Motor function performance in individuals with RYR1‐related myopathies

Abstract

Introduction The objective of this study was to obtain a 6‐month natural history of motor function performance in individuals with RYR1 ‐ related myopathy ( RYR1‐ RM) by using the Motor Function Measure‐32 (MFM‐32) and graded functional tests (GFT) while facilitating preparation for interventional trials . Methods In total, 34 participants completed the MFM‐32 and GFTs at baseline and 6‐month visits. Results Motor deficits according to MFM‐32 were primarily observed in the standing and transfers domain (D1; mean 71%). Among the GFTs, participants required the most time to ascend/descend stairs (>7.5 s). Functional movement, determined by GFT grades, was strongly correlated with MFM‐32 (D1; r ≥ 0.770, P < 0.001). Motor Function Measure‐32 and GFT scores did not reflect any change in performance between baseline and 6‐month visits. Discussion The MFM‐32 and GFTs detected motor impairment in RYR1 ‐RM, which remained stable over 6 months. Thus, these measures may be suitable for assessing change in motor function in response to therapeutic intervention. Muscle Nerve 60 : 80–87, 2019

Ryanodine Receptor 1-Related Myopathies: Quantification of Intramuscular Fatty Infiltration from T1-Weighted MRI

“…Of all three domains of the MFM-32, IMFI correlated strongest with domain 1 (standing and transfers) (upper leg: ρ =–0.698, p < 0.001; lower leg: ρ =–0.513, p = 0.002). This association is consistent with our previous findings that the standing and transfers domain of the MFM-32 reflects the greatest motor deficits in individuals with RYR1 -RM [ 33, 35 ]. We found that IMFI predicted MFM-32 scores in this study.…”

“…IMFI from both dominant and recessive cases showed moderate to strong inverse correlation with MFM-32 and 6MWT distance, two well-described and validated measures of motor function and capacity in neuromuscular diseases [ 33, 34 ]. Of all three domains of the MFM-32, IMFI correlated strongest with domain 1 (standing and transfers) (upper leg: ρ =–0.698, p < 0.001; lower leg: ρ =–0.513, p = 0.002).…”

Is Exercise-Induced Fatigue a Problem in Children with Duchenne Muscular Dystrophy?

“…A study of Montes et al from 2013 included 114 patients with various neuromuscular diseases 15 and most recently Whitherspoon et al presented data from a population of RYR1-associated myopathy patients. 16 The authors of the first study found that in the longitudinal course the distance walked by patients declined in Duchenne/ Becker muscular dystrophy whereas fatigue did not. In contrast to that weakness in SMA did not change while fatigue increased significantly.…”

“…14,15 Fatigability, measured by the 6MWT, was as well recently proposed to be a promising end point for evaluating therapeutic efficacy in a pharmacological trial in patients with RYR1-associated myopathy. 16 The aim of our study is to investigate the impact and diagnostic value of exercise-induced fatigue in DMD which has been proposed as a suitable outcome parameter for other conditions.…”

RYR-1-Related Diseases International Research Workshop: From Mechanisms to Treatments Pittsburgh, PA, U.S.A., 21-22 July 2022

“…The study also indicated a higher disease severity in patients with recessive or dominant de novo inheritance (personal observation). Recently, a 6-month natural history study completed at the National Institutes of Health on 34 ambulant patients of various ages showed that functional assessments and graded timed tests are able to detect motor impairment in RYR1-RM patients [40]. This motor impairment remained stable over six months.…”