What's Current?

Erratum

Epilepsia - Mon, 02/13/2017 - 04:50
Categories: What's Current?

Epilepsy drug discovered in fish model shows promise in small pediatric clinical trial

Medical News Today - Mon, 02/13/2017 - 03:00
"Bench-to-bedside" describes research that has progressed from basic science in animal models that has led to therapies used in patients.
Categories: What's Current?

Epilepsy drug discovered in fish model shows promise in small pediatric clinical trial

Science Daily - Fri, 02/10/2017 - 14:11
'Bench-to-bedside' describes research that has progressed from basic science in animal models that has led to therapies used in patients. Now, a study describes what could be considered a direct 'aquarium-to-bedside' approach, taking a drug discovered in a genetic zebrafish model of epilepsy and testing it, with promising results, in a small number of children with the disease.
Categories: What's Current?

Adult motor phenotype differentiates Dravet syndrome from Lennox-Gastaut syndrome and links SCN1A to early onset parkinsonian features

Epilepsia - Fri, 02/10/2017 - 06:35
Summary

Distinguishing adult patients with Lennox-Gastaut syndrome from those with Dravet syndrome is challenging. We have previously reported that patients with Dravet syndrome present a very peculiar motor phenotype. Here we sought to confirm that this association was not linked to the chronic use of antiepileptic drugs or the many lifetime seizures. To this aim, we studied 14 adult patients with Lennox-Gastaut syndrome and 14 adults with Dravet syndrome because both conditions share similar seizure severity. We found that antecollis and parkinsonian gait were significantly more common in the Dravet group, thus suggesting that these features are part of the Dravet syndrome adult phenotype.

Categories: What's Current?

Many older adults with epilepsy may not be receiving optimal care

Medical News Today - Fri, 02/10/2017 - 03:00
Many older adults with newly diagnosed epilepsy in the United States are being prescribed older anti-epileptic drugs (AEDs), and only half begin treatment with AEDs within the first 30 days of a...
Categories: What's Current?

Side and Site of Brain Surgery Affects Psychological Outcome

Epilepsy Research - Wed, 02/08/2017 - 05:00

The side and site of epilepsy surgery affects its psychological outcome according to a new study published in the journal Epilepsy and Behavior.

This finding highlights the importance of considering psychological changes that may occur as a result of epilepsy surgery, on an individual patient basis.

According to the authors, further studies are needed to identify potential risk factors that may make the symptoms of surgery more severe. Further research could also help provide patients with counselling before surgery and identify those who may be most in need of psychological surveillance following surgery.

For the study, the team of researchers led by Dr Robyn Busch, a clinical psychologist at Cleveland Clinic Epilepsy Centre analysed 228 adults with epilepsy who underwent temporal lobe or frontal lobe brain surgery. The patients completed the Personality Assessment Inventory (PAI), which provides an objective assessment of adult psychological problems, both before and after surgery.

The researchers then compared the psychological outcome of the operation between people who had surgery on the left side of their brain versus those who had right-sided surgery.

They found that people with left temporal lobe epilepsy had higher PAI scores (i.e. more psychological problems) before the operation compared to those with left frontal lobe epilepsy. Following surgery, the psychological problems, which included anxiety and depression, usually improved although a small subset of patients reported that their symptoms became worse after surgery. The most frequent improvements were seen in those undergoing temporal lobe surgery.

The researchers concluded that the side and site of brain surgery in epilepsy are important factors in determining the psychological outcome of the operation in adults. They stress that it is important to identify the risk factors that may be associated with the worsening of the symptoms seen in a subset of patients after surgery.

It is estimated that 20 to 40% of people with epilepsy are diagnosed with at least one form of psychological disorder and this percentage can be as high as 70% in people with drug resistant epilepsy. Previous studies have shown that depression is more frequent in people with a seizure focus on the left side of the brain.

Author: Dr Özge Özkaya

Click here for more articles about conditions related to epilepsy.

 

Categories: What's Current?

Nonsteroidal anti-inflammatory drugs in clinical and experimental epilepsy

Epilepsy Research Journal - Wed, 02/08/2017 - 00:00
Epilepsy affects 50 million people worldwide according to the World Health Organization and 20–30% of patients develop resistance to antiepileptic drugs. The side effects of antiepileptic treatments represent a heavy economic burden (de Kinderen et al., 2014) and have a significantly negative impact on the quality of life (Luoni et al., 2011).
Categories: What's Current?

