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Genetic Changes that Cause Loss of a Certain Type of Memory Can Also Protect Against Epilepsy

Fri, 12/02/2016 - 09:11

A new biological mechanism that damages only a specific type of memory can provide protection against epilepsy according to a study published in the scientific journal Cerebral Cortex.

The biological pathway involves a genetic modification in a protein called eEF2K, which regulates the expression of other proteins. According to the authors, the eEF2K protein could be a potential new target for antiepileptic drugs (AEDs).

The findings came by chance while the team of international researchers were trying to isolate molecular components involved in long-term memory whilst working on learning and memory.

Using a mouse model, the researchers made a molecular change to the eEF2K gene, which resulted in the complete lack of the protein that the gene encodes for. They then tested the mice behaviourally to assess their memory.

They saw that the lack of eEF2K protein caused damage to a specific type of memory called context memory, whilst keeping consolidation of other types of memory intact.

When they further analysed the brains of these animals, the researchers found that a certain part of a receptor called GABAAR and another protein called synapsin2b were over expressed. The over expression of GABAAR causes the nerve cells to be less active while the overexpression of synapsin2b causes them to be more active.

In a press release, one of the authors of the study, Elham Taha, explained: “We realized that, surprisingly, the change in the general translation control element, eEF2K, changes the excitation/inhibition ratio in a specific area of the brain. This area as well as the molecules whose expression changed are associated with epilepsy. For example, mutation in synapsin2b in humans or a decline in its expression may lead to epilepsy.”

As a next step, the researchers genetically-engineered mice with epilepsy that lacked eEF2K protein, to find out if eEF2K down-regulation decreases seizure activity. EEG tests revealed that these animals did not have any seizures.

The scientists also sought to find out whether chemically (rather then genetically) inhibiting the eEF2K protein would have the same effect. They gave mice with epilepsy (that had low levels of synapsin2b) a substance that inhibits the expression of eEF2K protein. They noticed that the mice did not experience any seizures during the following week.

For both the genetic and chemical methods, when the researchers looked at the expression of synapsin2b they saw that the levels had been brought to normal as a result of eEF2K absence/inhibition.

In the future, the researchers want to find ways to block the expression of eEF2K in only certain nerve cells “in order to improve our understanding of the basis of epilepsy and to create new possibilities for treating the disease.”

Author: Dr Özge Özkaya

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Children With Congenital Heart Disease Have a Higher Risk of Epilepsy

Tue, 11/29/2016 - 08:50

The risk of epilepsy is higher in children with congenital heart disease (CHD) compared with the general population, even if the condition is mild and does not require surgical intervention, according to a study published in the scientific journal, Circulation.

This finding suggests that epilepsy in children with CHD may be a consequence of  ‘non-surgical’ factors, such as an insufficient supply of oxygen to the brain during development and subsequent brain abnormality. However, the authors do speculate the existence of a genetic link between congenital heart disease and epilepsy.

For the study, the team, led by Dr Morten Olsen, identified children born with CHD between 1980 and 2010, using data from population-based registries covering all hospitals in Denmark. All of the children that were included in the study were diagnosed with CHD by the age of 15. For each child with CHD, the scientists identified 10 healthy children who were the same age and sex for comparison.

The results showed that there were 15,222 children born and diagnosed with CHD in Denmark during this period. A little more than half of them (51%) were male and 49% were female. Five percent of the children were diagnosed with epilepsy by the time they were 15 years of age. When only children born with CHD without extra-cardiac (outside of the heart) malformations were considered, this figure was 3%. It was more likely for children with CHD to develop epilepsy before the age of five than after the age of five.

The likelihood of developing epilepsy was not influenced by the age of the child when they had heart surgery, but it was highest among children who underwent multiple surgeries. However the risk of epilepsy was also higher than in the general population for children with mild CHD who did not undergo surgery.

Although it was previously known that neurological complications are associated with congenital heart disease, this is the first study that examined the long-term risk of epilepsy in people with congenital heart defects compared with the general population.

Previous work has identified genetic mutations that may link CHD with neurodevelopmental disabilities. According to the authors “there may be an as-yet-undiscovered genetic explanation for the heightened risk of epilepsy in the [CHD] population”.

