ALS pathophysiology: insights from the split-hand phenomenon.
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.


CONCLUSIONS
The present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development.


CONCLUSIONS
Axonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.
Sydney Medical School Westmead, University of Sydney, Sydney, Australia.
Parvathi
P
Menon
Neuroscience Research Australia, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
Matthew C
MC
Kiernan
Sydney Medical School Westmead, University of Sydney, Sydney, Australia; Neuroscience Research Australia, Sydney, Australia. Electronic address: s.vucic@neura.edu.au.
Steve
S
Vucic
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000503:physiopathology*; D001369:Axons / Q000502:physiology*; D005260:Female; D006225:Hand / Q000294:innervation / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000503:physiopathology*
ALS; Axonal excitability; Split-hand