Studies document brain-bladder network's role in urinary incontinence

One study included a group of six young women, ages 18 to 39 years, who were previously diagnosed with Fowler's syndrome. This condition, long misunderstood and misdiagnosed, is characterized by elevated maximum urethral closure pressure and abnormal electromyography readings.

Women with this syndrome tend to have enormous bladders and no sense of urgency. This level of impaired filling sensation-a highly abnormal brain response to bladder infusion-suggests that bladder afferent signals reaching the brain may be altogether absent, or at best, extremely weak, said study co-author Clare J. Fowler, MB, BS, professor of uro-neurology at the National Hospital of Neurology and Neurosurgery, London.

Brain responses measured

But it was a new approach to measuring brain responses to bladder filling using functional magnetic resonance imaging that, when concurrently paired with SNM and standard urodynamic tests, took this study and a partner U.S. study to new diagnostic levels. During scanning, 50 mL of saline solution was infused, then withdrawn from the bladder over a four-session cycle, mimicking repeated bladder filling and emptying.

Patients used push-button responses to report changes in their desire to void. The difference between functional MRI signals during infusion and withdrawal indicated the patient's brain response to bladder filling.

For the London study, the added data provided by brain scans supported the significance of the brain-bladder network, as it determined cerebral responses to bladder filling before and after SNM. In particular, SNM increased activation in the insular region of the cortex (representing increased bladder sensation) and in the midbrain periaqueductal gray, to validate the study's central hypothesis: that patient response can be restored by SNM.

Derek Griffiths, PhD, of the University of Pittsburgh, who helped develop the new approach, also added a crucial dimension to the study's data analysis with a methodology he developed using the Statistical Parametric Mapping Program.

"It took his genius and a lot of thinking to mine the relevant data and find the gems we needed to move forward on this work," Dr. Fowler said.

In the end, the team found that in this syndrome, SNM rectifies the situation by supplying afferents to the midbrain periaqueductal gray to restore voiding.

"Our expectation that altered responses at baseline in patients might be restored by SNM was confirmed," said Dr. Fowler. "After successful SNM treatment, the reliability of bladder sensation is improved, and brain responses to bladder infusion partially normalized."

Filling, brain activity linked

In a separate study on which Dr. Griffiths served as senior author, University of Pittsburgh researchers also focused on key regions of the brain involved in regulating the bladder, again pairing standard urodynamic studies with simultaneous brain imaging to investigate clinical symptoms in the scanner.

Fourteen women, ages 64 to 88 years, with moderate to severe urge urinary incontinence were recruited, qualifying for the study if they reported at least two urge incontinence episodes per week for a minimum of 3 months. Seven subjects had detrusor overactivity; seven did not.

As in Dr. Fowler's study, subjects were supine in the scanner and connected to urodynamic equipment. Two cycles of quick filling and emptying were repeated at low volume, then at high volume, until subjects signaled a strong urge to void, during which successive functional brain images were obtained.

Bladder filling provoked brain activity in multiple regions and led to deactivation in some medial orbitofrontal locations. Data analyses suggest that activity in key brain centers during bladder filling and urgency significantly correlates with severe incontinence in daily life as measured by voiding diaries or pads.

The findings also showed that the psychologic burden of urge incontinence negatively correlated with brain activity in the scanner, although in different regions of the brain, suggesting that the burden of incontinence may be related to an inability to cope with the disease, according to first author Stasa Tadic, MD, assistant professor of medicine at the University of Pittsburgh.

Fifteen years ago, imaging studies of brains were used to describe anatomic regions in classic ways-the so-called "phrenology" of the brain, Dr. Tadic noted.

"Now, with new research methods and techniques, brain imaging gives us additional insight into how the brain governs bladder control in our incontinent patients, which may give us clues about how to treat their condition," Dr. Tadic said.

In recognition of this research, the International Continence Society jointly honored both teams with its "Best Clinical Abstract" award.

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