Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study

BACKGROUND: Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. METHODS: This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. RESULTS: Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively.CONCLUSIONS: Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV(VLID)195291

Early electroencephalography in patients with Emergency Room diagnoses of suspected new-onset seizures: Diagnostic yield and impact on clinical decision-making

AbstractPurposeTo assess the utility of acute electroencephalography (EEG) performed in the emergency room (ER) and its impact on subsequent management of patients with new-onset seizures. Adults who recover fully in the ER following suspected isolated new-onset seizures are usually discharged to the neurology clinic for further review. An EEG at that stage may be normal. We sought to assess the feasibility and yield of early EEG in the ER setting, its impact on management.MethodsA prospective study from January 2008 to January 2011 of patients diagnosed by ER physicians with uncomplicated suspected first episodes of unprovoked convulsive seizures. All patients underwent routine 30-min EEG in the ER prior to discharge and specialist review was arranged in the epilepsy clinic within 2 weeks of presentation. Management decisions were at the discretion of the treating neurologist. Seizure recurrence was assessed during a follow up period between 9 months and 3 years.Results136 patients were included in the study (92 males). Mean age was 32 years (range 16–73). Forty had abnormal EEGs: 16 focal epileptiform discharges, 12 focal slowing, 10 generalized spike-wave discharges and 2 generalized slowing. Using multivariate analysis, those with abnormal EEG (51% vs 11%, p=0.003) and abnormal MRI (53% vs 28%, p<0.001) were more likely to be commenced on anticonvulsant therapy. Abnormal MRI (p=0.001) was independently associated with a higher risk of recurrence.ConclusionsFollowing an ER diagnosis of new-onset uncomplicated seizure, early EEG had a high diagnostic yield. Abnormal EEG and abnormal MRI significantly contributed to decision-making regarding treatment at specialist review. Abnormal MRI was associated with significantly higher risks of subsequent seizures

Decadal hindcasts initialized using observed surface wind stress: Evaluation and prediction out to 2024

We use surface air temperature to evaluate the decadal forecast skill of the fully coupled Max Planck Institut Earth System Model (MPI-ESM) initialized using only surface wind stress applied to the ocean component of the model (Modini: Model initialization by partially coupled spin-up). Our analysis shows that the greenhouse gas forcing alone results in a significant forecast skill on the 2–5 and 6–9 year range even for uninitialized hindcasts. For the first forecast year, the forecast skill of Modini is generally comparable with previous initialization procedures applied to MPI-ESM. But only Modini is able to generate a significant skill (correlation) in the tropical Pacific for a 2–5 year (and to a lesser extent for a 6–9 year) hindcast. Modini is also better able to capture the observed hiatus in global warming in hindcast mode than the other methods. Finally, we present forecasts for 2015 and the average of years 2016–2019 and 2020–2024, predicting an end to the hiatus

Early EEG predicts poststroke epilepsy

©2018 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Objective: Electroencephalography (EEG) can identify biomarkers of epileptogenesis and ictogenesis. However, few studies have used EEG in the prediction of poststroke seizures. Our primary aim was to evaluate whether early EEG abnormalities can predict poststroke epilepsy. Methods: A prospective study of consecutive acute anterior circulation ischemic stroke patients, without previous epileptic seizures, who were admitted to a stroke unit over 24 months and followed for 1 year. All patients underwent standardized clinical and diagnostic assessment during the hospital stay and after discharge. Video-EEG was performed in the first 72 h (first EEG), daily for the first 7 days, in case of neurological deterioration, at discharge, and at 12 months after stroke. The occurrence of epileptic seizures in the first year after stroke (primary outcome) was evaluated clinically and neurophysiologically during the hospital stay and at 12 months. A telephone interview was also performed at 6 months. The primary outcome was the occurrence of at least one unprovoked seizure (poststroke epilepsy). Secondary outcomes were the occurrence of at least one acute symptomatic seizure and (interictal and/or ictal) epileptiform activity on at least one EEG during the hospital stay for acute stroke. The first EEG variables were defined using international criteria/terminology. Bivariate and multivariate analyses with adjustment for age, admission National Institutes of Health Stroke Scale (NIHSS) score, and Alberta Stroke Program Early CT Score (ASPECTS) were performed. Results: A total of 151 patients were included; 38 patients (25.2%) had an acute symptomatic seizure and 23 (16%) had an unprovoked seizure.The first EEG background activity asymmetry and first EEG with interictal epileptiform activity were independent predictors of poststroke epilepsy during the first year after stroke (P = 0.043 and P = 0.043, respectively). No EEG abnormality independently predicted acute symptomatic seizures. However, the presence of periodic discharges on the first EEG was an independent predictor of epileptiform activity (p = 0.009) during the hospital stay. Significance: An early poststroke EEG can predict epilepsy in the first year after stroke, independently from clinical and imaging-based infarct severity.The 2012 Research Grant in Cerebrovascular Diseases (scientific promoter: Stroke Portuguese Society (SPAVC) – Sponsor: Tecnifar) supported this work.info:eu-repo/semantics/publishedVersio

