Parvathi Menon1, Matthew C Kiernan2, Steve Vucic3. 1. Sydney Medical School Westmead, University of Sydney, Sydney, Australia. 2. Neuroscience Research Australia, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. 3. Sydney Medical School Westmead, University of Sydney, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. Electronic address: s.vucic@neura.edu.au.
Abstract
OBJECTIVE: The 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). METHODS: Median 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. RESULTS: The split-hand index (SI), an objective biomarker of preferential atrophy of APB and FDI muscles, was significantly reduced in ALS (SI(ALS) 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. CONCLUSION: The present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development. SIGNIFICANCE: Axonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.
OBJECTIVE: The 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). METHODS: Median and ulnar nerve motor axonal excitability studies were undertaken on 21 ALSpatients 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. RESULTS: The split-hand index (SI), an objective biomarker of preferential atrophy of APB and FDI muscles, was significantly reduced in ALS (SI(ALS) 7.8 ± 1.7, SICONTROLS 13.1 ± 1.1, P<0.0001). Axonal excitability studies identified significant prolongation of strength-duration time constant in ALSpatients 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. CONCLUSION: The present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development. SIGNIFICANCE: Axonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.
Authors: James Howells; José Manuel Matamala; Susanna B Park; Nidhi Garg; Steve Vucic; Hugh Bostock; David Burke; Matthew C Kiernan Journal: J Physiol Date: 2018-10-17 Impact factor: 5.182
Authors: Mehdi A J van den Bos; Nimeshan Geevasinga; Mana Higashihara; Parvathi Menon; Steve Vucic Journal: Int J Mol Sci Date: 2019-06-10 Impact factor: 5.923
Authors: David Czell; Christoph Neuwirth; Markus Weber; Sabine Sartoretti-Schefer; Andreas Gutzeit; Carolin Reischauer Journal: Neurol Res Int Date: 2019-11-07