What's Current?

New Approach Could Treat Infantile Spams More Effectively

Epilepsy Research - Thu, 11/17/2016 - 04:14

Hormonal therapy combined with the antiepileptic drug vigabatrin is more effective in preventing infantile spasms (seen in West Syndrome) than hormonal therapy alone, according to a study published in The Lancet Neurology.

This conclusion is based on the results of a randomised clinical trial that was conducted at 102 different hospitals in five different countries, including the UK. The trial compared the efficacy of hormonal therapy and vigabatrin combined with the efficacy of hormonal therapy on its own, in 377 infants with a clinical diagnosis of infantile spasms.

The researchers randomly divided the infants into two groups and gave the infants in the first group hormonal therapy with vigabatrin and the infants in the second group hormonal therapy only. They then assessed whether the infants experienced any spasms between day 14 and 42 from the start of the trial.

The results showed that 133 of the 186 infants (72%) in the combined therapy group did not experience any spasms between day 14 and 42, compared with 108 out of 191 (57%) in the hormonal therapy only group.

Serious side effects requiring hospitalisation occurred in a total of 33 infants (16 on hormonal therapy alone and 17 on hormonal therapy with vigabatrin). The most common serious side effect was infection, which occurred in five infants on hormonal therapy alone and four infants on hormonal therapy with vigabatrin.

In a press release, the first author of the study, Dr Finbar O’Callaghan, Consultant Paediatric Neurologist at the Institute of Child Health, University College London, said: “Infantile spasms … is a devastating form of infantile epilepsy that is difficult to treat and is associated with a poor outcome. This study suggests a new treatment approach that will stop spasms faster and in more children than has previously been achieved with existing treatment strategies. It is therefore possible that this will lessen the long-term damage from this devastating epilepsy on developmental outcomes.”

Author: Dr Özge Özkaya

Click here for more news articles about epilepsy in children.

Categories: What's Current?

Maternal rheumatoid arthritis linked to childhood epilepsy

Medical News Today - Thu, 11/17/2016 - 03:00
New research examines the link between mothers and fathers with rheumatoid arthritis and the risk of their children developing epilepsy.
Categories: What's Current?

Study links mothers with rheumatoid arthritis and kids with epilepsy

Science Daily - Wed, 11/16/2016 - 16:07
A new study shows a link between mothers with rheumatoid arthritis and children with epilepsy. Rheumatoid arthritis (RA) is an autoimmune disease that causes the body’s own immune system to attack the joints. It differs from osteoarthritis, which is caused by wear and tear on the joints.
Categories: What's Current?

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality

Epilepsia - Wed, 11/16/2016 - 06:52
Summary Objective

To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD).

Methods

We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies.

Results

Rates of pathology subtypes differed between TLE and ETLE (χ2(3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray–white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ2(1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ2(1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ2(6) = 13.07, p = 0.042).

Significance

Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy.

Categories: What's Current?

Long-term monitoring of cardiorespiratory patterns in drug-resistant epilepsy

Epilepsia - Wed, 11/16/2016 - 06:50
Summary Objective

Sudden unexplained death in epilepsy (SUDEP) during inpatient electroencephalography (EEG) monitoring has been a rare but potentially preventable event, with associated cardiopulmonary markers. To date, no systematic evaluation of alarm settings for a continuous pulse oximeter (SpO2) has been performed. In addition, evaluation of the interrelationship between the ictal and interictal states for cardiopulmonary measures has not been reported.

Methods

Patients with epilepsy were monitored using video-EEG, SpO2, and electrocardiography (ECG). Alarm thresholds were tested systematically, balancing the number of false alarms with true seizure detections. Additional cardiopulmonary patterns were explored using automated ECG analysis software.

Results

One hundred ninety-three seizures (32 generalized) were evaluated from 45 patients (7,104 h recorded). Alarm thresholds of 80–86% SpO2 detected 63–73% of all generalized convulsions and 20–28% of all focal seizures (81–94% of generalized and 25–36% of focal seizures when considering only evaluable data). These same thresholds resulted in 25–146 min between false alarms. The sequential probability of ictal SpO2 revealed a potential common seizure termination pathway of desaturation. A statistical model of corrected QT intervals (QTc), heart rate (HR), and SpO2 revealed close cardiopulmonary coupling ictally. Joint probability maps of QTc and SpO2 demonstrated that many patients had baseline dysfunction in either cardiac, pulmonary, or both domains, and that ictally there was dissociation—some patients exhibited further dysfunction in one or both domains.

Significance

Optimal selection of continuous pulse oximetry thresholds involves a tradeoff between seizure detection accuracy and false alarm frequency. Alarming at 86% for patients that tend to have fewer false alarms and at 80% for those who have more, would likely result in a reasonable tradeoff. The cardiopulmonary findings may lead to SUDEP biomarkers and early seizure termination therapies.

Categories: What's Current?

Stereo electroencephalography–guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience

Epilepsia - Wed, 11/16/2016 - 06:50
Summary Objective

Stereo electroencephalography (SEEG)–guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC.

Methods

Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up.

Results

Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects.

Significance

Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.

Categories: What's Current?

Prevalence of juvenile myoclonic epilepsy in people <30 years of age—A population-based study in Norway

Epilepsia - Wed, 11/16/2016 - 06:35
Summary Objective

Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria.

Methods

This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999–2013. The study population consisted of 98,152 people <30 years of age. Subjects diagnosed with JME, unspecified genetic generalized epilepsy, or absence epilepsy were identified. All of these patients were contacted and asked specifically about myoclonic jerks. Electroencephalography (EEG) recordings and medical records were reevaluated for those who confirmed myoclonic jerks. Information about seizure onset was obtained from the medical records, and annual frequency of new cases was estimated.

Results

A total of 55 subjects fulfilled the diagnostic criteria for JME. The point prevalence was estimated at 5.6/10,000. JME constituted 9.3% of all epilepsies in the age group we investigated. Of subjects diagnosed with either unspecified genetic generalized epilepsy or absence epilepsy, 21% and 12%, respectively, had JME. We identified 21 subjects with JME (38%) who had not been diagnosed previously. Six subjects (11%) had childhood absence epilepsy evolving into JME. Between 2009 and 2013, the average frequency of JME per 100,000 people of all ages per year was estimated at 1.7.

Significance

A substantial portion of people with JME seem to go undiagnosed, as was the case for more than one third of the subjects in this study. By investigating subjects diagnosed with unspecified genetic generalized epilepsy or absence epilepsy, we found a prevalence of JME that was considerably higher than previously reported. We conclude that JME may go undiagnosed due to the underrecognition of myoclonic jerks. To make a correct diagnosis, clinicians need to ask specifically about myoclonic jerks.

Categories: What's Current?

Scientists Identify New Mutation Causing Progressive Myoclonus Epilepsy

Epilepsy Research - Tue, 11/15/2016 - 08:43

A team of international researchers have identified a new mutation in a gene called KCTD7, which causes progressive myoclonus epilepsy (PME). This discovery has important implications for genetic testing, and it may also lead to the design of new therapies for PME and other related conditions.

PME is a group of conditions characterized by muscle jerks, seizures, lack of voluntary muscle coordination and reduced thinking ability. It is usually diagnosed in young children and may result in death or severe disability.

Although scientists have already identified several genetic factors for PME, they have not been able to fully understand the exact mechanisms that cause the condition.

In the present study, published in the scientific journal Brain, the team reports the case of two brothers from Saudi Arabia with PME. The first boy developed muscle jerks and uncoordinated muscle movements at the age of nine months. By the age of two he had lost the ability to walk and talk and he developed drug-resistant PME. His younger brother developed similar symptoms when he was six months old.

The researchers genetically analysed both boys and their parents (who were first cousins) and found a new mutation in their KCTD7 genes. Both parents had one copy of the mutated gene and the boys inherited one copy from each parent. Having two copies of the mutated gene meant they developed the condition.

In a press release, the senior author of the study, Dr Farrukh Abbas Chaudhry, said: “The identification of the mutations now allows us to offer this and other affected families pre-natal genetic testing…More research on KCTD7 and other related proteins may identify their involvement in other forms of epilepsy and/or other diseases.”

The KCTD7 gene encodes for a protein that plays an important role in the responsiveness of neurons to external signals. The mutation causes the protein product of the gene to be shorter than normal and not to function properly. This results in neurons to become unstable and leads to PME by weakening the communication between neurons.

Author: Dr Özge Özkaya

Click here for more news articles about epilepsy in children.

Categories: What's Current?

New Method Could Pinpoint More Accurately Where Seizures Arise

Epilepsy Research - Fri, 11/11/2016 - 04:46

Researchers in the US and China have developed a new brain implant that can monitor the activity of individual brain cells at a much higher resolution than was previously possible. Their work is published in the leading scientific journal, Science Advances

According to Senior Author Dr György Buzsáki, at New York University, the implant could help recognise pathological activities in the brain such as epilepsy.

This could potentially be beneficial in epilepsy surgery, where pinpointing the exact origin or ‘focus’ of seizures (for removal) is vital, but often difficult. It could also assist with other therapeutic strategies that specifically target particular areas of the brain.

The implant, which the scientists called ‘NeuroGrid’, is a very thin (four micrometre thick) polymer grid that can record electrical signals from an area of 420 mm2. It has 120 conductive electrodes connected to a silicon chip, which amplifies the signal coming from the brain and sends it to a computer.

The new system offers several advantages over existing set-ups, for example it is cheaper and more comfortable than rigid electrode grids, which need to stay on the brain for up to two weeks, potentially causing inflammation.

The researchers tested the new grid in people who were undergoing epilepsy surgery, by temporarily inserting it onto the surface of the brain and recording electrical activity. They found that the grid was able to record individual brain cells ‘firing’.

Dr Mikhail Lebedev, a neuroscientist at Duke University, who was not involved in the study, commented that the new technique could “allow (neuroscientists) to localize the epileptic focus more accurately”.

