Detecting impaired muscle relaxation in myopathies with the use of motor cortical stimulation.

Impaired muscle relaxation is a notable feature in specific myopathies. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly halting corticospinal drive. Our aim was to quantify muscle relaxation using TMS in different myopathies with symptoms of muscle stiffness, contractures/cramps, and myalgia and explore the technique's diagnostic potential. In men, normalized peak relaxation rate was lower in Brody disease (n = 4) (-3.5 ± 1.3 s-1), nemaline myopathy type 6 (NEM6; n = 5) (-7.5 ± 1.0 s-1), and myotonic dystrophy type 2 (DM2; n = 5) (-10.2 ± 2.0 s-1) compared to healthy (n = 14) (-13.7 ± 2.1 s-1; all P ≤ 0.01) and symptomatic controls (n = 9) (-13.7 ± 1.6 s-1; all P ≤ 0.02). In women, NEM6 (n = 5) (-5.7 ± 2.1 s-1) and McArdle patients (n = 4) (-6.6 ± 1.4 s-1) had lower relaxation rate compared to healthy (n = 10) (-11.7 ± 1.6 s-1; both P ≤ 0.002) and symptomatic controls (n = 8) (-11.3 ± 1.8 s-1; both P ≤ 0.008). TMS-induced muscle relaxation achieved a high level of diagnostic accuracy (area under the curve = 0.94 (M) and 0.92 (F)) to differentiate symptomatic controls from myopathy patients. Muscle relaxation assessed using TMS has the potential to serve as a diagnostic tool, an in-vivo functional test to confirm the pathogenicity of unknown variants, an outcome measure in clinical trials, and monitor disease progression.