Tolterodine Activates the Prefrontal Cortex During Bladder Filling in OAB Patients: a Real-time NIRS-urodynamics Study

Aims: Studies of overactive bladder (OAB) have shown urothelial/suburothelial changes and increased bladder afferents, while in the brain the frontal micturition area that normally suppresses the bladder is deactivated. It has been unclear whether anticholinergic medication could reverse this suppression. To address this question, we performed a real-time NIRS (near-infrared spectroscopy)-urodynamic study in OAB patients before and after the administration of an anticholinergic agent, tolterodine.

Methods: We recruited 13 OAB patients in our outpatient clinic (9 males, 4 female; mean age 73 years). Before and after the administration of 4 mg/day tolterodine for 3 months, all patients completed the OAB-symptom scale and a NIRS-urodynamics examination. Cerebral changes in the oxy-hemoglobin concentration (oxy-Hb) were sampled. Concentration changes in oxy-Hb were calculated based on a modified Beer-Lambert approach.

Results: Tolterodine significantly reduced the OAB patients' nighttime frequency (P < 0.05) and increased their first-sensation volume (290-359 ml, P < 0.01). The number of patients with detrusor overactivity did not lessen significantly (11-9). The real-time NIRS-urodynamic study showed that, during slow bladder filling between start and bladder capacity, tolterodine significantly activated the right frontal micturition area of the OAB patients (P < 0.05). The activation was prominent in Brodmann's area 8, 9, 10 of the prefrontal cortex.

Conclusions: Tolterodine reduced bladder sensation together with a significant activation of the frontal micturition area of OAB patients, particularly Brodmann's area 8, 9, 10 of the right prefrontal cortex. This activation seems to be a secondary phenomenon, since tolterodine does not easily penetrate the blood-brain barrier.