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Updated: 23 min 45 sec ago

New gene for severe childhood epilepsies

Thu, 09/22/2016 - 07:53

A panel of international researchers has discovered that mutations in a gene called GRIN2D could cause severe epileptic encephalopathy.

GRIN2D is part of a gene family containing the information necessary to make proteins called NMDARs. These are ion channels found on the surface of nerve cells, and they play an important role in electrical signalling between them.

Mutations in NMDAR proteins are already known to cause childhood epilepsy by over-stimulating nerve signals and causing a toxic build-up of an important neurotransmitter called glutamate. However, until now, it was not known that GRIN2D could harbour disease-causing mutations.

The team, led by Dr Marni Falk, from the University of Pennsylvania and The Children’s Hospital of Philadelphia, reported a case of two unrelated children with epileptic encephalopathy in an article published in the American Journal of Human Genetics.

The researchers analysed the genes of both children and found a recurrent mutation in the GRIN2D gene in both. Conducting experiments on nerve cells grown in the laboratory, the scientists showed that this mutation causes NMDAR to remain open for too long, resulting in excess electrical signals that kill the neurons.

Based on this finding, the scientists gave the children a medicine called memantine, which blocks NMDAR and is already approved to treat people with Alzheimer’s disease. This led to a mild improvements and a modest reduction in their seizures.

However, one of the children began to deteriorate over time and had to be placed in an induced coma. Based on the results of previous animal studies, the researchers decided to treat the child with two other NMDAR blockers – magnesium and ketamine. Although neither drug is considered a standard treatment for epilepsy, they produced dramatic improvements, stopping the repeated non-convulsive seizures that the child was experiencing and allowed her to regain some developmental skills.

In a press release, Dr Falk said: “Much more work, including randomised clinical trials, remains to be done to learn whether therapies such as these, targeted to a specific gene disorder, can be applied to other patients with similar subtypes of epilepsy.”

This is a great example of how basic scientific research can be applied to develop treatments suitable to the unique genetic profile of a patient and reflect the potential of precision medicine.

Epileptic encephalopathy is a condition linked to neurodevelopmental disabilities and characterised by frequent seizures that cannot be controlled by common antiepileptic drugs.

Author: Dr Özge Özkaya

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Continuous Electrical Brain Stimulation Could be a Treatment Option for People with Drug-Resistant Epilepsy

Thu, 09/22/2016 - 07:15

Continuous electrical brain stimulation could help to suppress epileptic seizures, offering a new treatment option for people who have epilepsy that cannot be treated with surgery or medication. These findings are published in JAMA Neurology,

First Author Dr Brian Lundstrom, at Mayo Clinic in Rochester, US, said: “We think this approach not only provides an effective treatment for those with focal epilepsy, but will allow us to develop ways of assessing seizure likelihood for all epilepsy patients. It would be of enormous clinical benefit if we could personalise treatment regimens for individual patients without waiting for seizures to happen.”

Doctors have attempted to suppress seizures by electrically stimulating the focus, or area in the brain where they originate. However, this approach rarely stopped seizures altogether.

In the present study, researchers found that electrical brain stimulation that couldn’t be felt by the patient was able to suppress electrical discharges that occur intermittently during normal brain function. It was also able to reduce the frequency and, in some cases, the intensity and duration of seizures.

Dr Lundstrom and colleagues conducted their study on 13 people with drug-resistant epilepsy who were also not eligible for surgery. They placed a grid of electrical contacts on their brains and sent stimulation at levels unnoticeable by the participants. In people for whom the electrical stimulation provided clinical benefits, the researchers replaced the temporary grid with a more permanent one that could offer continuous stimulation.

They found that 10 of the 13 patients (77%) reported improvement in both the severity of the epilepsy and their life satisfaction. The majority experienced more than a 50% reduction in seizures, and 44% were free of disabling seizures.

Epileptic seizures can be controlled with drugs in approximately two third of cases. However, one third of people with epilepsy have drug-resistant epilepsy. A proportion of these patients may be eligible for surgery where the focus, or portion of the brain in which seizures arise, is removed. Sometimes the focus is situated in an area of the brain that controls speech, language, vision, sensation or movement. In these cases surgery cannot be performed and electrical brain stimulation may be the only option.

Dr Lundstrom said that the risks associated with this approach are relatively minimal and include the risk of infection, bleeding and the stimulation being noticed by the patient.

According to the authors, further studies are needed to measure the exact effects of this treatment and examine the mechanism by which it suppresses seizures. They hope to examine the efficacy of this approach in more depth in the near future.

Author: Dr Özge Özkaya

Click here for more articles about other treatments for epilepsy.