It is important to note that the increased risk of epilepsy that was observed in this study could be linked to other factors such as the mother having epilepsy, and the foetus being exposed to antiepileptic drugs in the mother’s uterus. However in the group with CHD that was analysed, the proportion of mothers with epilepsy was very low and so it is unlikely to be the only mechanism explaining the increased risk of epilepsy.

Author: Dr Özge Özkaya

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Modifying AEDs Used by Patients During Vagal Nerve Stimulation Does Not Improve Outcome

Mon, 11/28/2016 - 04:14

Changing people’s antiepileptic drugs (AEDs) during vagal nerve stimulation (VNS) does not seem to improve their outcomes, according to a study published in the journal Acta Neurochirurgica.

On the basis of this finding, the authors suggest that keeping the same AEDs following the implantation of a VNS device may help optimise its parameters and could improve its effectiveness.

In order to assess the influence of medication change following the implantation of a VNS device, researchers at University Hospital La Princesa, in Madrid, compared two groups of people with epilepsy treated with VNS, with and without medication changes.

They analysed a total of 85 people with epilepsy who were treated with VNS between 2005 and 2014. The AEDs given to 43 of the participants was not modified following the implantation of the VNS device, while the decision to make a change in medication was left to the neurologist in the case of the remaining 42 people.

Eighteen months after implantation, more than half of all the patients (54.1%) had at least a 50% reduction in seizure frequency. When the researchers compared patients whose medication was not modified following the procedure with the patients whose medication was modified, they found that in the first group (medication not modified) 63% of patients had at least 50% reduction in their seizures. This figure was 45.2% in the second group (medication modified).

The researchers concluded that there were no statistical differences in the reduction of seizure frequency between people whose medication was changed, and those whose medication remained the same, following implantation of a VNS device.

A VNS device (or stimulator) is a small device containing a generator that is implanted in the left side of the chest. It sends regular electrical impulses to the left vagus nerve in the neck and it is used to try and prevent seizures in people who don’t respond to medication alone. During the 12-18 months following the implantation of  VNS device, a neurologists will usually change the patient’s antiepileptic drugs (AEDs), which makes it difficult to know whether any reduction in seizure frequency is due to VNS or the change in medication.

Author: Dr Özge Özkaya

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Children with Epilepsy on the Ketonic Diet Should Have their Blood Selenium Levels Closely Monitored

Fri, 11/25/2016 - 05:00

An olive oil-based ketogenic-diet leads to a decline in selenium levels in children with drug-resistant epilepsy, according to a study published in the journal of Biological Trace Elements Research.

Previous research has shown that low amount of selenium, an element found in trace amounts in the blood that, may increase the risk of seizures. Therefore the levels of selenium in the blood of children with epilepsy who are on a ketogenic diet should be closely monitored.

For the study, the team led by Dr Orkide Guzel, at Behçet Uz Children Hospital in Izmir, Turkey, enrolled a total of 110 children with drug-resistant epilepsy, aged between three and 12 years, who were on ketogenic diet for at least 12 months.

The researchers measured the level of selenium in the children’s blood before the start of ketogenic diet treatment (baseline) and again at three, six and 12 months.

The results showed that although there were no significant differences in the level of selenium in the blood of the children after three months of treatment with ketogenic diet, selenium levels were significantly lower at six and 12 months compared with pre-treatment levels.

Almost half of the children (54 out of 110) were diagnosed with selenium deficiency, defined as selenium levels lower than 48 micrograms per litre, and treated with selenium supplements.

“The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element,” the authors wrote.

Author: Dr Özge Özkaya

Click here for more news articles about epilepsy in children.

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Impression Management Tactics May Positively Influence the Outcome of Job Interviews for People with Epilepsy

Thu, 11/24/2016 - 04:36

Impression management (IM) tactics, such as personal storytelling and self-promotion can have significant and positive effects on the outcome of job interviews for people with epilepsy, according to a study published in the scientific journal Epilepsia.

