Bladder Neuromodulation in Acute Spinal Cord Injury via Transcutaneous Tibial Nerve Stimulation: Cystometrogram and Autonomic Nervous System Evidence From a Randomized Control Pilot Trial

Argyrios Stampas, Kenneth Gustafson, Radha Korupolu, Christopher Smith, Liang Zhu, Sheng Li, Argyrios Stampas, Kenneth Gustafson, Radha Korupolu, Christopher Smith, Liang Zhu, Sheng Li

Abstract

Aim: Percutaneous tibial nerve stimulation is used to decrease incontinence in chronic neurogenic bladder. We report the findings from a subset of patients in a randomized control trial of transcutaneous tibial nerve stimulation (TTNS) for bladder neuromodulation in acute spinal cord injury (SCI) in whom heart rate variability (HRV) was recorded before and after cystometrogram (CMG). The aim was to correlate autonomic nervous system (ANS) changes associated with the CMG changes after the trial using HRV analyses. Methods: The study was a double-blinded sham-controlled 2-week trial with consecutive acute SCI patients admitted for inpatient rehabilitation, randomized to TTNS vs. control sham stimulation. Pre- and Post- trial CMG were performed with concurrent 5-min HRV recordings with empty bladder and during filling. Primary outcomes were changes with CMG between/within groups and associations to the HRV findings. Results: There were 10 subjects in the TTNS group and 6 in the control group. Pre-trial baseline subject characteristics, blood pressures (BPs), and CMG were similar between groups. In both groups, the pre-trial systolic BP increased during filling CMG. After the trial, the control group had significantly increased detrusor pressure and counts of detrusor-sphincter dyssynergia on CMG, not seen in the TTNS group. Also, the control group did not maintain rising BP post-trial, which was observed pre-trial and remained in the TTNS group post-trial. HRV was able to detect a difference in the ANS response to bladder filling between groups. Post-trial HRV was significant for markers of overall increased parasympathetic nervous system activity during filling in the controls, not seen in the TTNS group. Conclusion: Preliminary evidence suggests that TTNS in acute SCI is able to achieve bladder neuromodulation via modulation of ANS functions. Clinical Trial Registration: clinicaltrials.gov, NCT02573402.

Keywords: autonomic nervous system; heart rate variability; neurogenic urinary bladder; neuromodulation; spinal cord injuries; transcutaneous electric stimulation.

Figures

FIGURE 1
FIGURE 1
Study Timeline. tSCI, traumatic spinal cord injury; I/E, inclusion/exclusion criteria; CMG, cystometrogram; HRV, heart rate variability; TTNS, transcutaneous tibial nerve stimulation.
FIGURE 2
FIGURE 2
Bar graphs of significant differences between control (green) and TTNS (red) groups, pre- (top) and post-trial (bottom). DSD, detrusor-sphincter dyssynergia. All symbols are significant p < 0.05 and color-coded: ∧between group difference; ∼ pre- vs. post-difference.
FIGURE 3
FIGURE 3
Significant blood pressure (BP) changes during bladder filling, pre- and post-trial. Dashed line represents transition to post-trial testing, red brackets and green brackets are within group differences in the TTNS and controls, respectively. Blue brackets are pre- post-trial differences. (A) In both groups, SBP increases with filling pre-test. Post-test, this is only seen in the TTNS group. (B) Diastolic BP is significantly different in the controls post-trail compared to pre-trial. Pre, pre-trial; Post, post-trial; E, empty bladder; F1, filling phase 1; F2, filling phase 2; TTNS, transcutaneous tibial nerve stimulation; SBP, systolic blood pressure; DBP, diastolic blood pressure; ¥p = 0.04; ∗p = 0.01; £p < 0.01; ˆp = 0.03.
FIGURE 4
FIGURE 4
Significant HRV changes during bladder filling, pre- and post-trial. Dashed line represents transition to post-trial testing, red brackets and green brackets are within group differences in the TTNS and controls, respectively. Blue brackets are pre- post-trial differences. (A) STDHR increases pre-stimulation in the controls, not seen post-test. (B) pNN50 increases in the controls post-test during the first filling phase. (C) Decrease in LF during initial filling is maintained in the TTNS group post-trial. Pre, pre-trial; Post, post-trial; E, E = empty bladder; F1, filling phase 1; F2, filling phase 2; TTNS, transcutaneous tibial nerve stimulation; STDHR, standard deviation of heart rate; bpm, beats per minute; pNN50, the proportion of pairs of successive R–R beat lengths that differ by more than 50 ms (NN50) for total number of beats. LF, low frequency; ms2, milliseconds squared; ¥p = 0.04; #p = 0.03; ∗p = 0.01; £p < 0.01.

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