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People With Epilepsy Still More Likely to Experience Discrimination

Tue, 09/20/2016 - 08:05

A new study, published in the scientific journal Epilepsia, shows that people with epilepsy still feel discriminated against a lot more than the ‘general population’.

According to the authors, this could lead to psychological and social problems and may even lead to the development of psychiatric problems.

First Author on the study, Dr Victoria Nimmo-Smith, from the University of Bristol, said: “This paper demonstrates that despite all of the advances made over the last 100 years, the experience of discrimination continues to be a significant problem for people with epilepsy.”

Senior Author, Dr Dheeraj Rai, added: “We still don’t know enough about why people with epilepsy develop depression and anxiety disorders much more often than the general population. Our findings suggest that adverse life events such as discrimination may be important (…) if true, it may be possible to design interventions to help prevent mental health problems in some people with epilepsy.”

For the study, the researchers recruited people in England who were aged over 16 and living in private households. During the first part of the assessment, subjects were asked to declare whether or not they had received a diagnosis of epilepsy, asthma, diabetes or migraine from a doctor. The scientists then used the Adult Psychiatric Morbidity Survey 2007 to collect and quantify information about each person’s experiences of discrimination, domestic violence, abuse and other stressful life events. They collated all of the complete data sets and analysed them (taking care to avoid biases and incorrect conclusions).

The results showed that people with epilepsy were seven times more likely to report experiencing discrimination due to health problems compared to people without epilepsy. This figure was considerably higher than for people with diabetes, asthma and migraines; when compared with people without each of these conditions respectively.

According to the data, people with epilepsy were more likely to have suffered domestic violence and sexual abuse than the ‘general population’; however, these associations were similar in the people with other chronic conditions (diabetes, asthma and migraines).

It is recognised that people with epilepsy are more likely to have common mental health problems such as depression and anxiety disorders than persons in the ‘general population’. This may be linked to common neurobiological factors, but psychological and social factors may also contribute.

Author: Dr Özge Özkaya

Click here for more articles about conditions related to epilepsy.

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Valproic acid may be more effective than lamotrigine in some types of epilepsy

Mon, 09/19/2016 - 06:12

Valproic acid may be more effective than lamotrigine as a first-line drug for the treatment newly diagnosed idiopathic generalized tonic-clonic seizures (GTCS) in adults. This is according to a study published in the Journal of Clinical and Diagnostic Research.

Opinions among medical professionals differ as to which drug is more effective in adults newly diagnosed with idiopathic GTCS, and this prompted researchers in India to carry out a comparison of the two.

For the study, the team recruited 60 participants with idiopathic GTCS and divided them into two groups. Half of the participants received valproic acid while the other half received lamotrigine.

The results showed that, after 12 months, more than 75% of participants taking valproic acid and approximately 57% of participants taking lamotrigine were seizure-free. Adverse side effects were seen in almost a third of cases in the group taking valproic acid and included sedation, ataxia (lack of voluntary coordination of muscle movements) and tremor. More than half of the lamotrigine group experienced adverse effects, including nausea, indigestion, headache and skin rash.

According to the authors, both valproic acid and lamotrigine are effective as first-line treatments for newly diagnosed adults with idiopathic GTCS. However, valproic acid appears to be preferable to lamotrigine because it is more effective and better tolerated.

Further studies on a larger number of subjects, who are followed for a longer period of time, are needed to confirm the results obtained in this study and evaluate the long-term effects of these drugs.

Author: Dr Özge Özkaya

Click here for more articles about anti-epileptic drugs and pregnancy risks.

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Results of Extension Study Show Benefit of Drug in Controlling Seizures

Fri, 09/16/2016 - 11:16

Please note that Epilepsy Research UK does not endorse/promote individual epilepsy treatments or pharmaceutical companies.

Long-term use (up to two and a half years) of the antiepileptic drug (AED) Fycompa (perampanel), in addition to other AEDs, gives sustained seizure control in poorly-controlled idiopathic generalised epilepsy with primary generalised tonic clonic seizures. This is according to data presented at the 12thEuropean Congress on Epileptology, was held in Prague in September 2016.

Scientists had previously tested the safety and efficiency of the drug in a phase three clinical trial called study 332. Here they presented the results of an extension to this study, in which all of the participants received Fycompa, regardless of what they had received in the original ‘core’ study. Unlike the core study, the extension was open label, meaning that both the subjects and the clinicians knew what was being administered.

For the extension study, researchers recruited 138 participants and gave them a daily dose of Fycompa for up to 136 weeks. This followed a six-week ‘conversion period’, in which people who had received a placebo in the core trial were switched to Fycompa.

By the end of the conversion period, participants had achieved a similar average reduction in seizure frequency whether they had originally received Fycompa or a placebo (a 100% and a 93.1% reduction respectively). Seizure control that was achieved during the core study was maintained throughout the course of the extension.

