Cortical excitability distinguishes ALS from mimic disorders

Objective: The diagnosis of amyotrophic lateral sclerosis (ALS) relies on stringent clinical criteria, resulting in diagnostic delay and inevitably the institution of appropriate therapy. Cortical hyperexcitability, as assessed by the novel threshold tracking transcranial magnetic stimulation (TTTMS) technique, appears as an early feature of ALS. Consequently, the present study assessed the diagnostic utility of threshold tracking TMS and developed algorithms to aid the diagnosis of ALS. Methods: Prospective studies were undertaken on a cohort of 156 consecutive patients with neuromuscular symptoms (104 ALS and 52 lower motor neuron syndrome, non-ALS syndrome, NALS) and 62 healthy controls. Results: Short-interval intracortical inhibition (SICI) was significantly reduced in ALS patients (2.4 +/- 0.9%) compared to NALS (8.7 +/- 0.8%, P < 0.0001) and controls (10.6 +/- 0.8%, P < 0.0001). The MEP amplitude and intracortical facilitation were increased, while the cortical silent period duration was reduced in ALS, all indicative of cortical hyperexcitability. Analysis of receiver operating characteristic curves suggested that threshold tracking TMS distinguished ALS from NALS, with averaged (area under curve 0.76, P < 0.0001) and peak SICI 3 ms (area under curve 0.73, P < 0.0001) being the most robust diagnostic markers. Conclusions: The presence of cortical hyperexcitability distinguishes ALS from mimic disorders. Significance: The threshold tracking TMS techniques may prove useful as a diagnostic investigation for ALS. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.