Brain Targets in Patients With Bladder Emptying Difficulties

Difficulty in bladder emptying (Voiding dysfunction,VD) is a costly urinary condition that
leads to urinary tract infections/stones, sepsis, bladder loss, and permanent kidney damage.
VD can be present in patients with or without neurologic/brain disorders. Currently the only
available therapies for VD include bladder catheters or intermittent self-catheterization.
Catheterization is a burden especially in patients with nerve damage, hand skills may be
limited. The cost and morbid side effects of catheterizations in patients (blood in the
urine, pain, trauma, strictures, and infections) requires investigators to develop new
therapies that are beyond the bladder. Such new therapies could target the brain (where
bladder control is located).

In this proposal, investigators plan to further characterize the brain regions involved in
bladder emptying for each patient and ,perform brain modulation, targeting these regions as a
possible therapy for VD.

Patients with bladder dysfunction will be divided into two groups: Group 1: patients with VD;
and Group 2: patients without VD. Specific Aim 1: To evaluate brain pattern in both groups
and compare them to each other at the time of bladder emptying. Specific Aim 2: To evaluate
reliability of the nerve fibers in the brain and see whether damage to these fibers is
related to difficulty emptying the bladder. Specific Aim 3: To perform non-invasive brain
stimulation on specific regions of the brain responsible for bladder control to improve
bladder emptying.

This study is an interventional Study: The investigators have completed a well-powered study
on twenty-seven female MS patients during their bladder storage phase. Aims 1 and 2 use the
data from previously completed trial and investigators will perform additional imaging
analysis on it. Aim 3 is a new and small trial in which investigators planned to modulate the
regions of the brain that are related to bladder control.

Approximately 16 study participants will be enrolled at Houston Methodist, and 16 throughout
the study.

Inclusion Criteria:

Inclusion Criteria for subjects with neurogenic bladder:

- Patients with clinical diagnosis of neurogenic bladder

- History of any neurologic illness or injury (including but not limited to spinal cord
injury, Multiple Sclerosis, Stroke, spina bifida, Parkinson's, major spine surgery)

- 18 years or older

Specifics for MS patients:

Adult female patients with clinically stable MS [Expanded Disability Status Score (EDSS)
≤6.5], with bladder symptoms ≥3 months, will be screened. Patients will be considered to
have VD if they have an increased Postvoid Residual (≥ 20% Maximum Cystometric Capacity).
Patients who perform self-catheterization will be included in the VD category as well.

Exclusion Criteria:

Exclusion Criteria for subjects with neurogenic bladder:

- Men (for aims 1 and 2 only), anatomical bladder outlet obstruction (anti-incontinence
procedures, urethral strictures, or advanced pelvic organ prolapse). Severe
debilitating MS, history of seizures, pregnancy or planning to become pregnant,
contraindications to MRI, history of augmentation cystoplasty. Patients with active
UTI can be treated and subsequently screened for the trial.

- Positive urine pregnancy test at enrollment (There are no known risks to a subject's
fetus. There is no known teratogenic risk associated with urodynamics or fMRI) -
Cognitively impaired patients