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

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.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1

Scatter plots of the pressure–volume measurements obtained during urodynamics without scES (open circles) and from mapping with BC-scES (filled in circles) in participants using intermittent catheterization (A), n = 4, and in those using suprapubic catheters (B), n = 3. Ellipses show the 95% confidence interval for each participant after removing outliers. Vertical and horizontal lines indicate normative thresholds for minimum bladder capacity and maximum detrusor pressure, respectively. Blood pressure responses at maximum capacity for each participant are displayed next to each corresponding pressure–volume plot with optimal ranges targeted between 110–120 mmHg denoted by double horizontal lines. Note the shift toward normative bladder capacity, bladder pressure, and/or blood pressure with scES. BC-scES bladder compliance spinal cord epidural stimulation, cmH2O centimeters of water, mL milliliters, mmHg millimeters of mercury.

Figure 2

Improvement in bladder compliance using targeted scES parameters (BC-scES). (A) Example of detrusor pressure (black, top panel) and bladder capacity (red, top panel), sphincter EMG (µV, middle panel), blood pressure (mmHg, black, systolic—top line, diastolic—bottom line, lower panel) and heartrate (red, lower panel) in the absence of scES in a participant with chronic SCI (B24); Note the detrusor overactivity with incontinence at low capacity, and a simultaneous rise in systolic blood pressure; (B) in the same participant using BC-scES and parameters adjusted for bladder compliance. Maintenance of bladder compliance (increased bladder capacity without a change in detrusor pressure in response to bladder filling) was intensity (V, pink bar) dependent and participant- specific. Electrodes: cathodes = black; anodes = red; inactive = white.

Figure 3

Comparison of bladder capacity, detrusor pressure and systolic blood pressure without scES relative to optimized BC-scES parameters for participants intermittently catheterizing, n = 4 (A–C); and participants with a suprapubic catheter, n = 3 (D–F). BC-scES mapping significantly improved (reduced) detrusor pressure and systolic blood pressure at maximum capacity in those using intermittent catheterization and detrusor pressure in the suprapubic group.

Figure 4

Improvement in ability to initiate bladder voiding with targeted BV-scES. Example of detrusor pressure (upper panel) and sphincter EMG (µv, lower panel) in the absence of scES (A) in an individual with chronic SCI (B07) (Leak: 0 mL; Capacity: 622 mL); (B) Representative cystometry recording in the same individual using BV-scES and parameters adjusted for void initiation (VE: 51.2%, Capacity: 496 mL); Voiding initiation was intensity (pink bar) dependent and participant-specific. Note the rise in detrusor pressure timed with relaxation of sphincter EMG activity and a return of detrusor pressure to baseline. (C) Effective and non-effective BV-scES parameters for promoting volitional voiding during urodynamics mapping sessions for B07. Initiating a void occurred only in the presence of optimized BV-scES. Reflexive leaks are indicated as involuntary. Light gray indicates the voiding efficiency (VE) for a single leak/void and dark gray indicates total voiding efficiency for a mapping session when multiple void attempts were possible. Mapping sessions were approximately 1 week apart. VE = [Void Amount/Void + Residual] × 100; Electrodes in B: cathodes = black; anodes = red; inactive = white.

Figure 5

Heatmap plots of the amount of percent total electric charge delivered across each segment that resulted in best bladder storage outcomes (A) and bladder voiding (B) for each individual (x-axis) and the areas of the spinal cord that were directly targeted by the stimulation (y-axis) as well as the corresponding map configurations (black—cathodes; red—anodes) and stimulation parameters; (C) Example of MRI-based 3D model of the spinal cord at lumbosacral enlargement and location of scES paddle electrode with respect to the spinal cord levels. Distribution of electric current density is highlighted with heatmap. Simulations are performed using Sim4Life platform. BC bladder compliance, BV bladder voiding, L lumbar, S sacral, scES spinal cord epidural stimulation, T thoracic.