A total of 120 patients (87%) experienced adverse side effects associated with the treatment, including dizziness, upper respiratory tract infection, irritability, headache, sleepiness and common cold-like symptoms.

The results were announced in a press release by the drug’s manufacturer Eisai.

Fycompa is an orally available adjunctive drug for the treatment of partial-onset seizures, with or without secondarily generalized seizures, and primary generalized tonic clonic seizures, in people with epilepsy aged 12 years and above.

Author: Dr Özge Özkaya

Click here for more articles about anti-epileptic drugs and pregnancy risks.

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Scientists Develop New Non-invasive Method to Record Brain Activity

Thu, 09/15/2016 - 07:03

Scientists in Canada, Germany and Iran have discovered a new way to monitor brainwaves associated with epilepsy in a non-invasive way. This discovery could improve the diagnosis and treatment of epilepsy. The work is published in the scientific journal, Neuroscience.

First Author Zoya Bastany, a masters student at the University of British Columbia, comments: “Using this method, we found that the electrical signals acquired from the skin of the scalp were very similar to those acquired from the surface of the brain.”

According to the authors, the new approach, called amplified electroencephalogram (EEG), can produce results comparable to the current, more invasive, method whereby electrodes are directly placed on the surface of the brain. The key to this is the use of a specially-designed amplifier alongside the EEG recorder.

The amplifier, designed by Bastany and colleagues, detects signals in a much broader frequency range than standard clinical EEG systems. The researchers confirmed the accuracy of their new system by comparing brain and scalp recordings in anesthetised rodents.

According to Professor Guy Dumont, Co-author on the study, “The new method opens up uses for EEGs in studying cortical spreading depression in a non-invasive manner and without a significant increase in diagnostic costs compared to standard EEG.”

Cortical spreading depression is a low-frequency brainwave characteristic of epilepsy, and also migraines, and it is currently best studied by placing electrodes directly on the surface of the brain. However, this is a highly invasive and uncomfortable technique.

Author: Dr Özge Özkaya

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Do Omega-3 Supplements Have a Beneficial Effect in Drug-Resistant Epilepsy?

Wed, 09/14/2016 - 06:17

Scientists in Brazil suggest that the benefits of omega-3 supplements in people with drug-resistant epilepsy require further investigation. This comes after literature review, published in Cochrane Database of Systemic Reviews.

To assess the effectiveness and tolerability of omega-3 supplements in the control of seizures in people with drug-resistant epilepsy, the researchers, from Universidade Estadual de Ciências da Saúde de Alagoas, searched several databases for randomised and quasi-randomised studies, of both adults and children, where omega-3 supplements were taken as part of treatment.

The studies were assessed by two people, using pre-defined criteria, to see if they were suitable to be included in the review. These eligibility criteria specified: types of study design; forms of omega-3 supplement; types of participants; and outcome measurements. Three studies, involving a total of 155 people with epilepsy (85 adults and 70 children), were selected for the review.

The results showed that only the study involving children reported freedom from seizures with omega-3 supplementation. However, according to the authors, this study had a high risk of bias because the researchers knew which children were taking omega-3 supplements and which ones were taking a placebo.

When the team looked at the findings obtained from the two adult studies, they saw that there was no difference in average seizure frequency, quality of life or unwanted side effects between people taking omega-3 supplements and people taking placebo. Moreover, no differences in gastrointestinal effects were reported.

The authors conclude that there is not enough evidence (from this small number of studies and small sample sizes) to support the use of omega-3 supplements for the treatment of people with drug-resistant epilepsy, and that more trials are needed to assess their benefits.

Author: Dr Özge Özkaya

Click here for more articles about other treatments for epilepsy.

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Machine Learning Could Help The Diagnosis of Drug-Resistant Epilepsy

Tue, 09/13/2016 - 08:11

‘Machine learning’, a type of computer modelling, can detect areas of brain damage (lesions) associated with drug-resistant epilepsy. This is according to a new study published in the scientific journal PLOS One.

During the study, researchers led by Dr Carole Lartizien, from the University of Lyon, developed a complex system that is able learn features associated with healthy brain MRI scans. It can then be used to assess other MRI scans for abnormalities (i.e. how much they deviate from the normal ‘patterns’ it has learned).

The scientists focused on two parameters, detectable on MRI images, that are associated with lesions linked to epilepsy. These are the presence of grey matter within the white matter (heterotopia), and a blurred junction between grey and white matter.

Dr Lartizien and her team tested the performance of the system on brain MRI images from 11 people with drug-resistant epilepsy, who had a total of 13 lesions in their brains, and 77 healthy volunteers.

