Stroke survivors often experience lower urinary tract symptoms (LUTS) due to damage to the brain centers that control micturition affecting the quality of life of the affected individuals. 
Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation approach. While it has shown promising results in improving LUT function in these patients, the characteristics of patients who respond to this therapy remain unknown. 
Therefore, in this study, we aim to identify micturition-associated brain activity as a potential biomarker of responsiveness to TSCS therapy for LUT dysfunction secondary to stroke.

This study has a prospective design. Our Institutional Review Board approved the study protocol, and all participants provided informed consent. Simulations have suggested that a minimum of 12 subjects would be required to achieve 80% power at the individual voxel level to identify typical activations.

Twelve patients with LUTS associated with stroke were enrolled to receive TSCS for 12 weeks (24 sessions). During their baseline evaluation, patients underwent functional magnetic resonance imaging (fMRI) and simultaneous urodynamics study to detect Blood-oxygen dependent dissociation (BOLD) signal intensity during maximal urgency (defined as 10 seconds preceding a detrusor contraction).  LUTS were assessed using the International Consultation on Incontinence Overactive Bladder (ICIQ-OAB) questionnaire before and after completion of TSCS.

The outcome was categorized into Non-responder and Responders, and the latter was defined as a subject with over 60% reduction in the ICIQ-OAB score after 12 weeks of therapy. Then, the micturition-associated brain activity was compared between groups by detecting BOLD signal activity using statistical parametric mapping (p < 0.01, cluster size > 25 voxels). In order to identify typical activations, simulations have indicated that a sample size of at least 12 subjects would achieve 80% power at the single-voxel level.Models were adjusted for age, sex, and time since the stroke.

Twelve patients completed the study. The mean age was 52 years (SD±9.8), 58,3% were female, and 50% were defined as responders to therapy, reporting a mean decrease in ICIQ-OAB by 8.6±0.91 points (p<0.01). 
Responders exhibited significantly higher BOLD signals in 16 clusters, including the left insula, left middle cingulate cortex, bilateral cuneus, left precuneus, left precentral gyrus, left inferior frontal gyrus, and right temporal gyrus. In comparison, non-responders exhibited significantly higher BOLD signals in 7 clusters centered in the corpus callosum and the basal ganglia.

In this study, we demonstrate that a novel neuromodulation modality such as TSCS is a promising therapy that mitigates LUTS secondary to stroke.
Responders demonstrated higher BOLD signals in several cortical areas than non-responders, suggesting that a baseline level of brain activity may be necessary in order to have a successful outcome with TSCS.

In this study, we demonstrated that micturition-related brain activity might be a useful biomarker for predicting response to TSCS in patients with NLUTS secondary to stroke.

Continence 7S1 (2023) 100760
DOI: 10.1016/j.cont.2023.100760