Neurogenic overactive bladder (NOAB), characterized by urinary frequency, urgency or urgency incontinence
symptoms occurring during the storage phase of the bladder, is the most common urinary complaint in multiple
sclerosis (MS). Current management options for NOAB in MS have limited efficacy and considerable adverse
effects, which underscores the significance of our study and highlights the need for better, less invasive
therapies. Our novel study investigates brain therapeutic targets that could shift the focus of NOAB management
in MS from a bladder-centric focus to brain restoration; specifically modulating the brain regions identified in our
prior functional magnetic resonance imagining studies. Repetitive transcranial magnetic stimulation (rTMS) is a
noninvasive brain stimulation that can modulate neurons (excite or inhibit) to improve the connectivity of the
regions of interest (ROI). Our preliminary data demonstrate, for the first time, significant improvement in bladder
symptoms in ten women with MS who have voiding dysfunction following multifocal transcranial magnetic
stimulation without any treatment-related adverse effects.
This randomized double-blind, sham-controlled single center clinical trial with an optional open-label extension
(OLE) phase is designed to evaluate the effects of targeted rTMS in women with MS and NOAB by investigating
restorative reorganization of brain function and improvement of urinary frequency, urgency and incontinence.
We hypothesize that cortical alterations in bladder volume sensing and their response to stimulation contribute
to NOAB symptoms in MS, and that improving the response to bladder distention (ROI within circuits 1 and 2)
with neuronavigated rTMS can restore brain activity and improve symptoms (frequency, urgency, and
incontinence). We will test our hypothesis with thses specific aims: Aim 1: To determine the clinical effects of
neuronavigated and multifocal active/sham rTMS in women with MS and NOAB; Aim 2: To assess the
neuroimaging restorative effects of neuronavigated active/sham rTMS in women with MS and NOAB; Aim 3: To
assess the long-term safety and therapeutic effects of repeated rTMS in women with MS and NOAB who
participate in the OLE phase (which subjects from both groups will be invited to enter at the 3-month follow up).
Efforts to improve our current knowledge of brain contribution to lower urinary tract function and the development
of an individualized, noninvasive, and effective treatment modality at the level of the brain will greatly impact the
quality of life for individuals with MS and subsequently others with OAB, whether neurogenic or non-neurogenic.
