PracticeUpdate Neurology Best of 2018

ICNMD 2018 25

Some Neuromuscular Diseases Linked toMalignant Hyperthermia or Similar Reactions Neurologists may need to take or advise perioperative precautions in patients with diverse muscular diseases.

MRI in 19 individuals showed mean distal cross-sectional area of the right median nerve of 1.55 ± 0.49 (range 1 to 2.7) cm 2 and left median nerve, 1.57 ± 0.4 (range 1 to 2.7) cm 2 . Dr. Nalini noted, “Ultrasound of the nerves is an emerging, painless, easily accessible, affordable, and sensitive modality to study peripheral as well as proximal nerves to understand their involvement in carpal tun- nel syndrome. Particularly in this disorder, if we need objective follow-up assessment of any specific therapy, ultrasonography may be used repeatedly. These features of ultrasonography and its great utility in entrapment neuropathies prompted us to take up this study, also to obtain data in nor- mal controls for comparison and correlation. We plan to utilize ultrasonography to assess all our cases of carpal tunnel syndrome.” Dr. Nalini emphasized the importance of ultrasonography as a sensitive, cheaper, and effective alternate to MRI to confirm carpal tunnel syndrome. Cross-sectional area of the proximal median nerve may be used to predict severity of carpal tun- nel syndrome. Moreover, mean and inlet cross-sectional area may be valid and easy-to-acquire parameters for routine clinical use in con- firming carpal tunnel syndrome. www.practiceupdate.com/c/70789 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 myopathies caused by mutations in the gene encoding the ryanodine receptor 1 (RYR1) wereassumed to be susceptible tomalignant hyperthermia, unless an in vitro contracture test proved oth- erwise. This is a good, pragmatic assumption, 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.

" Malignant hyperthermia- like reactions in response to succinylcholine, and possibly volatile anesthetics,

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 investigations 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 myo- globin resulting fromdamage tomuscle cells. Severe rhabdomyolysis may lead to acute kidney failure, so kidney function is meas- ured frequently. Individualsmay 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 pre- sents as a very high temperature, increased heart rate, and abnormally rapid breath- ing, increased carbon dioxide production, increased oxygen consumption, mixed aci- dosis, 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 hyperthermia. Such case reports can cause neurologists to feel uncertain, and can lead to excessive presumption of individuals as being susceptible to malignant hyperther- mia, or even worse, missed diagnosis. 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 hyperthermia-like reactions is thought to differ from that of true malignant hyperthermia. Dr. Claeys concluded that certain neuro- muscular diseases have been associated with perioperative malignant 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

though only approximately 30%of these par- ticipants are estimated to be susceptible to malignant hyperthermia. The spectrum of myopathies and clinical syndromes linked tomalignant hyperthermia through RYR1 mutations now includes, among others, central core disease, multi- minicore myopathy, congenital myopathy with cores and rods, King-Denborough syndrome, centronuclear 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 dystrophy type 1, are now known to carry equal risk of developing malignant hyperthermia in response to volatile anesthetics as the gen- eral population. However, succinylcholine should still be avoided in these individuals because unpredictable muscle contractures can occur after administration. An exaggerated hyperkalemic response, such as a malig- nant hyperthermia-like reaction, can occur. Muscular dystrophies such as Duchenne and Becker muscular dystrophies can also be associated with a malignant hyperther- mia-like reaction to succinylcholine. Dr. Claeys explained that malignant hyper- thermia is a life-threatening hypermetabolic reaction that attacks susceptible individuals. It is caused by excessive calcium release from the sarcoplasmic reticulum in skeletal muscles in response to primarily volatile hal- ogenated anesthetics and the depolarizing muscle relaxant succinylcholine. Mutations in the gene encoding the ryan- odine receptor 1 (RYR1) are the most frequently identified underlying genetic have also been reported and are associated with severe hyperkalemia and rhabdomyolysis. "

VOL. 3 • NO. 4 • 2018