It has been postulated that hyperactive glycogen synthase kinase-3 (GSK-3) is an important factor in the pathogenesis of depression, and that this enzyme also contributes to the mechanism of antidepressant drug action. In the present study, we investigated the effect of prenatal stress (an animal model of depression) and long-term treatment with antidepressant drugs on the concentration of GSK-3beta and its main regulating protein kinase B (PKB, Akt). The concentration of GSK-3beta, its inactive form (phospho-Ser9-GSK-3beta), and the amounts of active (phospho-Akt) and total Akt were determined in the hippocampus and frontal cortex in rats. In order to verify our animal model of depression, immobility time in the forced swim test (Porsolt test) was also determined.We found that prenatally stressed rats display a high level of immobility in the Porsolt test and chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine normalize this change. Western blot analysis demonstrated that GSK-3beta levels were significantly elevated in the frontal cortex, but not in the hippocampus, of prenatally stressed rats. The concentration of its non-active form (phospho-Ser9-GSK-3beta) was decreased only in the former brain structure. No changes were found in the amounts of active (phospho-Akt) and total Akt in both studied brain structures. Chronic treatment with antidepressant drugs diminished stress-induced alterations in GSK-3beta and phospho-GSK-3beta the frontal cortex, but had no effect on the concentration of these enzymes in the hippocampus. Moreover, levels of Akt and phospho-Akt in all experimental groups remained unchanged. Since our animal model of depression is connected with hyperactivity of the HPA axis, our results suggest that GSK-3beta is an important intracellular target for maladaptive glucocorticoid action on frontal cortex neurons and in antidepressant drug effects. Furthermore, the influence of stress and antidepressant drugs on GSK-3beta does not appear to impact the kinase activity of Akt.

Out of the five putative biomarkers measured, blood concentration of S100B and orexin A may be helpful in differentiating parasomnic pediatric patients with and without epilepsy.

Higher incidence of dVRs was found in children with headache and epilepsy. No association was found between localization of dVRs and symptomatology of different nervous system diseases except for large dVRs probably due to the pressure on the surrounding tissues.

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Analyzed polymorphisms of coagulation factors are not significant determinants of pediatric IS in the studied population; however, these findings require a confirmation in a larger group of participants.

Background : At least 20 -30% of epileptic patients do not sufficiently respond to monotherapy. Some of them can benefit from drug combinations; hence, animal data may provide some useful novel clues for rational polytherapy. Objective : To review combinations of antiepileptic drugs, evaluated with the help of isobolographic analysis, in terms of their efficacy and adverse effects. Methods : A literature search, on the basis of experimental studies, with no time limit was carried out. Results/conclusion : Preclinical data indicate that a synergy occurred for the combinations of valproate + phenytoin, valproate + ethosuximide, lamotrigine + valproate, gabapentin + valproate, gabapentin + carbamazepine, topiramate + carbamazepine, topiramate + valproate, topiramate + oxcarbazepine, levetiracetam + topiramate, levetiracetam + oxcarbazepine, oxcarbazepine + gabapentin, tiagabine + gabapentin and lamotrigine + topiramate. On the other hand, lamotrigine combined with carbamazepine or oxcarbazepine resulted in a clear-cut antagonism. Interestingly, a combination of oxcarbazepine + clonazepam produced variable responses, including synergy, additivity or antagonism, depending on the dose ratio of these drugs. In no case did pharmacokinetic factors contribute to the final analysis of the effects of drug combinations. Pharmacokinetic factors can contribute to the final effect of drug combinations, such as when stiripentol is added to valproate, or clobazam is added to valproate. It may be concluded that the rational treatment of drug-resistant epilepsy needs to consider the results of preclinical studies.

Parry-Romberg syndrome is characterized by progressive unilateral facial atrophy affecting subcutaneous tissue, cartilage and bone structures. Headache attacks and epilepsy are commonly associated with this syndrome but the underlying pathophysiology is still unknown. A case of a 12-year-old boy with Parry-Romberg syndrome and syringomyelia suffering from severe headache attacks and epileptic seizures is reported herein. Headache attacks were associated with bilateral autonomic symptoms and hyperventilation and were usually followed by complex partial and sometimes by secondary generalized tonic seizures. Detailed neuroimaging examinations were performed (magnetic resonance imaging [MRI] of the head, orbits, and spinal cord, MR angiography, and MR spectroscopy of the cerebellum). The EEG pattern revealed localized discharges contralaterally to the affected side. Antiepileptic treatment with carbamazepine was instituted with minimal effect. Modification of treatment (replacement with oxcarbazepine) was successful. In the reported patient interesting correlation of headache attacks, autonomic symptoms and epileptic seizures was observed. Additionally we believe it is the first report of coincident syringomyelia and Parry-Romberg syndrome.

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