N-methyl-D-aspartate receptor blockade is neuroprotective in experimental autoimmune optic neuritis.

Optic neuritis is a common clinical manifestation of the chronic inflammatory CNS disease multiple sclerosis that can result in persistent visual impairment caused by degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs). Using a model of experimental autoimmune encephalomyelitis with optic neuritis (Brown Norway rats), we show that administration of the N-methyl-D-aspartate (NMDA) receptor antagonists memantine or MK801 results in RGC protection, axon protection, and reduced demyelination of optic nerves. Calcium imaging revealed that RGC responses to glutamate stimulation predominantly occurred via NMDA receptors and were inhibited by memantine in a dose-dependent manner. In contrast, oligodendrocytes were mainly responsive through the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor. This suggests that NMDA receptor blockade protected RGCs directly and that the protection was independent of effects on oligodendrocytes. Moreover, increased RGC survival was observed before the onset of optic nerve demyelination--when RGC degeneration had already started. These results indicate an important pathophysiologic role for NMDA receptor-mediated glutamate toxicity during the induction phase of this disease model and highlight a potential target for therapeutic neuroprotection in human optic neuritis.

Pilot study on the validity of the pupillographic sleepiness test in children and adolescents.

OBJECTIVE: To report preliminary validation data for the pupillographic sleepiness test (PST) in children and adolescents. METHODS: Twelve patients (13.1±4.4 years of age) underwent the multiple sleep latency test (MLST) and three PSTs at 09:00, 11:00, and 13:00 on one single day. Correlations were tested between mean sleep latency and gender-adjusted z-values of the natural logarithm of the pupillary unrest index (zlnPUI). RESULTS: Spearman's correlation (P-value) between the zlnPUI values obtained at 09:00 and 11:00 with the MSL was rS = -0.641 (0.025) and r = -0.553 (0.062). CONCLUSION: There was satisfactory agreement between PST and the MLST, which is similar to what is found in adults. The PST may be promising for the evaluation of daytime sleepiness in children and adolescents, and should be further evaluated in future studies.

Subjective and objective daytime sleepiness in schoolchildren and adolescents: results of a community-based study.

OBJECTIVES: We aimed to assess subjective and objective sleepiness in schoolchildren and adolescents by using questionnaires and the Pupillographic Sleepiness Test (PST). METHODS: An observational, cross-sectional, community-based study was performed. Participants were recruited and balanced by age and gender from schools using stratified random sampling. Sleep problems and subjective sleepiness were assessed using parent- and self-reported questionnaires. Objective sleepiness was assessed in schools under standardized conditions by using the PST and by calculating the natural logarithm of the pupillary unrest index (lnPUI). RESULTS: In total 163 children (82 boys; age range, 6.6-17.8 years) were enrolled. Age and sleep problems were predictors of subjective sleepiness. Nine PST recordings (5.5%) were excluded due to artifacts (feasibility, 94%). Gender, sleep problems, and sleep duration were predictors of objective sleepiness. Compared to adults (age range, 20-60 years), the lnPUI was higher in children (mean±standard deviation [SD], 1.5±0.4 vs. 2.0±0.4; P<.001) and showed significant gender differences. There was no agreement between measures of subjective sleepiness and the lnPUI (r<0.3). After excluding children with sleep problems, preliminary reference values (mean±SD) for the lnPUI were 2.01±0.43 for boys and 1.93±0.43 for girls, respectively. CONCLUSIONS: The PST is a feasible method in schoolchildren and adolescents. Sleep problems are predictors of both subjective and objective sleepiness; there is no agreement between the latter. Results of the PST are influenced by sleep duration and specific pediatric gender-stratified reference values are definitively needed.