Spinal Cord
Blair Calancie, PhD,
Professor
Natalia Alexeeva, PhD,
Assistant Professor
In our laboratory of Clinical Neurophysiology, we have two primary interests: 1) spinal cord synaptic reorganization (i.e. plasticity) and regeneration after injury; and 2) intraoperative Monitoring of CNS function during surgery.
Spinal Cord Plasticity after Injury
We use electrophysiological, functional, and kinematic measures to better understand the spontaneous (naturally-occurring) and therapy-related changes in brain and spinal cord function that occur after spinal cord injury (SCI). Much of our work is carried out on human volunteers, many of whom have sustained traumatic spinal cord injury. The information gained from these studies will help expand our understanding of the mechanisms underlying recovery from injury. From a practical viewpoint, this research may also help with subject selection and study effectiveness (i.e. through novel outcome measures we have developed) as our findings are incorporated into clinical trials of novel treatments for SCI.
Several projects in this area are currently underway in our lab. First, we are interested in quantifying the time course and extent of plasticity within the autonomic nervous system after acute SCI in humans, in order to study the basis for autonomic dysreflexia (AD). We typically begin studies within one week of each subject’s acute injury, repeating our measures over the intervening days, weeks, months, and years. Measures include blood pressure (real-time; noninvasive), cutaneous blood flow (laser doppler), and heart-rate variability in response to controlled afferent stimulation designed to mimic the earliest stages of dysreflexia. Our findings to date suggest that AD is a consequence of novel sprouting from afferent fibers lying caudal to a region of SCI onto partially denervated sympathetic preganglionic neurons lying within the thoracic spinal levels. We are also examining central motor conduction and the influence of repetitive, high-frequency transcranial magnetic stimulation (TMS) on brain excitability and muscle recruitment (via EMG). This project is funded through an R01 from NIH.
As many as 15-20% of persons admitted to the hospital with SCI have actually sustained damage to the nerve roots at the base of the cord (the cauda equina). Despite this relatively high incidence, attempts to repair nerve damage are rarely attempted, nor are there even animal models for this type of injury. In response, we have embarked on a multi-disciplinary project to develop and characterize a cauda equina injury model in the rat, and then treat damaged nerve roots with a combination approach involving implantation of a nerve conduit seeded with Schwann cells and nanospheres acting as molecular delivery agents for neurotrophins (e.g. GDNF) and anti-scarring agents. This project includes investigators from Syracuse University (Biomaterials) and from multiple departments within Upstate Medical University. Once we have demonstrated successful nerve root regeneration in the rat, our goal is to first translate this approach to a dog model, and ultimately take this method to the clinic for treating acute cauda equina injury. This project is funded by the New York State Department of Health.
In a recently completed and NIH-funded study, we looked at the role that different forms of rehabilitation play in the recovery of walking ability in persons with chronic (> 1 year post-injury) and neurologically-incomplete spinal cord injury. We compared 3 forms of therapy: 2 methods using body-weight support (support over a treadmill vs support over fixed ground) and comprehensive physical therapy. We found that nearly all subjects showed considerable improvements in gait and other functional tasks, regardless of the treatment they received. The biggest improvements were in balance and maximal walking speed. These results indicate that many persons with chronic, incomplete SCI have significant levels of ‘untapped’ movement capability that can be accessed through novel physical exercise.
Spinal Cord Injury, Recovery and Rehabilitation
Blair Calancie, PhD,
Professor
Natalia Alexeeva, PhD, Assistant Professor
Intraoperative monitoring of CNS function during surgery
We have a long history of developing electrophysiologic tests for helping to prevent neurologic injury to the brain, spinal cord, and nerve roots during surgical procedures that place these structures at risk. We were the first group to publish a technique for monitoring pedicle screw placement in the lumbosacral spine, with a method that is now considered a standard of care in most major spine centers. We also were instrumental in gaining FDA approval of a device for noninvasive stimulation of the brain’s motor cortex during surgery, in order to monitor the motor evoked potential (MEP). This approach, approved by the FDA in August of 2002 and now in widespread use across the US, has been shown to help prevent spinal cord injuries during such procedures as correction of scoliotic deformity, and resection of spinal cord tumors.
We have recently initiated a new study to develop a reliable method for preventing medially directed errors in placement of screws into thoracic-level pedicles. The technique combines key elements of our lumbar pedicle screw and MEP protocols. A thoracic pedicle screw placed medial to the pedicle will enter the canal space, and could potentially compress and/or lacerate the spinal cord. Needless to say, the neurologic consequences of such a placement can be devastating. Preliminary findings from our first 5 subjects indicate the technique is working exceptionally well, and we are confident we have already prevented the misdirection of several screws.
A new area of research we are considering is to apply novel monitoring techniques for detection of cerebral ischemia during cardiac surgery. The incidence of cognitive decline following cardiac surgery can exceed 25% in some studies, yet few centers are actively working to detect these events – caused by air or fat emboli, for example – and intervene with neuroprotective measures. Our goal is to develop an animal stroke model and evaluate the ability of these monitoring techniques to recognize such events.
Finally, we have begun an investigation into the neurologic basis for the development of scoliosis. This work is preliminary in nature, and is a direct result of our work in the operating room environment, summarized above. We hypothesize that the pattern of nerve connections from motor cortex to the spinal cord is different in persons with scoliosis than that seen in persons without scoliosis. To address this possibility, we are: 1) using single-pulse TMS and fMRI to map motor cortex; 2) testing manual dexterity; and 3) quantifying expression of key pathfinding genes. All of these procedures assess in a direct or indirect way the anatomy and physiology of the corticospinal tract; we suspect that abnormalities of this pathway’s innervation of the thoracic spinal cord contribute directly to the development of scoliosis.
