What's Current?

A virtual brain helps decrypt epilepsy

Medical News Today - 3 hours 43 min ago
Researchers at CNRS, INSERM, Aix-Marseille University and AP-HM have just created a virtual brain that can reconstitute the brain of a person affected by epilepsy for the first time.
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Virtual brain helps decrypt epilepsy

Science Daily - 6 hours 13 min ago
A virtual brain has been created that can reconstitute the brain of a person affected by epilepsy for the first time. From this work we understand better how the disease works and can also better prepare for surgery, say scientists.
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News: Epilepsy Foundation new grant and award opportunities

Epilepsy and Behavior - 12 hours 33 min ago

Targeted Research Initiative for Research Related to Cannabinoid and Epilepsy (Applications due 9/12/16)

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Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice

Epilepsia - Thu, 07/28/2016 - 02:06
Summary Objective

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data.

Methods

ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested.

Results

No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice.

Significance

Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and rats, and corneal-kindled mice. This study highlights the challenge of predicting clinical adverse effects with preclinical models.

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Investigating social cognition in epilepsy using a naturalistic task

Epilepsia - Wed, 07/27/2016 - 00:35
Summary Objective

The primary objective for this study was to assess social cognition in patients with focal epilepsy using a naturalistic task, which accurately models complex real-world social interaction.

Methods

We conducted an observational study of social cognition in 43 patients with focal epilepsy and in 22 controls. Patients and controls completed The Awareness of Social Inference Test, which measures both basic and advanced social cognition in a realistic video-based format. Patient and controls also completed standard measures of cognitive functioning and measures of depression.

Results

Compared to controls, we found that patients with epilepsy (PWEs) had no difficulty identifying positively valenced emotional states (happiness) yet had difficulty identifying most negatively valenced emotional states (anger, fear, and disgust). In addition, PWEs were able to identify sincere exchanges correctly but could not identify sarcastic and insincere exchanges. We found that basic social cognition significantly correlated with standard generalized cognitive measures, whereas advanced social cognition did not. Finally, age at onset had significant impact on social cognition, whereas other epilepsy characteristics did not.

Significance

PWEs have deficits in social cognition when measured using a naturalistic video-based task. Advanced social cognition may be an independent cognitive domain in PWEs that is not adequately measured using standard psychometric instruments. Problems with social cognition may arise as a consequence of epilepsy during the periods of robust social development in childhood and adolescence.

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Investigation of mechanisms of vagus nerve stimulation for seizure using finite element modeling

Epilepsy Research Journal - Wed, 07/27/2016 - 00:00
Vagus Nerve Stimulation (VNS) was FDA approved nearly 20 years ago in 1997, implanted in over 65,000 patients and yet its mechanisms of action in treating epileptic seizures remain unclear. While responder rates are over 50% for the 30–40% of patients who are resistant to anti-seizure medications, most responders do not become seizure-free, but rather have the severity and frequency of seizures reduced by approximately 40–50% on average (Amar et al., 2009; Wu and Sharan, 2013).
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Novel compounds arrested epilepsy development in mice

Medical News Today - Mon, 07/25/2016 - 03:00
A team led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans' Neuroscience Center of Excellence, has developed neuroprotective compounds that may prevent the...
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US suicide rate for people with Epilepsy exceeds levels in general population

Medical News Today - Mon, 07/25/2016 - 03:00
Researchers at Columbia University's Mailman School of Public Health and the Centers for Disease Control studied the prevalence of suicide among people with epilepsy compared to the population...
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Novel compounds arrested epilepsy development in mice

Science Daily - Fri, 07/22/2016 - 09:29
Neuroprotective compounds have been developed by scientists that may prevent the development of epilepsy. The researchers explained that the compounds prevented seizures and their damaging effects on dendritic spines, specialized structures that allow brain cells to communicate. In epilepsy, these structures are damaged and rewire incorrectly, creating brain circuits that are hyper-connected and prone to seizures, an important example of pathological plasticity.
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The antiepileptic medications carbamazepine and phenytoin inhibit native sodium currents in murine osteoblasts

Epilepsia - Thu, 07/21/2016 - 01:45
Summary Objective

Fracture risk is a serious comorbidity in epilepsy and may relate to the use of antiepileptic drugs (AEDs). Many AEDs inhibit ion channel function, and the expression of these channels in osteoblasts raises the question of whether altered bone signaling increases bone fragility. We aimed to confirm the expression of voltage-gated sodium (NaV) channels in mouse osteoblasts, and to investigate the action of carbamazepine and phenytoin on NaV channels.