They found that the system was able to detect all of the lesions in the MRI positive cases (where the lesions on MRI images were detectable by experts) and 70% of lesions in MRI negative cases (where the lesions weren’t visible to experts). In addition, the rate of false positives (i.e. cases where the system “thought” there was a lesion when there was not) was low.

The authors conclude that machine learning “may be a versatile system for unbiased lesion detection.” If used in clinical practice, it could potentially allow people more prompt access to the most appropriate treatment for their condition.

Computer-aided diagnosis based on MRI has been suggested in the past few years to help screen lesions associated with epilepsy. The researchers propose that their system could also be used to detect other conditions where lesions are formed in the brain, such as multiple sclerosis and dementia; to study ageing; and to predict risk factors associated with stroke.

Author: Dr Özge Özkaya

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New Computer Model May Explain Spread of Seizures in the Brain

Sun, 09/11/2016 - 12:53

Researchers at the University of Pennsylvania have developed a new computer model that may explain why some seizures spread throughout the brain whilst others stay localized.

The seizure networks model, which the scientists developed using direct recordings from the brain of people with epilepsy, proposes that, whereas some regions in the brain promote seizure activity, others dampen it.

The leader of the study, Dr Danielle Basset, said in a press release: “We think this regulatory network has what is known as a ‘push-pull regulatory control.’ There are some regions of the regulatory network that can push the seizure network into a less active state, or pull it out of that state.”

According to the authors, understanding which parts of the network promote seizure activity and which parts dampen it could be invaluable in developing new therapies to treat people with epilepsy.

The regulatory networks could be targeted using different approaches to stop the spread of seizures in the brain. For example, areas that help quieten seizure activity could be strengthened with implantable devices, whilst regions that promote it could be ‘eliminated’ with laser surgery.

The team demonstrated that, using a technique called “virtual cortical resection” on their model, they could mimic the surgical removal of different areas of the brain that are implicated in seizure networks; making it possible to predict the impact that surgery may have in terms of stopping seizures.

The scientists had previously used their model to predict areas of the brain where seizures originate and spread.

The study was published in the leading scientific journal, Neuron.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

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3D Structure of Brain Receptor Could Help Develop Better Epilepsy Drugs

Fri, 09/09/2016 - 06:07

Researchers at Columbia University Medical Center have described, in detail, the structure and function of a type of receptor called the AMPA receptor. This plays an important role in the activation of neurons, but in epilepsy it contributes to seizure spread.

Currently there is only one approved drug, known as perampanel, that inhibits AMPA receptors to try and stop seizures. However, because AMPA receptors are present throughout the central nervous system, blocking them produces unwanted effects. There is a need for new drugs that are more targeted in their action (ideally working only where the epileptic activity is), and hopefully more effective.

To develop these, researchers first need to know exactly how AMPA receptors are formed and work, and precisely how compounds like perampanel inhibit them.

The team at Columbia University took AMPA receptors from rodents and used a technique called crystallography to map their 3D structure. They also managed to pinpoint where on the AMPA receptor perampanel and two other similar drugs bind, thereby inhibiting/silencing neurons.

Dr Alexander Sobolevsky, Senior Author, said: “Our data suggest that the inhibitors wedge themselves into the AMPA receptor, which prevents the opening of a channel within the receptor. When that channel is closed, ions cannot pass into the cell to trigger an electrical signal.”

Existing antiepileptic drugs (AEDs) are effective in preventing seizures in approximately two thirds of people with epilepsy. The remaining third, however, will not respond to medication alone. A new, more selective, AMPA receptor inhibitor would potentially offer more people with epilepsy the chance of seizure freedom. It might also be more effective than current AEDs, with fewer side effects.

The study was published in the scientific journal Neuron.

Author: Dr Özge Özkaya

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UKCRC Tissue Directory and Coordination Centre

Thu, 09/08/2016 - 06:45

The UKCRC Tissue Directory and Coordination Centre is a new jointly-funded project based at UCL, in collaboration with the University of Nottingham.  It is an exciting initiative, which aims to improve access to human tissue samples for research purposes in the UK. There is a need for researchers to be able to find human samples for high-quality research. To facilitate this, the centre has created a tissue directory, which will hold the information for UK collections. You can read more about us and search the directory here.

The centre’s annual meeting, ‘UK Biobanking Showcase, will take place on 16 November 2016, at the Oval, London, and it will feature the range of exciting biobanking capabilities that we have. There’ll be debates, discussion panels, workshops and lots of chances to shape the development of the centre. You’ll hear about our progress to date, our ambitious work plans for the upcoming year and our links to BBMRI-ERIC. It will be a unique opportunity to shape the future of UK biobanking. You can now register here.

Click here to read news from Epilepsy Research UK and around the world.

