ALS pathophysiology: Insights from the split-hand phenomenon

• Axonal dysfunction, as assessed by the axonal excitability technique, is a ubiquitous feature in amyotrophic lateral sclerosis (ALS) evident across the range of intrinsic hand muscle.
• The split-hand phenomena is a specific clinical feature of ALS.
• Axonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.

ObjectiveThe aim of the present study was to assess whether peripheral mechanisms, mediated through axonal dysfunction, may contribute to development of the split-hand in amyotrophic lateral sclerosis (ALS).MethodsMedian and ulnar nerve motor axonal excitability studies were undertaken on 21 ALS patients with motor responses recorded over the abductor pollicis brevis (APB), abductor digit minimi (ADM) and first dorsal interosseous (FDI) muscles, and results compared to 24 controls.ResultsThe split-hand index (SI), an objective biomarker of preferential atrophy of APB and FDI muscles, was significantly reduced in ALS (SIALS 7.8 ± 1.7, SICONTROLS 13.1 ± 1.1, P < 0.0001). Axonal excitability studies identified significant prolongation of strength-duration time constant in ALS patients when recording over the APB (P < 0.05) and ADM axons (P < 0.05) but not FDI axons (P = 0.22). Greater changes in depolarising threshold electrotonus were also evident across the range of intrinsic hand muscles and were accompanied by increases of superexcitability in APB (P < 0.01) and FDI (P < 0.05) axons.ConclusionThe present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development.SignificanceAxonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.