Muscle Ultrasound Abnormalities in Individuals with RYR1-Related Malignant Hyperthermia Susceptibility

Luuk R. Van Den Bersselaar*, Nens Van Alfen, Nick Kruijt, Erik Jan Kamsteeg, Miguel A. Fernandez-Garcia, Susan Treves, Sheila Riazi, Chu Ya Yang, Ignacio Malagon, Lucas T. Van Eijk, Baziel G.M. Van Engelen, Gert Jan Scheffer, Heinz Jungbluth, Marc M.J. Snoeck, Nicol C. Voermans

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. Objective: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. Methods: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. Results: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. Conclusions: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

Original languageEnglish
Pages (from-to)541-554
Number of pages14
JournalJournal of Neuromuscular Diseases
Volume10
Issue number4
DOIs
Publication statusPublished - 4 Jul 2023

Keywords

  • Anesthesia
  • exertional rhabdomyolysis
  • malignant hyperthermia
  • muscle ultrasound
  • myopathy
  • ryanodine receptor-1
  • RYR1

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