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  • A Novel Paraplegia Model in Awake Behaving Rhesus Macaques

    Final Number:

    Max Ostrinsky Krucoff MD; Katie Zhuang PhD; David MacLeod MD; Allen Yin BS ME; Yoon Woo Byun BS BA; Dennis A. Turner MA, MD; Laura Oliveira MD; Mikhail Lebedev PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting

    Introduction: Lower limb paralysis from spinal cord injury (SCI) carries a poor prognosis for recovery and remains a large societal burden. Neural interface and neuroprosthetic research has the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable non-human primate model for paraplegia is hindering its advancement, as current models require cord transections, ischemia, or rhizotomies. Therefore, our group developed a way to recapitulate a thoracolumbar SCI in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for temporary sensorimotor blockade.

    Methods: Two adult rhesus macaques were utilized for this study. Each was implanted with an epidural catheter placed at L4-5 (7 lumbar vertebrae, anesthetic delivered L1-sacrum) using fluoroscopic guidance and secured to a subcutaneous injection port. After healing, each animal was trained in treadmill walking. Aliquots of 1-2% lidocaine with and without 1:200,000 epinephrine were percutaneously injected into the ports while surface EMGs recorded muscle activity from the quadriceps and gastrocnemii.

    Results: Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 mins in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards. Both catheter-port systems remain patent after two and four months.

    Conclusions: Here we demonstrate a technique to induce paraplegia in non-human primates for an investigational time block, thus negating the need to permanently injure otherwise high-value research animals for development of certain neural interface paradigms. Interfaces that decode signals from either the brain or proximal spinal cord to activate simulations on a computer, exoskeletons, leg musculature via functional electrical stimulation (FES), or distal peripheral nerves will be the most likely to benefit.

    Patient Care: Neural interface development is crucial for patients with spinal cord injury who currently have no hope for functional recovery on their own. However, there is no currently no sustainable non-human primate model with which to develop these techniques in the laboratory (animals with cord transections or other permanent neurological injuries tend to self-mutilate and lose bowel/bladder function, therefore are not good candidates for high value chronic implants). Our model is simple enough for any primate lab to incorporate and works well. Ideally, this should help streamline development and translation of neural interfacing techniques for paralyzed patients.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of having a sustainable non-human primate paraplegia model for neural interface research, 2) Discuss possible applications for the model and how it might help translate theoretical prosthetic ideas into practical applications, and 3) Identify limitations to the model and which applications and paradigms it will not be helpful in developing

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