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Updated: 38 min 23 sec ago

Absence Seizures Could Be Prevented, Experimental Study Suggests

Tue, 12/20/2016 - 05:02

It may be possible to reduce, stop or even prevent absence seizures, the most common form of childhood epilepsy, according to a study published in the leading scientific journal Neuron.

Using an advanced technology called optogenetics and a rodent model, researchers at Stanford University School of Medicine showed that it is possible to trigger seizures by inducing synchronized, rhythmic activity within a particular structure in the brain called the thalamocortical tract. Importantly, they also demonstrated that disrupting this activity is sufficient to terminate the seizures.

For the study the team, led by Dr Jeanne Paz, inserted a gene that encodes for a light-sensitive cell-surface protein into a set of nerve cells situated in the thalamocortical tract of rat and mice models of absence seizures. This way, the scientists were able to prevent these cells from firing by shining a yellow light onto them.

In a press release, Dr John Huguenard,one of the authors of the study said:

“A single pulse of yellow light was enough to generate rhythmic firing activity throughout the cortex, in both hemispheres of the brain”.

The researchers then inserted a different kind of light sensitive protein into the brain of the rodents, which made  thalamocortical neurons more excitable when blue light was shone onto them. This disrupted their collective firing synchrony and seizure activity was blocked.

“Our study shows that the thalamus is a choke point whose involvement is essential to the maintenance of absence seizures,” said Dr Paz.

The authors suggested that treatments that are capable of guiding excitatory thalamocortical nerve cells from a tightly synchronized firing pattern (pro-seizure) to a more chaotic one could stop absence seizures.

Absence seizures, also called petit-mal seizures, are a form of epilepsy that is mostly seen in children aged between six to 15. They account for about 1 in 20 cases of epilepsy and are characterized by a sudden loss of consciousness that can last for up to 15 seconds, accompanied by a freezing in place.

Absence seizures are thought to be caused by patterns of rhythmic nerve-cell firing activity that originate in one area of the brain and then spread to the rest of the brain. A nerve circuitry called the thalamocortical tract is involved in this type of seizure.

Author: Dr Özge Özkaya

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Neural Stem Cells Found in Brain Tissue Removed During Epilepsy Surgery

Mon, 12/19/2016 - 09:56

Researchers at the University of Gothenburg, in Sweden, have found neural stem cells in epileptic brain tissue where they normally do not reside. This work is published in the scientific journal, Cerebral Cortex.

Neural stem cells are immature cells in the brain that are able to mature into neurons, astrocytes (non-neuronal support cells) or oligodendrocytes (producers of myelin, which is needed for effective neuronal signalling). They are normally found in the hippocampus, an area of the brain that is involved in learning and memory, and in the subventricular domains.

This finding helps improve scientists’ understanding of how the brain responds to epilepsy.

The team, led, Dr Milos Pekny, analysed the brain tissue obtained from people with drug-resistant epilepsy who underwent surgery. In eight out of 14 tissue samples (57%), they discovered neural stem cells in areas where these types of cells are not normally found.

According to the authors of the study, “This may point to a greater plasticity in the epileptic tissue, which to some extent can be compared to the brain tissue of a newborn.”

When the scientists cultured the brain samples, they saw that the cells that gave rise to neural stem cells were not astrocytes as was previously thought.

New neurons are formed in the brain of adults throughout life. These originate from neural stem cells that are found in the subventricular zone, hippocampus and striatum of the brain. Experiments conducted on mice have shown that in neurological conditions such as brain injury or stroke, astrocytes exhibit neural stem cell-like properties. This study shows that this is not the case in the human brain, at least not in epilepsy.

Author: Dr Özge Özkaya 

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Scientists Identify Network of Genes that Could Be Targeted to Treat Epilepsy

Wed, 12/14/2016 - 03:23

Researchers led by Professor Michael Johnson, at Imperial College London, have identified a network of genes that is associated with epilepsy.

The team believes that targeting the expression of this “epileptic network” of 320 genes, which they called M30, could be a new strategy to treat the condition.

In a news release, Professor Johnson said: “The discovery of this network of genes linked to epilepsy opens avenues for finding new treatments. This uses an approach that is entirely different to the past 100 years of anti-epilepsy drug development.”

The genes that are part of the network are widely expressed in the brain and code for proteins involved in the communications between brain cells.

When the network is impaired, due to genetic mutations or as a result of brain injury, epilepsy is triggered. According to the researchers, potential new treatments for epilepsy should focus on restoring the network.

The team analysed thousands of genes and mutations associated with epilepsy in people with and without the condition. They found that the genes in the M30 network were consistently dampened in the brains of people with epilepsy, as well as in mouse models of the condition. They then used a technique called network biology to determine how these genes interact with each other.