IM tactics could therefore be used as a “powerful strategy for empowering people with epilepsy to combat disability stigma, and offset negative perceptions of employers about the potential of this population to be productive workers,” according to the authors.

In order to determine the effect of assertive IM on the subjective impressions of the interviewers and outcome of job interviews, the team, led by Dr Fomg Chan, at the University of Wisconsin, carried out an experiment with 99 masters students in business or human resources.

They randomly assigned the students to one of three 15-minute videos of a job interview, where the candidate was applying for a position in computer sales. The candidate in the first video did not disclose any disability, the one in the second video had epilepsy but was not using any IM tactics and the candidate in the third video had epilepsy and was using IM tactics.

After watching the video, the researchers asked the students to rate the job applicant in terms of general impression and employability for the described position.

The results showed that IM tactics have a significant effect on the outcome of job interviews. The average rating of the students on both general impression and employability of an applicant with epilepsy who used IM tactics were significantly higher than for the applicant with epilepsy who did not use IM tactics.

It is important to note that the study has several limitations. For instance, the study participants were students and not actual business people. Moreover, the scenarios used in the study described an active athlete with epilepsy who had complete seizure control, however only a third of people with epilepsy actually have complete seizure control. “Hence, results should be interpreted with caution,” the authors wrote.

IM tactics are behaviours used by people to protect and promote their self-image and influence how they are perceived by others.  Assertive IM tactics utilised in this study include actively constructing an image of oneself with a cohesive set of beliefs, opinions, characteristics, or experiences. Previous work has shown that IM tactics can influence the evaluation of a candidate by interviewers and the outcome of an interview including job offers.

Author: Dr Özge Özkaya

Click here to read more stories about living with epilepsy.

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Electronic Diary May Improve Adherence to AEDs in Women with Epilepsy Who Are Planning Pregnancy

Wed, 11/23/2016 - 10:20

A study published in the scientific journal, Epilepsia, shows that electronic diaries may help women with epilepsy who are planning a pregnancy adhere to treatment schedules.

The results of the study, conducted at New York University Langone Epilepsy Center, Mount Sinai School of Medicine and Brigham and Women’s Hospital, suggest that electronic diaries could be useful in clinical settings to enhance patient and medication management.

In a press release, the senior author of the study, Dr Jacqueline French, said: “Monitoring of medication adherence presents a tremendous challenge to clinicians and to clinical researchers. Poor adherence has been shown to negatively impact health care spending by resulting in more emergency room visits and hospitalizations, and may result in incomplete seizure control and increased risk of sudden death. Many times, patients do not report to their doctor about missed medication doses. This information could be used to discuss and improve compliance.”

Women with epilepsy who are pregnant are at particular risk of missing antiepileptic drug (AED) doses (e.g. due to sickness, or fear of harming their baby), but breakthrough seizures can be more harmful to both the mother and child (and so adherence to prescribed treatment is very important).

For the study, the researchers gave women with epilepsy who were planning to become pregnant an iPod Touch loaded with a customised mobile application called the WEPOD App that can track daily data.

A total of 86 women with epilepsy tracked their seizures and AED use and were included in the study. The researchers followed these women from the time of study enrolment throughout their pregnancy, and up to the birth of their child, or for women who did not become pregnant, for up to 12 months.

The results showed that 75% of women who used the electronic diary tracked their use of AEDs on a daily basis for more than 80% of the study period. These women were included in the data analysis and they showed a 97.7% adherence to medication. In addition, 44% of them admitted to missing an AED on at least one day.

Interestingly women who tracked their use of both AEDs and non-epilepsy medications reported a higher rate of adherence with AEDs than with other medications, suggesting that perceived importance of medications may influence adherence.

According to the authors the high rate of adherence may, in part, be a result of  some of the electronic diary’s properties, such as daily reminders and real time feedback given to the provider.

Further research is needed to confirm these findings, and also to investigate how electronic diaries might help other groups of people with epilepsy (who aren’t women planning a pregnancy) adhere to their AED regimens.