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Promising Results From Phase Three Clinical Trial for People With Tuberous Sclerosis Complex

Thu, 09/08/2016 - 06:06

Please note that Epilepsy Research UK does not endorse/promote individual epilepsy treatments or pharmaceutical companies.

The antiepileptic drug (AED) everolimus significantly reduces seizure frequency in people with drug-resistant epilepsy and tuberous sclerosis complex (TSC), according to a study published in the leading medical journal The Lancet.

The phase three clinical trial was conducted by a team of researchers led by Dr David Franz, from Cincinnati Children’s Hospital Medical Center, and funded by Novartis, the manufacturer of the drug.

A total of 336 people with TSC and epilepsy, aged between two and 65 years, were recruited from 25 different countries. Almost half of the participants had failed to respond to six or more AEDs.

The participants were randomly divided into three groups and received either a low dose of everolimus, a high dose of everolimus or an identical-looking placebo.

The results showed that in people who received a low dose of the drug, seizure frequency was reduced by more than 29%. This figure was nearly 40% in the high-dose group.

Adverse side effects such as inflammation of the mouth and lips, diarrhoea, common cold, fever and upper respiratory tract infection occurred in 3% of subjects who received placebo and 14% of those who received a low dose or high dose of everolimus. Dr Franz notes that these figures are consistent with findings from previous everolimus trials.

TSC is a genetic disease that causes malformations and tumours in the brain and other organs. It is estimated to affect approximately one million people around the world.

Everolimus is a derivative of the drug sirolimus and works in a similar way by inhibiting a signalling complex called ‘mammalian target of rapamycin complex 1’ (mTORC1). There is evidence that this signalling pathway plays a role in both acquired forms of epilepsy and TSC.

Author: Dr Özge Özkaya

Click here to read about an ERUK-funded pilot study into TSC, led by Professor Alexander Hammers, at King’s College London.

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An Important breakthrough for infantile epilepsies

Wed, 09/07/2016 - 05:21

Scientists at the University of Queensland have made an important discovery about severe infantile epilepsies, which, unexpectedly, links to Parkinson’s disease. The results are published in the Journal of Cell Biology.

According to Professor Frédéric Meunier, Senior Author on the study, this discovery could open new avenues for the development of different classes of drugs to treat epilepsy.

In a press release, Dr Emma Sierecki, Co-author, said: “This is the first time that a communal mode of action has been found for an epileptic syndrome and neurodegeneration.”

Munc18-1 is a protein that plays an important role in the communication between neurons. The team used cellular and genetic techniques to show that faults in the Munc18-1 gene caused the protein to gather in lumps (aggregates).

On further analysis, the researchers saw that these aggregates also contained another protein called α-Synuclein, a form of which is known to be involved in Parkinson’s diseases.

In a separate part of the investigation, they showed that, whilst ‘healthy’ Munc-18 does bind α-Synuclein, it does not form these aggregates.

“The unexpected co-aggregation of α-Synuclein and Munc18-1 in disease reveals how these two proteins function together,” added Dr Sierecki.

The scientist wanted to find out what happened to both ‘healthy’ α-Synuclein and Parkinson’s-associated α-Synuclein, when healthy Munc18-1 was experimentally removed from the ‘system’. They  discovered that, in both cases, the α-Synuclein became more likely to form aggregates, and that this effect was reversed when healthy Munc18-1 levels were restored.

These findings suggest that they ‘healthy’ Munc18-1 protein functions as a chaperone/helper of α-Synuclein to protect neurons.

It was already known that mutations in the Munc18-1 gene cause infantile epileptic encephalopathy, but to date the exact mechanism by which this happens was not fully understood. These findings reveal Munc18-1 as a potential new treatment focus for these devastating conditions.

Author: Dr Özge Özkaya

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The ketogenic diet shows mood and behavioural benefits in children

Tue, 09/06/2016 - 05:51

The ketogenic diet may have a positive impact on behaviour and thinking skills in children with drug-resistant epilepsy, according to a study conducted in the Netherlands. The results are published in the scientific journal Epilepsy and Behavior.

The randomised controlled trial, led by Dr Albert Aldenkamp, from Epilepsy Center Kempenhaeghe, recruited 50 children with drug-resistant epilepsy, aged between one and 18 years. After a one-month baseline period, subjects were randomly divided into two groups: one that received the ketogenic diet for four months (28 people) and the other that continued with their usual diet (22 people). All participants continued to take their usual epilepsy medication throughout the study.

The children underwent behavioural and cognition (thinking skills) assessments at two time points – at ‘baseline’ (just before randomisation) and after the ketogenic diet group was four months into treatment. The assessments  involved a combination of questionnaires filled by the children’s parents and psychological tests completed by the children themselves. They were designed to examine how much epilepsy affected the child’s ability to take part in everyday activities such as swimming, riding a bicycle, staying outside of their home overnight and participating in physical education; their relationships with their peers; their productivity; their level of dependency; and their mood (hostility, anxiety/depression and withdrawal).