Finally, the researchers used a computer to ‘test’ 1.300 known drugs and predict which ones could increase the expression of these genes and restore the M30 network. They discovered that valproic acid, a drug already used to treat epilepsy, was one of the drugs that could restore the network. The team also identified a number of drugs such as withaferin A that were not formerly considered to be antiepileptic drugs.

“Until recently we have been looking for individual genes associated with diseases, which drug companies then target with treatments. However, we are increasingly aware that genes don’t work in isolation. Identifying groups of genes that work together, and then targeting these networks of genes, may lead to more effective treatments. Our proof of concept study suggests this network biology approach could help us identify new medications for epilepsy, and the methods can also be applied to other diseases,” the authors said.

The study was published in the scientific journal, Genome Biology.

Author: Dr Özge Özkaya

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Carbamazepine Safe and Effective in Newborn Babies with Epilepsy

Tue, 12/13/2016 - 08:52

A new study published in the scientific journal, Epilepsia, suggests that low-dose oral carbamazepine (CBZ – an antiepileptic drug) is safe and effective in newborn babies with benign familial neonatal epilepsy (BFNE); even in status epilepticus where the seizures occur very close together or last a long time. The authors therefore propose that CBZ should be the drug of choice in babies with this condition.

The researchers, led by Dr Maria Roberta Cilio, at the University of California, analysed 19 children with epilepsy from four different centres in the US and Italy. Sixteen children had a family history of newborn seizures and one child had a family history of infantile seizures. Seizures began at 2-5days of life for all children included in the study and happened several times a day. A total of four children developed status epilepticus.

Genetic analysis revealed that 14 of the children had a mutation in the KCNQ2 gene and two of them had a mutation in the KCNQ3 gene. These two genes encode for potassium channels and play an important role in the communication between neurons.

Twelve of the children were treated with up to four AEDs without satisfactory response before being switched to CBZ. These included phenobarbital, pyridoxine, levetiracetam, benzodiazepines and clonazepam. Seventeen of the children (88%) became seizure-free within hours of receiving CBZ or oxcarbazepine (OXC), another antiepileptic drug.

The earlier treatment with CBZ was started the shorter was the time spent in hospital. CBZ did not have any reported side effects.

The authors, who followed, the children for an average of 7.8 years wrote: “All patients had normal development and remain seizure-free”.

Author: Dr Özge Özkaya

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Cannabidiol May Reduce the Frequency and Severity of Epileptic Seizures

Mon, 12/12/2016 - 11:22

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

Treatment with cannabidiol (CBD) improves the frequency and severity of seizures in children and adults with epilepsy, according to research presented at the American Epilepsy Society annual meeting in Huston, Texas.

The findings are based on an open label,* expanded access clinical trial to test the effect of CBD in epilepsy.

The study involved 81 people (42 children and 39 adults) with drug-resistant epilepsy whose condition was confirmed by Video EEG. All participants had failed to respond to at least four antiepileptic drugs (AEDs) and experienced, on average, four seizures per month. The severity of the seizures was measured using the Chalfont Seizure Severity Scale.

The results showed that after one month of treatment with CBD, the frequency of seizures was reduced in the majority of participants. Two third of the subjects also experienced a reduction in the severity of their seizures of more than 50%. This reduction was maintained for up to six months.

In a press release, Senior Author Dr Jerzy Szaflarski, at the University of Alabama at Birmingham, said: “It is encouraging that both frequency and severity of seizures appear to improve in the majority of patients in our study, patients who have limited treatment options. Our research adds to the evidence that CBD may reduce frequency of seizures, but we also found that it appears to decrease the severity of seizures, which is a new finding”.

Dr Martina Bebin, also a senior author on the study, added: “These are encouraging results, but it is important to note that each patient may respond differently to CBD, and the dose for optimal seizures control varies. There appears to be an optimal CBD dose range where the patient achieves maximum benefit. If outside this CBD dosing range, the seizure frequency may not improve and may even increase.”

Author: Dr Özge Özkaya

* Open label clinical trials do not try to disguise the new drug or treatment, meaning that no standard treatment or placebo control is used. This creates bias, as both the patient and the physician are aware of which groups are receiving what type of treatment.

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Outcome of AED Therapy Similar in People with Epilepsy Related to Blood Vessel Malformation and People with General Epilepsy

Mon, 12/12/2016 - 09:07

The outcome of antiepileptic drug (AED) therapy in people with epilepsy related to blood vessel malformation in the brain is similar to the outcome of  those with ‘general’ epilepsy, according to a study published in the scientific journal Seizure.

According to the authors, failure to achieve seizure-freedom after the adequate trial of two AEDs seems an appropriate criterion for surgical referral of people with epilepsy related to blood vessel malformation. The researchers note, however, that in cases when blood vessel malformation is in the temporal lobe, earlier pre-surgical evaluation may be justifiable (once the first AED has failed).