Author: Dr Özge Özkaya

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

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New Imaging Method Could Help Predict Which Patients Will Benefit From Surgery

Tue, 11/22/2016 - 04:42

A new imaging method could help predict which patients are likely to be free of seizures and which ones are likely to experience recurring seizures following brain surgery, according to a study published in the scientific journal Brain.

The authors state that there is very little information that can help predict the outcome of surgery in epilepsy, and that this study is the first to rigorously investigate the characteristics of the temporal lobe in a way that can help classify future seizures.

The team of international researchers, led by Dr Leonardo Bonilha, at the Medical University of South Carolina, analysed the tissue characteristics of certain areas of the temporal lobe known to be important in the generation and spread of temporal lobe seizures, using an MRI-based imaging technique called diffusion tensor imaging (DTI).

They studied 43 people with mesial temporal lobe epilepsy, who subsequently underwent surgery, and 44 healthy volunteers.

Approximately half of the patients (51.2%) were completely seizure-free following surgery, whilst the other 48.8% continued to experience seizures.

When they analysed the results of the DTI, the researchers saw that both the patients who were seizure-free and those who had recurrent seizures following surgery had abnormalities in white matter bundles (areas composed of nerve cell projections) in the temporal lobe, compared with healthy controls. However, certain abnormalities were only present in the brains of patients whose seizures persisted following surgery.

Using their newly-developed method, the researchers were able to predict the outcome of brain surgery with 84% sensitivity and 89% specificity.

Surgery is a treatment option for some people with drug-resistant temporal lobe epilepsy, but in around half of the cases, it fails to prevent seizures. Being able to predict the outcome of brain surgery could be invaluable in deciding which patient should undergo surgery.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

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Children Whose Mothers Have Rheumatoid Arthritis Are at Higher Risk of Developing Childhood Epilepsy

Mon, 11/21/2016 - 13:01

Children whose mothers have rheumatoid arthritis (RA) – an autoimmune disease where the immune system attacks the joints – have an increased risk of developing childhood epilepsy, according to a study published in the scientific journal Neurology. The risk is not increased if it is the child’s father who has RA, which suggests that it may be changes in the environment inside the uterus that play a role rather than genetics.

The first author of the study, Dr Ane Lilleore Rom, at Copenhagen University Hospital, said in a press release: “These results suggest that changes in the environment for the fetus may play a role in the development of epilepsy. We don’t know yet how this may work, but it could involve the production of maternal antibodies that could affect the unborn child.”

The team performed a nationwide study that included almost two million children born in Denmark between 1977 and 2008. They followed the children for an average of 16 years and identified those who developed epilepsy and those whose parents had RA.

The researchers then divided the children with epilepsy into four groups: those who developed the condition in early childhood (between 29 days and four years of age), those who developed it in late childhood (between 5 and 15 years of age), those who developed it in adolescence (on or after the age of 15), and those who developed it at any age until the end of the follow-up period, which was 31 December 2010.

In total 31,491 (1.6%) of the children followed developed epilepsy and 13,556 (0.7%) had a mother with RA. This included women with clinical RA (already diagnosed) and those with ‘preclinical’ RA (diagnosed after the birth). 

The results showed that children born to a mother with RA had a 34% and 27% increased chance of developing early and late childhood epilepsy, respectively, than children born to women without RA. The risk of developing epilepsy in adolescence or adulthood was not influenced by exposure to maternal RA.

Looking at children exposed to RA in the womb (clinical RA), the researchers found that they had up to 90% more risk of developing epilepsy in early childhood than children whose mothers did not have RA. In cases where a mother had pre-clinical RA, the child was shown to have a 26% greater chance than an unexposed child of developing epilepsy in early childhood.*

Paternal RA was not associated with a higher risk of epilepsy in the children at any age.

According to Dr Rom, the increased epilepsy risk posed by preclinical RA suggests an important role for RA itself (rather than RA treatments) in epilepsy development. However, she notes that the specific influence of RA treatments requires further investigation.

Over all, these results suggest that changes in the environment of the foetus caused by RA may play a role in the development of epilepsy. More work is needed to clarify the effect that RA has on the developing nervous system and the mechanism that associates it with epilepsy.

*The actual figures are low: 3% of children whose mothers had clinical RA and 2% of children whose mothers had preclinical RA at the time of birth developed epilepsy.