The investigators compared the baseline and four-month assessment scores, both within and across the groups, and found that the ketogenic diet was linked to an increase in activity and productivity ratings; and an improvement in anxiety and other mood problems. It was also associated with an improvement in thinking skills.

According to the authors, these results add to the growing body of evidence that the ketogenic diet is a viable treatment option for children with drug-resistant epilepsy.

Author: Dr Özge Özkaya

Click here for more articles about other treatments for epilepsy.



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ERUK study shows promising results for two antiepileptic drugs in pregnancy

Thu, 09/01/2016 - 04:53

An Epilepsy Research UK-funded study has shown that taking the antiepileptic drugs (AEDs) levetiracetam or topiramate during pregnancy may not have a negative impact on the baby’s IQ and thinking skills. The research, which also confirms the risks associated with valproate (another AED), is published in Neurology® online.

There is accumulating evidence that exposure to valproate before birth is linked to a significantly increased chance of birth defects, developmental problems and lower IQ, especially at higher dosages. However, valproate is an effective and widely-prescribed AED, so it is important to establish what the alternatives are for women with epilepsy during pregnancy (they need to be effective at controlling seizures and safe for the baby). Levetiracetam and topiramate are newer drugs, and to date few studies have looked at their effects on child development and thinking.

Lead Researcher, Dr Rebecca Bromley, at the University of Manchester, comments: “As doctors move away from prescribing valproate, we need to know about the alternatives for pregnant women with epilepsy. Lower IQs early on can harm a child’s educational success for years to come and so it is important that we gain a full understanding about any impact on development these medications may have.”

During the study, the researchers used data from the UK Epilepsy and Pregnancy Register to identify 171 women with epilepsy who had a child between the ages of five and nine years. Forty-two of the women had taken levetiracetam during pregnancy; 27 had taken topiramate; and 47 had taken valproate. A control group of 55 women who did not take AEDs during pregnancy was also included. The team carried out assessments of the children to measure their IQ, verbal and non-verbal comprehension, and the speed at which they could process visual information.

The results showed that the children of women who took levetiracetam or topiramate did not have reduced IQs, or other thinking skills, compared to the control group, regardless of the dosage of medication their mother took. Children whose mothers had taken valproate were found to have the lowest IQs; scoring an average of 11 points lower on the IQ test (which has an average of 100 points). Nine of the 47 children whose mothers took valproate (19%) were shown to be below the average range on the IQ score, compared to three of the 55 children whose mothers did not take any epilepsy drugs during pregnancy ((6%).

These findings are encouraging; however Dr Bromley adds a note of caution: “While our findings represent a promising start, larger studies need to be done ensure that these drugs will not change the thinking abilities of children.”

She notes that one limitation of the study is that the pregnancy registry represents only a small proportion of women with epilepsy, and that therefore the results may not be representative of all women with epilepsy. She also observes that topiramate has been associated with an increased risk of birth defects such as cleft lip and palate. Due to the fact that few children exposed to topiramate were included in the study, the results should be interpreted carefully.

Click here for more articles about anti-epileptic drugs and pregnancy risks.



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A Possible Explanation as to Why Some Children Outgrow Epilepsy in Adolescence

Tue, 08/30/2016 - 04:17

Results from the US and China may help to explain why some children with epilepsy outgrow their condition in adolescence.

At the heart of these findings is ‘GABA’; a brain chemical that acts via structures called receptors to dampen down electrical activity in neurons (and prevent them from becoming hyperexcitable). Recent evidence shows that there is a specific type of GABA receptor, called α4βδ, that is only made in the brain during puberty.

In the current study, the team, led by Dr Sheryl Smith, at SUNY Downstate, New York, wanted to explore the role of α4βδ receptors in regulating seizure activity. To do this they used animal brain tissue, from before puberty and during puberty, and induced seizure-like activity in it using approved methods.

The researchers found that when they tried to induce seizure-like activity in the pre-pubertal tissue, they were successful in 60% of cases. However, when they used the same techniques in the ‘pubertal’ tissue, only 7% developed seizure-activity.

To make sure that it was the α4βδ receptor that accounted for this difference at not another factor, the team repeated their experiment using tissue from pubertal animals that had been bred to lack the gene that encodes α4βδ (instead of pubertal animals with normal α4βδ).

Here they found no reduction in seizure-like activity in the pubertal tissue compared with pre-pubertal tissue. This suggests that the α4βδ receptor does indeed play a role in reducing seizure-like activity at puberty, in this model of epilepsy.

