Brain stimulation reveals slow muscle relaxation in muscle diseases

Slow muscle relaxation is a key feature in specific muscle diseases. Patients with slow muscle relaxation suffer from muscle stiffness, cramps and contractures. Despite its importance, testing muscle relaxation is often overlooked by clinicians, partly because no reliable technique is available to objectively measure the rate of muscle relaxation. This leads to incomplete recognition and underdiagnosis of muscle diseases with slow muscle relaxation, resulting in the omission of potential treatments and (genetic) counselling.

Researchers Joery Molenaar and Jonne Doorduin, from the department of Neurology at the Radboud University Medical Center, developed a technique to reliably measure the rate of muscle relaxation by stimulating the brain using transcranial magnetic stimulation (TMS), and determined the technique’s diagnostic potential in patients with a muscle disease. The results of their study were published this month in Neuromuscular Disorders.

With the TMS technique, a strong magnetic pulse is delivered at the motor cortex in the brain while the patient is performing a maximal voluntary muscle contraction of the forearm. Brain stimulation first leads to a short phase of excitation. However, more importantly, is directly followed by a longer period of corticospinal inhibition to the muscle, called the silent period. This silent period leads to abrupt relaxation of the muscle that can be measured with force sensor.

In 59 patients and 24 healthy controls, the researchers found that with the TMS technique, slow muscle relaxation could be detected with high discriminative power in patients with muscle diseases with signs of muscle stiffness, contractures/cramps, and muscle pain: Brody disease, nemaline myopathy type 6, McArdle disease, and myotonic dystrophy type 2.  

Thus, muscle relaxation rate assessed using the TMS technique has the potential to serve as a diagnostic tool and monitor disease progression, and can be used as an in-vivo functional test to confirm the pathogenicity of unknown variants in genes associated with slow muscle relaxation.

Publication

Molenaar JP, van Kleef E, van Zandvoort E, van Alfen N, van Engelen BG, Voermans NC, Doorduin J. Detecting impaired muscle relaxation in myopathies with the use of motor cortical stimulation. Neuromuscul Disord. 2023 Mar 4;33(5):396-404.