Analysis of histomorphology in malignant hyperthermia-susceptible patients

Abstract

Background Malignant hyperthermia (MH) is a potentially lethal disorder of skeletal muscle triggered by anesthetic agents. A histomorphological examination of diseased muscle may provide insight into MH pathophysiology, but it is not a routine part of standardof-care practice for the identification of MH-susceptibility. In this study, we investigated muscle histomorphology in a large cohort of MH-susceptible (MHS) patients and examined its relationship to genotype and phenotype.Methods All consenting patients who were identified as MHS based on a caffeine-halothane contracture test (CHCT) performed during 1992-2011 were retrospectively identified and recruited for this study. Results of the histomorphological examination, which is a routine part of our centre-specific practice, were reviewed. Patient demographics, MH proband status, histological features, CHCTs, and genetic results for MH-causative mutations were summarized. Results Seven of the 399 patients classified as MHS had histological characteristics consistent with central core disease, and one patient was a carrier of Duchenne's muscular dystrophy. Eighty-six (22%) patients had histological abnormalities, and five (6%) of these had evidence of ''frank'' myopathy. No histologic abnormalities were consistent among the MHS patients; however, a higher proportion of MH probands had abnormal histomorphology compared with the general MHS population, and patients with evidence of ''frank'' myopathy showed similarities in clinical history, biochemistry, CHCT, and genetic testing. Author contributions David Orlov and Sheila Riazi participated in the analysis and interpretation of data. David Orlov wrote the original draft. David Orlov, Julia Keith, Derek Rosen, Sidney Croul, and Sheila Riazi were involved with the critical revision of the original manuscript. Julia Keith, Derek Rosen, Sidney Croul, Natalia Kraeva, and Sheila Riazi were involved with the acquisition of data. Julia Keith and Sidney Croul were involved with the analysis and interpretation of the histomorphological results. Derek Rosen, Natalia Kraeva, and Sheila Riazi were involved with the conception and design of the study.

Idiopathic hyperCKemia and malignant hyperthermia susceptibility

“…Anatomopathological study does not allow for a diagnosis of MH susceptibility as up to 78% of the MHS patients can have normal features. 34 Histomorphometric analysis does not reveal any distinctive features in the MHS patients, with the exception of occasional cores (regions without oxidative activity in the muscle fibre). This technique, however, makes it possible to suspect or exclude other muscle diseases that may express as idiopathic hyperCKemia, such as muscular dystrophies (dystrophinopathy, dyspherlinopathy, caveolinopathy, and calpainopathy), myofibrillar myopathies, inflammatory myopathies, metabolic myopathies (glycogenosis or mitochondrial myopathies), adenylate deaminase deficiency, myopathy with tubular aggregates, carnitine palmitoyltransferase II deficiency, and myotonia.…”

Sustainable rare diseases business and drug access: no time for misconceptions

“…Orphan Medicinal Products (OMPs) are intended for the diagnosis, prevention or treatment of serious, rare diseases that substantially affect life expectancy, physical and social functioning of patients and their families [1-4]. Since the introduction of EU OMP regulation in the year 2000, there has been a powerful impetus for research and development (R&D) in the rare diseases field and there are now more than 1,000 medicines with OMP designation.…”

Perioperative management of malignant hyperthermia during general anesthesia: A report of two cases

“…Three genes-RYR1, calcium voltage-gated channel subunit alpha1 S, and SH3 and cysteine-rich domain 3-are associated with MH susceptibility and the extreme dysregulation of skeletal muscle Ca 2+ homeostasis that produce the clinical features of MH under anesthesia. [5][6][7][8][9][10][11] Anesthesiologists must increase awareness of MH susceptibility. Although large-scale CHCT and gene mutation detection may be difficult to achieve, these tests can identify patients with diseases that increase MH risk.…”