Interestingly, the administration of drugs that selectively enhance inhibitory activity mediated by this receptor further decreased seizure-like activity in the brain of the animals. If the findings from this study are translatable to humans, a brand new avenue for epilepsy treatment will open.

Dr Smith and colleagues concluded: “These findings suggest a mechanism for remission of epilepsy in adolescence and also suggest potential new therapies for childhood epilepsy.”

The study was published in the leading journal Scientific Reports.

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Irritable Bowel Syndrome More Common in People With Epilepsy

Fri, 08/26/2016 - 04:03

A new study, published in the scientific journal Epilepsy and Behavior, shows that irritable bowel syndrome (IBS) is more common in people with epilepsy than in the ‘general’ population.

The research also suggests that, although IBS itself doesn’t have a negative impact on health-related quality of life in people with epilepsy, it is associated with a greater likelihood of depression/anxiety symptoms and insomnia.

During the study, scientists, led by Dr Marco A. Díaz-Torres, at Universidad Autónoma de Nuevo León in Monterrey, Mexico, recruited 65 people with epilepsy and a group of people with similar characteristics, e.g. age, social demographic, who did not have epilepsy.

The team was interested in finding out how common (how prevalent) IBS and another bowel condition called functional dyspepsia were in each group.  They also investigated the subjects’ sleep, symptoms of depression/anxiety and health-related quality of life.

The results showed that the prevalence of IBS was significantly higher in people with epilepsy than in those without epilepsy; but that the prevalence of functional dyspepsia was similar in the two groups.

Particpiants with both epilepsy and IBS had higher rates of insomnia (inability to sleep) and symptoms of depression/anxiety than those with epilepsy who did not have IBS; however, the presence of IBS itself in people with epilepsy did not appear to have a negative effect on health-related quality of life scores.

People with epilepsy are not routinely screened for IBS. This means that treatment may be delayed or withheld altogether. Moreover, gastrointestinal complaints may be wrongly attributed to antiepileptic drugs (AEDs), leading to unnecessary treatment changes. The authors therefore concluded that clinicians should screen for the presence of IBS in people with epilepsy complaining of gastrointestinal (bowel) symptoms.

Author: Dr Özge Özkaya

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Small Device Could Detect and Stop Epileptic Seizures on the Spot

Thu, 08/25/2016 - 05:42

Researchers in Sweden and France have developed a tiny device that can detect epileptic seizures at the exact point in which they arise, and deliver, to that precise point, a substance that can stop them before they spread to other areas of the brain.

The device, called a bioelectronic neural pixel, is 20×20 μm* in size (approximately the size of a human hair follicle) and combines recording electrodes with a pump mechanism to administer treatment.

If it can be safely applied in humans, this technology could potentially be used to locally record brain activity and regulate the targeted release of specific therapeutic agents; minimising side effects. It “creates a range of opportunities,” write the authors, whose results are published in the leading scientific journal Proceedings of the National Academy of Sciences (PNAS).

These findings come from work in animal brain tissue, in which the scientists chemically induced seizure-like activity. They used the device to first locate the origin of the seizures and then deliver a substance called GABA, which dampens neuronal activity, to try and stop them.

The team found that the GABA was able to stop seizure activity on the spot, whilst a recording at that point was being taken.

Antiepileptic drugs (AEDs), which are taken orally or injected into the blood stream, spread throughout the body and often cause unpleasant side effects. Therefore, being able to deliver a therapeutic compound to the exact place where it is needed could minimise or completely eliminate its side effects.

Dr Daniel T. Simon, Senior Author of the study, said in a press release: “Our technology makes it possible to interact with both healthy and sick neurons. We can now start investigating opportunities for finding therapies for neurological illnesses so rapidly and so locally that the patient doesn’t notice them.”

Author: Dr Özge Özkaya

*1 μm is one millionth of a metre

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Assessing anti-epileptic drug risk in pregnancy: are new methods as reliable as traditional ones?

Wed, 08/24/2016 - 06:37

These are the findings of an Epilepsy Research UK (ERUK) grant, which was awarded to Dr Rachel Charlton, at the University of Bath, in 2014.


For women with epilepsy pregnancy requires very careful planning, because exposure to some anti-epileptic drugs (AEDs) in the womb, valproate in particular, has been linked to an increased chance of birth defects, behavioural problems and delayed cognitive development.

Traditional methods for assessing the risk of behavioural and developmental issues in unborn babies (i.e. face-to-face interviews) require a lot of work and they are very expensive. In recent years, databases that contain routinely-collected electronic medical records have been increasingly used for research; however, whilst this approach offers many advantages, including lower cost and access to larger numbers of exposed children, it is not clear whether it is a reliable way of detecting developmental and behavioural problems. This is important to know, because if the risks of exposure to an AED in the womb are overestimated via a database, the drug may not be recommended by doctors when it is in fact safe. Conversely, if the risks are underestimated, doctors may recommend an AED that could inadvertently cause harm.

