Cortical inexcitability defines an adverse clinical profile in amyotrophic lateral sclerosis

Background and purpose In amyotrophic lateral sclerosis, studies using threshold‐tracking transcranial magnetic stimulation (TMS) have identified corticomotoneuronal dysfunction as a key pathogenic mechanism. Some patients, however, display no motor response at maximal TMS intensities, termed here an ‘inexcitable’ motor cortex. The extent to which this cortical difference impacts clinical outcomes remains unclear. The aim of this study was to determine the clinical profile of patients with inexcitability to TMS. Methods Motor cortex excitability was evaluated using TMS. Patients in whom a motor evoked potential could not be recorded in one or more limbs at maximal TMS intensities were classified as four‐limb or partially inexcitable. Demographic information, clinical variables and survival data were analysed. Results From 133 patients, 40 were identified with inexcitability. Patients with four‐limb inexcitability were younger (P = 0.03) and had lower‐limb disease onset (64%), greater functional disability (P