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Transcranial magnetic stimulation in ALS

Utility of central motor conduction tests

From the Clinical Motor Physiology Laboratory (A.G.F., Q.P.Y., P.P., Y.F., W.A.S., J.Y., S.L.P.) and Eleanor and Lou Gehrig MDA/ALS Research Center (L.P.R., H.M.), Department of Neurology, and Department of Biostatistics and Sergievsky Center (M.X.T.), Columbia University Medical Center, New York, NY.

Address correspondence and reprint requests to Dr. Seth L. Pullman, The Neurological Institute, 710 West 168th Street, New York, NY 10032 sp31{at}columbia.edu

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.

Abbreviations: ADM = abductor digiti minimi; ALS = amyotrophic lateral sclerosis; ANOVA = analysis of variance; CI = confidence interval; CMAP = compound motor action potential; CMCT = central motor conduction time; DTR = deep tendon stretch reflex; fALS = familial ALS; GEE = generalized estimation equations; LMN = lower motor neuron; MEP = motor evoked potential; PLS = primary lateral sclerosis; PMA = progressive muscular atrophy; sALS = sporadic ALS; TA = tibialis anterior; TMS = transcranial magnetic stimulation; UMN = upper motor neuron.

Funded by NIH grant NS41672-01 (H.M.), the Muscular Dystrophy Association, and MDA Wings Over Wall Street.

Disclosure: The authors report no disclosures.

Received August 1, 2008. Accepted in final form October 31, 2008.

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