The study

Here, Dr Charlton and colleagues aimed to compare the two methods, looking at the risk of specific neurodevelopmental disorders – autism, attention deficit hyperactivity disorder (ADHD) and dyspraxia (coordination difficulties) – associated with different types of AED exposure in the womb.

The researchers used an electronic database, called the Clinical Practice Research Datalink, to collect anonymised information about 7,066 mother-child pairs. Pairs were classified into three groups: 1) in which the mother had epilepsy and received AED treatment during pregnancy (546) 2) in which the mother had epilepsy but did not receive AED treatment during pregnancy (472) and 3) in which the mother did not have epilepsy and had not taken an AED (6,048).

The investigators used the data to identify all of the children in each group who had developed a neurodevelopmental disorder, and they were then able to calculate risk estimates. Risk in the ‘AED-treated group’ was broken down according to the different AEDs/combinations of AEDs taken by the mothers. Finally, the scientists compared their results with those obtained in an earlier UK study that used traditional methods.


Both studies found an increased risk of neurodevelopmental disorders in children born to women with epilepsy than in those born to women without epilepsy; however the database study produced risk estimates that were much lower. Moreover, the risk found amongst the children born to women without epilepsy was lower than that seen in the general population.

In the database study, neurodevelopmental disorders were found in a small number of children born to women with epilepsy who appeared not to have taken any medication during pregnancy. However, on closer examination, it was discovered that these women may still have been coming off their AEDs in the early stages of pregnancy. To look at the impact of this, the team adjusted the groups so that the ‘treated’ mothers also included women who had taken AEDs in the six months before pregnancy.

In both studies, the risk of neurodevelopmental disorders differed between AED exposure groups. Although the database study showed a higher risk with valproate monotherapy (valproate taken alone), it was a) a lot lower than that seen in the traditional study and b) not statistically significant, even when the exposure groups were modified to include the six months before pregnancy. This means that, according to recognised statistical rules, the chance that the finding could have occurred by chance was too high for it to be conclusive. Valproate polytherapy (taken with other AEDs), however, was associated with a significantly increased risk of neurodevelopmental disorders, although this risk was slightly lower than that reported in the traditional study.


These results suggest that neurodevelopmental disorders in children exposed to AEDs before birth are under-recorded in the Clinical Practice Research Datalink. This in turn means that some databases might not be as reliable as traditional methods for assessing the risks associated with AED exposure in the womb. Future research must take the findings of this study into consideration, so that women with epilepsy can be offered the most accurate pregnancy advice possible.

Earlier this year, the Medicines and Healthcare Products Regulatory Authority (MHRA) issued important new guidance about the risks of valproate in pregnancy. Click here to find out more. 

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The Impact of AEDs on Bone Health

Wed, 08/24/2016 - 06:14

Paediatric researchers from Taiwan, who compared the effects of old and new antiepileptic drugs (AEDs) on bone health, found that new AEDs may be safer and better tolerated. They note, however, that further research is needed to fully understand the effects of newer AEDs on bone health and growth.

According to the scientists, whose study is published in the International Journal of Molecular Sciences, their analysis “emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.”

There have been some conflicting findings to date regarding the effects of AEDs on bone health. This prompted Dr Ching-Shiang Chi and colleagues, at Tungs’ Taichung Metroharbor Hospital, to conduct a review of past studies, which involved almost 69,000 people with epilepsy.

The results of their analysis suggest that taking AEDs is associated with a decrease in bone mass density and an increased risk of fractures.

The team found strong evidence that older or classical AEDs, such as benzodiazepines carbamazepine, phenytoin, phenobarbital and valproic acid, cause vitamin D deficiency and have a negative impact on bone health. Newer AEDs, such as levetiracetam, oxcarbazepine, lamotrigine, topiramate, gabapentin, and vigabatrin, were found to be safer and better tolerated; although more research is required to determine their effect on bone health.

The authors conclude: “Proper use of a new medication may avoid serious disabilities in users. In addition, supplementation of calcium and vitamin D are still recommended to epileptic patients on AEDs.”

AEDs are the first choice of treatment for epilepsy and approximately two thirds of people respond to them. However, they do carry a risk of side effects, including dizziness, drowsiness and weight gain.

Previous research has shown that AEDs may also have a negative impact on bone health, especially if used long-term. In fact, more than half of people with epilepsy who take AEDs are reported to have bone abnormalities. This is a cause for concern, especially in younger children who are at a critical stage of growth.

Author: Dr Özge Özkaya

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