Early diagnosis of amyotrophic lateral sclerosis by threshold tracking and conventional transcranial magnetic stimulation

• Published in: European journal of neurology Vol. 28; no. 9; pp. 3030 - 3039
• Main Authors: Tankisi, Hatice, Nielsen, Christina S.‐Z., Howells, James, Cengiz, Bülent, Samusyte, Gintaute, Koltzenburg, Martin, Blicher, Jakob U., Møller, Anette T., Pugdahl, Kirsten, Fuglsang‐Frederiksen, Anders, de Carvalho, Mamede, Bostock, Hugh
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2021; John Wiley and Sons Inc
• Subjects: Amplitudes; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Biomarkers; Conventional TMS; Degeneration; Diagnosis; Early Diagnosis; Electromyography; Evoked Potentials, Motor; Humans; Magnetic fields; Motor Neuron Disease - diagnosis; Motor neuron diseases; Motor neurone disease; Muscles; Nerve conduction; Original; Patients; Sensitivity; short‐interval intracortical inhibition; Stroke; Threshold tracking TMS; Tracking; Transcranial Magnetic Stimulation; transcranial magnetic stimulation; threshold tracking TMS; amyotrophic lateral sclerosis; short-interval intracortical inhibition; conventional TMS
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.15010

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Background and purpose: Short-interval intracortical inhibition by threshold tracking (T-SICI) has been proposed as a diagnostic tool for amyotrophic lateral sclerosis (ALS) but has not been compared directly with conventional amplitude measurements (A-SICI). This study compared A-SICI and T-SICI for sensitivity and clinical usefulness as biomarkers for ALS. Methods: In all, 104 consecutive patients referred with suspicion of ALS were prospectively included and were subsequently divided into 62 patients with motor neuron disease (MND) and 42 patient controls (ALS mimics) by clinical follow-up. T-SICI and A-SICI recorded in the first dorsal interosseus muscle (index test) were compared with recordings from 53 age-matched healthy controls. The reference standard was the Awaji criteria. Clinical scorings, conventional nerve conduction studies and electromyography were also performed on the patients. Results: Motor neuron disease patients had significantly reduced T-SICI and A-SICI compared with the healthy and patient control groups, which were similar. Sensitivity and specificity for discriminating MND patients from patient controls were high (areas under the receiver operating characteristic curves 0.762 and 0.810 for T-SICI and A-SICI respectively at 1-3.5 ms). Paradoxically, T-SICI was most reduced in MND patients with the fewest upper motor neuron (UMN) signs (Spearman ρ = 0.565, p = 4.3 × 10-6 ). Conclusions: Amplitude-based measure of cortical inhibition and T-SICI are both sensitive measures for the detection of cortical involvement in MND patients and may help early diagnosis of ALS, with T-SICI most abnormal before UMN signs have developed. The gradation in T-SICI from pathological facilitation in patients with minimal UMN signs to inhibition in those with the most UMN signs may be due to progressive degeneration of the subset of UMNs experiencing facilitation.