Spinal cord injury (SCI) can result from primary physical insults such as acute trauma,
or secondary insults that result from chronic compression and ischemia. The resultant
neurological impairment leads to high personal and societal burden. There are few
effective therapies to improve function for those living with SCI. Spinal cord
stimulation (SCS) represents a safe and potentially effective treatment for persons with
SCI-related pain and paralysis. The aim of this study is to investigate the potential
clinical utility of SCS delivered transcutaneously in patients at various stages of SCI,
resulting from traumatic and non-traumatic mechanisms. This study will evaluate the
ability to safely stimulate the injured spinal cord at defined intervals and record
autonomic and sensorimotor function of participants across their admission,
rehabilitation, and clinical follow-up.
Various upper and lower extremity-related functional measures will be assessed at
baseline and at established follow-up timepoints across a 12-month period. The safety of
this intervention, and the utility of each outcome measure will be the primary outcome of
the study. To our knowledge, there are no reported clinical trials that have evaluated
multi-modal outcomes of SCS. Furthermore, there are no proposed trials of SCS for these
SCI subtypes across the post-injury spectrum posted to the platform clinicaltrials.gov.
Data obtained from this pilot evaluation will be used to inform an early phase Ib/II
trial of efficacy for improvement of paralysis, autonomic dysfunction, and pain following
SCI.
Over 2.5 million Americans are living with various forms of SCI, equating to substantial
individual and societal burden (1). Acute traumatic SCI average costs alone range from
$380K to $1.4M. This high socioeconomic impact has undergone significant inflation with
estimated annual costs of $4 billion in 1990, recently increasing to $23 billion.
Approximately 13,000 new traumatic SCI events are noted yearly in North America.
Degenerative cervical myelopathy (DCM) represents the most prevalent etiology of
nontraumatic spinal cord (ntSCI) and dysfunction in adults. The prevalence of ntSCI is
order(s) of magnitude higher than that of tSCI.
Together, these conditions significantly impact millions of North Americans often with
greater personal impact that chronic conditions such as diabetes or cardiac disease. The
considerable societal concern due to this individual disability is compounded by the lack
of viable treatment options.
DCM arises from age-related degenerative processes, leading to osteophyte development,
facet joint enlargement, ossification of spinal ligaments, and disk protrusion. These
arthritic changes collectively compress the spinal cord causing injury with associated
ischemia and inflammation. In turn, a similar constellation of symptoms develop including
extremity pain, reduced motor function, numbness, hemodynamic lability, urinary
incontinence, bowel dysfunction, and walking instability contributing towards higher
years lived with disability (DALYs) as well as overall economic burden.
Currently, effective evidence-proven treatments are restricted to surgical decompression
and rehabilitation. Narrative studies have shown that patients living with paralysis want
options for neural modulation therapies, as they perceive the risk-to-benefit ratio of
implanted devices more favorably than healthcare professionals. Given overall suboptimal
outcomes in patients with SCI, it is critical to further enhance both the recovery rates
and the extent of recovery beyond what is achievable through surgical decompression.
Spinal cord stimulation has been shown to mediate functional improvement following acute
traumatic SCI in terms of limb function, ambulation, hand strength, autonomic
dysfunction, intractable pain, and bladder control. The majority of published studies
have applied stimulation during the chronic phase of recovery, and largely in a single or
small group of participants.
Variable applications of SCS for SCI have yet to be demonstrated using multi-modality
stimulation, such as spinal transcutaneous, spinal epidural, and transcranial magnetic
stimulation of the motor cortex. Harkema and colleagues demonstrated that epidural SCS
can return volitional motor control in participants who had none following chronic
thoracic injury. Their work at the University of Louisville also has shown that
multilevel transcutaneous spinal cord stimulation can be applied to several
cervicothoracic regions spanning across the entire limb enlargement, and provide
sensorimotor functional improvements during neurorehabilitation. These approaches have
subsequently been applied at other centers with success for sensorimotor recovery.
The utilization of SCS in managing Failed Back Surgery Syndrome (FBSS), Complex Regional
Pain Syndrome (CRPS), and chronic leg ischemia has been well documented. However, there
is limited evidence indicating the use of SCS in patients with tSCI or ntSCI with regards
to improving motor functions. This application of SCS could identify important
differentiators in neural modulation that will correspond to improved functional
outcomes, patient reported outcome measures (PROM), and quality of life (QoL). Should
differentiators be observed, these conclusions will inform phase Ib/II study of SCS-based
neuromodulation vs standard-of-care rehabilitation. This is directly in line with the
best-of-practice and goals promoted by the leaders in SCI clinical research and
patient-driven goals.
To date, there are no reported clinical trials involving participants in the subacute
phase of tSCI, despite the widely-held belief that this phase offers the greatest
potential for therapeutic intervention to reduce secondary injury and preserve functional
networks.
Likewise, there are no clinical trials examining the role of perioperative SCS in
patients diagnosed with any form of ntSCI (including patients with DCM who undergo
surgical decompression).
The proposed study will directly address whether neuromodulation has a specific
therapeutic potential for persons having sustained acute traumatic and non-traumatic
spinal injuries. This study will specifically address whether this can be achieved with a
non-significant risk device such as transcutaneous spinal cord stimulation. Lastly, this
study will comparatively assess the modalities that can be used to reliably stimulate and
measure the physiologic effects of neuromodulation of the injured spinal cord.
Additionally, this study aims to test the hypothesis that transcutaneous electrical
spinal cord stimulation has equivalent modulatory effect on sensorimotor pathways and
spinal cord function. This study will prospectively record neurologic outcomes to fully
leverage the technologies at our disposal and maximize the potential benefit for each
participant. The subsequent results will further help determine whether spinal cord
neuromodulation can be directly correlated to either patient reported outcome or
functional performance measures. Moreover, to determine feasibility of transcutaneous SCS
at various timepoints after presentation, this study will measure spinal signal outputs
before and after standard-of-care treatments including surgery and intensive neural
rehabilitation.
The preliminary data in support of SCS for individuals with tSCI applied at chronic
recovery phases has demonstrated promising outcomes, potentially ameliorating this severe
condition. The investigation into utilizing SCS as a management approach for acute tSCI
and ntSCI (ie. DCM), in conjunction with surgical interventions and rehabilitation,
represents a promising prospect for enhancing the quality of life of those afflicted with
this debilitating neurological disorder.