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Electrical Brain Stimulation to Treat Drug Resistant Epilepsy in Children

Mon, 11/21/2016 - 08:53

The findings of a small study, led by researchers at King’s College London, suggest that electrical stimulation of the brain may be a safe and effective treatment for children with drug-resistant epilepsy, although further research is required. The work is published in the European Journal of Paediatric Neurology.

Limited information exists about the effects of brain stimulation in children and, according to the authors, “Given the significant long-term effects of chronic childhood epilepsy on educational attainment, employment, marital status, and psychological health into adulthood, this study may offer the potential to significantly improve the long-term quality of life of children with refractory [or drug-resistant] epilepsy.”

The study involved eight children with drug-resistant epilepsy who were already undergoing detailed investigation of their condition.Three of the children received deep brain stimulation (DBS) whilst the other five received a newer treatment called subacute cortical stimulation (SCS).

DBS is used to treat a number of neurological conditions and requires electrodes to be implanted within the brain. The device is then programmed to emit electrical pulses either continuously or at certain intervals. SCS is slightly less invasive and involves a relatively short period of stimulation (20-161 hours in this case) to the brain surface, following a 24 hour ‘baseline’ video EEG recording. SCS can be used both to treat epilepsy and to identify areas in which seizures originate. These regions can then be targeted either surgically or with continuous electrical stimulation.

The effectiveness of DBS in reducing seizures was assessed by comparing the frequency of the children’s seizures before treatment and after a 6-36 month follow-up period. SCS was evaluated by counting the number of seizures and interictal discharges (characteristic brain activity that occurs between epileptic seizures) before (baseline), during and after treatment.

Amongst the children who received DBS, two showed more than a 60% improvement in their seizure frequency and severity. One, in fact, had more than a 90% reduction in seizures, but the stimulation parameters had to be changed during follow-up. The third child did not show any improvement with DBS.

In the SCS group, four showed more than a 50% improvement in seizure frequency and a greater than 75% decrease in interictal (between seizure) activity. Two of these four in fact became seizure free (one after removal of their electrodes and the other after an area stimulated with SCS had been surgically removed). One child did not show any improvement with SCS.

Electrical stimulation was well-tolerated by the children, although one who received DBS experienced a worsening of seizures and another a worsening of behaviour.

These results suggest that electrical brain stimulation may be effective in children with drug-resistant epilepsy, although this was only a small study and larger ones are required. The authors emphasise that care should be taken to adapt brain stimulation to the developing brain of children, and highlight the need for further research to find the most suitable and least disruptive stimulation parameters.

An interview with one of the patients who underwent the procedure and is now seizure free was published in the Daily Express.

Note: The data from this study was analysed and published as part of an ERUK-funded project led by Dr Antonio Valentin, which focuses on SCS as a treatment for people with epilepsy. You can read more about the project here.

Click here for more articles about other treatments for epilepsy.


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Epilepsy Surgery May Lead to Decline in word-finding as well as Memory

Sun, 11/20/2016 - 15:58

People who undergo epilepsy surgery should be counselled about a potential decline in their word-finding ability, according to a study published in the scientific journal, Neurology.

Before a person undergoes left temporal lobe surgery for drug-resistant epilepsy, their doctor will discuss with them the risk of subsequent memory problems. However, not much attention has been given to the effects of surgery on word-finding (also known as naming).

During the study, researchers at the University of Pittsburgh wanted to explore how changes in word-finding ability after surgery vary depending on the region of the brain that is operated on. To do this they looked back at records from 875 adults who underwent surgery (421 on the right side of the brain and 454 on the left side of the brain) for drug-resistant epilepsy.

Of the 875 subjects, 763 had temporal lobe surgery, 87 people had frontal lobe surgery and 25 people had surgery in the back of their brain. All completed an assessment called the Boston Naming Test, which is designed to measure a person’s ability to name objects from line drawings, before and after their surgery.

The findings showed that 41% of people who had left TLES experienced a decrease in word-finding ability, compared with 10-12% of people who had surgery of other areas on the left side of the brain. A decline in word-finding was rarely seen (only in 5%) amongst those who had surgery on the right side of the brain.

