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

Abstract

Purpose: Voiding dysfunction (VD) leading to urinary retention is a common neurogenic lower urinary tract symptom in patients with multiple sclerosis (MS). Currently, the only effective management for patients with MS with VD is catheterization. Transcranial Rotating Permanent Magnet Stimulator (TRPMS) is a noninvasive, portable, multifocal neuromodulator that simultaneously modulates multiple cortical regions and the strength of their functional connections. In this pilot trial (ClinicalTrials.gov Identifier: NCT03574610), we investigated the safety and therapeutic effects of TRPMS in modulating brain regions of interest (ROIs) engaged with voiding initiation to improve VD in MS women.

Materials and methods: Ten MS women with VD (having % post-void residual/bladder capacity [%PVR/BC] ≥40% or being in the lower 10th percentile of the Liverpool nomogram) underwent concurrent functional magnetic resonance imaging/urodynamic study (fMRI/UDS) with 3 cycles of bladder filling/emptying, at baseline and post-treatment. Predetermined ROIs and their activations at voiding initiation were identified on patients' baseline fMRI/UDS scans, corresponding to microstimulator placement. Patients received 10 consecutive 40-minute treatment sessions. Brain activation group analysis, noninstrumented uroflow, and validated questionnaires were compared at baseline and post-treatment.

Results: No treatment-related adverse effects were reported. Post-treatment, patients showed significantly increased activation in regions known to be involved at voiding initiation in healthy subjects. %PVR/BC significantly decreased. Significant improvement of bladder emptying symptoms were reported by patients via validated questionnaires.

Conclusions: Both neuroimaging and clinical data suggested TRPMS effectively and safely modulated brain regions that are involved in the voiding phase of the micturition cycle, leading to clinical improvements in bladder emptying in patients with MS.

Keywords: magnetic resonance imaging; multiple sclerosis.

Conflict of interest statement

Disclosure of Conflict of Interest: SAH is listed as an inventor on issued U.S. patent numbers 9456784, 10398907, 10500408 and 10874870 covering the device used in this study. The patent is licensed to Seraya Medical, LLC. Other authors declared no conflict of interest.

Figures

Figure 1.

Schematic representation of clinic visits where clinical data are collected and patients receive treatment. Validated questionnaires include the American Urological Association Symptom Score (AUASS), NBSS, Urogenital Distress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7), Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A).

Figure 2.

a, concurrent 7T fMRI/UDS setup where MRI-compatible bladder and rectal catheters are passed through small opening in wall between control and scanner room to connect to UDS machine (not to scale). b, concurrent fMRI/UDS testing protocol.

Figure 3.

MS patient receiving TRPMS treatment with individualized treatment cap. Five microstimulators were secured on treatment cap, corresponding to 5 ROIs identified from patient’s fMRI scan.

Figure 4.

CONSORT diagram. FU, followup.

Figure 5.

Group analysis for change in BOLD signals, which correspond to activation/deactivation compared to resting state, following treatment (post-treatment minus baseline, p a) and voiding initiation (b). Red indicates significant increase in BOLD signals and blue indicates significant decrease in BOLD signals at post-treatment compared to baseline. Following treatment: a, at strong desire to void, there was significant increase in activation in bilateral postcentral gyrus, inferior parietal lobule, middle cingulate cortex, thalamus, precuneus, left IFG, left superior, middle and inferior temporal gyrus, caudate nucleus, hippocampus, putamen and right posterior cingulate cortex. Significant decrease in activation was observed in bilateral precentral gyrus, left middle and superior frontal gyri, left insula and right cerebellum cortex. b, at voiding initiation, there was significant increase in bilateral inferior, superior and middle frontal gyri, superior and middle temporal gyri, supramarginal gyrus, rectal gyrus, SMA, precentral and postcentral gyri, precuneus, thalamus, middle cingulate cortex, left anterior cingulate, left cerebellum, right insula and right parietal lobe. Decreased activation was observed in bilateral hippocampus and right fusiform gyrus.

Figure 6.

Clinical outcomes following treatment. Noninstrumented uroflow (a), validated questionnaire (b), specific questions from validated questionnaires pertaining to voiding symptoms (c) and NBSS sub-scores. Lower score indicates improvement in symptoms. Asterisks indicate significant difference compared to baseline (p <0.05, also circled in red).

Figure 7.

Clinical outcomes at 4-month followup. Noninstrumented uroflow (a), validated questionnaire (b), specific questions from validated questionnaires pertaining to voiding symptoms (c) and NBSS sub-scores. Lower score indicates improvement in symptoms. Asterisks indicate significant difference compared to baseline (p <0.05); significant differences at 4-month followup compared to baseline are circled in red.