By John L. Lin, M.D., FACP, FAAPMR
From ATLANTA Medicine Vol. 84, No. 4
As a subspecialty of rehabilitative medicine, spinal cord injury medicine has evolved extensively since its first historical description 5,000 years ago by the Egyptian physician Imhotep on a papyrus as “an ailment not to be treated.”
More than 2,000 years ago, Hippocrates treated spinal injuries with traction and recognized the correlation of spinal cord injury and paralysis. Galen deduced that respiratory dysfunction in animals corresponded with high spinal cord transection. The middle ages saw the evolution of spinal manipulations in reducing thoraco-lumbar dislocations. By Renaissance, surgical refinement brought forth treatments with laminectomy. The year 1860 saw descriptive details of incomplete hemiparetic spinal cord injury by Brown-Sequard and introduction of the term “quadriplegia” in 1881.
Despite the increasing medical knowledge by the turn of 20th century, mortality from spinal cord injury reached 95 percent, with four in five succumbing within two weeks of a cervical injury. It was not until the second half of the last century that progression of spinal cord medicine has taken a significant leap forward with the introduction of halo in managing high cervical injury, along with other spinal orthotics, improved bladder management in decreasing mortality due to reflux nephropathy, evolution of bladder surgical interventions, functional electrical stimulation for paralytic muscles and transcutaneous electrical stimulation for afferent dysesthesia as well as enhanced imaging with computed tomography and magnetic resonance imaging amongst other technological advances.
Nevertheless, the last decade has witnessed geometric growth in advances of spinal cord medicine, from researches in regeneration and neuroprotection to promotion of neuroplasticity. Other advances include functional electrical stimulation, advanced electronic/computer assisted mobility and assistive devices and novel implanted organ function augmentation devices, in addition to the myriad of pharmacological agents treating secondary co-morbidities as well as enhanced understanding of spinal cord medicine through multi-center collaborations.
Although stem cell transplantation has been a well-recognized research front for spinal cord injury, decades of hard work has yet to result in the panacea that was once sought. Initial studies involving amphibian models demonstrated ependymal regeneration. Mammalian models were less robust in inducible regeneration, although it was noted that lifelong proliferation and differentiation of spinal tissues occur in uninjured rodent models.
Around the world, multiple sources of stem cells have been studied. These include autologously derived bone marrow progenitor cells, fetal neural tissues and allelic human embryonic stem cells. The latest of these clinical trials in the U.S. was the oligodendrocyte progenitor cell implantation trial involving several spinal cord injury model system centers. Without any breakthrough regeneration and recovery, the trial has ceased to enroll further subjects since the second half of 2012, although follow through for post-injection evolution of complications continues.
Though not technically stem cell in nature, other cell therapies and surgical implantations are also noteworthy. The autologous incubated macrophage implantation attempted to minimize secondary spinal cord injury at the cellular level from forming intra-spinal scar tissues that are thought to be prohibitive of neurological regeneration. In addition, hope was to have macrophage derived growth factor stimulate neuronal regeneration. Lack of funding and subject recovery ceased further trial enrollment in 2006.
The discovery of potential regenerative ability of olfactory ensheathing cells lead to trials in Portugal, Australia, and Russia. Despite early encouraging anecdotes in non-controlled observations, no success has been duplicated under the rigor of scientific methodology. Other trials, too, including peripheral nerve derived Schwann cell transplantation and omental transplantation have not proven to be efficacious.
Still, other non-cell therapy based interventions have garnered enthusiasms since the methylprednisolone trials of 1980s, undaunted by the lack of success of GM-1 ganglioside and 4-aminopyridine. These treatments aim at halting the secondary spinal cord injury associated with the molecular level of chemical releases and physiological sequelae of primary assault causing spinal cord injury.
The most publicized of these is undoubtedly the hypothermia treatment received by a national football league player from Buffalo, N.Y., who sustained a tetraplegic injury during a kickoff tackle. Although touted as a significant advancement and re-awakening of a decades-old intervention due to the significant neurological recovery of the football player in subsequent months, the much vaunted hypothermia received much criticism in the medical/scientific community, both for the haphazard administration by the medical staff as well as for the lack of scientific evidence and medical safety of the intervention. However, other neuroprotective agents under trial today such as basic fibroblast growth factor infusion continue to engender interest and promise. Enrollment of the latter continues yet at Grady Hospital’s trauma center.
Non-pharmacological interventions for spinal cord injury have entered the fray over the last decade. These mostly come at the heels of suggestive feline and rodent models. The most widely studied are the body weight supported resistive treadmill ambulation with robotic assistance. Data showing improved gait, decreased supportive staff assistance and some improved spasticity for motor incomplete syndrome with potential for ambulation using assistive devices such as a walker reflects the growing popularity of this intervention. Data on gait or neurological improvement for motor-complete patients are unproven, although effects on secondary endpoints, e.g. cholesterol and glycemic markers, are being investigated.
An anecdotal case presentation over the last year has fueled the speculation on the effect of epidural spinal stimulation on signal conduction through the injured spinal cord and possible effect on neuronal recovery. This, along with functional magnetic stimulation, reflects the continued interests in advances in neurological recovery using non- pharmacological interventions.
Despite the lack of significant progress in neurological recovery, technical advances continue to improve the quality of life for persons living with spinal cord injury. Recovery in rehabilitation medicine may not always reflect physiological changes, but rather, functional adaptations, psychological normalization and social re-integration. To that extent, improved computer technology has brought environmental/ computer control to those with high-level tetraplegia using the eye gaze system. Those with ventilator dependence have seen non-invasive ventilation and diaphragm pacing systems replace permanent ventilation. Non-functional tetraplegics now have tongue control drive possibilities for power wheelchair control. Paretic limbs have seen improved and accelerated functional return with devices such as functional electrical stimulation coupled with computational resistance to maintain muscle bulk and minimize atrophy.
Implantable sacral nerve stimulators improve urinary function. External neuro-electrical stimulator of the peroneal nerve during active gait cycle improves ambulation and minimizes contact orthotics that may lead to skin pressure ulcers. Most intriguingly, wearable robotic devices such as exoskeletons are making the transition from military applications to aiding paraplegics in ambulation. While mostly still in pre-market stages, the next years will witness persons with paraplegic spinal cord injuries walk without the use of their spinal cord.
In summary, it is an exciting time to be involved in spinal cord medicine. Advances on multiple fronts, scientifically, technically, functionally and even accessibility-wise, such as through the evaluation and adaptation of the Americans with Disability Act by the European Union, ultimately lead to better lives for persons with spinal cord injury and a society with equality and independence for all.
John L. Lin, M.D., FACP, FAAPMR is a staff physiatrist in the Spinal Cord Injury Program at the Shepherd Center. Dr. Lin is board certified in physical medicine and rehabilitation, spinal cord injury medicine and internal medicine and is a graduate of Medical University of South Carolina and Emory University. He completed a dual residency in internal medicine and rehabilitation medicine at Temple University Hospital in Philadelphia, where he also served as the chief resident in his final year. Dr. Lin is an assistant professor at Emory University School of Medicine and has served as Associate Residency Program Director for the Department of Rehabilitation Medicine at Emory. He has also served as the director of Spinal Cord Injury Service and as a primary- care physician at the Atlanta Veterans Administration Medical Center.