Malignant hyperthermia

The danger of poor calcium regulation…

Malignant hyperthermia (MH) is a fatal condition triggered by volatile anaesthetic agents. Once a patient is subjected to the anaesthetic (e.g. halothane), symptoms of MH appear within minutes. The most prominent symptoms are involuntary muscle contractions and elevated body temperatures (>40˚C), the latter due to increased skeletal muscle metabolism. The cause of MH is due to mutations in the ryanodine receptors located in the sarcoplasmic reticulum.

These receptors form part of the channels that release calcium into the cytosol to initiate contraction. The mutation causes the ryanodine receptors to be highly sensitive to caffeine and certain anaesthetics (e.g. halothane). The increased sensitivity triggers the release of calcium, leading to involuntary muscle contraction. Treatment is usually a large dose of dantrolene, which blocks the release of calcium from the sarcoplasmic reticulum.

Genetic vs. functional diagnosis

A number of ryanodine receptor mutations have already been identified. Patients who has a reaction during anaesthesia would be genetically screened from a mere blood sample. However, an unknown mutation can easily go undetected. The only sure way to establish whether an individual is susceptible to  MH, is to perform a muscle biopsy and subject it to the In Vitro Contracture Test (IVCT). This test requires a large muscle sample (approximately 30 mm in length and 3 – 5 mm thick), rendering the process very invasive. Most patients complain about severe pain during the healing process, and are usually left with significant scaring.

The IVCT test itself involves the muscle to be bathed in a solution containing various amounts of caffeine and halothane. If muscle contraction starts before the recommended threshold, the patient is usually classified as MH susceptible and confirmed with a genetic screening test. Muscle testing on the rest of the family will also be required. Unfortunately, no accredited IVCT facility exists in South Africa.

What are we doing?

Technology has since evolved so that contracture tests may be performed on single isolated muscle fibres. The upside of this technology is that a very small muscle biopsy may be sufficient (5 mm in length) and could be obtained using a muscle biopsy needle. To confirm the validity of using the single fibre method to assist in diagnosing MH, and because there is no IVCT facility available in Africa, the MyoLab has embarked on developing, establishing and validating a single fibre technique to assist in diagnosing MH. This research heavily relies on small muscle biopsy samples from individuals that have previously been diagnosed with MH. For more information, please contact the MyoLab.

Collaborators

Franclo Henning (Tygerberg Hospital, University of Stellenbosch)

Jo Wilmshurst (Red Cross Children’s Hospital)

Caroline D’Alton (University of Cape Town)

Past students

Matthew Leppan (Honours 2016, University of Cape Town)