Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 microg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.
Objective: To examine the psychometric properties of the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T) in an autism spectrum disorder (ASD) clinic for children aged 18 to 36 months. Methods: The RITA-T (level 2 screening instrument) was integrated into an ASD screening and diagnostic process for evaluating children aged 18 to 36 months who were referred to a pediatric tertiary care center. Scoring of the RITA-T to differentiate ASD from non-ASD developmental concerns was evaluated. Screening instrument measurements included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR−). Results: From a total of 239 participants aged 18 to 36 months (males = 78% and females = 22%), 201 (84%) were diagnosed with ASD (4:1 male-to-female ratio). An ASD diagnosis was significantly associated with RITA-T scores, with ASD patients scoring higher than non-ASD patients [F (1,235) = 170, mean difference: males 9.21, mean difference: females 12.4, p < 0.001]. The RITA-T score was not statistically correlated with age or sex. The optimal cutoff score of ≥14 was determined from a receiver operator curve analysis (area under the curve = 0.953). In the study group, with a cutoff score of ≥14, the RITA-T showed a sensitivity of 0.97, specificity of 0.71, PPV of 0.95, NPV of 0.79, LR+ of 3.33, and LR− of 0.05. Conclusion: The RITA-T, as a level 2 screening instrument for ASD, exhibits discriminative psychometric properties similar to previously published results. When integrated into an ASD screening and diagnostic process for families for whom concerns about ASD have been raised with their children aged 18 to 36 months, the RITA-T helps to predict a best-estimate clinical diagnosis of ASD.
Introduction. Acute complete external ophthalmoplegia is a rare finding in clinical practice that is associated with diseases affecting the neuromuscular junction, the oculomotor nerves, or the brainstem. Ophthalmoplegia has been reported with acute ataxia in Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE). Up to 95% of these cases are associated with anti-GQ1b antibodies. Only a small number of cases of anti-GQ1b negative MFS have been documented in pediatric patients. This is the first case reporting a recurrence of ocular symptoms in an anti-GQ1b antibody negative patient with BBE. Case Presentation. An 8-year-old Caucasian boy presented with complete external ophthalmoplegia without ptosis, cerebellar ataxia, and a disturbance of consciousness. He had recently recovered from a confirmed Campylobacter jejuni infection. On subsequent laboratory testing he was anti-GQ1b antibody negative. He had a recurrence of diplopia at four-week follow-up. Conclusions. This patient's recurrence of diplopia was treated with a five-week course of oral corticosteroids which did not worsen his condition, and this may be a therapeutic option for similar patients. We will discuss the symptoms and treatment of reported pediatric cases of anti-GQ1b antibody negative cases of MFS and the variation between cases representing a spectrum of illness.
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