It is important to note that the technique is still in its infancy and more work is needed before it can be used in the clinic. The researchers are hoping to make the grid smaller, and to take longer recordings from the brains of people with epilepsy.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

Categories: What's Current?

Analysis of Genetic Variations Could Help Develop New Therapies for Epilepsy

Epilepsy Research - Thu, 11/10/2016 - 13:49

A new study, published in the  American Journal of Human Genetics, sheds light onto how variations in genes can influence the activity of important proteins in the brain and may lead to neurological disorders.

The study focused on two genes called GRIN2A and GRIN2B, which are linked to epilepsy, intellectual disability and a number of other neurological conditions. These genes encode for two components – known as the GluN2A and GluN2B domains-of NMDA receptors, which play a crucial role in communication between brain cells.

Genetic variants in GluN2A and GluN2B are seen in the ‘general’ population without necessarily affecting the function of the NMDA receptor. However some rare variants do disrupt NMDA receptor activity, causing neurological disorders.

During the study the team, led by Dr Hongjie Yuan, at Emory University School of Medicine, in Atlanta, assessed genetic variation in the GluN2A and GluN2B ‘domains’, using data from the Exome Aggregation Consortium (ExAC). This is a large database that combines DNA sequences from more than 60,000 unrelated people. They were particularly interested in finding out what parts of the GLuN2 domains are most susceptible to disease-causing variations (identified via other gene databases).

They discovered that three different regions on theGluN2 domains – the region that binds to the molecules that activate the receptor; the region that anchors the receptor to the cell surface and the region that links the two domains – are particularly vulnerable to genetic variation. In other words, variations that cause functional problems in the NMDA receptor are more likely to be found in the sections of DNA that encode these areas.

In a press release, co-senior author Dr Stephen F. Traynelis, said:”This is one of the first analyses like this, where we’re mapping the spectrum of variation in a gene onto the structure of the corresponding protein. We’re able to see that the disease mutations cluster where variation among the healthy population disappears.”

In order to better understand how genetic variations in the GluN2 domains can affect the function of the NMDA receptor, the researchers explored 25 rare genetic GluN2A and GluN2B variants that had already been linked to different neurologic conditions, including epilepsy and intellectual disability. They found most of the GluN2A variants in the DNA of people with epilepsy, and most of theGluN2B variants in the DNA of people with intellectual disability with or without seizures.

Using the DNA, and genetic techniques, the team discovered that the effects of the GluN2 variants were complex and sometimes opposing. For example variants that resulted in both the receptor losing its function or acquiring function when it shouldn’t were associated with similar neurological conditions.

According to the authors, understanding how variants in GLuN2A and GluN2B cause disruption of NMDA receptor function could help scientists develop new strategies to restore it. These strategies could potentially serve as new treatments for epilepsy and other neurological conditions

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

 

Categories: What's Current?

Huperzine A provides seizure protection in genetic epilepsy models

Science Daily - Thu, 11/10/2016 - 12:53
The compound huperzine A can increase resistance to induced seizures in mouse models of genetic epilepsy, scientists have found. In particular, huperzine A shows potential for protecting against febrile seizures, which are a feature of both Dravet syndrome, a severe form of childhood epilepsy, and a related condition, GEFS+ (genetic epilepsy with febrile seizures plus).
Categories: What's Current?

Issue Information–ISSN page

Epilepsia - Thu, 11/10/2016 - 02:42
Categories: What's Current?

Announcements

Epilepsia - Thu, 11/10/2016 - 02:42
Categories: What's Current?

Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain-of-function variant

Epilepsia - Wed, 11/09/2016 - 15:54
Summary

Variants in KCNQ2 encoding for Kv7.2 neuronal K+ channel subunits lead to a spectrum of neonatal-onset epilepsies, ranging from self-limiting forms to severe epileptic encephalopathy. Most KCNQ2 pathogenic variants cause loss-of-function, whereas few increase channel activity (gain-of-function). We herein provide evidence for a new phenotypic and functional profile in KCNQ2-related epilepsy: infantile spasms without prior neonatal seizures associated with a gain-of-function gene variant. With use of an international registry, we identified four unrelated patients with the same de novo heterozygous KCNQ2 c.593G>A, p.Arg198Gln (R198Q) variant. All were born at term and discharged home without seizures or concern of encephalopathy, but developed infantile spasms with hypsarrhythmia (or modified hypsarrhythmia) between the ages of 4 and 6 months. At last follow-up (ages 3–11 years), all patients were seizure-free and had severe developmental delay. In vitro experiments showed that Kv7.2 R198Q subunits shifted current activation gating to hyperpolarized potentials, indicative of gain-of-function; in neurons, Kv7.2 and Kv7.2 R198Q subunits similarly populated the axon initial segment, suggesting that gating changes rather than altered subcellular distribution contribute to disease molecular pathogenesis. We conclude that KCNQ2 R198Q is a model for a new subclass of KCNQ2 variants causing infantile spasms and encephalopathy, without preceding neonatal seizures.

Categories: What's Current?

Pages