What's Current?

Neuropsychological profiles of patients with juvenile myoclonic epilepsy and their siblings: An extended study

Epilepsia - Mon, 06/15/2015 - 06:14
Summary Objective

To examine executive function, intelligence, visuospatial skills, language, memory, attention, reaction time, anxiety, depression, and emotional and behavioral traits most frequently associated with executive dysfunction in patients with juvenile myoclonic epilepsy (JME) compared with a sibling and a normal control group under video–electroencephalography (video-EEG) conditions.

Methods

Twenty-two sibling pairs, one with JME, were compared with 44 controls matched for age, gender, and educational level. All participants were administered a comprehensive set of neuropsychological and questionnaire measures during and without video-EEG recording.

Results

The JME group differed significantly from controls in measures of phonemic and semantic verbal fluency. They scored significantly higher on the dysexecutive self-rating questionnaire, being more likely to report traits associated with executive dysfunction than both siblings and controls. Patients with JME reported significantly low mood than both controls and their siblings. Unaffected siblings differed significantly from controls on psychomotor speed, phonemic verbal fluency and were considered to exhibit traits associated with executive dysfunction by others. Qualitative inspection of data suggested a convincing trend for patients with JME and their siblings to perform worse than controls on most measures.

Significance

This study supports the existence of a distinct neuropsychological profile among patients with JME and their siblings, which is likely to be genetically determined. The similarity of neuropsychological profiles between JME patients and their siblings is independent of antiepileptic drug effects or subclinical EEG activity. The significant differences between the sibling and controls suggests that there is a neurocognitive endophenotype for JME.

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Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy

Epilepsy Research Journal - Mon, 06/15/2015 - 00:00
De novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathy. We described a person with epileptic encephalopathy associated with a mosaic deletion of the SCN8A gene.
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Scalp High Frequency Oscillations (HFOs) in absence epilepsy: An Independent Component Analysis (ICA) based approach

Epilepsy Research Journal - Sun, 06/14/2015 - 00:00
Electroencephalograph (EEG) for clinical interpretation has for a long time been restricted to the Berger's frequency band (1 – 25Hz). However, improvement in the acquisition systems with improved analogue to digital conversion (ADC) has allowed researchers to look beyond the standard frequency bands. This has resulted in the evolution of the “fullband EEG (FbEEG)” which encompasses both the narrow band and wide band EEG (beyond the conventional 50 – 70Hz)(Vanhatalo et al., 2005). FbEEG includes infra slow frequency oscillations (0.01-0.1Hz), sub delta frequency analysis (0.1 - 0.9Hz), Conventional Frequency Analysis (CFA: 1-70Hz), high frequency oscillations (80-500/600Hz), ultra high frequency oscillations (>600-1000Hz)(Andrade-Valenca et al., 2011; Niedermeyer, 2005; Rodin et al., 2008; Rodin and Funke, 2006; Vanhatalo et al., 2005; Zafeiriou and Vargiami, 2012)(Andrade-Valenca et al., 2011; Niedermeyer, 2005; Rodin et al., 2008; Rodin and Funke, 2006; Vanhatalo et al., 2005; Zafeiriou and Vargiami, 2012).
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Subjective Sleep Disturbance in Epilepsy Patients at an Outpatient Clinic: A Questionnaire-Based Study on Prevalence

Epilepsy Research Journal - Sun, 06/14/2015 - 00:00
The interaction between epilepsy and sleep is complex (Bazil, 2000; Bazil and Walczak, 2003). Sleep may influence seizures in a variety of ways. In general, seizures and interictal epileptiform discharges are facilitated during non-rapid-eye-movement (NREM) sleep and suppressed during rapid-eye-movement (REM) sleep (Bazil, 2000; Bazil and Walczak, 2003).
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Autonomic Changes Following Generalized Tonic Clonic Seizures: An Analysis of Adult and Pediatric Patients with Epilepsy

Epilepsy Research Journal - Sun, 06/14/2015 - 00:00
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of mortality directly related to epilepsy. Its incidence is higher in adult patients and its pathophysiology remains poorly understood, but likely involves autonomic dysregulation following generalized tonic clonic seizures (GTCS). In the current study, we aimed to analyze post-ictal autonomic changes following GTCS in adult and pediatric patients.
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Preserved anterograde and remote memory in drug-responsive temporal lobe epileptic patients

Epilepsy Research Journal - Sun, 06/14/2015 - 00:00
Despite the availability of various newly developed antiepileptic drugs (AEDs), about 75% of patients suffering from mesial temporal lobe epilepsy (mTLE) are still considered to have drug-resistant epilepsy (Serrano-Castro et al., 2012). This percentage is even higher (up to 89%) when hippocampal sclerosis (HS) is present (Semah et al., 1998).
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In-hospital costs in patients with seizures and epilepsy after stroke

Epilepsia - Sat, 06/13/2015 - 02:12
Summary Objectives

To verify the net effect of seizures after stroke on the use of in-hospital health care resources.