Exploring the impact of CMIP5 model biases on the simulation of North Atlantic decadal variability

Instrumental observations, palaeo-proxies, and climate models suggest significant decadal variability within the North Atlantic subpolar gyre (NASPG). However, a poorly sampled observational record and a diversity of model behaviours mean that the precise nature and mechanisms of this variability are unclear. Here, we analyse an exceptionally large multi-model ensemble of 42 present-generation climate models to test whether NASPG mean state biases systematically affect the representation of decadal variability. Temperature and salinity biases in the Labrador Sea co-vary and influence whether density variability is controlled by temperature or salinity variations. Ocean horizontal resolution is a good predictor of the biases and the location of the dominant dynamical feedbacks within the NASPG. However, we find no link to the spectral characteristics of the variability. Our results suggest that the mean state and mechanisms of variability within the NASPG are not independent. This represents an important caveat for decadal predictions using anomaly-assimilation methods

The phenotype of bilateral hippocampal sclerosis and its management in “real life” clinical settings

Objective: There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. Methods: Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. Results: In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80 years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P =.002; Fisher's exact test). Significance: The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures

PURPOSE: Childhood convulsive status epilepticus (CSE), in particular prolonged febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS). Previous studies have shown that hippocampal injury occurs in the acute phase immediately following CSE, but little is known about the longer term evolution of such injury. This study aimed to investigate the longer term outcome of childhood CSE with sequential magnetic resonance imaging (MRI) looking for progressive hippocampal injury during the first year post-CSE. METHODS: Eighty children (0.18–15.5 years) underwent brain MRI 1 month post-CSE, 50 with a repeat MRI at 6 months and 46 with repeat MRI at 12 months post-CSE. Thirty-one control subjects without neurologic problems had a single brain MRI for comparison. Hippocampal volumes were measured from each MRI scan by two independent observers, and hippocampal growth rates were estimated in each patient with suitable imaging. KEY FINDINGS: Hippocampal volume loss was found in 20–30% of patients and was not associated with the etiology or clinical features of CSE, including seizure duration or focality. A borderline association was found between a history of previous seizures (p = 0.063) and the number of previous febrile seizures (p = 0.051), suggesting that multiple insults may be important in the pathogenesis of progressive hippocampal injury. SIGNIFICANCE: It is apparent that progressive hippocampal damage can occur after CSE of any etiology and is not limited to PFS. Repeated seizures may play an important role, but further follow-up is needed to determine any other risk factors and proportion of children showing initial volume loss progress to clinical MTS and temporal lobe epilepsy

Anxiety disorders in people with epilepsy.

Anxiety disorders are frequent, though probably underdiagnosed, comorbidities in epilepsy. Epilepsy and anxiety may share common neurobiological correlates as shown in animal models and suggested by studies demonstrating anxiety disorders before the manifestation of epilepsy. Comorbid anxiety disorders have a major impact on the affected patients' quality of life and may increase the risk for suicidality. Successful treatment of the epilepsy may alleviate anxiety symptoms. Treatment of anxiety is based on selective serotonin reuptake inhibitors, benzodiazepines (although only as second-line choices), and psychotherapy. Specific AEDs (especially pregabalin) have been shown to have anxiolytic properties. This paper is aimed at reviewing anxiety disorders in patients with epilepsy discussing current scientific evidence about pathophysiology, clinical aspects, and treatment strategies

Recent progress in understanding and predicting Atlantic decadal climate variability

Recent Atlantic climate prediction studies are an exciting new contribution to an extensive body of research on Atlantic decadal variability and predictability that has long emphasized the unique role of the Atlantic Ocean in modulating the surface climate. We present a survey of the foundations and frontiers in our understanding of Atlantic variability mechanisms, the role of the Atlantic Meridional Overturning Circulation (AMOC), and our present capacity for putting that understanding into practice in actual climate prediction systems