Transcranial magnetic stimulation in ALS: utility of central motor conduction tests

Abstract

Objective: To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS).

Methods: We prospectively studied 60 patients with ALS subtypes (sporadic ALS, familial ALS, progressive muscular atrophy, and primary lateral sclerosis) using single pulse TMS, recording from abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We evaluated three measures: 1) TMS motor response threshold to the ADM, 2) central motor conduction time (CMCT), and 3) motor evoked potential amplitude (correcting for peripheral changes). Patients were evaluated at baseline, compared with controls, and followed every 3 months for up to six visits. Changes were analyzed using generalized estimation equations to test linear trends with time.

Results: TMS threshold, CMCT, and TMS amplitude correlated (p < 0.05) with clinical upper motor neuron (UMN) signs at baseline and were different (p < 0.05) from normal controls in at least one response. Seventy-eight percent of patients with UMN (41/52) and 50% (4/8) of patients without clinical UMN signs had prolonged CMCT. All three measures revealed significant deterioration over time: TMS amplitude showed the greatest change, decreasing 8% per month; threshold increased 1.8% per month; and CMCT increased by 0.9% per month.

Conclusions: Transcranial magnetic stimulation (TMS) findings, particularly TMS amplitude, can objectively discriminate corticospinal tract involvement in amyotrophic lateral sclerosis (ALS) from controls and assess the progression of ALS. While central motor conduction time and response threshold worsen by less than 2% per month, TMS amplitude decrease averages 8% per month, and may be a useful objective marker of disease progression.

Figure Longitudinal tracings from a sample patient with sporadic amyotrophic lateral sclerosis from prestudy through visits 1 to 6 Amplitude and time are standardized across all visits. (A) Transcranial magnetic stimulation (TMS) motor evoked potential (MEP) responses from cortical stimulation over the vertex. Traces are from the right and left abductor digiti minimi (ADM) (A1 and A2), right and left tibialis anterior (TA) (A3 and A4). (B) Peripheral MEP responses stimulating over the cervical spine to the right and left ADM (B5 and B6), and lumbar spine to the right and left TA (B7 and B8).