Glia and epilepsy: experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation.

Purpose: The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes.

Long-term safety and efficacy of eslicarbazepine acetate as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy: results of a 1-year open-label extension study.

Objective: To evaluate the long-term safety, tolerability and efficacy of once-daily eslicarbazepine acetate (ESL) as adjunctive therapy in adults with partial-onset seizures.

Methods: One-year open-label extension (OLE) study with ESL in patients who completed a randomised, double-blind placebo-controlled trial (study BIA-2093-302; Epilepsy Res. 89 (2010) 278-285).

Long-term assessment of topiramate for epilepsy: an open-label, single-arm, multicentre, prospective study in a naturalistic setting.

Background And Objective: Most patients with epilepsy require long-term medical therapy. Newer antiepileptic drugs (AEDs) appear to be overall similarly effective to older agents but may be better tolerated. However, most of the clinical data available for newer AEDs derive from a number of short-term studies.

Substitution of anticonvulsant drugs.

Changing from branded drugs to generic alternatives, or between different generic formulations, is common practice aiming at reducing health care costs. It has been suggested that antiepileptic drugs (AEDs) should be exempt from substitution because of the potential negative consequences of adverse events and breakthrough seizures. Controlled data are lacking on the risk of substitution.

Interhemispheric transfer of predictive force control during grasping in cerebellar disorders.

When an object is repeatedly grasped and lifted, the balance between grip force (normal to the object's surface) and lift force (tangential to the object's surface) is programmed according to the mechanical object features within a few lifts. Information related to the mechanical object properties is easily transferred in between both hands, and the cerebellum may play an essential role for the integration and generalization of this information. Recently, we have shown that the transfer of weight-related information in between both hands is impaired in cerebellar degeneration (Nowak et al.

Saccade induced cortical activation in patients with post-stroke visual field defects.

Substantial disability in patients with hemianopia results from reduced visual perception. Several studies have shown that these patients have impaired saccades but may improve search strategies with appropriate training of saccades. We used fMRI to study the representation of saccades in patients with post-stroke hemianopia to the left.

Brain perfusion following single seizures.

Purpose: The aim of this study was to assess the regional relative interictal and postictal perfusion changes in temporal and parietal lobe epilepsy.

Methods: We investigated interictal and postictal magnet resonance perfusion changes in five patients with temporal lobe epilepsy either with hippocampal sclerosis (n = 3) or without (n = 2), and in one patient with extratemporal (parietal lobe) epilepsy. T(2)*-weighted single-shot echo-planar images were acquired after bolus application of 0.

Expression time course and spatial distribution of activated caspase-3 after experimental status epilepticus: contribution of delayed neuronal cell death to seizure-induced neuronal injury.

Pilocarpine-induced status epilepticus (PCSE) is a widely used model to study neurodegeneration in limbic structures after prolonged epileptic seizures. However, mechanisms mediating neuronal cell death in this model require further characterization. Examining the expression time course and spatial distribution of activated caspase-3, we sought to determine the role of apoptosis in PCSE-mediated neuronal cell death.

Levetiracetam inhibits Na+-dependent Cl-/HCO3- exchange of adult hippocampal CA3 neurons from guinea-pigs.

The novel anticonvulsant levetiracetam (LEV) was tested for effects on bioelectric activity and intracellular pH (pHi) regulation of hippocampal CA3 neurons from adult guinea-pigs. In 4-aminopyridine-treated slices, LEV (10-100 microm) reduced the frequency of action potentials and epileptiform bursts of CA3 neurons by 30-55%, while the shape of these potentials remained largely unchanged. Suppressive effects were reversed by an increase of pHi with trimethylamine (TMA).

A new Chrna4 mutation with low penetrance in nocturnal frontal lobe epilepsy.

Purpose: To identify and characterize the mutation(s) causing nocturnal frontal lobe epilepsy in a German extended family.

Methods: Neuronal nicotinic acetylcholine receptor (nAChR) subunit genes were screened by direct sequencing. Once a CHRNA4 mutation was identified, its biophysical and pharmacologic properties were characterized by expression experiments in Xenopus oocytes.

Clinical characteristics of patients with comorbidity of migraine and epilepsy.

Objective: Neuronal hyperexcitability might explain the comorbidity of migraine and epilepsy. Spreading depression, a postulated pathophysiological mechanism of epileptic seizures and migraine with aura, may hypothetically be the link between the disorders in these comorbid conditions. The aim of the present study was to determine whether certain clinical characteristics associated with spreading depression are overrepresented in patients with comorbidity.

Presurgical evaluation of epilepsy by brain diffusion: MR-detected effects of flumazenil on the epileptogenic focus.

Purpose: After focal status epilepticus, focal alterations of the apparent diffusion coefficient (ADC) have been demonstrated in the epileptogenic zone by using diffusion-weighted magnetic resonance (MR)imaging (DWI). Effects of flumazenil on an epileptogenic focus have been demonstrated by EEG recordings, but not by functional MRI. We hypothesized that dynamic spatiotemporal alterations of brain diffusion of the epileptogenic focus after application of flumazenil will be detectable by DWI and correlate with the epileptogenic zone.

Brain diffusion after single seizures.

Purpose: Diffusion-weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone.

Methods: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2-210 min after a seizure.

Brain diffusion during hyperventilation: diffusion-weighted MR-monitoring in patients with temporal lobe epilepsy and in healthy volunteers.

Hyperventilation (HV) can be used to provoke epileptiform activity and occasionally seizures in generalised and in focal epilepsies. Based on the hypothesis that HV might alter brain diffusion in the epileptogenic areas of patients with temporal lobe epilepsy (TLE), we examined these alterations using quantitative diffusion MR imaging (DI) in four patients with TLE and unilateral hippocampal sclerosis (TLE-HS) and six patients with TLE without hippocampal sclerosis (TLE-pure), and in 10 healthy volunteers. Brain diffusion was measured at baseline and immediately after 4 min of HV.

Clinical outcome and neuropsychological deficits after right decompressive hemicraniectomy in MCA infarction.

Background And Purpose: The purpose of this study was to analyse in detail the functional outcome and the neuropsychological deficits in patients with space-occupying infarction of the non-dominant hemisphere one year after surgery.

Methods: Postoperative complications and retrospective consent to surgery were assessed in a semi-structured interview in 26 patients. Functional outcome was measured with the Barthel-Index (BI) and Rankin-Scale.

Valproate acidifies hippocampal CA3-neurons--a novel mode of action.

Various hypotheses try to explain the anticonvulsive and mood stabilizing effects of valproate. Among them, amplification of GABAergic inhibition and reduction of membrane excitability is favored. Here we show that superfusion with 0.

Carbonic anhydrase inhibitor sulthiame reduces intracellular pH and epileptiform activity of hippocampal CA3 neurons.

Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame's anticonvulsant properties.

Methods: The effects of sulthiame (a) on pHi of 2',7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxymetyl ester (BCECF-AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 microM 4-aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide.