The bladder and the brain : Studies on the pathogenesis and the treatment of nocturnal enuresis

Abstract: Opinions differ as to whether nocturnal enuresis is caused by high arousal thresholds, nocturnal polyuria or nocturnal bladder instability. In spite of the currently available therapeutic options - the antidiuretic drug desmopressin and alarm treatment - approximately 25% of children suffering from enuresis cannot be successfully treated.In this thesis the pathogenesis of enuresis has been examined and new treatment options for previously therapy-resistant children have been found.A survey of 1 413 school children was performed, and a significant association between enuresis and both subjectively deep sleep and symptoms suggesting bladder instability was found.Osmoregulatory and urodynamical parameters of bedwetting children responsive and nonresponsive to desmopressin were examined. Without medication, the responders were found to produce larger amounts of less concentrated urine, whereas the functional bladder capacity was smaller in the nonresponding group.The sleep electroencephalogram of 25 bedwetting children was examined, and the enuretic event was found to be associated with non-REM (rapid eye movement) sleep. In 35 children with enuresis resistant to conventional treatment it was noted that the time point of nocturnal bladder voidings were not delayed by desmopressin administration, indicating that detrusor hyperactivity rather than bladder filling was the direct cause of the voidings in these children. High-dose (0.8mg) desmopressin treatment was successful in 5 of the children, and 20 patients responded to desmopressin combined with anticholinergic treatment.It is concluded that impaired arousal mechanisms, polyuria and bladder instability are all implicated in the pathogenesis of enuresis, but that bedwetting children are pathogenetically heterogeneous. Many previously therapy-resistant children can be helped with high-dose desmopressin treatment or by adding anticholinergic medication.