Valproic acid use in pediatric partial epilepsy after initial medication failure

We retrospectively identified 46 children and adolescents with partial epilepsy, who failed prior treatment with phenytoin, carbamazepine, phenobarbital and/or primidone. All patients were subsequently treated with valproate (VPA). Outcome measurements were stratified into seizure type, simple partial seizures (SPS), complex partial seizures (CPS) or secondarily generalized seizures (SGS), or lesions detected by magnetic resonance images (MRI). The majority of the patients had a ≥ 75% reduction of seizure frequency. Complete seizure freedom was achieved in 7 (15%) patients. "Worthwhile" seizure reduction, defined as ≥ 75% decrease (but < 100%) in seizure activity, was found in 30 (65%) patients. VPA was efficacious in SPS (2/2), CPS (9/12) and SGS (26/32) patients. Patients with MRI lesions of vascular insult (6/6), mesial temporal lobe sclerosis (8/10), or malformation of cortical development (6/7) had a higher response percentage than those patients with normal MRI findings (11/15) and tumors (5/7). Although the numbers of patients used in this study were too small for statistical significance, our results suggest that VPA is a useful medication for previous medication failures in childhood partial seizures across seizure types as well as MRI lesions. There is some suggestion that a higher percentage of patients with MRI lesions may respond favorably to VPA than patients with non-lesional partial seizures and tumors. (J Pediatr Neurol 2004; 2(4): 199-203)

Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder

Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2)  = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes