Summary

Background and objective: To analyse the use of standardized application of ryanodine for in vitro muscle contracture testing to define cut-off values separating malignant hyperthermia susceptible from malignant hyperthermia negative subjects. Furthermore, we compared the results of in vitro muscle-contracture tests following the halothane, caffeine and ryanodine challenges.

Methods: In 113 subjects, halothane, caffeine and ryanodine muscle-contracture tests were performed according to the protocol of the European Malignant Hyperthermia Group.

Results: Malignant hyperthermia susceptible subjects (n = 77) had significantly shorter onset times in the ryanodine in vitro muscle-contracture test (1 μmol ryanodine) compared with malignant hyperthermia negative subjects (n = 36), median 4.8 vs. 20.1 min, respectively, without any influence of age or gender. The best cut-off value was 10 min (sensitivity 0.78 and specificity 0.94, respectively). Shorter cut-off values had greater specificity, but lower sensitivity. Groups could not be separated without an overlap. In susceptible subjects, we found a correlation between onset time and threshold concentrations for halothane and caffeine (ρ = 0.47 and 0.52, respectively). In addition, muscle bundles with high susceptibility to halothane and caffeine also showed high susceptibility to ryanodine.

Conclusions: The ryanodine in vitro muscle-contracture test confirmed the malignant hyperthermia status that was determined using the halothane and caffeine in vitro muscle-contracture tests. Due to an overlap between the two groups, discrimination ability was not always perfect and short cut-off values with higher specificity had reduced sensitivity and vice versa. The correlation of contractures following the halothane, caffeine and ryanodine challenges points towards a similar individual pharmacogenetic effect rather than a specific, different pharmacological action between the three agents.

Aponeurotic deformation measurements have traditionally been taken by loading dissected muscles; thus the values obtained may not reflect in vivo function. In the present study, we estimated dimensional changes in the central aponeurosis of the intact human tibialis anterior muscle upon loading induced by muscle contraction. Measurements were taken in seven males, and involved real-time ultrasound scanning of the tibialis anterior muscle at 30° of plantarflexion at rest and during isometric dorsiflexion maximum voluntary contraction (MVC). At each contraction state, the length of the aponeurosis, the width along its length, and its area were estimated from sagittal-plane and axial-plane sonographs. In the transition from rest to MVC, the length of the aponeurosis increased by 7% (P < 0.05), its width increased by up to 21% (P < 0.05), and its area increased by 17% (P < 0.05). These results indicate that the in vivo tibialis anterior aponeurosis behaves as a compliant material upon active muscle shortening. The methodology employed allows cross-sectional and longitudinal design investigations, circumventing the problems associated with epimysial removal under in vitro experimental conditions.

A 6-months pregnant woman suffering from severe tetanus was successfully treated with intrathecal baclofen. She delivered a premature but healthy neo-nate, and was safely discharged home 40 days after the onset of symptoms of tetanus. Specific aspects of intrathecal baclofen therapy in the pregnant woman are discussed.

A case of oculostapedial synkinesis occurring after Bell’s palsy is described. This rare phenomenon has not previously been reported following Bell’s palsy. The authors discuss the method of objectively proving the diagnosis, which can be difficult. The patient was successfully treated by stapedius tendon section under local anaesthesia.

The quantity and spatial distribution of calcium bound to myofilaments is of considerable interest to physiologists studying the regulation of contraction in striated muscle, but few techniques allow these distributions to be directly measured. Methods are described here by which such data can be derived from electron probe X-ray microanalysis (EPXMA) images. Combination of data from multiple half sarcomeres improves the signal-to-noise level and allows assessment of variation between half sarcomeres. Profiles of calcium counts, calcium counts normalized to local bremstrahlung counts, and calcium counts normalized to the average bremstrahlung counts for the entire half sarcomere provide differing but complementary information. Such data help to identify and characterize spatial variations in Ca binding to regulatory proteins in muscle.