What's Current?

Nucleus accumbens stimulation in partial epilepsy—A randomized controlled case series

Epilepsia - Mon, 05/04/2015 - 02:41
Summary

Neuromodulative treatment options are warranted in patients with difficult-to-treat epilepsy. However, acquisition of controlled data on deep brain stimulation has so far been achieved only for the centromedian and anterior thalamic nucleus. In a case series of four patients with intractable partial epilepsy, a randomized controlled cross-over protocol was used to get insight into efficacy and safety of 3-month nucleus accumbens stimulation. Seizure frequency, neurocognitive testing, “Liverpool Seizure Severity Score,” “Quality of Life in Epilepsy Inventory,” “Beck Depression Inventory,” and “Mini International Neuropsychiatric Interview” were obtained at every visit. In a subsequent open-label phase, nucleus accumbens stimulation responders underwent concomitant anterior thalamic nucleus stimulation, whereas nonresponders received solely thalamic stimulation. Under nucleus accumbens stimulation, three of four patients had ≥50% reduction in frequency of disabling seizures without further improvement with additional anterior thalamic nucleus stimulation. Patient-reported outcome and neurocognitive testing remained unchanged. Accumbens stimulation is safe and seems to be a suitable option in intractable partial epilepsy. The current findings require substantiation by an adequately powered multicenter study.

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Epilepsy alters organization of brain networks and functional efficiency

Medical News Today - Sun, 05/03/2015 - 03:00
Epilepsy, a disorder characterized by abnormal neuronal activity in certain regions of the brain, leads to organizational changes that can alter brain efficiency at the level of the whole brain.
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Parents describe arduous journey from diagnosis to pediatric epileptic surgery

Medical News Today - Sun, 05/03/2015 - 03:00
Interventions should be developed to help tear down barriers to surgical evaluationHaving a child diagnosed with epilepsy can be a frightening and confusing time.
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Cortico–cortical evoked potentials for sites of early versus late seizure spread in stereoelectroencephalography

Epilepsy Research Journal - Sun, 05/03/2015 - 00:00
For the past decade, connectivity patterns within the brain have been the subject of intense investigation in the neurophysiological literature, as the capabilities of non–invasive methods such as fMRI and MEG have been coupled with the ubiquitous adoption of powerful computing technology to analyze the large quantity of associated data (Reijneveld et al., 2007; Stam et al., 2009). These studies have demonstrated altered connectivity in epilepsy patients for local and global connections, including limbic and default mode network structures (Pittau et al., 2012).
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Adjunctive brivaracetam for patients with refractory partial seizures: A meta-analysis of randomized placebo-controlled trials

Epilepsy Research Journal - Fri, 05/01/2015 - 00:00
Epilepsy is a common neurological condition affecting 0.5% to 1% of the general population.(Hesdorffer et al., 2011) Although great efforts have been made to find the optimal therapy, some patients remain inadequately treated due to adverse effects and up to 30% patients develop refractory epilepsy. (French, 2007) Patients with refractory epilepsy account for most of the burden of epilepsy because of the substantial frequencies, such as comorbid disease, psychological dysfunction, social stigmatization, reduced quality of life, and a decreased life expectancy.
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Cognitive Outcomes of Prenatal Antiepileptic Drug Exposure

Epilepsy Research Journal - Fri, 05/01/2015 - 00:00
There have been numerous animal studies demonstrating poor behavioral, cognitive, and motor functioning in offspring that were prenatally exposed to antiepileptic drugs (AEDs). The early studies included phenobarbital (Roger-Fuchs et al.,1992), valproate (Schneider and Przewlocki, 2005) and phenytoin (Vorhees, 1987). In the 1980s and 1990s, Vorhees published a series of studies examining the behavioral effects on the offspring of maternal rats that had received phenytoin during days 7-18 of gestation, the prime period of organogenesis, at serum levels comparable to the therapeutic range for humans.
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Lack of Effect of Perampanel on QT Interval Duration: Results From a Thorough QT Analysis and Pooled Partial Seizure Phase III Clinical Trials

