Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Antisaccades and memory-guided saccades in genetic generalized epilepsy and temporal lobe epilepsy.

OBJECTIVE: Oculomotor tasks can be used to measure volitional control of behavior sensitive to frontal dysfunction. This study aimed to examine the saccadic eye movement in Genetic Generalized Epilepsy (GGE) which could correlate with the abnormality of the frontal lobe or the thalamo-frontal network. METHODS: Twenty-one patients with GGE were compared with 22 patients with Temporal Lobe Epilepsy (TLE) and 39 healthy controls. Visual-guided saccades, Antisaccades, and Memory-guided saccades as oculomotor tasks were performed using a novel gaze-tracker designed for clinical practice use. RESULTS: Patients with epilepsy (either GEE or TLE) had similar latency, accuracy, and velocity in visual-guided saccades and memory-guided saccades. Patients with epilepsy had similar latencies and correct antisaccade number. However, healthy volunteers, matched by age, had faster responses and more accurate results than patients with epilepsy. CONCLUSIONS: Our investigations did not reveal differences between TLE and GGE patients' groups in visually guided saccades, antisaccades, and memory-guided saccades, thus suggesting that the frontal cortical mechanisms responsible for them are not explicitly impaired in patients with GGE.

Utilidad de la electroencefalografía en la valoración de la amnesia global transitoria / Usefulness of electroencephalograms in evaluating transient global amnesia

Introducción. La amnesia global transitoria (AGT) es un cuadro clínico perfectamente definido, pero hoy día aún representa una incógnita desde el punto de vista etiológico. Las tres teorías más aceptadas sugieren un origen vascular del episodio, una relación con la fisiopatología de la migraña o un carácter epileptiforme. Objetivo. Analizar si existe algún patrón electroencefalográfico que se repita de manera consistente en una serie de electroencefalogramas (EEG) de pacientes con AGT. Pacientes y métodos. Análisis retrospectivo de una muestra de 345 pacientes remitidos para la realización de EEG tras un episodio de AGT. Resultados. En casi el 20% de los EEG se encontró algún hallazgo fuera de la normalidad, si bien la mayor parte de ellos (64%) era de escaso significado patológico. Del 26% restante cabe destacar la presencia de dos pacientes con descargas electroencefalográficas rítmicas subclínicas del adulto (patrón de significado incierto que previamente ya se ha asociado con AGT). Conclusiones. Existe un porcentaje no despreciable de pacientes con AGT y alteraciones en el EEG, si bien la mayor parte de ellas es de escaso significado patológico o atribuible a otra patología de base. No hemos sido capaces de identificar ningún patrón que se repita de manera consistente. Nuestros resultados sugieren que el EEG es una prueba con bajo rendimiento diagnóstico en esta patología y que habría que plantearse la necesidad de realizarla sistemáticamente ante una AGT (AU)

Introduction. Transient global amnesia (TGA) is a perfectly well defined clinical picture, but nevertheless even today its aetiology remains unknown. The three most widely accepted theories suggest it has a vascular origin, it is related with the pathophysiology of migraine or it is of an epileptiform nature. Aim. To analyse whether there is an electroencephalographic pattern that is consistently repeated in a series of electroencephalograms (EEG) carried out on patients with TGA. Patients and methods. The study consists in a retrospective analysis of a sample of 345 patients referred to have an EEG after an episode of TGA. Results. In almost 20% of the EEGs something that could be considered abnormal was found, although most of these findings (64%) were of little pathological significance. Of the remaining 26%, attention should be drawn to the cases of two patients with subclinical rhythmic electroencephalogram discharges of adults (a pattern with a meaning that is not altogether clear and which has previously been associated with TGA). Conclusions. A considerable percentage of patients have TGA and EEG alterations, although most of them are of scarce pathological significance or can be attributed to some other underlying condition. We have not succeeded in identifying any pattern that is consistently repeated. Our results suggest that the EEG is a test with low diagnostic effectiveness in this pathology and it is necessary to reconsider the need to systematically perform such tests in suspected cases of TGA (AU)

Ca2+/calmodulin-dependent modulation of cell cycle elements pRb and p27kip1 involved in the enhanced proliferation of lymphoblasts from patients with Alzheimer dementia.

Failure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epstein-Barr virus showed an enhanced rate of proliferation and increased phosphorylation of the retinoblastoma protein (pRb) and other members of the family of pocket proteins compared with cell lines derived from normal age-matched controls. The calmodulin antagonist calmidazolium, as well as W-7 and W-13, abrogated the enhanced activity of AD cells without altering the normal basal rate of proliferation. The effect of calmidazolium was accompanied by partially dephosphorylation of pRb. No changes were found in the expression levels of the G1 cyclin/Cdks complexes. However, lymphoblasts derived from AD patients showed reduced levels of the Cdk inhibitor p27(kip1), which were restored after anti-calmodulin treatment of the cultures. These observations suggest that in AD cells the enhanced rates of cell proliferation and phosphorylation of pRb and the intracellular content of p27(kip1) may be interrelated events controlled by a mechanism dependent on the Ca(2+)/calmodulin signaling pathway. The distinct functional features of lymphoblastoid cells from AD patients offer an invaluable, noninvasive tool to investigate the etiopathogenesis, and eventually, for the early diagnosis and prognosis of this devastating disease.