Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

https://journals.sagepub.com/doi/pdf/10.1177/10738584221145570

Mapping the Iceberg of Autonomic Recovery: Mechanistic Underpinnings of Neuromodulation following Spinal Cord Injury.

Introduction Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled “Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury” is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. Methods and analysis Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. Ethics and dissemination Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders.

Effects of non-invasive spinal cord stimulation on lower urinary tract, bowel, and sexual functions in individuals with chronic motor-complete spinal cord injury: Protocol for a pilot clinical trial

Central Nervous Stimulation for Neurogenic Lower Urinary Tract Dysfunction: Current Application and Emergent Therapies

This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord.This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions.Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans. 

/pdf/targeted-selection-of-stimulation-parameters-for-restoration-1ra00nor.pdf

Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury.

Spinal cord injury (SCI) results in severe cardiovascular dysfunction due to the disruption of supraspinal control. Autonomic dysreflexia (AD), an uncontrolled rise in blood pressure in response to peripheral stimuli including common bowel routine, digital anorectal stimulation (DARS), reduces the quality of life, and increases morbidity and mortality. Recently, spinal cord stimulation (SCS) has emerged as a potential intervention to mitigate unstable blood pressure following SCI. The objective of this case series was to test the real-time effect of epidural SCS (eSCS) at the lumbosacral spinal cord, the most common implant location, on mitigating AD in individuals with SCI. We recruited three individuals with cervical and upper thoracic motor-complete SCI who have an implanted epidural stimulator. We demonstrated that eSCS can reduce the elevation in blood pressure and prevent DARS-induced AD. The blood pressure variability analysis indicated that eSCS potentially reduced vascular sympathetic nervous system activity during DARS, compared to without eSCS. This case series provides evidence to support the use of eSCS to prevent AD episodes during routine bowel procedures, improving the quality of life for individuals with SCI and potentially reducing cardiovascular risks.

/pdf/spinal-cord-stimulation-prevents-autonomic-dysreflexia-in-11qy579c.pdf

Spinal Cord Stimulation Prevents Autonomic Dysreflexia in Individuals with Spinal Cord Injury: A Case Series

Abstract Profound dysfunctional reorganization of spinal networks and extensive loss of functional continuity after spinal cord injury (SCI) has not precluded individuals from achieving coordinated voluntary activity and gaining multi-systemic autonomic control. Bladder function is enhanced by approaches, such as spinal cord epidural stimulation (scES) that modulates and strengthens spared circuitry, even in cases of clinically complete SCI. It is unknown whether scES parameters specifically configured for modulating the activity of the lower urinary tract (LUT) could improve both bladder storage and emptying. Functional bladder mapping studies, conducted during filling cystometry, identified specific scES parameters that improved bladder compliance, while maintaining stable blood pressure, and enabled the initiation of voiding in seven individuals with motor complete SCI. Using high-resolution magnetic resonance imaging and finite element modeling, specific neuroanatomical structures responsible for modulating bladder function were identified and plotted as heat maps. Data from this pilot clinical trial indicate that scES neuromodulation that targets bladder compliance reduces incidences of urinary incontinence and provides a means for mitigating autonomic dysreflexia associated with bladder distention. The ability to initiate voiding with targeted scES is a key step towards regaining volitional control of LUT function, advancing the application and adaptability of scES for autonomic function. 

https://www.nature.com/articles/s41598-022-15315-2.pdf

Karthik Kalvakuri

Papers

Targeting bladder function with network-specific epidural stimulation after chronic spinal cord injury