Magnetic facial nerve stimulation in animal models of active seizure

Epilepsy Research Journal - Wed, 02/08/2017 - 00:00
We are developing a non-invasive facial nerve stimulator device as an emergency treatment for ischemic stroke. It is well-known that electric stimulation of the parasympathetic petrosal components of the facial nerve causes dilation of the cranial arteries and an increase in cerebral blood flow in normal animals (Forbes et al., 1937, 1939; Meyer et al., 1967; Adams et al., 1989; Goadsby, 1989, 1990a,b, 1991; Goadsby and Hoskin, 1994; Sato et al., 1997; Toda et al., 2000a,b) and in animals with brain ischemia (Yarnitsky et al., 2005, 2006; Henninger and Fisher, 2007; Takahashi et al., 2011).
Categories: What's Current?

What does the U.S. Medicare administrative claims database tell us about initial antiepileptic drug treatment for older adults with new-onset epilepsy?

Epilepsia - Tue, 02/07/2017 - 23:56
Summary Objective

Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs (AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries.

Methods

We conducted retrospective analyses of 2008–2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision (ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment (QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [LIS], and ZIP code level poverty) factors.

Results

Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [AI/AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment.

Significance

Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted. Interventions should be developed and tested to develop paradigms that lead to better care.

Categories: What's Current?

Children and Young People with Temporal Lobe Epilepsy More Likely to Have Mental Health Problems

Epilepsy Research - Tue, 02/07/2017 - 05:00

Young people with temporal lobe epilepsy are more likely to have mental health conditions than those with other types of epilepsy, a new study published in the scientific journal Epilepsy and Behavior suggests.

According to the authors Dr William Schraegle and Dr Jeffrey Titus, these findings reinforce the relationship between depression and temporal lobe epilepsy.

In order to determine whether the region of the brain causing the epilepsy (i.e. the seizure focus) had an impact on rates of psychiatric conditions, the researchers looked at data from 132 children and adolescents aged between six and 18 years with either generalised or partial epilepsy. Those with partial epilepsy had either frontal lobe epilepsy or temporal lobe epilepsy.

The researchers measured the rates of depression, anxiety and withdrawal behaviours using two questionnaires: the Behavior Assessment System for Children (BASC-2), a measure of a caregiver’s perceptions of a child’s emotional and behavioural functioning, and the Quality of Life in Childhood Epilepsy (QOLCE) scale.

The results showed that almost half of the children (41%) had evidence of a psychiatric condition.  The rates of these conditions were similar between children with generalised epilepsy and those with partial epilepsy and did not differ depending on the side of the brain (i.e. left or right) from which the epilepsy arose.

However, when the researchers compared children with temporal lobe epilepsy against those with frontal lobe epilepsy, they found that those with temporal lobe epilepsy had higher rates of depression.

In addition, increased numbers of antiepileptic drugs used and higher depression scores, as assessed by their parents, were also associated with a reduction in health-related quality of life in children with temporal lobe epilepsy.

Children and young people with epilepsy often have additional psychiatric problems such as depression and anxiety associated with their epilepsy. It is important that these problems are examined carefully as they can reduce the patient’s overall quality of life.

Author: Dr Özge Özkaya

Click here for more articles about conditions related to epilepsy.

 

Categories: What's Current?

Interictal network synchrony and local heterogeneity predict epilepsy surgery outcome among pediatric patients

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

Epilepsy is a disorder of aberrant cortical networks. Researchers have proposed that characterizing presurgical network connectivity may improve the surgical management of intractable seizures, but few studies have rigorously examined the relationship between network activity and surgical outcome. In this study, we assessed whether local and global measures of network activity differentiated patients with favorable (seizure-free) versus unfavorable (seizure-persistent) surgical outcomes.

Methods

Seventeen pediatric intracranial electroencephalography (IEEG) patients were retrospectively examined. For each patient, 1,200 random interictal epochs of 1-s duration were analyzed. Functional connectivity networks were constructed using an amplitude-based correlation technique (Spearman correlation). Global network synchrony was computed as the average pairwise connectivity strength. Local signal heterogeneity was defined for each channel as the variability of EEG amplitude (root mean square) and absolute delta power (μV2/Hz) across epochs. A support vector machine learning algorithm used global and local measures to classify patients by surgical outcome. Classification was assessed using the Leave-One-Out (LOO) permutation test.

Results

Global synchrony was increased in the seizure-persistent group compared to seizure-free patients (Student's t-test, p = 0.006). Seizure-onset zone (SOZ) electrodes exhibited increased signal heterogeneity compared to non-SOZ electrodes, primarily in seizure-persistent patients. Global synchrony and local heterogeneity measures were used to accurately classify 16 (94.1%) of 17 patients by surgical outcome (LOO test, iterations = 10,000, p < 0.001).