The study, conducted by scientists in the Republic of Korea, included 34 participants with epilepsy related to blood vessel malformation who had not previously been treated with an AED. Subjects were followed up for at least two years and their response to AED treatment was monitored  .

Seizure remission for at least one year was achieved in 22 of the 34 people (64.7%). In 18 people (52.9%), this was following treatment with one AED, whilst in the remaining four it was following treatment with a second AED.

Nine people (26.5%) failed to respond to both AEDs and were diagnosed with drug-resistant epilepsy. Finally, three people (8.8%) had only one seizure in the past year and were classed as having “epilepsy with rare seizures”.

The location of the blood vessel malformation in the temporal lobe was the only factor that could predict poor seizure outcome. According to the authors, the location of the malformations and the probability that the epilepsy will be drug-resistant should be discussed with patients. The possibility of surgery should also be introduced.

This study provides important information about the long-term clinical outcome of medical treatment of epilepsy related to blood vessel malformation.

Author: Dr Özge Özkaya

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Factors Contributing to Anxiety and Depression One Year After Being Diagnosed with Epilepsy

Thu, 12/08/2016 - 08:52

Lack of social support is a risk factor for developing anxiety and depression one year after being diagnosed with epilepsy, according to results presented at the American Epilepsy Society’s annual meeting in Houston, Texas.

The findings also suggest that epilepsy-related factors such as the number of antiepileptic drugs (AEDs) a person is prescribed and seizure recurrence also significantly contribute to depression one year after diagnosis.

For the study, the researchers enrolled 153 people who were newly diagnosed with epilepsy. They measured the participants’ level of anxiety and depression at the time they were diagnosed with epilepsy and one year later, using a method called the Hospital Anxiety Depression Scale (HADS). They also collected information about the participants such as their level of social support, stigma, marital status, education, and employment status.

The results showed that 28% of participants experienced anxiety and 36% experienced depression one year after being diagnosed with epilepsy. The factors contributing to anxiety one year after diagnosis were the level of anxiety at the time of diagnosis and a lack of social support. For depression, the factors included the number of antiepileptic drugs prescribed, seizure recurrence, the level of depression at the time of diagnosis and a lack of social support. The authors did not find any significant correlations between the level of anxiety and depression and marriage, education or employment status.

Anxiety and depression are common in people with epilepsy. They can develop as a side effect of AEDs as well as being part of epilepsy itself. Identifying factors contributing to the development of anxiety and depression can help doctors better diagnose and treat these conditions.

Author: Dr Özge Özkaya

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Infantile Spasms are Being Diagnosed Late

Thu, 12/08/2016 - 04:39

There is a substantial delay in diagnosing and treating infantile spasms in children with epilepsy, according to a study presented at the annual meeting of the American Epilepsy Society, in Huston, Texas.

This may be due to lack of awareness of infantile spasms amongst healthcare professionals, and it could have “catastrophic“ consequences.

According to the researchers, “There is a desperate need for effective interventions to increase basic familiarity with infantile spasms among healthcare providers.”

For the study, the team led by Dr Shaun Hussain, at the University of California, surveyed the parents of 100 children with past or current infantile spasms.

They found that only 29% of the children were seen by an effective provider within one week of the onset of the spasms. The median time to be seen was 24.5 days.

Many parents reported that their suspicions that “something was wrong” with their child were often disregarded by paediatricians, emergency room physicians and, in some cases, even neurologists. Many parents reported that they diagnosed their children themselves using the internet and referred them to an effective provider themselves.

Factors such as the family’s race, ethnicity, religion, household income, education level, type of healthcare insurance, and distance of home to healthcare centre were not associated with the timing of first effective care provision.

In a press release, Dr Amy Brooks-Kayal, at Children’s Hospital Colorado and University of Colorado, who was not involved in the study said: “If parents are worried, they should request to see a pediatric neurologist for a video EEG and ask that their primary care provider facilitate an urgent appointment so that the child can be seen quickly.”

Infantile spasms are different from other types of seizures in that they last a short period of time (about a second). They are therefore difficult to notice and diagnose. However, a delay in diagnosis and treatment can cause substantial reduction in long-term developmental outcomes, including autism, lifelong epilepsy or cognitive disability.

Author: Dr Özge Özkaya

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Siblings of Children with Epilepsy Experience both Positive and Negative Feelings

Wed, 12/07/2016 - 08:52

Having a sibling with epilepsy affects children both positively and negatively, according to a study presented at the annual meeting of the American Society of Epilepsy in Huston, Texas.

In a press release, Study Lead Dr Barbara Kroner, at RTI International, said: “We found very few disapproving feelings among siblings toward their brothers and sisters with epilepsy. The negative feelings they had were more internal, showing they were sad for or worried about them.”

