A prospective study on split-hand index as a biomarker for the diagnosis of amyotrophic lateral sclerosis

To determine the practical diagnostic utility of split-hand index (SI) values calculated from F-wave persistence (SI_FP) and the F/M amplitude ratio (SI_F/M) for differentiating patients with amyotrophic lateral sclerosis (ALS) from other conditions. Methods: This prospective study recruited consecutive patients from Peking Union Medical College Hospital, China, between June 2019 and December 2019. Patients 18-80 years old who had clinical neuromuscular symptoms affecting the upper limbs and required electrophysiological examinations to aid diagnosis were eligible. Compound muscle action potentials (CMAPs) and F-waves recorded from the abductor pollicis brevis (APB), first dorsal interosseous muscle (FDI), and abductor digiti minimi (ADM) were examined. SI_FP and SI_F/M were calculated as: SI = (APB × FDI)/ADM. The sensitivity and specificity of SI_FP and SI_F/M in differentiating ALS from non-ALS conditions were derived using receiver operating characteristic (ROC) curves. Results: A total of 309 participants, comprising 91 (29.4%) with ALS and 218 (70.6%) with other neuromuscular disorders, were enrolled after 54 were excluded. SI_FP was significantly reduced and SI_F/M increased in the ALS group compared with the non-ALS group (p < 0.001). By ROC curve analysis, an SI_FP cutoff of 73.3 showed 85.7% sensitivity and 80.7% specificity for differentiating ALS from non-ALS. SI_F/M and SI_CMAP showed lower sensitivity (67% and 75.8%, respectively, p < 0.001) than SI_FP for ALS diagnosis. SI_FP and SI_F/M combined did not outperform SI_FP alone. Conclusion: SI_FP could be a sensitive, noninvasive neurophysiological diagnostic marker for ALS patients with affected upper limbs. In particular, an SI_FP value of 73.3 might be the optimal cutoff for diagnosing ALS.