Abstract Details

Describe our experience using TMS of the motor cortex in a PLS patient cohort.

Primary lateral sclerosis (PLS) is a chronic neurodegenerative disease affecting motor neurons in the motor cortex resulting in progressive motor dysfunction, most often manifesting as limb stiffness, weakness, slowed voluntary movements, and imbalance when walking. There is no known effective treatment or biomarker.

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique used to study cortical states in various neurological disorders, including motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). TMS induces motor evoked potential (MEP) responses when applied to the primary motor cortex, often recording from small hand muscles. Diseases affecting the motor cortex would be expected to alter the normal response. Some investigators have demonstrated motor cortex hyperexcitability in patients with ALS.¹

Data was acquired retrospectively from a multicenter IRB-approved study of patients with a diagnosis of PLS. Baseline characteristics including amyotrophic lateral sclerosis functional rating scale (ALSFRS) and the clinical and physiological motor response to TMS over the motor cortex identified by surface landmarks and neuronavigation equipment. A Mann-Whitney U group test was performed to compare the mean ALSFRS of the responders and non-responders.

Of the 20 patients with PLS studied, 8 patients had resting motor threshold (RMT) less than 83% of machine output (mean 69%, ±10.9) using a monophasic pulse (responders). Twelve (60%) showed no clinical or physiological response (non-responder). ALSFRS data is available for 7/8 responders and 3/12 non-responders, (means 38.3 and 36.7 respectively), p=0.67 (U=12.5). Therefore, there was minimal clinical disease burden despite lack of cortical response. 

Many patients with PLS fail to show a motor response to TMS unrelated to severity of disease burden, suggesting motor cortex inexcitability exists early in the disease course. Our findings suggest that PLS may be an intrinsically different degenerative disease of the motor system.