Significance

Measures of global network synchrony and local signal heterogeneity represent promising biomarkers for assessing patient candidacy in pediatric epilepsy surgery.

Categories: What's Current?

An evaluation of national birth certificate data for neonatal seizure epidemiology

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

Seizures are a common manifestation of neurologic dysfunction in neonates and carry a high risk for mortality and adverse long-term outcomes. U.S. birth certificates are a potentially valuable source for studying the epidemiology of neonatal seizures. However, the quality of the data is understudied.

Methods

We reviewed all U.S. birth records from 2003 to 2013 to describe the following: (1) rates of missing data, (2) evidence of underreporting, and (3) effect of the 2003 revision of the birth certificate form. We evaluated missingness by state, year, demographic, infant health, and medical care factors using bivariate analyses. To measure potential underreporting, we compared estimates to a published reference (0.95 per 1,000 term births). We developed criteria for data plausibility, and reported which states met these criteria.

Results

Of 22,834,395 live term births (≥36 weeks of gestation) recorded using the revised form from 2005 to 2015, there were 5,875 with neonatal seizures, suggesting an incidence of 0.26 per 1,000 term births, one fourth of the expected incidence. Although the overall degree of missing seizure data was low (0.5%), missingness varied significantly by state, year, demographic, infant health, and medical care factors. After the 2003 birth certificate form revision, missing data and evidence of potential underreporting increased. Nine states met criteria for plausibility.

Significance

The value of U.S. birth certificate data for neonatal seizure epidemiology is limited by biased missingness, evidence suggestive of underreporting, and changes in reporting subsequent to the 2003 revision. There are plausible data from nine states, which merit investigation for further research.

Categories: What's Current?

Perampanel in 12 patients with Unverricht-Lundborg disease

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

Perampanel (PER) was used in 12 patients with Unverricht-Lundborg disease (ULD) to evaluate its efficacy against myoclonus and seizures.

Methods

We treated 11 patients with EPM1 mutations (6 F, 5 M, aged 13–62 years) and a 43-year-old man with de novo KCNC1 mutation. PER was introduced by 2 mg steps at 2–4 week intervals until 6 mg/day, with a possible dose reduction or dose increase.

Results

Ten patients had a clear clinical response of myoclonus, and five were able to reduce concomitant therapy. Improvement was noted sometimes as soon as with 2 mg/day. Epileptic seizures stopped on PER in the six patients who still had experienced generalized tonic–clonic or myoclonic seizures (100%). Some abatement of efficacy on myoclonus was seen in two patients who still retained some benefit. Weight gain was reported in six patients (50%). Psychological and behavioral side-effects were observed in six patients (50%) and led to withdrawal of PER in three cases and dose reduction in three, with abatement of the problems.

Significance

This study provides evidence that for ULD patients, PER may show marked efficacy even in severe cases, particularly against myoclonus, but also against seizures. PER should thus be tried in ULD patients whose seizures are not satisfactorily controlled. Its use is limited because of psychological and behavioral side effects, with higher doses of approximately 6 mg/day or greater likely risk factors.

Categories: What's Current?

Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation.

Method

Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained.

Results

Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases.

Significance

Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males.

Categories: What's Current?

Toll-like receptor 3 deficiency decreases epileptogenesis in a pilocarpine model of SE-induced epilepsy in mice

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE).

Methods

To test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls. In this model, a single SE event leads to spontaneous recurrent seizures (SRS). Two weeks after SE, mice were implanted with wireless electroencephalography (EEG) transmitters for up to 1 month. The impact of TLR3 deficiency on SE was assessed using separate cohorts of mice regarding EEG activity, seizure progression, hippocampal microglial distribution, and expression of the proinflammatory cytokines tumor necrosis factor (TNF)α and interferon (IFN)β.

Results

Our data indicate that TLR3 deficiency reduced SRS, microglial activation, and the levels of the proinflammatory cytokines TNFα and IFNβ, and increased survival following SE.

Significance

This study reveals novel insights into the pathophysiology of epilepsy and the contribution of TLR3 to disease progression. Our results identify the TLR3 pathway as a potential future therapeutic target in SE.

Categories: What's Current?

Interrater agreement in the interpretation of neonatal electroencephalography in hypoxic-ischemic encephalopathy

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

Research using neonatal electroencephalography (EEG) has been limited by a lack of a standardized classification system and interpretation terminology. In 2013, the American Clinical Neurophysiology Society (ACNS) published a guideline for standardized terminology and categorization in the description of continuous EEG in neonates. We sought to assess interrater agreement for this neonatal EEG categorization system as applied by a group of pediatric neurophysiologists.

