Reappraisal of the Diagnostic Significance of Transcranial Magnetic Stimulation and Triple Stimulation in Amyotrophic Lateral Sclerosis

Objective: To reassess the importance of transcranial magnetic stimulation (TMS), including the triple stimulation technique (TST), to detect upper motor neuron (UMN) involvement in amyotrophic lateral sclerosis (ALS). Methods: In this single-center prospective study, 144 consecutive patients suspected of having motor neuron disease were included over 5 years at the time of diagnosis. All patients were examined clinically and with EMG to assess UMN and lower motor neuron (LMN) involvement, and survival was ascertained 2 years after inclusion of the last patient. Our TMS protocol consisted of TST in both arms and conventional motor evoked potentials (MEP) in arms and legs to assess central motor conduction time (CMCT). Results: The TST could be performed in 142 patients who showed central conduction failure in 63%, which was often markedly asymmetrical, and 50% had prolonged CMCT in the legs. Combining TST in the arms and conventional MEP in the legs showed central abnormalities in 77%. In 62 patients with only signs of LMN involvement at clinical and EMG assessment, the TST amplitude ratio was reduced in 45%, and combined TST to the arms and conventional MEP to the legs disclosed a central abnormality in 61%. Conclusion: The main clinical significance was the subclinical corticospinal involvement at TMS with TST in a large proportion of patients without clinical UMN involvement. TMS with TST is a sensitive, non-invasive electrophysiological method to detect corticospinal dysfunction in ALS.