Epilepsy Research Journal - Fri, 05/01/2015 - 00:00
The QT interval is the duration of ventricular depolarization and subsequent repolarization as measured on an electrocardiogram (ECG) from the beginning of the QRS complex to the end of the T wave (ICH Expert Working Group, 2005). Prolongation of the QT interval has been identified as a potential risk for cardiac arrhythmias, most commonly torsade de pointes (TdP), during treatment with a variety of drugs (ICH Expert Working Group, 2005; Pollard et al., 2008; Redfern et al., 2003). Delayed repolarization results from suppression of potassium current in cardiac tissues, the rapidly-activating delayed rectifier that is mediated by the human ether-à-go-go-related gene (hERG)-encoded voltage-dependent potassium channel (hERG K+ channel) (Pollard et al., 2008; Redfern et al., 2003).
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AAN: Maternal valproate linked to kids’ physical, cognitive problems

Clinical Neurology News - Thu, 04/30/2015 - 15:18

WASHINGTON – One-quarter of valproate-exposed children in an ongoing study had a major birth defect or reduced IQ, Dr. Kimford Meador reported at the annual meeting of the American Academy of...

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Parents describe arduous journey to pediatric epileptic surgery when their child's disease becomes resistant to anti-seizure meds

Science Daily - Wed, 04/29/2015 - 14:06
Now, parents share their arduous and “circuitous” journey to get referrals for pediatric epilepsy surgery once their child’s disease stops responding to anti-seizure medications. The study sheds light on the difficulties parents face obtaining specialty and sub-specialty care for their children during an already stressful time.
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Epileptogenic zone localization using magnetoencephalography predicts seizure freedom in epilepsy surgery

Epilepsia - Wed, 04/29/2015 - 02:53
Summary Objective

The efficacy of epilepsy surgery depends critically upon successful localization of the epileptogenic zone. Magnetoencephalography (MEG) enables noninvasive detection of interictal spike activity in epilepsy, which can then be localized in three dimensions using magnetic source imaging (MSI) techniques. However, the clinical value of MEG in the presurgical epilepsy evaluation is not fully understood, as studies to date are limited by either a lack of long-term seizure outcomes or small sample size.

Methods

We performed a retrospective cohort study of patients with focal epilepsy who received MEG for interictal spike mapping followed by surgical resection at our institution.

Results

We studied 132 surgical patients, with mean postoperative follow-up of 3.6 years (minimum 1 year). Dipole source modeling was successful in 103 patients (78%), whereas no interictal spikes were seen in others. Among patients with successful dipole modeling, MEG findings were concordant with and specific to the following: (1) the region of resection in 66% of patients, (2) invasive electrocorticography (ECoG) findings in 67% of individuals, and (3) the magnetic resonance imaging (MRI) abnormality in 74% of cases. MEG showed discordant lateralization in ~5% of cases. After surgery, 70% of all patients achieved seizure freedom (Engel class I outcome). Whereas 85% of patients with concordant and specific MEG findings became seizure-free, this outcome was achieved by only 37% of individuals with MEG findings that were nonspecific to or discordant with the region of resection (χ2 = 26.4, p < 0.001). MEG reliability was comparable in patients with or without localized scalp electroencephalography (EEG), and overall, localizing MEG findings predicted seizure freedom with an odds ratio of 5.11 (95% confidence interval [CD] 2.23–11.8).

Significance

MEG is a valuable tool for noninvasive interictal spike mapping in epilepsy surgery, including patients with nonlocalized findings receiving long-term EEG monitoring, and localization of the epileptogenic zone using MEG is associated with improved seizure outcomes.

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Erratum

Epilepsia - Wed, 04/29/2015 - 02:52
Categories: What's Current?

Descriptive epidemiology of epilepsy in the U.S. population: A different approach

Epilepsia - Wed, 04/29/2015 - 02:50
Summary Objective

Determine prevalence and incidence of epilepsy within two health insurance claims databases representing large sectors of the U.S. population.

Methods

A retrospective observational analysis using Commercial Claims and Medicare (CC&M) Supplemental and Medicaid insurance claims data between January 1, 2007 and December 31, 2011. Over 20 million continuously enrolled lives of all ages were included. Our definition of a prevalent case of epilepsy was based on International Classification of Diseases, Ninth Revision, Clinical Modification–coded diagnoses of epilepsy or seizures and evidence of prescribed antiepileptic drugs. Incident cases were identified among prevalent cases continuously enrolled for ≥2 years before the year of incidence determination with no epilepsy, seizure diagnoses, or antiepileptic drug prescriptions recorded.

