One of the major challenges impacting overall health and quality of life following spinal cord injury (SCI) is the development of lower urinary tract dysfunction. Deficits in urological function post-injury include neurogenic detrusor overactivity and uncoordinated bladder and external urethral sphincter contractions (detrusor sphincter dyssynergia), resulting in inefficient emptying and high bladder pressure. An inability of the bladder to store urine under appropriately low pressure and the associated complications from chronic catheter use can lead to serious clinical conditions, including urinary tract infections, calculi, bladder cancer, and renal deterioration. Bladder distention is also the primary trigger of autonomic dysreflexia in individuals with cervical and upper thoracic SCI. Such exaggerated blood pressure responses to bladder distention limit appropriate bladder storage in these individuals. The standard of care for bladder dysfunction includes the use of pharmacological agents to promote bladder storage and intermittent catheterization for bladder evacuation. However, there is a critical need for a successful treatment that restores normal lower urinary tract function as these management strategies along with the impact of cardiovascular dysregulation continue to diminish the capacity of the bladder and lead to numerous side effects, increasing morbidity and mortality. Thus, the aim of this study was to investigate whether spinal cord epidural stimulation (scES) can be configured to safely maintain urinary continence without triggering autonomic dysreflexia and to test whether daily training with scES targeted specifically for these interrelated autonomic systems for at-home use can help restore bladder function.

Four participants [2 motor and sensory complete – cervical level of injuries (1 female, 1 male), both using indwelling suprapubic catheters; 2 motor complete – cervical and upper thoracic level of injuries (2 males), both using intermittent catheterization] implanted at L1-S1 spinal cord level with a Medtronic 5-6-5 electrode array and neurostimulator, underwent bladder mapping experiments including cystometry with continuous measurements of blood pressure and heart rate using the non-invasive blood pressure monitoring system (ADInstruments). Over a period of 4-6 weeks, optimal scES configurations (anode/cathode selection, amplitude, frequency and pulse width) were identified at the lumbosacral level (L1-S1) that promoted both the neural control of bladder storage (capacity) within the recommended International Continence Society guidelines [1] (detrusor filling pressure <10 cmH2O up to target capacity range of 400 – 450 mL for intermittent catheterization and > 300 mL for those using suprapubic catheters) as well as the maintenance of normative blood pressure (targeting systolic pressure of 110-120 mmHg). Home-training blood pressure was logged throughout bladder storage using a wireless unit (QardioArm).

Filling cystometry, conducted without scES prior to mapping (n=4), revealed detrusor instability, characterized by high detrusor pressure (69 ± 29 cmH2O), non-voiding contractions, and a concomitant rise in systolic blood pressure (to 164 ± 5 mmHg) at maximum cystometric capacity (351 ± 172 mL). Bladder-scES configured caudally with frequencies at and above 60 Hz improved or maintained overall bladder capacity (461 ± 206 mL) within target ranges and decreased maximum detrusor pressure to (54 ± 10 cmH2O), but systolic blood pressure remained elevated (159 ± 9 mmHg) at maximum cystometric capacity. However, maintenance of both detrusor and blood pressures (30 ± 13 cmH2O, 126 ± 12 mmHg, respectively) within clinically acceptable ranges for urinary continence required scES configured for both bladder and cardiovascular function. Participant specific combinations of scES parameters were required in order to obtain the most effective outcomes. Currently, 1 participant who completed lab-based training and transitioned to daily home-based training with scES demonstrated the ability to maintain bladder storage volumes and continence without distention-associated increases in systolic blood pressure in the community.

Coupled stimulation parameters targeted for both bladder capacity and blood pressure regulation resulted in successful bladder storage for each participant, which included capacity volumes and detrusor pressures during filling within the recommended guidelines of the International Continence Society [1] without triggering autonomic dysreflexia. The results of this study demonstrate that scES can be used to simultaneously and safely control urinary continence while managing distention-associated blood pressure dysregulation. Importantly, these initial findings reveal the complex dynamics and interplay between autonomic systems that is being integrated and regulated within the spinal cord below the level of SCI.

Targeted Bladder-scES for urinary continence and blood pressure regulation provide a means for regular standard time intervals between bladder emptying under safe pressures without pharmacological treatments that may have unwanted side-effects. Given many individuals use symptoms of autonomic dysreflexia as an indicator of the need to empty, an unsafe practice and significant health concern, the integration of stimulation for bladder and cardiovascular function is highly relevant and demonstrates the unique impact of epidural stimulation on controlling multiple systems simultaneously.

Rosier, P., et al. 5th International Consultation on Incontinence: Recommendations of the International Scientific Committee: Urodynamics Testing. in Incontinence (eds. Abrams, P., Cardozo, L., Khoury, S. & Wein, A.) 429-506 (International Continence Society, Paris, 2013).