Impact of long-term epidural electrical stimulation enabled task-specific training on secondary conditions of chronic paraplegia in two humans

In the recent case report by Beck et al.,¹ the authors discuss off-target effects of spinal cord epidural stimulation combined with task-specific motor training on two key secondary consequences of spinal cord injury (SCI), bladder function and body composition. The focus of the report is appreciated, as lower urinary tract impairment is an area of highest priority post-SCI and historically, has had a dramatic negative impact on overall health and quality of life.^2–4 As acknowledged by the authors, spinal cord epidural stimulation of the lumbosacral circuitry combined with intense task-specific training has been shown to produce coordinated and controlled volitional lower extremity movement.^5–10 It should also be clarified that improvements in autonomic function are optimal when stimulation is specifically mapped and configured for that system, such as cardiovascular^11–14 and bladder function.¹⁵ However, several studies have also shown that autonomic function is also enhanced even when stimulation is intended to elicit motor activity, resulting in subsequent gains in cardiovascular,^16,17 bladder,^7,18–20 and bowel function.^7,18,20 While we are in agreement with the authors that the impact of spinal cord epidural stimulation on bladder function in humans is not entirely characterized, we feel that the main conclusion provided by the authors suffers from a lack of internal and external validity due to the very small sample size, limited assessment time points, and uncertainty regarding the establishment of a cause and effect relationship between stimulation-induced changes in detrusor pressure. At the very least, a post-implant pre-treatment urodynamic study should have been performed and used as the baseline due to the invasive nature of the surgery. Thus, generalization that stimulation optimized for standing and stepping negatively impacts detrusor pressure, a conclusion drawn from one of two individuals assessed, may not be representative of the target population and is unlikely to provide a meaningful inference of the study results. Furthermore, the impact of the untreated symptomatic urinary tract infection reported for Patient 1 is not addressed.

In order to appropriately assess and interpret the relevant physiological outcome measurements presented in the report, it is important to include the entire representative urodynamic study record. With three primary urodynamic recorded pressures (intravesical, abdominal, and detrusor), one can appreciate the real-time changes in detrusor pressure across the entire fill cycle and its relationship to any sensations of filling, if present. Furthermore, the relationship between detrusor pressure and sphincter electromyography responses can indicate the presence of the guarding reflex, important for storage, and/or detrusor-sphincter-dyssynergia, which can contribute to increased intravesical pressure. Without these components, it is unclear how and at which point bladder compliance was impacted during testing given both participants had bladder capacity values within the upper limit of normative ranges (≥500 mL). The measurement of pressure is one of the most important aims of a urodynamic study, and thus, it is important to present the entire study record in order to rule out the occurrence of artifacts that could abnormally alter the detrusor pressure value (e.g. due to peristalsis or involuntary spasm of the lower extremity musculature). Although not thoroughly described in the methods section, the actual set-up (participant position) and instrumentation (type of catheter, balancing, and placement/taping) of the test can also play an important role in influencing detrusor pressure outcomes.²¹

Indeed, we are supportive of efforts that continue to expand our understanding of the use, safety, and implications of spinal cord epidural stimulation on both motor and autonomic function. However, we urge caution in making statements of stimulation-based effects without a complete discussion of other potential contributing factors.