For the study, which has not yet been published in a peer-reviewed journal, the researchers recruited 69 children with epilepsy who had an unaffected sibling who was at least four years old. They asked the caregivers of the children with epilepsy to complete a survey about their child’s condition and its impact on the family.

The results showed that children who had witnessed their sibling have a seizure (around 61%) were more likely to worry about seizures, think that their sibling was suffering or feeling pain from a seizure, and be proud and protective of their sibling. Having witnessed a seizure was also associated with a negative school performance.

Siblings who worried about seizures (almost half) were also significantly more likely to think their sibling felt pain during a seizure, have their academic performance impacted by epilepsy, and be protective of their sibling. In addition, they were more likely to feel sad.

A little more than 10% of siblings felt angry, less than 3% felt embarrassed, 7.2% wanted to keep epilepsy a secret, and 13% complained about a lack of attention from their parents.

According to the authors, siblings might benefit from education about seizures to reduce negative feelings and impact on school performance. “It’s important to help siblings understand what is happening during a seizure and how the child feels, which will help relieve some of that anxiety,” Dr Kroner said.

Author: Dr Özge Özkaya

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New Study May help Determine Who Could and Who Shouldn’t Drive with Epilepsy

Tue, 12/06/2016 - 04:25

The results of a new study, presented at the annual meeting of the American Epilepsy Society, in Houston, Texas, could help predict which individuals with epilepsy should not be driving and which ones could be driving safely.

Study Lead Dr Hal Blumenfeld, at Yale University, commented: “We want to unearth more detail, to learn if there are people with epilepsy who are driving who shouldn’t be, as well those who aren’t driving who can safely drive”.

For the study, the team conducted an experiment where they have asked 16 people with epilepsy to use a driving simulator for between one and 10 hours.

The results showed that the participants experienced a total of 20 seizures, of which seven resulted in “crashes” in the simulator.

The researchers divided the participants into two groups – those who had a “crash” and those who didn’t – and found that seizures lasted an average of 75 seconds in the first group and 30 seconds in the second group.

The researchers concluded that the longer the seizures were, the more likely they were to cause a “crash.”

“Our goal is to identify if certain types of seizures, coming from a specific part of the brain or causing a particular brain wave pattern, are more likely to lead to a crash,” said Dr Blumenfeld. “That information could then be used by doctors to objectively determine who can safely drive and who should not,” he added.

Approximately two third of people with epilepsy use antiepileptic drugs (AEDs) to keep their seizures under control and can drive. However, for about a third of people with epilepsy, AEDs are not able to control seizures. These people often keep a diary and record the incidence and duration of their seizures, which doctors then use to decide whether or not it is safe for them to drive. However this is a highly subjective way of determining who should and shouldn’t drive.

Being able to objectively determine which individuals should not be driving and which ones could safely be driving would have direct implications for the lives of people with epilepsy.

Author: Dr Özge Özkaya

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Reducing Calorie Intake May Reduce Epileptic Seizures

Mon, 12/05/2016 - 04:15

Reducing calorie intake could reduce seizures and be beneficial for people with epilepsy, according to a study published in the leading scientific journal, Neuron.

It has been known for several years that fasting can offer health benefits and expand life span, but scientists at the Buck Institute for Research on Aging, in the US, together with colleagues from Canada, offer for the first time an explanation as to how reducing calorie intake may be beneficial for the nervous system.

Professor Pejmun Haghighi, the senior author of the study, said in a press release: “Our findings suggest that one of the reasons that fasting is beneficial is that it gives the nervous system a break.”

Using fruit fly larvae as a model, the team showed that acute fasting, or transient removal of food lowers synaptic activity at the neuromuscular junction, which is where the neurons come into contact with muscle cells to control their contraction. According to the authors, the neuromuscular junction is representative of the rest of the nervous system with (respect to synaptic activity).

Until this study, nobody had examined how fasting affects synaptic activity (the release of signalling molecules called neurotransmitters between neurons or between neurons and muscle cells). What was known, however, was that a protein called TOR is able to increase synaptic activity. TOR is better known for increasing cell metabolism by blocking the action of another protein called 4E-BP (a metabolic inhibitor).

In the present study, using genetic, electrophysiological and imaging techniques, the researchers showed that the same interaction between TOR and 4E-BP also happens at the synapse when food is plenty. However, when food is unavailable, another protein called FOXO is activated. FOXO activates the expression of 4E-BP, which means that there is not enough TOR to silence 4E-BP and the balance is tilted in favour of reduced synaptic activity.

“We might have some real insight into the advantages of dampening of synaptic activity that is caused by fasting,” said Prof.Haghighi, “for example, how fasting can be beneficial for epileptic patients, who can experience reduced seizures when restricting calories”.

Author: Dr Özge Özkaya

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