Methods

Consecutive patients with first-ever stroke were admitted to the stroke unit of a Moscow hospital and followed prospectively until death or discharge. Each patient experiencing seizures was matched for age, sex, stroke type, National Institutes of Health Stroke Scale score at admission, and stroke risk factors to 2+ patients with no seizures, as controls. Resources consumed included length of hospital stay, admission to the intensive care unit (ICU), diagnostic tests, medical consultations and treatments. Cost estimates were based on the Russian National Health Service perspective.

Results

The sample comprised 30 patients with in-hospital seizures and 70 matched controls. Patients dying in hospital were 15 of 30 (50%) versus 4 of 70 (5.7%) (p < 0.001). The overall cost of hospital stay was only slightly (nonsignificantly) higher in patients with seizures, but the cost was significantly higher in patients who died than in patients who were discharged alive. Compared to the controls, patients with seizures spent more intensive care unit (ICU) days and required more computed tomography (CT) scans, x-rays, endoscopies, and specialist consultations, causing higher in-hospital costs.

Significance

In patients with first-ever stroke, seizures per se do not increase the overall in-hospital costs. However, the higher than expected mortality in patients with seizures is associated with additional hospital costs.

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Perampanel efficacy and safety by gender: Subanalysis of phase III randomized clinical studies in subjects with partial seizures

Epilepsia - Thu, 06/11/2015 - 03:28
Summary

The antiepileptic drug (AED) perampanel is approved in ≥40 countries as adjunctive therapy for drug-resistant partial seizures in patients with epilepsy. This post hoc analysis of pooled data from three phase III, double-blind, randomized studies of perampanel examines between-gender differences in perampanel efficacy and safety. Of the 1,478 subjects in the pooled analysis (719 male, 759 female), 1,109 were included in the pharmacokinetic/pharmacodynamic analysis. Perampanel oral clearance was 17% lower in female than in male patients not receiving enzyme-inducing AEDs. Pooled efficacy analysis revealed that seizure frequency was reduced with perampanel treatment regardless of gender; a greater numerical reduction in seizure frequency and increased responder rates occurred in female participants at perampanel doses of 4, 8, and 12 mg. Tolerability was similar between groups, although common adverse events such as dizziness and headache occurred more frequently in female subjects. Modest elevations in perampanel exposure in female patients may result in meaningful between-gender differences in efficacy and safety; therefore, dosing should be individualized and clinical response monitored.

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Been there? Done that? If you are sure, thank your 'memory cells'

Medical News Today - Tue, 06/09/2015 - 12:00
The witness on the stand says he saw the accused at the scene of the crime. Is he sure? How sure? The jury's verdict could hinge on that level of certainty.
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Validation of the 6 Hertz refractory seizure mouse model for intracerebroventricularly administered compounds

Epilepsy Research Journal - Sat, 06/06/2015 - 00:00
The six hertz (6Hz) model of partial seizures is currently considered an indispensable chain of the Anticonvulsant Screening Project (Löscher and Schmidt, 2012; Löscher and Schmidt, 2011; Stables and Kupferberg, 1997; White et al., 2006) and is a useful model of therapy-resistant seizures when applying high (suprathreshold) current intensities of at least 44mA (Barton et al., 2001; White et al., 2006). To allow testing of promising compounds with unknown or limited blood-brain barrier (BBB) permeability (e.g.
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Genetic variation of stress hormone receptor may affect vulnerability to major depression; schizophrenia; neurodevelopmental disorders

Medical News Today - Thu, 06/04/2015 - 11:00
Three papers on the genetics of psychiatric disorders published June 3 in Neuron1.
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Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients

Epilepsia - Thu, 06/04/2015 - 06:33
Summary

In view of the regulatory function of the thalamus in the sleep-wake cycle, the impact of deep brain stimulation (DBS) of the anterior nucleus thalami (ANT) on sleep was assessed in a small consecutive cohort of epilepsy patients with standardized polysomnography (PSG). In nine patients treated with ANT-DBS (voltage 5 V, frequency 145 Hz, cyclic mode), the number of arousals during stimulation and nonstimulation periods, neuropsychiatric symptoms (npS), and seizure frequency were determined. Electroclinical arousals were triggered in 14.0 to 67.0% (mean 42.4 ± SD 16.8%) of all deep brain stimuli. Six patients reported npS. Nocturnal DBS voltages were reduced in eight patients (one patient without npS refused) and PSGs were repeated. Electroclinical arousals occurred between 1.4 and 6.7 (mean 3.3 ± 1.7) times more frequently during stimulation periods compared to nonstimulation periods; the number of arousals positively correlated with the level of DBS voltage (range 1 V to 5 V) (Spearman′s rank coefficient 0.53121; p < 0.05). No patient experienced seizure deterioration and four patients reported remission of npS. This case-cohort study provides evidence that ANT-DBS interrupts sleep in a voltage-dependent manner, thus putatively resulting in an increase of npS. Reduction of nocturnal DBS voltage seems to lead to improvement of npS without hampering efficacy of ANT-DBS.

