Kroczka S

Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex

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.

Pharmacodynamic interactions between antiepileptic drugs: preclinical data based on isobolography

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.

Cluster headache in 2-year-old Polish girl

Cluster headache (CH) is one of the most severe types of primary headache. Intense, unilateral pain in orbital, supraorbital and/or temporal location accompanied by autonomic symptoms is the most characteristic feature. Diagnostic criteria for CH described in the International Classification of Headache Disorders (ICHD), 2nd edition are very helpful in clinical practice and prevent misdiagnosis of this rare type of headache (1). However, diagnosis of CH in the youngest patients is very troublesome due to the lack of patient cooperation. Thorough case history taking and careful parental observation of the child’s behaviour during attacks are crucial in the diagnosis of this type of headache. The patient reported in this paper is one of the youngest with well-documented early childhoodonset CH.

Stiripentol – characteristic of a new antiepileptic drug

Background: As 20 – 30% of patients are refractory to the presently available antiepileptic drugs, there is a strong need for the development of newer antiepileptics. Objective: A question arises whether stiripentol fulfills the criteria for a promising newer antiepileptic drug. Methods: A literature search, including experimental and clinical studies, with no time limit was performed. Results/conclusion: Stiripentol represents a group of drugs indirectly enhancing GABA-ergic neurotransmission and it exerts a protective activity in some experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazol-, bicuculline-, strychnine-, and cocaine-induced convulsions. The drug potently inhibits metabolism of other antiepileptic drugs, significantly elevating their plasma and brain concentrations. This requires dosage adjustments of the concomitant antiepileptic drugs used in combination. In the form of an add-on therapy, stiripentol has proved to be effective in partial and atypical absence epilepsies. Considering its particular efficacy against severe myoclonic seizures in infancy (Dravets syndrome), stiripentol has been awarded an orphan drug status for an adjunctive therapy of this difficult-to-treat condition.

Clinical and videoEEG findings in a girl with juvenile moyamoya disease

Moyamoya disease is present throughout the course of development, including juvenile development. Very careful EEG analysis may be a diagnostic method in such cases where clinical symptoms are not sufficient for diagnosis. Herein, we report a Polish case of moyamoya disease in a 13-year-old girl with polymorphic clinical symptoms. Even though her diagnosis was made late in the course of her disease, it was due to successful EEG analysis and not due to clinical symptoms that a diagnosis was made at all. Re-build up phenomenon was registered as well as an asymmetric slowing in background activity. High-voltage slow frontal and generalized activity was seen during hyperventilation.

Wpływ stresu ortostatycznego na równowagę współczulno -przywspółczulną i przepływ mózgowy krwi u dzieci z migreną

STRESzCzENIE Wprowadzenie: Pacjenci chorujący na migrenę często zgłaszają objawy wskazujące na dysfunkcję autonomicznego układu nerwowego, a ryzyko wystąpienia omdlenia jest u nich większe niż u osób bez bólu głowy. Celem pracy była ocena wpływu stresu ortostatycznego na równowagę współczulno-przywspółczulną oraz przepływ mózgowy krwi u dzieci z migreną. Materiał i metody: Badaniem objęto 86 dzieci z migreną i 33 dzieci bez bólów głowy. W spoczynku, podczas 10-minutowej biernej, następnie 3-minutowej czynnej pionizacji przeprowadzono za pomocą aparatu Task Force Monitor 3030i/3040i zapis EKG i pomiar ciśnienia tętniczego, jednocześnie monitorując przepływ krwi w tętnicach mózgu środkowych, MCA za pomocą aparatu Nicolet Companion III. Wyniki: Migrenę bez aury rozpoznano u 36 dzieci, a z aurą u 47 pacjentów. Omdlenie wystąpiło podczas pionizacji biernej u 2,3% pacjentów z migreną bez aury (dodatkowo 2,3% zgłaszało objawy przedomdleniowe) oraz u 6,1% dzieci z grupy kontrolnej, towarzyszyło mu zmniejszenie rozkurczowej prędkości przepływu krwi w MCA. Zespół ortostatycznej tachykardii posturalnej, POTS rozpoznano u 5,8% dzieci z migreną. Nie było istotnych różnic wskaźnika niskich do wysokich częstotliwości zmienności rytmu serca i parametrów hemodynamicznych pomiędzy dziećmi z migreną i z grupy kontrolnej. Wnioski: W obecnym badaniu wskaźnik równowagi współczulno-przywspółczulnej oraz parametry hemodynamiczne krążenia systemowego i mózgowego u chorych z migreną w okresie bez bólu głowy, nie różniły się istotnie od wyników uzyskanych w grupie kontrolnej, zarówno w spoczynku, jak i podczas pionizacji. Nietolerancja stresu ortostatycznego towarzysząca migrenie może mieć charakter omdlenia lub POTS. Typowe dla omdlenia zmiany widma Dopplerowskiego w MCA rejestrowane są także w przypadku fałszywie dodatniego wyniku testu pionizacyjnego. Słowa kluczowe: migrena, omdlenie, pionizacja SummARy Introduction: Migraine patients commonly describe symptoms of dysautonomia and they are also at higher risk for syncope than people without headaches. The aim of the study was to establish changes of sympatho-vagal balance as well as cerebral blood flow during an orthostatic challenge in children with migraine. Matherial and methods: The group consisted of 86 children with migraine and 33 without headaches. ECG and blood pressure monitoring using Task Force Monitor 3030i/3040i with parallel cerebral blood flow registration in middle cerebral arteries and MCA using Nicolet Companion III was performed during the rest, during a 10-min head-up tilt test and a 3-min active standing test. Results: Migraine without aura was diagnosed in 36 and with aura in 47 patients. Syncope occurred during a passive tilting in 2,3% of patients with migraine without aura (other 2,3% reported presyncopal symptoms), and in 6,1% of controls. During syncope preferential reduction in diastolic velocity was registered in MCA. Postural orthostatic tachycardia syndromePOTSwas diagnosed in 5,8% of migraine patients. There were no significant differences of low to high frequency index of heart rate variability or hemodynamic parameters between children with migraine and controls. Conclusions: This research did not reveal significant differences of sympatho-vagal balance, or hemodynamic parameters of systemic and cerebral blood flow between patients with migraine during headache-free period and children without headaches both at rest and during an orthostatic challenge. Syncope or POTS can be both manifestation of an orthostatic intolerance associated with migraine. A typical transcranial Doppler pattern of blood flow in MCA during syncope can be registered during syncope, as well as a false positive head-up tilt test.