It is known that sensorimotor gating measured by the prepulse inhibition of the startle reflex (PPI) matures during childhood. Since certain disorders in children, for example, enuresis, show a significant loss in PPI, the PPI as a tool for investigating brainstem reflex control mechanism gains in importance. Therefore, it is crucial to know the natural course of PPI maturation in childhood. A total of 122 healthy children aged from 3-10 years and 10 healthy adults were examined. PPI was initiated by a 120 ms and a 60 ms prepulse and was measured by the EMG of M. orbicularis oculi. For the respective prepulse intervals, the PPI level in each age group increased from 3 to 9 or 10 years and showed a similar course. The findings confirm and extend knowledge about the maturation of PPI during childhood and emphasize the importance of age-dependent standard values when investigating PPI in children.

A prospective identification of the estimated 20-50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance - T-cell subpopulations or gene expression profiles - have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8-265 months (median 89) were investigated 1-180 months (median 44) after LTX under ongoing immunosuppression. T-cell subpopulations were measured during regular post-transplant visits using FACS (Vδ1- vs. Vδ2-γδ-T cells and Tregs). A Vδ1/Vδ2-γδ-T-cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per μL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD3(+) -T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2-γδ-T-cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2-γδ-T-cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long-time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2-γδ-T-cell ratio and/or Tregs under immunosuppression.

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The observed correlation between clinical events and iATP concentrations is similar to the findings previously reported in adult patients who underwent transplantation. The lack of correlation of iATP with trough drug concentrations suggests that the ImmuKnow assay provides independent information that may be useful to guide immunosuppressive therapy in pediatric (liver) transplant patients. However, the wide range of iATP levels in event-free patients suggests that serial iATP measurements will be necessary to assess and guide the individual immunosuppressive therapy. Further investigations are needed to evaluate and extend these findings.

Evidence is growing that monosymptomatic enuresis (ME) is a maturational disorder of the central nervous system with a lack of arousal and lacking inhibition of the micturition reflex. Previous studies have shown a significant reduction of prepulse inhibition (PPI) of startle in children with enuresis. However, it is still unclear whether the abnormal PPI in enuresis is based on an inhibitory deficit at brainstem or cortical level. Nine children with ME and ten healthy children were investigated using simultaneous recording of EMG from the M. orbicularis oculi and functional MRI. The experimental paradigm consisted of acoustic startle stimulation, with startle-alone stimuli and prepulse-startle combinations. Functional MRI data were processed using multiple regression and parametric modulation with startle amplitudes as a parameter. Neither patients with enuresis nor healthy children revealed measurable PPI in the MRI scanner. Startle stimuli caused equal hemodynamic changes in the acoustic cortex, medial prefrontal and orbitofrontal cortex in both groups. The amplitude of startle correlated with more prominent BOLD signal changes in the anterior cingulate cortex in healthy subjects than in patients with ME. This pronounced frontal activation in healthy controls was related to the PPI condition, indicating that the prefrontal cortex of healthy children was activated more strongly to inhibit startle than in patients with ME. In conclusion, apart from the possibility that recordings of PPI inside the MRI scanner may be compromised by methodological problems, the results of this study suggest that high cortical control mechanisms at the prefrontal level are relevant for the pathogenesis of ME.

The increase of PPI trough alarm therapy was comparable with that under dDAVP, suggesting an analogous method of action and explaining the alternative or synergistic effect of both therapies. In addition, it further substantiates the hypothesis of a maturational delay of reflex control in NE.

Heterogeneity of ADHD is confirmed with a wide range of baseline PPI. The improvement of reduced baseline PPI through MPH suggests impaired sensorimotor gating in this subgroup.

Aim: To evaluate the effect of 1-desamino-8-D-Arginine Vasopressin (DDAVP) on sleep architecture and arousal reactions in children with primary monosymptomatic nocturnal enuresis (PME). Methods: A prospective, placebo-controlled, randomized, double-blind, cross-over study was performed on children suffering from bed-wetting. Placebo and DDAVP were given for 7 days each after which an unattended home polysomnography (PSG) was recorded. After lifting the blinding, the PSGs were compared. Results: A total of 20 children with PME, aged 6-15 years, were enrolled in the study. The number of wet nights decreased significantly with DDAVP treatment. Delta power, distribution of sleep stages, number of arousals, arousal index and the effect of arousals on sleep stages did not differ significantly. Bed-wetting occurred within each sleep stage and did not follow any particular pattern. In most cases, it was preceded by an arousal reaction, but no awakening occurred.Conclusion: DDAVP has no effect on the sleep architecture of children with PME when analysed by classical PSG, which is determined by collecting the electric activity of cortical neurons. Taking recent research findings into account, this supports the thesis that the disturbances causing PME occur at brain stem level and do not reach consciousness.