Neural innervation of the newborn exstrophic bladder: An immunohistochemical study

Purpose: Continence in bladder exstrophy is not always easy to attain. Some patients have a small noncontractile bladder while in others an adequate capacity bladder may not contract normally. Innervation of the detrusor determines its ability to contract. The exstrophic bladder during organogenesis does not store urine. Therefore, its requirements for contraction are limited and its innervation would potentially reflect this difference in function. The availability of specific immunostains allows better differentiation of the neural elements in tissue specimens. Our study focuses on myelinated nerves innervating the newborn exstrophic detrusor. Materials and Methods: Biopsies were obtained from the anterior wall of 10 newborn exstrophic bladders at the time of initial closure and compared to 10 newborn controls. Patient age at bladder closure ranged from 1 to 90 days (mean 22). Specimens were formalin fixed and paraffin embedded. Then 4 mu. thick sections were stained with S100, an immunostain that stains neural crest elements including Schwann's elements (myelinated nerve fibers). The entire tissue section was examined. Microscopic fields were sequentially examined with a morphometric system comprising a microscope, video camera and personal computer with a video frame grabber. The output image was displayed on a second monitor and the nerves in each field and numbers of fields in each section were counted. To be considered, fields had to have greater than 75% tissue coverage. The average number of nerves per field was compared between the exstrophic bladders and normal controls. Results: The average number of myelinated nerves per field in the newborn exstrophic bladders (0.13 per field) was significantly reduced compared to normal controls (1.25 per field) and statistically significant (p <0.001). This reduction in nerve fibers appeared to be due to lack of smaller fibers with preservation of larger fibers. There was no difference in innervation in cases closed at birth compared to those closed after month 1 of life. Conclusions: The newborn exstrophic bladder has fewer myelinated nerve fibers than normal controls primarily due to reduction in the smaller fibers which may represent a maturational delay in the development of the exstrophic bladder. Another possible explanation may be degeneration of the fibers due to lack of bladder contraction but no indication of nerve degeneration was evident in our study. Followup studies of patients at various stages of reconstruction will determine the evolution of neural innervation in the exstrophic bladder.