Beyond ALS: split-hand syndrome in immune-mediated motor neuropathies

Split-hand syndrome describes selective wasting and weakness of the abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with relative preservation of the abductor digiti minimi (ADM). Beyond clinical definition, two neurophysiological ratios and one index have been proposed to quantify this pattern. It is considered a potential diagnostic criterion for amyotrophic lateral sclerosis (ALS). Its occurrence in immune-mediated neuropathies, as differential diagnoses, remains unclear. We aimed to investigate clinical and electrophysiological manifestations of split-hand syndrome in multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) compared to ALS.

We prospectively examined 26 MMN, 16 MADSAM, and 22 ALS patients. All underwent neurological examination and neurophysiological measurements of compound muscle action potentials (CMAP) from the APB, FDI, and ADM bilaterally after median (APB) and ulnar nerve (FDI, ADM) stimulation. Split-hand ratios (APB/ADM; FDI/ADM) and split-hand index (SI) were calculated.

Clinical split-hand syndrome was present in 16/26 (62%) MMN, 7/16 (44%) MADSAM, and 12/22 (54%) ALS patients. Electrophysiological criteria (abnormal split-hand ratios or SI; ≥ 1 parameter fulfilled) were similarly frequent across groups (MMN 17/26, 65%, MADSAM 11/16, 69%, and ALS 16/22, 73%). CMAP ratios and SI did not differ between groups in the overall analysis and showed no correlation with disease duration or severity. Diagnostic models showed limited discriminatory power (area under the curve ≤ 0.61).

Split-hand syndrome occurs in MMN, MADSAM, and ALS at comparable frequencies and lacks robust or consistent diagnostic discrimination across disease groups.