Methods

Immunocytochemistry was performed on primary calvarial osteoblasts extracted from neonatal C57BL/6J mice and additional RNA sequencing (RNASeq) was included to confirm expression of NaV. Whole-cell patch-clamp recordings were made to identify the native currents expressed and to assess the actions of carbamazepine (50 μm) or phenytoin (50 μm).

Results

NaV expression was demonstrated with immunocytochemistry, RNA sequencing, and functionally, with demonstration of robust tetrodotoxin-sensitive and voltage-activated inward currents. Application of carbamazepine or phenytoin resulted in significant inhibition of current amplitude for carbamazepine (31.6 ± 5.9%, n = 9; p < 0.001), and for phenytoin (35.5 ± 6.9%, n = 7; p < 0.001).

Significance

Mouse osteoblasts express NaV, and native NaV currents are blocked by carbamazepine and phenytoin, supporting our hypothesis that AEDs can directly influence osteoblast function and potentially affect bone strength.

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Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE – Commission on European Affairs and the European Epilepsy Monitoring Unit Association

Epilepsia - Thu, 07/21/2016 - 01:45
Summary

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)—Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.

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Scientists apply new imaging tool to common brain disorders

Science Daily - Wed, 07/20/2016 - 14:35
A new approach has been developed to scanning the brain for changes in synapses that are associated with common brain disorders. The technique may provide insights into the diagnosis and treatment of a broad range of disorders, including epilepsy and Alzheimer's disease, say authors of a new report.
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FDA accepting comments on draft guidelines on compounding law

Clinical Neurology News - Wed, 07/20/2016 - 10:51

The Food and Drug Administration is currently accepting public comments on the agency’s proposed plans to implement a law that will restrict compounding of human drug products.

A <a...

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Erratum

Epilepsia - Wed, 07/20/2016 - 08:01
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Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury

Epilepsia - Tue, 07/19/2016 - 08:20
Summary Objective

Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury.

Methods

Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011–2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism).

Results

The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively.

Significance

The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility.

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Lacosamide use in children with epilepsy: Retention rate and effect of concomitant sodium channel blockers in a large cohort

Epilepsia - Tue, 07/19/2016 - 08:15
Summary Objectives

To evaluate the effectiveness of lacosamide (LCM) in pediatric patients, using time to treatment failure as the outcome measure, and to assess the impact of concomitant sodium channel blocker (SCB) use on LCM retention.

Methods

This is a retrospective cohort study of patients <21 years old receiving LCM from 2010 to 2015. Kaplan-Meier survival curves were generated for time to LCM failure, defined as discontinuation of LCM or addition of another antiepileptic therapy. The impact of concomitant use of traditional SCB agents (phenytoin, carbamazepine, oxcarbazepine, and/or lamotrigine) and other factors including age, seizure types, fast drug titration, and prior antiepileptic drug history were evaluated using Cox regression.

Results

The analysis cohort included 223 patients, of whom 116 were taking one or more SCBs, with median follow-up of 7.4 months (1–53 months). For all patients, the probability of remaining on LCM without addition of another therapy was 44.7% at 12 months and 25.6% at 24 months. Concomitant SCB use was an independent predictor of time to LCM failure (hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.38–2.65, p < 0.001).Although treatment emergent adverse effects were reported more often in patients taking SCB (65% vs. 39%, p < 0.001), intolerability was rarely the sole reason cited for LCM discontinuation, and SCB use was strongly associated with LCM failure, even when controlling for presence of treatment emergent adverse effects (adjusted HR 1.99, 95% CI 1.36–2.90, p < 0.001).

Significance

This study provides observational evidence for treatment persistence of LCM in children, in a large cohort with long-term follow-up, using time to treatment failure as the outcome measure. Concomitant SCB use was a key factor increasing risk of LCM failure, but not due to treatment-emergent adverse effects alone.

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