Therapeutic effects of non-invasive, individualized, transcranial neuromodulation treatment for voiding dysfunction in multiple sclerosis patients: study protocol for a pilot clinical trial

Abstract

Background Voiding dysfunction (VD) is a common neurogenic lower urinary tract dysfunction (NLUTD) in multiple sclerosis (MS) patients. Currently, the only effective management for VD and urinary retention in MS patients is catheterization, prompting us to look for novel therapeutic options beyond the bladder, such as the brain. Transcranial rotating permanent magnet stimulator (TRPMS) is a non-invasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions, enhancing or attenuating strengths of functional connections between these regions. The objective of this pilot clinical trial is to evaluate the feasibility of a TRPMS trial to address lower urinary tract symptoms in MS patients, through investigating the therapeutic effects of TRPMS in modulating brain regions during voiding initiation and mitigating VD in female MS individuals. Methods Ten adult female MS patients with VD (defined as having %post-void residual/bladder capacity (%PVR/BC) ≥ 40% or Liverpool nomogram percentile < 10%) will be recruited for this study. Concurrent urodynamic and functional MRI evaluation with a bladder filling/emptying task repeated three to four times will be performed at baseline and post-treatment. Predetermined regions of interest and their blood-oxygen-level-dependent (BOLD) activation at voiding initiation will be identified on each patient’s baseline anatomical and functional MRI scan, corresponding to the microstimulators placement on their individualized TRPMS treatment cap to either stimulate or inhibit these regions. Patients will receive 10 40-min treatment sessions. Non-instrumented uroflow and validated questionnaires will also be collected at baseline and post-treatment to evaluate clinical improvement. Discussion Despite the crucial role of the central nervous system in urinary control and its sensitivity to MS, there has been no treatment for urinary dysfunction targeting the brain centers that are involved in proper bladder function. This trial, to our knowledge, will be the first of its kind in humans to consider non-invasive and individualized cortical modulation for treating VD in MS patients. Results from this study will provide a better understanding of the brain control of neurogenic bladders and lay the foundation for a potential alternative therapy for VD in MS patients and other NLUTD in a larger neurogenic population in the future. Trial registration This trial is registered at ClinicalTrials.Gov (NCT03574610, 2 July 2018.) and Houston Methodist Research Institute IRB (PRO00019329)

Effect of transcutaneous posterior tibial nerve stimulation and repetitive transcranial magnetic stimulation on neurogenic overactive bladder symptoms in female patients with multiple sclerosis: The study protocol of a randomized controlled study

“…Patients with MS experience adverse conditions, such as sleep disturbance, fatigue, urinary tract infection, low self-esteem, and mood disorders due to lower urinary system dysfunction. Studies have reported that the recommended treatment should have the least side effects ( 22 ). For this reason, we searched for neuromodulation methods that were reported to have the least side effects in the literature.…”

Noninvasive, Individualized Cortical Modulation Using Transcranial Rotating Permanent Magnet Stimulator for Voiding Dysfunction in Women with Multiple Sclerosis: A Pilot Trial

“…Structural and functional MRI images were collected per our previous protocol. 9 During the concurrent functional magnetic resonance imaging (fMRI)/UDS, the bladder was filled with sterile saline at 75 ml/minute until subjects signaled a “strong desire to void.” Subjects were instructed to hold for 30 seconds, after which permission to void was given. UDS was performed concurrently during fMRI to monitor the entire filling and voiding cycles.…”

“…Validated questionnaires, noninstrumented uroflow, and PVR volume were collected for inclusion criteria and as baseline values, and again at post-treatment, and 4-month and 12-month followups. 9…”

“…Validated questionnaires, noninstrumented uroflow, and PVR volume were collected for inclusion criteria and as baseline values, and again at posttreatment, and 4-month and 12-month followups. 9 Prior to baseline scans, subjects received a treatmentcap fitting session, where their head measurement was recorded according to the 10-20 system. 10 Subjects entered a 7-Tesla Siemens MAGNETOM Terra magnetic resonance imaging (MRI) scanner (3T Siemens MAGEN-TOM Vida MRI scanner if contraindicated for 7T).…”

Altered bladder‐related brain network in multiple sclerosis women with voiding dysfunction

“…One patient dropped out due to COVID‐19 and one patient was excluded from analysis because of a significant loss of brain tissue found during the magnetic resonance imaging (MRI) scanning. Ten healthy women and nine MS women were included for the analysis 4,10 . Patients with prior slings, bladder/bladder neck suspension operations, or previous bladder reconstruction procedures were excluded from the study.…”