Methods

A total of 60 neonatal EEG studies were collected from three institutions. All EEG segments were from term neonates with hypoxic-ischemic encephalopathy. Three pediatric neurophysiologists independently reviewed each record using the ACNS standardized scoring system. Unweighted kappa values were calculated for interrater agreement of categorical data across multiple observers.

Results

Interrater agreement was very good for identification of seizures (κ = 0.93, p < 0.001), with perfect agreement in 95% of records (57 of 60). Interrater agreement was moderate for classifying records as normal or having any abnormality (κ = 0.49, p < 0.001), with perfect agreement in 78% of records (47 of 60). Interrater agreement was good in classifying EEG backgrounds on a 5-category scale (normal, excessively discontinuous, burst suppression, status epilepticus, or electrocerebral inactivity) (κ = 0.70, p < 0.001), with perfect agreement in 72% of records (43 of 60). Other specific background features had lower agreement, including voltage (κ = 0.41, p < 0.001), variability (κ = 0.35, p < 0.001), symmetry (κ = 0.18, p = 0.01), presence of abnormal sharp waves (κ < 0.20, p < 0.05), and presence of brief rhythmic discharges (κ < 0.20, p < 0.05).

Significance

We found good or very good interrater agreement applying the ACNS system for identification of seizures and classification of EEG background. Other specific EEG features showed limited interrater agreement. Of importance to both clinicians and researchers, our findings support using the ACNS system in identifying seizures and classifying backgrounds of neonatal EEG recordings, but also suggest limited reproducibility for certain other EEG features.

Categories: What's Current?

Efficacy of mGlu2-positive allosteric modulators alone and in combination with levetiracetam in the mouse 6 Hz model of psychomotor seizures

Epilepsia - Mon, 02/06/2017 - 12:45
Summary Objective

The metabotropic glutamate receptor subtype 2 (mGlu2) possesses both orthosteric and allosteric modulatory sites, are expressed in the frontal cortex and limbic structures, and can affect excitatory synaptic transmission. Therefore, mGlu2 is a potential therapeutic target in the treatment of epilepsy. The present study seeks to evaluate the anticonvulsant potential of mGlu2-acting compounds.

Methods

The anticonvulsant efficacy of two selective mGlu2-positive allosteric modulators (PAMs) (JNJ-42153605 and JNJ-40411813/ADX71149) and one mGlu2/3 receptor agonist (LY404039) were evaluated alone and in combination with the antiseizure drug levetiracetam (LEV) in the mouse 6 Hz model.

Results

In the 6 Hz (32 mA stimulus intensity) model, median effective dose (ED50) values were determined for JNJ-42153605 (3.8 mg/kg), JNJ-40411813 (12.2 mg/kg), and LY404039 (10.9 mg/kg). At the 44 mA stimulus intensity, ED50 values were determined for JNJ-42153605 (5.9 mg/kg), JNJ-40411813 (21.0 mg/kg), LY404039 (14.1 mg/kg), and LEV (345 mg/kg). In addition, subprotective doses of each mGlu2-acting compound, administered in combination with various doses of LEV, were able to shift the 6 Hz 44 mA ED50 for LEV by >25-fold. When JNJ-42153605 was administered at varying doses in combination with a single dose of LEV (10 mg/kg), the potency of JNJ-42153605 was increased 3.7-fold. Similarly, when a moderately effective dose of LEV (350 mg/kg) was administered in combination with varying doses of JNJ-40411813, the potency of JNJ-40411813 was increased approximately 14-fold. Plasma levels of JNJ-40411813 and LEV were not different when administered alone or in combination, suggesting that increases in potency are not due to pharmacokinetic effects.

Significance

These studies suggest a potential positive pharmacodynamic effect of mGlu2-acting compounds in combination with LEV. If this effect is translated in a clinical setting, it can support a rational polypharmacy concept in treatment of epilepsy patients.

Categories: What's Current?

Upcoming Event in Glasgow: Rare Disease Day

Epilepsy Research - Mon, 02/06/2017 - 05:00

This event is the first of its kind in Glasgow, held at the University of Glasgow, on the 28th February 2017. The day has a neurological / genetics theme with a number of local speakers with a specialism in epilepsy.

The event is open to the public and is free to attend but registration is essential.  Policy makers, researchers, clinicians, charities or anyone with an interest in the area are also welcome.

Lunch, tea and coffee will be provided. Click here for more information.

 

Categories: What's Current?

Pages