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Parasomnia as pathophysiological mechanism in a subgroup of nocturnal enuresis
Sebastian Schulz-Juergensen, M.D., Soenke Freischmidt, cand. med., Paul Eggert, Prof., M.D..
University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

BACKGROUND:
The sleep of enuretic children has been widely investigated for abnormalities explaining why a child continent during the day shows a loss of bladder control during the night. While single studies point towards deeper or lighter sleep, the majority of this research has not shown different sleep stages or arousal parameters.
Neurophysiologic measurements (prepulse inhibition of the startle reflex, PPI) have shown reduced central reflex control in a majority of enuresis patients. Its physiologic maturation during childhood as well as the effects of desamino arginine vasopressine (dDAVP) and alarm therapy on central reflex control explain the spontaneous remission rate as well as the therapeutic effect of these approaches in the majority of patients. However, a smaller subgroup of patients is therapy resistant to dDAVP and alarm therapy and was analyzed in detail in this study.
METHODS:
Measurements of prepulse inhibition (PPI) of the acoustic startle reflex were performed in consecutive patients presenting to the Pediatric Nephrology Outpatient Department for monosymptomatic nocturnal
enuresis (MNE), before initiation of therapy. The patient collective was
divided into responders to dDAVP and/or alarm therapy and those resistant to those therapies. The second group was then treated with imipramine and the effects of this treatment was investigated with polysomnographies after a 10 day medication of imipramine vs. placebo, respectively (randomized, double-blind, cross-over design).
RESULTS:
Out of 121 patients with MNE, 23 were identified who showed clinical therapy resistance to dDAVP and alarm therapy. These patients showed a high PPI (72%) compared to the responders to those therapies (26%, p<0.0001). In contrast, 18 of these 23 patients (78%) showed success or full success to imipramine therapy. In 19 patients, polysomnographies were performed with and without imipramine. Imipramine therapy was associated with significantly reduced number or wet nights (15% vs. 45%, p=0.001), and sleep evaluation showed reduced REM fraction (15.6% vs. 20.5%, p=0.01), delayed REM latency (211 min. vs. 124 min., p=0.009) and increased arousal index in REM sleep (8.5 vs. 5.2, p=0.02).
CONCLUSIONS:
The findings of normal central reflex control in the clinical subgroup with therapy resistance to dDAVP and alarm therapy identifies a distinct pathophysiological entity in these patients. The response rate to imipramine in this subgroup is significantly increased compared to the
general collective of enuretic children. As imipramine is also used in
parasomnias, this suggests the assignment of this subgroup to this etiology. The findings of REM changes through this medication further support the idea of a parasomnia, interpreted as a predominantly REM phenomenon.
In summary, remarkably good therapeutic efficacy of imipramine, sleep changes through imipramine and absence of alternative pathomechanisms are highly supportive for the previously advocated concept of parasomnia in a subgroup of patients with nocturnal enuresis.


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