title: Tolterodine activates the prefrontal cortex during bladder filling in OAB patients: a real-time NIRS-urodynamics study.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan.
authors.lastname: Sakakibara
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Tateno
authors.forename: Masashi
authors.initials: M
authors.lastname: Yano
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahashi
authors.forename: Megumi
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogata
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kishi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tsuyusaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yamanishi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Shibata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D003408:Cresols / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D010665:Phenylpropanolamine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D019265:Spectroscopy, Near-Infrared; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects* / Q000502:physiology; D064804:Urological Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D064804:Urological Agents; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate
keywords: near-infrared spectroscopy (NIRS); overactive bladder; prefrontal cortex; tolterodine; urodynamics