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Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy., Methods: All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database., Results: Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands., Conclusion: Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the wake of acquired brain insults such as status epilepticus (SE), time-dependent neuronal network alterations may occur resulting in cortical hyperexcitability and enhanced synchrony merging into chronic epilepsy. To better understand the underlying processes, we performed electrophysiological and optical imaging studies on combined hippocampal-entorhinal cortex slices. These were prepared from rats 1, 4 and 8 weeks after electrically-induced SE. Non-invasive imaging using intrinsic optical signal changes allowed detailed analysis of onset and spread patterns of seizure-like events (SLE) since coverage of the entire preparation is possible. The latency to occurrence of first SLEs after omission of Mg(2+) from the artificial cerebrospinal fluid was significantly reduced at 4 and 8 weeks after SE compared with all other groups indicating increased brain excitability. Optical imaging displayed multiregional onset and discontiguous propagation of SLEs 8 weeks after SE. Such patterns indicate neuronal hypersynchrony and are not encountered in naïve rodents in which SLEs commonly begin in the entorhinal cortex and display contiguous spread to invade adjacent regions. The electrophysiological and optical findings of the current study indicate evolving fundamental brain plasticity changes after the detrimental event predisposing to chronic epilepsy. The current results should be incorporated in any strategies aiming at prevention of chronic epilepsy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The semiology of epileptic seizures changes during the lifetime. Hence, it can be assumed that age-related changes in brain plasticity influence the patterns of seizure onset, spread and propagation velocity. We employed the 4-aminopyridine model of epilepsy to study seizure-like events in vitro. Combined entorhinal cortex-hippocampus brain slices from juvenile (10-13 days), adult (2-3 months), and senile (24-27 months) rats were examined using electrophysiological recordings and imaging of intrinsic optical signals. In the juvenile group, seizure onset was multifocal in all slice regions including the hippocampus. Onset in adult animals was confined to the entorhinal cortex and to neocortical regions. In slices from senile animals, there was a preponderance of seizure onsets in the neocortex. Spread patterns were highly variable in the juvenile group and became gradually more monomorph with increasing age. Propagation velocities were highest in the adult group, with maximum values of 1.51 +/- 0.68 mm/s. In the juvenile group, they amounted to 0.97 +/- 0.39 mm/s, and to 1.18 +/- 0.42 mm/s in senile slices. The results of this study indicate that age-related changes in brain plasticity profoundly affect spread patterns, which may contribute to the clinically observed changes in seizure semiology during early childhood, adulthood and senescence.

The spatiotemporal features of spreading depression (SD) were analyzed in vitro by using combined hippocampal-entorhinal cortex slices. SDs were induced by microinjection of 1 M KCl in the stratum radiatum of the CA1 region of the hippocampus. Measurements of extracellular field potentials, extracellular space (ECS) volume changes and intrinsic optical signal changes were combined to study SD features in different regions of the slice. Each SD was associated with a pronounced shrinkage of the extracellular space (ECS) volume and a decrease in light transmittance. The beginning of the optical signal change occurred simultaneously with the electrographic onset as measured with extracellular microelectrodes but outlasted the dc shift for tens of seconds. The amplitude of the intrinsic optical signal change displayed marked regional variations with greatest changes of 12% in cortical regions. The signal amplitudes were considerably lower in hippocampal regions. The analysis of spread patterns revealed two types of waves: fully propagated waves spreading from CA1 all the way to the temporal neocortex and abortive waves that ceased earlier. The spread velocities displayed pronounced regional differences with highest velocities of 5.4 +/- 0.3 mm/min in the area CA3 of the hippocampal formation and lowest velocities of 2.7 +/- 0.1 mm/min in cortical regions., (Copyright 2002 Elsevier Science (USA).)

Idiopathic CD4+ T cell lymphocytopenia was unexpectedly detected in a 33-year-old, otherwise healthy young woman with no HIV or other viral infection, autoimmune, or neoplastic disease or increased susceptibility to infection. CD4+ T cell levels were 60-140/microl over a 3.5-year period. Following an uneventful pregnancy, the patient developed anemia and interstitial nephritis associated with a plasma cell dyscrasia with a monoclonal IgA gammopathy and a shifting immunoglobulin pattern that included IgG and IgA monoclonal proteins and increased urinary light chains. Osteolytic lesions were never detected and bone marrow aspirations revealed up to 10% atypical plasma cells. Various therapies often used in treating multiple myeloma only temporarily controlled the increasing renal damage. IL-2 therapy of 600,000 to 1 million units subcutaneously daily resulted in increased CD4+ T cells to normal levels, a decrease in the gammopathy, a return of renal function, energy, and weight gain, and apparently normal health status sustained for 2 years. The findings are compatible with a potentially fatal but nonmalignant immunoregulatory disorder that can be controlled by IL-2 administration., (Copyright 2001 Academic Press.)

We have combined recordings with extracellular microelectrodes or ion-sensitive electrodes and imaging of intrinsic optical signal changes to study the spatiotemporal pattern of seizure onset and spread during development. We have employed the entorhinal cortex-hippocampus brain slice preparation of juvenile rats at different stages of postnatal maturation. Three age groups were analyzed: 4-6 days (age group I), 10-14 days (age group II), and 20-23 days (age group III). Seizure-like events were induced by perfusion of slices with Mg(2+)-free artificial cerebrospinal fluid thereby removing the Mg(2+) block of the N-methyl-d-aspartate receptor. Seizure susceptibility was highest in age groups II and III. In age group I seizure-like events originated mainly in the hippocampus proper. Seizure-like events in age group II originated mainly in the entorhinal cortex and this tendency was even more pronounced in age group III. Invasion of the hippocampal formation via the perforant path-dentate gyrus and via the subiculum was seen in age groups I and II. In contrast, in age group III the hippocampus was invaded exclusively via the subiculum pathway. The velocity of spread at which seizure-like events propagated within different regions of the slice increased with postnatal age. The characteristics of onset, spread patterns, and propagation velocities as revealed by this study allow insight into the evolving properties of the developing brain., (Copyright 2000 Academic Press.)