Looking at the data more closely, the researchers found that seventeen percent of people who underwent left TLES had what are considered to be substantial declines in word-finding. They also found that a decline in word-finding after left TLES was associated with a later age of epilepsy onset, an older age at the time surgery and higher word-finding ability prior surgery.

The authors have created a decision tree to assist clinicians in identifying those at a low, moderate or high risk of word-finding decline, and help them to counsel people about the risk of word-finding decline after left TLES.

“Development of risk models to predict naming outcome, akin to those that have been developed for memory, are needed to improve preoperative counselling for patients considering epilepsy surgery,” they note.

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New Approach Could Treat Infantile Spams More Effectively

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

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Scientists Identify New Mutation Causing Progressive Myoclonus Epilepsy

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

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New Method Could Pinpoint More Accurately Where Seizures Arise

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

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Analysis of Genetic Variations Could Help Develop New Therapies for Epilepsy

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

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New Antiepileptic Drug Candidate Discovered

Tue, 11/08/2016 - 14:26

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

Researchers at Elli Lilly and Co., in Indiana, have discovered a new compound that specifically targets neural circuits involved in epilepsy and could potentially be developed into an antiepileptic drug (AED). The findings are published in the leading scientific journal, Nature Medicine.

The compound, known as CERC-611, selectively blocks a protein associated with a receptor called AMPA found in the forebrain, an area involved in the generation of focal seizures. As the AMPA-associated protein is absent in most other parts of the brain, it is thought that blocking it will not cause side effects such as dizziness, lack of muscle coordination and falling (which are seen with other drugs that block the AMPA receptor directly).

Dr Michael Rogawski, a professor of neurology and pharmacology at the University of California, said:”Targeting these receptors may lead to improved antiseizure efficacy, safety and tolerability, and make a significant impact on treatment outcomes. No prior epilepsy treatment targets a subset of brain receptors involved in seizure generation in a regionally-selective fashion.”

The researchers tested the specificity of the compound in brain tissue obtained form an epilepsy patient. They then tested it in rodent models of epilepsy and found that it prevented multiple seizures without causing motor side effects.

Dr Uli Hacksell, CEO of Crecor, the company that is developing the potential drug said: “We believe CERC-611 has the potential to provide a true advancement in epilepsy therapy.”

The company hopes to file an investigational new drug application with the US Food and Drug Administration (FDA), and start a phase one clinical trial to test the compound, in 2017.

Author: Dr Özge Özkaya

Click here for more articles about other treatments for epilepsy.

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Taking Antidepressants in Pregnancy May Increase Child’s Risk of Epilepsy

Fri, 11/04/2016 - 12:23

According to a study published in the journal Pharmacoepidemiology and Drug Safety, children exposed to antidepressants in the womb have an increased risk of being diagnosed with epilepsy later on if their mothers are diagnosed with depression during pregnancy*. A child’s risk of epilepsy also appears to increase if its mother takes antidepressants 2-6 months before, but not during, pregnancy.

Interestingly, the findings suggest that if a women takes antidepressants during pregnancy, but does not receive a clinical diagnosis of depression during this time, their child’s risk of epilepsy does not increase.

The study, conducted at Aarhus University Hospital, in Denmark, identified 734,237 Danish children born between 1997 and 2008. The researchers used the Danish National Registers to collect information about their epilepsy diagnoses, and about their mothers’ use of antidepressants and diagnoses of depression.

The results showed that, of the 734,237 children, 12,438 (1.7%) were born to women who took antidepressants between 1 month prior to conception and delivery. Amongst these 12,438, 5829 (0.8%) were diagnosed with epilepsy an average of 6.7 years later.

The researchers calculated that the children exposed to antidepressants before birth had (overall) a 27% higher risk of epilepsy compared with the children who were not exposed to antidepressants.

They then separated the data for cases where the mother took antidepressants during pregnancy and received (1)/ did not receive (2) a clinical diagnosis of depression during pregnancy. They found that for (1) the children had a 71% increased risk of epilepsy compared with unexposed children, but that for (2) there was actually no increase in risk compared with the unexposed group.

