders that may be linked with malignant hyper- thermia or malignant hyperthermia-like reactions and to suggest an appropriate approach to interpret accompanying risks. They searched studies published from the 1960s to 2018 and included case reports, reviews, and retrospective cohort studies. In 1012 papers, participants with myopa- thies caused by mutations in the gene encoding the ryanodine receptor 1 (RYR1) were assumed to be susceptible to malig- nant hyperthermia, unless an in vitro contracture test proved otherwise. This is a good, pragmatic assumption, though only approximately 30% of these partici- pants are estimated to be susceptible to malignant hyperthermia. The spectrum of myopathies and clinical syndromes linked to malignant hyper- thermia through RYR1 mutations now includes, among others, central core disease, multi-minicore myopathy, con- genital myopathy with cores and rods, King-Denborough syndrome, centronu- clear myopathy, and nemaline myopathy. In addition, idiopathic hyperCKemia and exertional rhabdomyolysis are also part of the spectrum of RYR1 disease. Mutations in CACNA1S mainly cause periodic paral- ysis. STAC3 mutations are a known cause of Native American myopathy. Finally, muscle diseases long presumed to be linked to increased risk of malignant hyperthermia, such as myotonic dystro- phy type 1, are now known to carry equal risk of developing malignant hyperther- mia in response to volatile anesthetics as the general population. However, succinylcholine should still be avoided in these individuals because unpredictable muscle contractures can occur after administration. An exagger- ated hyperkalemic response, such as a malignant hyperthermia-like reaction, can occur.

Malignant hyperthermia-like reactions in response to succinylcholine, and possi- bly volatile anesthetics, have also been reported and are associated with severe hyperkalemia and rhabdomyolysis. The cause of these malignant hyperther- mia-like reactions is thought to differ from that of true malignant hyperthermia. Dr. Claeys concluded that certain neuro- muscular diseases have been associated with perioperativemalignant hyperthermia or malignant hyperthermia-like reactions. Neurologists may need to take or advise perioperative precautions in individuals

with diverse muscular diseases. www.practiceupdate.com/c/70787

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