Botox Increases Activity of Brain Regions Involved in Urinary Sensation, New Study Shows

Botox injections in the bladder muscle increase the activity of brain regions involved in the sensation of urinary urgency in female multiple sclerosis (MS) patients who have neurogenic overactive bladder (NOAB), a new study shows.

The study, “Higher Neural Correlates in Multiple Sclerosis Patients with Neurogenic Overactive Bladder Following Treatment with Intradetrusor Injection of OnabotulinumtoxinA,” was published in The Journal of Urology.

It is estimated that from 37 to 99 percent of all MS patients will experience bladder issues at some point. Urinary frequency, urgency, and incontinence are among the most common symptoms reported by these patients and usually are grouped under the global definition of neurogenic overactive bladder (NOAB).

Botox (onabotulinumtoxinA, OnabotA) is a toxin produced by the bacteria Clostridium botulinum that blocks the communication between the nerves and the muscles, resulting in short-term muscle relaxation. Once injected in the bladder muscle (the detrusor), Botox helps relieve the symptoms of NOAB and has, since its approval by the U.S. Food and Drug Administration (FDA) in August 2011, become a well-established treatment option for MS patients affected by NOAB.

Although the motor effects of Botox on the detrusor muscle have been studied extensively, not much is known regarding its sensory effects, in particular on the brain regions responsible for perception/localization of bladder fullness, urgency, and frequency.

Researchers evaluated the effects of Botox on brain activity in female MS patients with NOAB, using functional magnetic resonance imaging (fMRI) — measuring brain activity through changes in cerebral blood flow — coupled with urodynamic study (a procedure that assesses bladder functionality).

Brain activity was measured in specific regions of the brain (cingulate cortex, insula, prefrontal cortex, pons, cerebellum, thalamus, and amygdala) when patients expressed a strong urge to urinate (know as “full urge”).

“Our trial is the first study of its kind to evaluate the possible effects of intradetrusor [in the detrusor muscle] injection of OnabotA at the level of human brain where the perception and processing of fullness is located,” the authors wrote.

The prospective observational study (NCT03033355) analyzed 12 female MS patients (10 ambulatory and two wheelchair-bound). Ten patients received 200 units of Botox and the remaining two, 100 units of Botox. Data collected before and after Botox injection was normalized to healthy female control participants from a previous study done by the same group.

Brain activity increased after Botox injection in most brain regions. Brain areas that exhibited lower activity were sparse and included the left cerebellum, the left fusiform gyrus and the bilateral lentiform nucleus. These areas are responsible for controlling muscle movements on the left side of the body, facial recognition and movement execution and learning, respectively.

Overall, following Botox injection, brain activity patterns of MS patients and healthy controls were almost identical at full urge, except in the frontal lobes where the differences were still evident.

These findings suggest that Botox injection in the detrusor muscle increases brain activity in most areas responsible for sensation and processing of urinary urgency in MS patients with NOAB. Researchers now believe these brain activity patterns might be used to optimize current therapies or to drive research on the effects of Botox.

“We were able to show that injection of OnabotA in the bladder appears to have distinct effects on the activation pattern of brain regions associated with the sensation of bladder filling, urgency, and micturition,” the authors wrote. “Further studies are undoubtedly needed in a larger population of patients (OAB and NOAB) undergoing OnabotA injection to increase our understanding of brain and potentially sensory effects of intradetrusor OnabotA,” they concluded.