Non-invasive Neuromodulation of Spinal Cord Restores Lower Urinary Tract Function After Paralysis

Abstract

It is commonly assumed that restoration of locomotion is the ultimate goal after spinal cord injury (SCI). However, lower urinary tract (LUT) dysfunction is universal among SCI patients and significantly impacts their health and quality of life. Micturition is a neurologically complex behavior that depends on intact sensory and motor innervation. SCI disrupts both motor and sensory function and leads to marked abnormalities in urine storage and emptying. Current therapies for LUT dysfunction after SCI focus on preventing complications and managing symptoms rather than restoring function. In this study, we demonstrate that Transcutaneous Electrical Spinal Stimulation for LUT functional Augmentation (TESSLA), a non-invasive neuromodulatory technique, can reengage the spinal circuits' active in LUT function and normalize bladder and urethral sphincter function in individuals with SCI. Specifically, TESSLA reduced detrusor overactivity (DO), decreased detrusor-sphincter dyssynergia (DSD), increased bladder capacity and enabled voiding. TESSLA may represent a novel approach to transform the intrinsic spinal networks to a more functionally physiological state. Each of these features has significant clinical implications. Improvement and restoration of LUT function after SCI stand to significantly benefit patients by improving their quality of life and reducing the risk of incontinence, kidney injury and urinary tract infection, all the while lowering healthcare costs.

Keywords: Non-invasive spinal cord stimulation; bladder function; lower urinary tract; paralysis; spinal cord injury; urodynamics.

Figures

Figure 1

An example of TSCS evoked pressure changes and EMG responses (average of 5 responses) from the vesicular (Pves), urethral (Pura), abdominal (Pabd) and detrusor (Pdet) pressures and Urethral sphincter (EUS) EUS, Hamstring (HM) and Tibialis Anterior (TA) EMGs at 150 mA TSCS between T11-T12 and L1-L2 vertebral processes from a subject (566729, AIS A, T4). Recruitment curves for the example showed on the left.

Figure 2

Examples of urodynamic recording from a representative subject (566729) (A) without TESSLA, with (B) TESSLA at 1 Hz (T11) and with (C) TESSLA at 30 Hz (T11). Note the presence of detrusor over activity (DO) with 205 ml infused (Table 1) and high level of detrusor sphincter dyssynergia (DSD) in the absence of TESSLA but a greater level of reciprocal activation between the Pura and Pdet in the presence of TESSLA and during voiding. Note the increased bladder capacity (281 ml, Table 1) in the presence of TESSLA at 30 Hz compared to baseline as well as the reduced DSD during voiding. Pdet is defined as Pves-Pabd and Pclo is defined as Pves-Pura.

Figure 3

Pdet and Pura during voiding without and with TESSLA (1 Hz) for the 6 individual subjects. Yellow highlight identifies the region of voiding. Note: 2 subjects (955941, 573487) demonstrated a non-voiding responses during TESSLA Off, thus the pressure traces are not included.

Figure 4

(A) Voiding efficiency for the 7 individuals tested in the absence of TESSLA and TESSLA at 1 Hz. (B) Bladder capacity in the absence of TESSLA and TESSLA at 30 Hz. * significantly different from TESSLA Off at P < 0.05 (Statistical difference identified via paired t-test).

Figure 5

(A) Co-activation between Pdet and Pura during voiding with TESSLA off (black) and TESSLA at 1 Hz (red) in a single subject (566729). (B) Normalized (to TESSLA Off) co-activation between Pdet and Pura per second during voiding for the subjects (n = 5) that demonstrated voiding with TESSLA off. * significantly different from TESSLA Off, demonstrating lowered level of DSD with TESSLA 1 Hz compared to TESSLA Off (Statistical difference identified via paired t-test).

Figure 6

Representative Uroflow conducted on one subject in the absence and presence of TESSLA (150 mA, 1 Hz at T11). Note the start of voiding and flow only after TESSLA is turned on (Supplementary movie).