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Frontiers in Neurology


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Front. Neurol. | doi: 10.3389/fneur.2019.00565

Reassessment of Split-Leg Signs in Amyotrophic Lateral Sclerosis: Differential Involvement of the Extensor digitorum brevis and Abductor hallucis muscles

Zhi-li Wang1,  Liying Cui2*, Mingsheng Liu2, Kang Zhang2, Shuangwu Liu2,  Qingyun Ding2 and Youfang Hu3
  • 1Department of Medical Oncology, Peking Union Medical College Hospital (CAMS), China
  • 2Peking Union Medical College Hospital (CAMS), China
  • 3Peking Union Medical College Hospital (CAMS) , Beijing , China, China

Background: The muscles patterns involved in the “split-leg” syndrome of amyotrophic lateral sclerosis (ALS) remain controversial. We sought to evaluate and reassess the pattern of extensor digitorum brevis (EDB) and abductor hallucis (AH) muscle involvement in the split-leg syndrome in ALS.
Methods: We recruited 60 consecutive patients with ALS and 25 healthy controls (HCs). Compound muscle action potentials (CMAPs) and F-waves were recorded over the EDB and AH muscles in all subjects. For comparison, we classified patients into two categories based on the presence or absence of lower limbs symptoms.
Results: The EDB/AH CMAP amplitude ratio was significantly reduced in patients with affected legs (0.33 ± 0.21, P = 0.007), whereas patients with unaffected legs had a ratio similar to that of HCs. The EDB/AH ratios for the F-wave latencies, mean F-wave amplitude, mean F/M amplitude ratio, and the persistence of the total repeater F-wave shapes (index Freps) of the EDB-AH were significantly increased in the affected leg group, whereas the EDB/AH ratio for F-wave persistence was significantly reduced. These findings indicated greater loss of lower motor neurons (LMNs) innervating the EDB and dysfunction of spinal motoneurons innervating the EDB. In the unaffected leg group, the EDB, but not the AH, F-wave latencies, mean and maximal F/M amplitude ratios, and index Freps were significantly altered. Receiver operating characteristic curve analysis suggested that the EDB F-wave latencies, mean F/M amplitude ratios, and index Freqs (area under the curve [AUC] > 0.8) more strongly differentiated patients with ALS from HCs compared with the EDB/AH CMAP amplitude ratio (AUC = 0.61). Notably, the EDB maximal F-wave latency and index Freqs reliably differentiated patients with unaffected legs HCs, with AUCs of 0.83 (95% CI 0.76–0.91) and 0.81 (95% CI 0.72–0.89), sensitivities of 76 and 78%, and specificities of 76 and 78%, respectively.
Conclusions: These results suggest preferential EDB compared with AH involvement in the split-leg syndrome of ALS. The EDB maximal F-wave latency and index Freqs robustly differentiated patients with ALS from HCs, which might facilitate an earlier identification of ALS.

Keywords: Amyotrophic Lateral Sclerosis, F-wave, motor neuron, Extensor digitorum brevis muscle, Motor Neuron Disease, Split leg

Received: 21 Jan 2019; Accepted: 13 May 2019.

Edited by:

Francesca Trojsi, Università degli Studi della Campania Luigi Vanvitelli Caserta, Italy

Reviewed by:

Evangelos Anagnostou, National and Kapodistrian University of Athens, Greece
Susana Pinto, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal  

Copyright: © 2019 Wang, Cui, Liu, Zhang, Liu, Ding and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Liying Cui, Peking Union Medical College Hospital (CAMS), Beijing, China,