Proof of concept for multiple nerve transfers to a single target muscle

  1. Matthias Luft
  2. Johanna Klepetko
  3. Silvia Muceli
  4. Jaime Ibáñez
  5. Vlad Tereshenko
  6. Christopher Festin
  7. Gregor Laengle
  8. Olga Politikou
  9. Udo Maierhofer
  10. Dario Farina
  11. Oskar C Aszmann
  12. Konstantin Davide Bergmeister  Is a corresponding author
  1. Medical University of Vienna, Austria
  2. Chalmers University of Technology, Sweden
  3. Imperial College London, United Kingdom
  4. Karl Landsteiner University of Health Sciences, Austria

Abstract

Surgical nerve transfers are used to efficiently treat peripheral nerve injuries, neuromas, phantom limb pain or improve bionic prosthetic control. Commonly, one donor nerve is transferred to one target muscle. However, the transfer of multiple nerves onto a single target muscle may increase the number of muscle signals for myoelectric prosthetic control and facilitate the treatment of multiple neuromas. Currently, no experimental models are available for multiple nerve transfers to a common target muscle in the upper extremity. This study describes a novel experimental model to investigate the neurophysiological effects of peripheral double nerve transfers. For this purpose, we developed a forelimb model to enable tension-free transfer of one or two donor nerves in the upper extremity. Anatomic dissections were performed to design the double nerve transfer model (n=8). In 62 male Sprague-Dawley rats the ulnar nerve of the antebrachium alone (n=30) or together with the anterior interosseus nerve (n=32) was transferred to reinnervate the long head of the biceps brachii. Before neurotization, the motor branch to the biceps’ long head was transected at the motor entry point and resected up to its original branch to prevent auto-reinnervation. In all animals, coaptation of both nerves to the motor entry point could be performed tension-free. Mean duration of the procedure was 49 ± 13 min for the single nerve transfer and 78 ± 20 min for the double nerve transfer. Twelve weeks after surgery, muscle response to neurotomy, behavioral testing, retrograde labeling and structural analyses were performed to assess reinnervation. These analyses indicated that all nerves successfully reinnervated the target muscle. No aberrant reinnervation was observed by the originally innervating nerve. Our observations suggest a minimal burden for the animal with no signs of functional deficit in daily activities or auto-mutilation in both procedures. Furthermore, standard neurophysiological analyses for nerve and muscle regeneration were applicable. This newly developed nerve transfer model allows for the reliable and standardized investigation of neural and functional changes following the transfer of multiple donor nerves to one target muscle.

Data availability

Muscle mass data have been deposited in Dryad under the DOI: https://doi.org/10.5061/dryad.3j9kd51jb.Retrograde labeling data has been deposited in Dryad under the DOI: https://doi.org/10.5061/dryad.6q573n60c.

The following data sets were generated

Article and author information

Author details

  1. Matthias Luft

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9161-4125
  2. Johanna Klepetko

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Silvia Muceli

    Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0310-1021
  4. Jaime Ibáñez

    Department of Bioengineering, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Vlad Tereshenko

    Clinical Laboratory for Bionic Extremity Reconstruction, Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7761-5191
  6. Christopher Festin

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Gregor Laengle

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1011-3482
  8. Olga Politikou

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Udo Maierhofer

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  10. Dario Farina

    Department of Bioengineering, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7883-2697
  11. Oskar C Aszmann

    Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  12. Konstantin Davide Bergmeister

    Karl Landsteiner University of Health Sciences, St. Poelten, Austria
    For correspondence
    kbergmeister@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3910-9727

Funding

European Research Council (ERC Synergy Grant: No 810346)

  • Matthias Luft
  • Vlad Tereshenko
  • Christopher Festin
  • Gregor Laengle
  • Olga Politikou
  • Udo Maierhofer
  • Dario Farina
  • Oskar C Aszmann
  • Konstantin Davide Bergmeister

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The protocols for the experiments were approved by the ethics committee of the Medical University of Vienna and the Austrian Ministry for Research and Science (reference number BMBWF- 66.009/0413-V/3b/2019) and strictly followed the principles of laboratory animal care as recommended by the Federation of European Laboratory Animal Science Associations (FELASA).

Copyright

© 2021, Luft et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,149
    views
  • 159
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Matthias Luft
  2. Johanna Klepetko
  3. Silvia Muceli
  4. Jaime Ibáñez
  5. Vlad Tereshenko
  6. Christopher Festin
  7. Gregor Laengle
  8. Olga Politikou
  9. Udo Maierhofer
  10. Dario Farina
  11. Oskar C Aszmann
  12. Konstantin Davide Bergmeister
(2021)
Proof of concept for multiple nerve transfers to a single target muscle
eLife 10:e71312.
https://doi.org/10.7554/eLife.71312

Share this article

https://doi.org/10.7554/eLife.71312

Further reading

    1. Neuroscience
    Tai-Ying Lee, Yves Weissenberger ... Johannes C Dahmen
    Research Article

    Hearing involves analyzing the physical attributes of sounds and integrating the results of this analysis with other sensory, cognitive, and motor variables in order to guide adaptive behavior. The auditory cortex is considered crucial for the integration of acoustic and contextual information and is thought to share the resulting representations with subcortical auditory structures via its vast descending projections. By imaging cellular activity in the corticorecipient shell of the inferior colliculus of mice engaged in a sound detection task, we show that the majority of neurons encode information beyond the physical attributes of the stimulus and that the animals’ behavior can be decoded from the activity of those neurons with a high degree of accuracy. Surprisingly, this was also the case in mice in which auditory cortical input to the midbrain had been removed by bilateral cortical lesions. This illustrates that subcortical auditory structures have access to a wealth of non-acoustic information and can, independently of the auditory cortex, carry much richer neural representations than previously thought.

    1. Genetics and Genomics
    2. Neuroscience
    Thomas P Spargo, Lachlan Gilchrist ... Alfredo Iacoangeli
    Research Article

    Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Parkinson’s disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between ALS and AD. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at: https://github.com/ThomasPSpargo/COLOC-reporter.