How does onabotA affect brain activity?


OnabotulinumtoxinA (Botox) appears to increase the activity of brain regions involved in sensation and processing of urinary urgency in female patients with neurogenic overactive bladder, says Rose Khavari, MD.

New research into the brain effects of intradetrusor injection of onabotulinumtoxinA (onabotA [Botox]) could uncover alternate sensory pathways of this treatment modality.

Furthermore, increased understanding of bladder dysfunction at the level of the brain may lead to novel supraspinal modulation as a potential treatment modality for bladder dysfunction, researchers say.

OnabotA appears to increase the activity of brain regions involved in sensation and processing of urinary urgency in female patients with neurogenic overactive bladder (OAB), said Rose Khavari, MD, of Houston Methodist Hospital, Houston and Weill Cornell Medical College, New York.

"If we can better modulate the brain regions involved in bladder function, we may be able to use the same concept and help patients with any bladder storage or emptying problem," Dr. Khavari told Urology Times.She presented the study findings at the AUA annual meeting in San Francisco.

Also see: Telemedicine appears viable for neurogenic bladder

Previous research has extensively described onabotA’s effects on detrusor muscle activity (motor effects), but little is known about its sensory or supraspinal neural effects. Functional neuroimaging studies have suggested increased activity in the cingulated cortex, insula, and frontal cortex of women with OAB in response to bladder filling.

And previous studies have shown that therapies such as biofeedback, anticholinergic medications, and sacral neuromodulation can alter brain areas involved in bladder control.

So Dr. Khavari and her colleagues wanted to evaluate the effects of intradetrusor onabotA on brain activity in female multiple sclerosis (MS) patients with neurogenic overactive bladder.

They recruited 12 women diagnosed with stable MS for at least 3 months and neurogenic detrusor overactivity who were refractory to conservative and oral pharmacologic management. The women ranged in age from 38 to 71 years, with a mean age of 43.9 years. The authors excluded men from the study to avoid confounding the results with bladder outlet and prostate pathology.

The women underwent functional magnetic resonance imaging (fMRI) with simultaneous urodynamic studies prior to and 6 weeks following treatment with intradetrusor injection of onabotA.

During the filling phase, patients signaled strong urgency. The authors created average fMRI activation maps at strong urgency identifying areas of significant activation (p<.05).

Following intradetrusor injection of onabotA, they recorded a decrease in urge urinary incontinence (UUI) from 1.64 per day to 0.42 per day, along with improvements on validated questionnaires and assessments.

Next:What the authors foundBrain activity on fMRI increased after treatment with onabotA in the right cingulate body, the left posterior cingulate, the left anterior cingulate, the right prefrontal cortex, the insula, and the pons micturition center. The few areas that showed decreased activity included the left cerebellum, left fusiform gyrus, and bilateral lentiform nucleus.

This showed that the injection of onabotA into the bladder has distinct effects on the activation pattern in brain regions associated with the sensation of bladder filling, urgency, and micturition, the authors concluded.

In particular, the amygdala/parahippocampal region (areas responsible for negative emotions and fear, in this case possibly secondary to incontinence) becomes less active after successful treatment of UUI, they found.

Read: How do you manage noncompliant OAB patients?

The entire micturition cycle, including the voiding phase, changed following treatment with onabotA, they noted. The strong impact on the voiding phase contrasts with other therapies used in overactive bladder, which could explain the different brain activation patterns seen in this study, said Dr. Khavari.

She speculated that this negative effect on the voiding phase could have a compensatory effect on the brain, causing an exaggerated activation pattern in order to allow for voiding, or an attempt of voiding.

In the next phase of this research, Dr. Khavari is working on optimizing a cap that can be individualized to deliver noninvasive transcranial magnetic stimulation to the superficial brain regions that control a patient's bladder.

The technique might work for patients with Fowler's syndrome, stroke, underactive bladder, and other causes of bladder dysfunction, she said.

Until 20 years ago, urologists had focused too narrowly on below the beltline and the bladders, she said.


"I had to train myself about brain imaging and MRIs," Dr. Khavari said. "We have to cross the disciplines to increase our understanding of all aspects of bladder control and to be the leaders in innovations in this field."

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