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Updated: 1 hour 27 min ago

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.

Background

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.

Findings

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.

Significance

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

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

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The Burden of Headaches in People With Epilepsy

Tue, 08/23/2016 - 15:07

The majority of people with epilepsy experience headaches, regardless of their sex or age, according to a study published in Seizure – European Journal of Epilepsy.

Headaches can have an extremely negative impact on quality of life. Their high prevalence in people with epilepsy (shown here) suggests they need to be recognised and managed.

The authors, based at Vilnius University, in Lithuania, write: “Clinicians should recognise headache as a common comorbidity of epilepsy, as it may influence antiepileptic drug choice, and may need specific treatment.”

For the study, the researchers recruited 280 people with epilepsy and asked them to complete a carefully-designed questionnaire. This requested information about various social and demographic factors, their health status, whether or not they experienced headaches and the type of headaches they suffered. An expert neurologist also interviewed the participants.

The results showed that more than 83% of subjects reported some type of headache. Almost 78% of these were inter-ictal (occurring in between seizures) and included: tension-type headaches (39%), migraines (31.7%), headaches caused by medication-overuse (7.8%) and persistent headache attributed to earlier traumatic head injury (16%).

To analyse the burden headaches had on people’s lives, the researchers used a recognised measure called the ‘Headache-Attributed Lost Time (HALT)’ index. They found that more than 40% of the headaches were grade 1 on the index, corresponding to minimal or infrequent impact; approximately 10% were grade 2, corresponding to mild or infrequent impact; almost 15% were grade 3, corresponding to moderate impact; and around 35% were grade 4, corresponding to severe impact.

When they compared their findings with those from an earlier study of the ‘general population’, the team discovered that the frequencies of most types of headache were similar. However, they found migraines to be more common in men with epilepsy than in the general population, and headaches caused by medication overuse to be more common in people with epilepsy than in the general population.

The authors conclude that headaches in epilepsy may need specific treatment and should receive more clinical attention.

Author: Dr Özge Özkaya

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Epilepsy surgery in childhood does not impact on language in the long term

Mon, 08/22/2016 - 03:32

Language skills remain largely unchanged following epilepsy surgery in childhood, according to new research published in the scientific journal Epilepsy and Behaviour.

There have been few investigations into brain function after epilepsy surgery in childhood, and these have largely focused on memory and intelligence rather than language.

During the current study, researchers at the Hospital for Sick Children, in Toronto, recruited 97 children who were being considered for epilepsy surgery. Sixty-one of the 97 subsequently underwent surgery.

Following recruitment, subjects underwent an initial (baseline) assessment of their language skills, using standardised tests of picture naming, vocabulary, letter fluency, understanding and intelligence.  An average of seven years later, the participants (61 of whom had undergone surgery, 36 of whom had not) underwent ‘follow-up’ language assessment with the same types of tests.

The researchers used the data to compare language between a range of population ‘categories’,  e.g. surgical vs non-surgical, pre-surgical vs post- surgical and seizure freedom vs seizure continuation.

The results showed that the language performance of people who underwent surgery and those who didn’t were similar at baseline and at follow-up. This suggests that surgery itself does not have a detrimental effect on language skills in the longer term.

The team found that children who had spent a larger proportion of their lives free of seizures at follow-up generally obtained higher scores in all language tasks. However, interestingly, this was only the case across comparison groups, because at an individual level no significant improvement in language was seen after seizures became controlled. This implies that the effects of uncontrolled seizures may prevent the improvement of language, even once seizures have stopped.

The researchers also found that people who were older at the onset of epilepsy, those who had a higher IQ, and those who attained higher scores at baseline also tended to achieve higher scores at follow-up in all language tasks. People who had a localised, one-sided seizure focus tended to do better in some languages tasks at follow-up.

Identifying the long-term effects of surgery in childhood on cognitive ability is important, because it provides information to doctors, families and people with epilepsy to allow them to make informed decisions about whether or not to pursue epilepsy surgery.

