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The Effect of Non-Gabapentinoid Anticonvulsants on Sensorimotor Recovery After Human Spinal Cord Injury

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Abstract

Background

Recent observational studies have shown an association between gabapentinoid anticonvulsants and greater motor recovery after spinal cord injury. There is preclinical evidence to suggest that other anticonvulsants, such as sodium channel blockers, may also confer beneficial effects.

Purpose

The aim of the current study was to determine if non-gabapentinoid anticonvulsants were associated with neurological recovery after acute, traumatic spinal cord injury.

Methods

This was an observational cohort study using data from the Sygen clinical trial. The primary outcome was total motor score recovery in the first year after injury. Anticonvulsant use was extracted from concomitant medication records; individuals were classified based on early administration (within 30 days of injury), or late/no administration. Motor recovery was compared using linear mixed effects regression models with a drug-by-time interaction, and adjustment for confounders. A secondary analysis incorporated a propensity score matched cohort.

Results

Of the cohort (n = 570), 6% received anticonvulsants (carbamazepine, phenytoin, clonazepam, phenobarbital, and valproic acid) early after injury. After adjustments for initial injury level and severity, early exposure to non-gabapentinoid anticonvulsants was not associated with motor neurological outcomes (p = 0.38 for all anticonvulsants, p = 0.83 for sodium channel blockers, p = 0.82 in propensity-matched cohort).

Conclusion

Non-gabapentinoid anticonvulsant exposure was not associated with greater or lesser neurological recovery. This suggests that these medications, as administered for the acute management of spinal cord injury, do not impact long-term neurological outcomes.

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Author information

Authors and Affiliations

  1. School of Kinesiology, University of British Columbia, Vancouver, BC, Canada

    Freda M. Warner, Catherine R. Jutzeler & John K. Kramer

  2. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Freda M. Warner, Catherine R. Jutzeler, Jacquelyn J. Cragg, Bobo Tong & John K. Kramer

  3. Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland

    Catherine R. Jutzeler

  4. Department of Neurosurgery and Center for Spinal Cord Injuries, Trauma Center Murnau, Murnau, Germany

    Lukas Grassner

  5. Department of Neurosurgery, Medical University Innsbruck, Innsbruck, Austria

    Lukas Grassner

  6. Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria

    Lukas Grassner

  7. Axon Growth and Regeneration Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Frank Bradke

  8. Department of Medical Imaging, University of Saskatchewan, Saskatoon, SK, Canada

    Fred Geisler

Authors
  1. Freda M. Warner
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  2. Catherine R. Jutzeler
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  3. Jacquelyn J. Cragg
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  4. Bobo Tong
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  5. Lukas Grassner
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  6. Frank Bradke
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  7. Fred Geisler
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  8. John K. Kramer
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Corresponding author

Correspondence to John K. Kramer.

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Funding

F. Warner is supported by the University of British Columbia Four Year Fellowship. Dr. Jutzeler is supported by the International Foundation for Research in Paraplegia (IRP) and is a Craig H. Nielsen Foundation postdoctoral fellow. Dr. Cragg is supported by the Society in Science—Branco Weiss Postdoctoral Fellowship and the Michael Smith Foundation for Health Research (MSFHR). Dr. Kramer is supported by a Scholar Award from the MSFHR and Rick Hansen Institute as well as the Canadian Institutes of Health Research (CIHR), ERA-NET NEURON, Wings for Life, and IRP.

Conflict of interest

The authors Freda M. Warner, Catherine R. Jutzeler, Jacquelyn J. Cragg, Bobo Tong, Lukas Grassner, Frank Bradke, Fred Geisler, and John K. Kramer declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Ethical approval

Approval for this study (secondary analysis) was received from an institutional ethical standards committee on human experimentation at the University of British Columbia.

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Warner, F.M., Jutzeler, C.R., Cragg, J.J. et al. The Effect of Non-Gabapentinoid Anticonvulsants on Sensorimotor Recovery After Human Spinal Cord Injury. CNS Drugs 33, 503–511 (2019). https://doi.org/10.1007/s40263-019-00622-6

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  • DOI: https://doi.org/10.1007/s40263-019-00622-6

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