Knuiman, GJ;
Kusters, B;
Eshuis, L;
Snoeck, M;
Lammens, M;
Heytens, L;
De Ridder, W;
... Voermans, NC; + view all
(2019)
The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations.
Journal of Neurology
, 266
(4)
pp. 876-887.
10.1007/s00415-019-09209-z.
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Quinlivan_The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations_VoR.pdf - Published Version Download (1MB) | Preview |
Abstract
OBJECTIVE: The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases. METHODS: We performed a retrospective multi-centre cohort study focussing on the histopathological features of patients with MH or RM due to RYR1 mutations (1987–2017). All muscle biopsies were reviewed by a neuromuscular pathologist. Additional morphometric and electron microscopic analysis were performed where possible. RESULTS: Through the six participating centres we identified 50 patients from 46 families, including patients with MH (n = 31) and RM (n = 19). Overall, the biopsy of 90% of patients showed one or more myopathic features including: increased fibre size variability (n = 44), increase in the number of fibres with internal nuclei (n = 30), and type I fibre predominance (n = 13). Abnormalities on oxidative staining, generally considered to be more specifically associated with RYR1-related congenital myopathies, were observed in 52%, and included unevenness (n = 24), central cores (n = 7) and multi-minicores (n = 3). Apart from oxidative staining abnormalities more frequently observed in MH patients, the histopathological spectrum was similar between the two groups. There was no correlation between the presence of cores and the occurrence of clinically detectable weakness or presence of (likely) pathogenic variants. CONCLUSIONS: Patients with RYR1-related MH and RM exhibit a similar histopathological spectrum, ranging from mild myopathic changes to cores and other features typical of RYR1-related congenital myopathies. Suggestive histopathological features may support RYR1 involvement, also in cases where the in vitro contracture test is not informative.
| Type: | Article |
|---|---|
| Title: | The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00415-019-09209-z |
| Publisher version: | http://dx.doi.org/10.1007/s00415-019-09209-z |
| Language: | English |
| Additional information: | © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | RYR1, RyR1, Rhabdomyolysis, Malignant hyperthermia (MH), Muscle biopsy, Histology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10079999 |
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