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December 15, 2020; 95 (24) Article

Association of timing of gabapentinoid use with motor recovery after spinal cord injury

Freda M. Warner, Jacquelyn J. Cragg, Catherine R. Jutzeler, Lukas Grassner, Orpheus Mach, Doris D. Maier, Benedikt Mach, View ORCID ProfileJan M. Schwab, View ORCID ProfileMarcel A. Kopp, John L.K. Kramer
First published September 28, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010950
Freda M. Warner
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Jacquelyn J. Cragg
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Catherine R. Jutzeler
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Lukas Grassner
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Orpheus Mach
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Doris D. Maier
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Benedikt Mach
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Jan M. Schwab
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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  • ORCID record for Jan M. Schwab
Marcel A. Kopp
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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  • ORCID record for Marcel A. Kopp
John L.K. Kramer
From the School of Kinesiology (F.M.W., J.L.K.K.), International Collaboration on Repair Discoveries (ICORD) (F.M.W., J.J.C., J.L.K.K.), and Faculty of Pharmaceutical Sciences (J.J.C.), University of British Columbia, Canada; Department of Biosystems Science and Engineering (C.R.J.), ETH Zurich, Switzerland; Department of Neurosurgery (L.G.), Medical University Innsbruck; Institute of Molecular Regenerative Medicine (L.G.), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Austria; Spinal Cord Injury Center (L.G., O.M., D.D.M., B.M.), Trauma Center Murnau; Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology) (J.M.S., M.A.K.), Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; and QUEST–Center for Transforming Biomedical Research (M.A.K.), Berlin Institute of Health, Germany. Dr. Kramer is currently affiliated with the Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Canada.
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Association of timing of gabapentinoid use with motor recovery after spinal cord injury
Freda M. Warner, Jacquelyn J. Cragg, Catherine R. Jutzeler, Lukas Grassner, Orpheus Mach, Doris D. Maier, Benedikt Mach, Jan M. Schwab, Marcel A. Kopp, John L.K. Kramer
Neurology Dec 2020, 95 (24) e3412-e3419; DOI: 10.1212/WNL.0000000000010950

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Abstract

Objective To explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans.

Methods This is an observational study using a cohort from the European Multi-Centre Study about Spinal Cord Injury. Patient charts were reviewed to extract information regarding the administration and timing of gabapentinoid anticonvulsants. The primary outcome measure was motor scores, as measured by the International Standards for Neurological Classification of Spinal Cord Injury, collected longitudinally in the first year after injury. Sensory scores (light touch and pinprick) and functional measures (Spinal Cord Independence Measure) were secondary outcomes. Linear mixed effects regression models included a drug-by-time interaction to determine whether exposure to gabapentinoids altered recovery of muscle strength in the first year after injury.

Results A total of 201 participants were included in the study and had a median age of 46 and baseline motor score of 50. Participants were mostly men (85%) with sensory and motor complete injuries (50%). Seventy individuals (35%) were administered gabapentinoids within the first 30 days after injury, and presented with similar demographics. In the longitudinal model, the administration of gabapentinoids within 30 days after injury was associated with improved motor recovery when compared to those who did not receive gabapentinoids during this time (3.69 additional motor points from 4 to 48 weeks after injury; p = 0.03). This effect size increased as administration occurred earlier after injury (i.e., a benefit of 4.68 points when administered within 5 days).

Conclusions This retrospective, observational study provided evidence of the beneficial effect of gabapentinoid anticonvulsants on motor recovery after spinal cord injury. More critically, it highlighted a potential time dependence, suggesting that earlier intervention is associated with better outcomes.

Classification of evidence: This study provides Class IV evidence that gabapentinoids improve motor recovery for individuals with acute spinal cord injury.

Glossary

AIS=
American Spinal Cord Injury Association Impairment Scale;
ANOVA=
analysis of variance;
CI=
confidence interval;
EMSCI=
European Multi-Centre Study about Spinal Cord Injury;
ISNCSCI=
International Standards for the Neurological Classification of Spinal Cord Injury;
SCIM=
Spinal Cord Independence Measure

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received December 9, 2019.
  • Accepted in final form August 12, 2020.
  • © 2020 American Academy of Neurology
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