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Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis

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Abstract

It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is greater than to ankle plantar flexor muscles, despite the finding that plantar flexors are no less active than TA during walking and standing. The present study was undertaken to determine whether there was differential involvement of distal lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate pathophysiological mechanisms of selective muscle involvement. Prospective studies were undertaken in 52 ALS patients, including clinical assessment, disease staging (revised ALS functional rating scale), Medical Research Council sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle dorsiflexors and plantar flexors were used to provide objective measures. A novel ‘split leg index’ was calculated as follows: SLI = CMAPDF ÷ CMAPPF. In ALS, there was significantly greater reduction of MUNE and CMAP amplitude recorded from plantar flexors when compared to dorsiflexors, suggesting preferential involvement of plantar flexor muscles, underpinning a ‘split leg’ appearance. The SLI correlated with clinical plantar flexor strength (R= −0.56, p < 0.001). In no patient did the SLI suggest preferential dorsiflexor involvement. In subgroup analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the present study has established dissociated involvement of muscles acting around the ankle in ALS. We suggest this reflects underlying differences in cortical, descending or local spinal modulation of these muscles.

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Acknowledgments

Dr. Simon gratefully acknowledges funding from the National Health and Medical Research Council of Australia and the Motor Neurone Disease Research Institute of Australia (grant #1039520). This work was supported by funding to Forefront, a collaborative research group dedicated to the study of motor neurone disease, from the National Health and Medical research Council of Australia Program Grant (#1037746). We are grateful to the research participants involved with the ForeFront research studies. Preliminary results from this study were presented in abstract form at the American Academy of Neurology Annual Meeting, San Diego, CA, March 21, 2013: Simon N, Bae JS, Mioshi E, Lin C, Vucic S, Kiernan M. The split leg in amyotrophic lateral sclerosis. Neurology February 12, 2013; 80 (Meeting Abstracts 1): P07.083.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Prince of Wales Clinical School, University of New South Wales, Sydney, Australia

    Neil G. Simon

  2. Brain and Mind Research Institute, The University of Sydney, Room 438, Level 4, M04G, 100 Mallett Street, Camperdown, NSW, 2050, Australia

    Neil G. Simon, Michael Lee & Matthew C. Kiernan

  3. Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Sydney, Australia

    Michael Lee

  4. Department of Neurology, Hallym University, Seoul, Korea

    Jong Seok Bae

  5. Department of Psychiatry, University of Cambridge, Cambridge, UK

    Eneida Mioshi

  6. Exercise Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia

    Cindy S.-Y. Lin

  7. Centre for Clinical Research, The University of Queensland, School of Medicine, Brisbane, Australia

    Casey M. Pfluger

  8. Department of Neurology, Royal Brisbane and Women’s Hospital, Brisbane, Australia

    Robert D. Henderson

  9. Westmead Clinical School, C24 Westmead Hospital, The University of Sydney, Sydney, Australia

    Steve Vucic

  10. Department of Neurology, The Royal London Hospital, London, United Kingdom

    Michael Swash

  11. Sydney Medical School, K25-Medical Foundation Building, The University of Sydney, Sydney, Australia

    David Burke

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  1. Neil G. Simon
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  2. Michael Lee
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  11. Matthew C. Kiernan
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Correspondence to Neil G. Simon or Matthew C. Kiernan.

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Simon, N.G., Lee, M., Bae, J.S. et al. Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis. J Neurol 262, 1424–1432 (2015). https://doi.org/10.1007/s00415-015-7721-8

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  • DOI: https://doi.org/10.1007/s00415-015-7721-8

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