Author: Dr Özge Özkaya

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Grey Matter Loss Differs in Right and Left Temporal Lobe Epilepsy

Fri, 08/19/2016 - 05:22

In people with temporal lobe epilepsy (TLE), grey matter – the darker part of the brain that consists of densely packed nerve cell bodies – becomes reduced in particular areas. A recent study, published in the Journal of Clinical Neurology, has now shown that this decrease is more pronounced in people with right-sided TLE than in those with left-sided TLE.

The research also suggests that the extent of grey matter ‘volume’ reduction is linked to clinical characteristics such as the duration of the person’s condition and the frequency of their seizures.

During the study, the researchers, led by Dr Seung Bong Hong, at Sungkyunkwan University School in South Korea, recruited a total of 60 people with TLE, half left-sided and half right-sided, who had undergone successful epilepsy surgery. They also enrolled 30 age-matched, healthy controls for comparison. The researchers examined the brains of the subjects using magnetic resonance imaging (MRI) and made measurements of their grey matter volume.

The results showed a decrease in grey matter in four structures of the brain in people with left TLE compared with controls. Two of the four structures were only affected on one side of the brain, one was affected on both sides and the other was affected only on the right side.

In subjects with right-sided TLE, grey matter loss was found to affect more brain structures than in those with left-sided TLE, but a large proportion were affected on both sides of the brain.  This meant that grey matter reduction was more extensive in the right-sided TLE group overall.

In people with right-sided TLE, more extensive loss of grey matter was associated with a longer duration of epilepsy, a lower age of onset and more frequent seizures. In those with left-sided TLE, however, it was linked to a lower age of onset and a history of febrile seizures.

The results of this study, which correlate epilepsy pathology with clinical outcomes, suggest that the imaging methods used here may be useful in gaining a deeper understanding of the epileptic networks involved in TLE. This will hopefully lead to better management of the condition.

As the findings were in people who had responded well to epilepsy surgery for previous two years, this work could also contribute to the complex field of surgical assessment in the future.

Author: Dr Özge Özkaya

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‘Sirolimus’ for seizures in tuberous sclerosis complex needs further investigation

Thu, 08/18/2016 - 05:02

According to a recent study, published in the journal Neurology, sirolimus* add-on treatment does not significantly reduce seizure frequency in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy.

The authors state, however, that due the small size of the study, larger ones are needed to verify this finding.

TSC is a genetic condition that causes tumours to form in different organs, and very often the brain. Here they can cause difficult-to-treat (drug-resistant) seizures, developmental delay, intellectual disability and autism. Previous research has suggested that sirolimus might be effective in reducing seizure frequency in children with TSC and many doctors prescribe it off-label.

During the present study, a team at Erasmus MC, in Rotterdam, recruited 23 children with TSC and drug-resistant epilepsy, aged between one and 11 years. The children were then randomly assigned to one of two groups: 1) in which sirolimus was added to their existing (‘standard’) epilepsy treatment regime immediately, and 2) in which sirolimus was added after six months. The team examined seizure frequency in both groups during the sixth month of sirolimus treatment.

The scientists found that, although sirolimus add-on treatment decreased seizure frequency by an average of 40% compared with standard therapy, this reduction was not ‘statistically significant’ (meaning that the chance that the result could have occurred by chance was too high for it to be conclusive). No change was seen in the children’s cognitive performance (which was also tested) when sirolimus was added to standard therapy.

Adverse side effects associated with sirolimus were also a problem, with five children leaving the trial before it had ended because of these.

However, the number of participants in the study may have been too small for the ‘true’ effects of sirolimus to be detected, particularly as recruitment targets weren’t met. Larger studies are warranted, to properly assess the effects of sirolimus add-on treatment in this population.

*Sirolimus is an inhibitor of a signalling complex called ‘mammalian target of rapamycin complex 1’ (mTORC1). This signalling pathway plays a role in acquired forms of epilepsy and may also be involved in TSC.

Author: Dr Özge Özkaya

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