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Genetic variation in the adenosine regulatory cycle is associated with posttraumatic epilepsy development

Epilepsia - Thu, 06/04/2015 - 06:32
Summary Objective

Determine if genetic variation in enzymes/transporters influencing extracellular adenosine homeostasis, including adenosine kinase (ADK), [ecto-5′-nucleotidase (NT5E), cluster of differentiation 73 (CD73)], and equilibrative nucleoside transporter type-1 (ENT-1), is significantly associated with epileptogenesis and posttraumatic epilepsy (PTE) risk, as indicated by time to first seizure analyses.

Methods

Nine ADK, three CD73, and two ENT-1 tagging single nucleotide polymorphisms (SNPs) were genotyped in 162 white adults with moderate/severe traumatic brain injury (TBI) and no history of premorbid seizures. Kaplan-Meier models were used to screen for genetic differences in time to first seizure occurring >1 week post-TBI. SNPs remaining significant after correction for multiple comparisons were examined using Cox proportional hazards analyses, adjusting for subdural hematoma, injury severity score, and isolated TBI status. SNPs significant in multivariate models were then entered simultaneously into an adjusted Cox model.

Results

Comparing Kaplan-Meier curves, rs11001109 (ADK) rare allele homozygosity and rs9444348 (NT5E) heterozygosity were significantly associated with shorter time to first seizure and an increased seizure rate 3 years post-TBI. Multivariate Cox proportional hazard models showed that these genotypes remained significantly associated with increased PTE hazard up to 3 years post-TBI after controlling for variables of interest (rs11001109: hazard ratio (HR) 4.47, 95% confidence interval (CI) 1.27–15.77, p = 0.020; rs9444348: HR 2.95, 95% CI 1.19–7.31, p = 0.019) .

Significance

Genetic variation in ADK and NT5E may help explain variability in time to first seizure and PTE risk, independent of previously identified risk factors, after TBI. Once validated, identifying genetic variation in adenosine regulatory pathways relating to epileptogenesis and PTE may facilitate exploration of therapeutic targets and pharmacotherapy development.

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A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy

Epilepsia - Thu, 06/04/2015 - 06:32
Summary Objective

To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy.

Methods

Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values.

Results

Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers.

Significance

Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.

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One center's experience with complications during the Wada test

Epilepsia - Thu, 06/04/2015 - 06:31
Summary

This study aimed to define the number and type of complications associated with the Wada test at an academic medical center for comparison to previous reports. We performed a retrospective review of medical records for patients who underwent the Wada test at the University of Michigan between April 1991 and June 2013. Information was collected regarding the angiography procedure and the immediate postoperative period to assess for both clinical and angiographic complications. A total of 436 patients were identified who underwent the Wada procedure between April 1991 and June 2013, and 431 patients were included in the final analysis. Twenty-five patients (5.8%) had notable clinical events associated with the Wada test. Nine patients (2.1%) had clinical events meeting criteria for complication, which included seizures, status epilepticus, internal carotid artery vasospasm, inadvertent injection of anesthetic in the external carotid artery, and transient encephalopathy. No complications were associated with significant morbidity or mortality. This retrospective review of patients undergoing the Wada test found significantly fewer associated complications in comparison to previously published studies, with no patients experiencing long-term morbidity. The Wada test should be considered a safe diagnostic tool for lateralizing language and memory.

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Epilepsy in children with tuberous sclerosis complex: Chance of remission and response to antiepileptic drugs

Epilepsia - Thu, 06/04/2015 - 06:28
Summary Objective

To describe treatment and outcome of epilepsy in children with tuberous sclerosis complex (TSC).

Methods

Seventy-one children with TSC and epilepsy treated at the ENCORE TSC Expertise Center between 1988 and 2014 were included. Patient characteristics and duration and effectiveness of antiepileptic treatments were extracted from our clinical database. Correlations were made between recurrence of seizures after response to treatment, and several patient characteristics.

Results

Median age at time of inclusion was 9.4 years (range 0.9–18.0). Seizure history showed that 55 children (77%) of 71 became seizure-free for longer than 1 month, and 21 (30%) of 71 for longer than 24 months. Remission of seizures was associated with higher IQ, and a trend was observed between seizure remission and age at onset of seizures. A total of 19 antiepileptic drugs (AEDs) were used. Valproic acid, vigabatrin, levetiracetam, and carbamazepine were used most frequently. Nonpharmacologic therapies (ketogenic diet, epilepsy surgery, and vagus nerve stimulation) were used 13 times. Epilepsy surgery was most effective, with four of five children becoming seizure-free. AEDs prescribed as first and second treatment were most effective. Valproic acid was prescribed most frequently as first and second treatment, followed by vigabatrin. Thirty-one children had infantile spasms, preceded by focal seizures in 18 children (58%). Vigabatrin was used by 29 children (94%), and was first treatment in 15 (48%). Vigabatrin was more effective than other AEDs when prescribed as first treatment.

Significance

We showed that, although 77% of children with epilepsy due to TSC reached seizure remission, usually after their first or second AED, this was sustained for at least 24 months in only 38%. Almost half of those with 24 months of remission later had relapse of seizures. Our results support vigabatrin as first choice drug, and show the need for better treatment options for these children.

Categories: What's Current?

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