Diagnostic utility of threshold tracking TMS paradigms in early amyotrophic lateral sclerosis

Objective: Threshold tracking transcranial magnetic stimulation (TMS) has exhibited utility as a diagnostic technique in Amyotrophic Lateral Sclerosis (ALS). Different threshold tracking paradigms have recently been proposed. The present study assessed the diagnostic utility of serial ascending and parallel threshold tracking TMS in ALS. Methods: Threshold tracking TMS was undertaken on 90 prospectively recruited participants suspected of ALS. Short interval intracortical inhibition (SICI) was recorded with serial ascending and parallel threshold tracking paradigms between Interstimulus Interval (ISI) 1-to-7 ms. The primary outcome measure was differences in diagnostic utility of the paradigms in differentiating ALS from ALS mimicking disorders using receiver operating characteristic (ROC) analysis (DeLong statistical method). Results: Reduction in SICI reliably differentiated ALS from mimic disorders, irrespective of the threshold tracking paradigm. Comparison of area under the curve (AUC) established a significantly higher value for mean SICI (1-7 ms) with the serial ascending SICI paradigm (0.81, 95 % confidence interval 0.72-0.91) compared to the parallel paradigm (SICI 0.72, 95 % confidence interval 0.61-0.83, p = 0.0065). The better diagnostic utility of serial ascending paradigm was evident for SICI recorded between 1-to-5 ms, and was maintained irrespective of disease onset site, degree of functional impairment, and the degree of lower motor neuron dysfunction. A comparable diagnostic utility across threshold tracking paradigms was evident in ALS participants who presented with a relative paucity of upper motor neuron signs. Conclusion: While threshold tracking TMS reliably differentiated ALS from mimic disorders, the present study established better diagnostic utility with the serial ascending threshold tracking TMS paradigm. Significance: The serial ascending threshold tracking TMS should be used in a clinical setting as a diagnostic tool for ALS.