Children of women who took antidepressants 2-6 months before pregnancy, but not during pregnancy, were found to have a 36% increased risk of epilepsy compared with unexposed children. However, these women had a number of characteristics that could, themselves, have influenced the baby’s epilepsy risk; e.g. they were more likely to be older, to have a history of epilepsy/psychiatric disorders and to take antiepileptic/antipsychotic drugs.

The authors acknowledge that this study has a number of limitations, and they recommend further research to a) verify their findings and b) differentiate the effects of antidepressant medication from depression itself, upon the risk of epilepsy.

*In this article, reference to the diagnosis of depression ‘during pregnancy’ also extends to a diagnosis in the six months prior to pregnancy.

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

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The Behaviour of Children with Epilepsy Could Predict Their Risk of Severe Psychiatric Conditions

Thu, 11/03/2016 - 08:39

The behaviour of children with epilepsy could help identify those at a greater risk of severe psychiatric conditions, according to a study published in the journal, Epilepsia.

This finding is important, because it means that children who are identified in this way can be given the necessary care and treatment so that chronic mental health problems (which may negatively influence quality of life and increase the risk of suicide) are not carried into adulthood.

During the study, researchers led by Dr Rochelle Caplan, at the University of California, recruited 328 children with epilepsy and divided them into two groups: a ‘younger’ group (aged 5-12) and an ‘older’ group (aged 13-18). They then asked the parents of the children to complete the Child Behavior Checklist (CBCL) questionnaire, which includes 113 items to assess children’s behaviour.

The team also conducted psychiatric interviews with the children and their parents, to try and identify or diagnose some of the children with a psychiatric disorder (e.g. depression, anxiety and attention deficit and hyperactivity disorder (ADHD)).

The results showed that seven characteristics on the CBCL – clinginess, cruelty/bullying, perfectionism, nervousness, poor schoolwork, inattentiveness and sulkiness – were helpful in identifying/diagnosing children in the younger group with multiple psychiatric conditions, but not those with a single psychiatric condition.

Similarly, amongst the older group of children, three traits on the CBCL – disobedience at school, loner behaviour and lying/cheating – were found to be useful in identifying/diagnosing those with multiple psychiatric conditions (but again, not those with a single condition).

The authors conclude that CBCL is a simple and accurate screening tool, which could easily be used to identify children with epilepsy who are at an increased risk of multiple psychiatric conditions and need to be referred to a psychiatrist.

People with epilepsy have a higher risk of suicide compared with the general population, and the risk significantly increases if one or more psychiatric conditions are also present.

Author: Dr Özge Özkaya

Click here for more news articles about epilepsy in children.


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New Approach Could Alter the Course of Epilepsy After Brain Injury

Wed, 11/02/2016 - 16:18

Removing granule cells (types of neuron) at a certain time point after an epilepsy-causing brain injury could have disease-modifying effects, according to a study published the Journal of Neuroscience.

Granule cells that are generated in the weeks before and after an epilepsy-causing brain injury can abnormally integrate into certain areas of the brain, mediating the development of temporal lobe epilepsy.

The authors, based in Cincinnati, write: “These findings support the long-standing hypothesis that newly generated … granule cells are pro-epileptogenic and contribute to the occurrence of seizures.”

For the study, the researchers induced status epilepticus in a rodent model using a chemical. Three days later they removed the granule cells from the animals’ brains that had been generated up to five weeks before the chemical ‘injury’, and they noticed a 50% reduction seizure frequency.

The scientists also noticed a 20% increase in seizure duration, which wasn’t expected. They explain that this paradoxical effect may reflect a disruption of the balancing mechanisms that normally act to reduce seizure duration when seizures occur frequently.

Previous studies had shown that inhibiting granule cell production before an epilepsy-causing brain insult could reduce the development of epilepsy. This new study provides proof-of-concept data demonstrating that granule cell removal therapy applied at a certain time point after injury can have disease-modifying effects in epilepsy.

Author: Dr Özge Özkaya

Click here for more articles about brain science including genetics.

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