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

TY - JOUR

T1 - Muscle Ultrasound Abnormalities in Individuals with RYR1-Related Malignant Hyperthermia Susceptibility

AU - Van Den Bersselaar, Luuk R.

AU - Van Alfen, Nens

AU - Kruijt, Nick

AU - Kamsteeg, Erik Jan

AU - Fernandez-Garcia, Miguel A.

AU - Treves, Susan

AU - Riazi, Sheila

AU - Yang, Chu Ya

AU - Malagon, Ignacio

AU - Van Eijk, Lucas T.

AU - Van Engelen, Baziel G.M.

AU - Scheffer, Gert Jan

AU - Jungbluth, Heinz

AU - Snoeck, Marc M.J.

AU - Voermans, Nicol C.

N1 - Funding Information: The authors are grateful to all study participants and to the Canisius Wilhelmina –Radboudumc regional junior research funds for their financial support. Several authors of this publication are members of the Netherlands Neuromuscular Center (NL - NMD) and the European Reference Network for rare neuromuscular diseases (EURO-NMD). Funding Information: This research was performed with the financial support of the Canisius-Wilhelmina Hospital –Radboudumc regional junior research funds. The Radboudumc and Canisius Wilhelmina Hospital were not involved in the study design, data collection, data analysis and/or writing of this manuscript. Publisher Copyright: © 2023 - The authors.

PY - 2023/7/4

Y1 - 2023/7/4

N2 - 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.

AB - 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.

KW - Anesthesia

KW - exertional rhabdomyolysis

KW - malignant hyperthermia

KW - muscle ultrasound

KW - myopathy

KW - ryanodine receptor-1

KW - RYR1

UR - http://www.scopus.com/inward/record.url?scp=85164266328&partnerID=8YFLogxK

U2 - 10.3233/JND-230018

DO - 10.3233/JND-230018

M3 - Article

C2 - 37154182

AN - SCOPUS:85164266328

SN - 2214-3599

VL - 10

SP - 541

EP - 554

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

IS - 4

ER -