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Towards Clinical Testing of Intraspinal Microstimulation for Restoration of Walking after Spinal Cord Injury
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- Author / Creator
- Toossi, Amirali
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The overall goal of this thesis was to advance intraspinal microstimulation (ISMS) towards clinical testing for the purpose of restoring walking after spinal cord injury. ISMS implants focus on restoring mobility after spinal cord injury by activating the intact spinal motor networks below the injury. This is done by delivering electrical stimulation to the ventral horns of the lumbosacral enlargement through implanted microelectrodes, and activating the motoneuronal pools controlling the leg muscles. Preclinical studies have shown that by tapping into the spinal cord motor networks, ISMS can activate synergistic leg muscles across single or multiple joints. This is shown to be the case even after a complete spinal cord injury. Combining the functional synergies using physiologically-based control algorithms has allowed ISMS to produce balanced weight-bearing standing and over-ground walking. Standing and walking produced by ISMS are significantly more fatigue-resistant than those produced with intramuscular electrical stimulation. Collectively, these results suggest that ISMS has potential to become an effective intervention for restoring leg mobility after a complete spinal cord injury.This thesis aimed to move ISMS closer to clinical testing by addressing two main questions: 1) What are the design specifications for chronic ISMS implants in humans? 2) Where should the ISMS implants be placed in the human spinal cord for functional success? The first question was addressed with a focus on the requirements for mechanical stability of ISMS implants in the spinal cord. The biomechanics of the spine and spinal cord near the implant region was studied in domestic pigs as a model for the human spinal anatomy. The critical forces for dislodging implanted electrodes were also measured. Based on this information, design specifications for mechanically stable implants were provided.While the second question is best answered by direct investigation of the functional organization of the motoneuronal pools (functional map) in the lumbosacral enlargement of humans, this thesis took an intermediate step. The functional map of the lumbosacral enlargement was obtained in non-human primates for the first time. Results showed that ISMS can produce functional leg movements in monkeys, similar to those studied in smaller animals. They also suggest that the relative organization of the motoneuronal pools in the functional maps of monkeys is similar to those known for cats. The findings demonstrated that the functional maps are preserved across species. Therefore, the maps from the monkeys and cats will guide the first clinical tests of ISMS. In preparation for the first clinical testing of ISMS, a spinal-stereotactic-system was also developed for accurate placement of ISMS implants in the human spinal cord. This system is mounted onto the subject’s spine to minimize relative movement between the implanted electrode and the stereotactic system. It also utilizes intraoperative ultrasound imaging for target selection and guidance of the implantation trajectory. The targeting accuracy of this stereotactic system for implants into the ventral horns was found to be <0.32 mm. This system will be used for the first clinical tests of ISMS for walking. Finally, the effect of a common clinical neurosurgical anesthetic protocol on the motor responses to ISMS was investigated. Understanding the effect of anesthesia on the evoked responses to ISMS is critical for optimal placement of its microelectrodes. It is also important for the correct interpretation of the intraoperative responses to ISMS, especially in human studies. Therefore, a comparison was made between the effect of a common clinical neurosurgical anesthetic protocol and those of two anesthetic protocols commonly used in preclinical studies. Results demonstrated that a clinical total intravenous anesthesia (TIVA) protocol with propofol allows ISMS to produce strong movements with large ranges of motion. The responses produced under this clinical protocol were also not different from those produced under the most common preclinical anesthesia (pentobarbital) used in ISMS studies. Taken together, these results suggest that clinical TIVA protocol with propofol is a suitable anesthetic protocol for use in humans. It also suggests that clinical intraoperative observations would be comparable with those in the preclinical literature. Collectively, this thesis proposed mechanical design specifications for chronic ISMS implants in large animals and addressed the requirements for the first clinical testing of ISMS.
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- Graduation date
- Spring 2019
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.