Results

During 2010 and 2011, overall age-adjusted prevalence estimate, combining weighted estimates from all datasets, was 8.5 cases of epilepsy/1,000 population. With evaluation of CC&M and Medicaid data separately, age-adjusted prevalence estimates were 5.0 and 34.3/1,000 population, respectively, for the same period. The overall age-adjusted incidence estimate for 2011, combining weighted estimates from all datasets, was 79.1/100,000 population. Age-adjusted incidence estimates from CC&M and Medicaid data were 64.5 and 182.7/100,000 enrollees, respectively. Incidence data should be interpreted with caution due to possible misclassification of some prevalent cases.

Significance

The large number of patients identified as having epilepsy is statistically robust and provides a credible estimate of the prevalence of epilepsy. Our study draws from multiple U.S. population sectors, making it reasonably representative of the U.S.-insured population.

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Juvenile Myoclonic Epilepsy: a System Disorder of the Brain

Epilepsy Research Journal - Mon, 04/27/2015 - 00:00
The first patient with what we now call juvenile myoclonic epilepsy (JME) was described in 1867 by Théodore Herpin (Herpin Th, 1867), and the first comprehensive description of the syndrome was given 90 years later by Janz and Christian (Janz et al., 1957) who proposed the term “impulsive petit mal”. It took some time to gain international recognition but in 1985 it was included in the first proposal for an international classification of epilepsies and epileptic syndromes (Commission for Classification and Terminology of the ILAE, 1985).
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Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials

Epilepsia - Sat, 04/25/2015 - 03:17
Summary Objective

To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959).

Methods

Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations.

Results

Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received <1,600 mg/day (n = 174) and ≥1,600 mg/day (n = 29) carbamazepine. Cyclodextrin exposure was not associated with clinically relevant changes in AEs or renal biomarkers. Seizure control was maintained as patients transitioned between oral and IV carbamazepine.

Significance

IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations.

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Development and assessment of a shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55)

Epilepsia - Sat, 04/25/2015 - 03:17
Summary Objective

To develop and validate a shortened version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). A secondary aim was to compare baseline risk factors predicting health-related quality of life (HRQoL) in children newly diagnosed with epilepsy, as identified using the original and shortened version.

Methods

Data came from the Health-Related Quality of Life in Children with Epilepsy Study (HERQULES, N = 373), a multicenter prospective cohort study. Principal component analysis reduced the number of items from the original QOLCE, and factor analysis was used to assess the factor structure of the shortened version. Convergent and divergent validity was assessed by correlating the Child Health Questionnaire (CHQ) with the shortened QOLCE. Multiple regression identified risk factors at diagnosis for HRQoL at 24 months.

Results

A four-factor, higher-order, 55-item solution was obtained. A total of 21 items were removed. The final model represents functioning in four dimensions of HRQoL: Cognitive, Emotional, Social, and Physical. The shortened QOLCE demonstrated acceptable fit: Bentler's Comparative Fit Index = 0.944; Tucker-Lewis Index = 0.942; root mean square approximation = 0.058 (90% CI: 0.056–0.061); weighted root mean square residuals (WRMR) = 1.582, and excellent internal consistency (α = 0.96, subscales α > 0.80). Factor loadings were good (first-order: λ = 0.66–0.93; higher-order λ = 0.66–0.85; p < 0.001 for all). The shortened QOLCE scores correlated strongly with similar subscales of the Child Health Questionnaire (ρ = 0.38–0.70) while correlating weakly with dissimilar subscales (ρ = 0.30–0.31). While controlling for HRQoL at diagnosis, predictors for better HRQoL at 24 months were the following: no cognitive problems reported (p = 0.001), better family functioning (p = 0.014), fewer family demands (p = 0.008), with an interaction between baseline HRQoL and cognitive problems (p = 0.011).

Significance

Results offer initial evidence regarding reliability and validity of the proposed 55-item shortened version of the QOLCE (QOLCE-55). The QOLCE-55 produced results on risk factors consistent with those found using the original measure. Given the fewer items, QOLCE-55 may be a viable option reducing respondent burden when assessing HRQoL in children with epilepsy.

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