Micro-gene protects brain from developing epilepsy

On December 16, 1997, hundreds of Japanese children were brought to hospital suffering from epilepsy-like seizures. They all had one thing in common: they had been watching an episode of the Pokemon TV show when their symptoms began. Doctors determined that their symptoms were triggered by five seconds of intensely bright flashing lights on the popular TV program. But why did the lights affect a few hundred children while thousands of other viewers were unharmed?

In new research published in the Proceedings of the National Academy of Sciences, a team of researchers headed by Prof. Hermona Soreq at the Hebrew University of Jerusalem sought to answer this question. Drawing on her previous research, Prof. Soreq, the Charlotte Slesinger Professor of Molecular Neuroscience at the Edmond and Lily Safra Center for Brain Sciences and the Alexander Silberman Institute of Life Sciences, hypothesized that healthy brains may be protected from epileptic seizures by rapidly produced molecules called short RNAs, or microRNAs (miRs). MicroRNAs are a recently-discovered class of non-coding RNAs that can prevent genes from expressing particular proteins.

To test this idea, Soreq and her colleagues at the Hebrew University developed a transgenic mouse producing unusually high amounts of one micro-RNA called miR-211, which the researchers predicted was involved. The levels of this molecule could be gradually lowered by administering the antibiotic Doxycycline, enabling tests of its potency to avoid epilepsy.

Working with colleagues at Ben-Gurion University of the Negev in Israel and Dalhousie University in Canada, they suppressed excess miR-211 production in the engineered mice to the levels found in normal brains. Within four days, this caused the mice to display electrically-recorded epilepsy and hypersensitivity to epilepsy-inducing compounds. “Dynamic changes in the amount of miR-211 in the forebrains of these mice shifted the threshold for spontaneous and pharmacologically induced seizures, alongside changes in the cholinergic pathway genes,” said Prof. Soreq.

These findings indicated that mir-211 plays a beneficial role in protecting the brain from epileptic seizures in the engineered mice.

Noting that miR-211 is known to be elevated in the brains of Alzheimer’s patients who are at high risk for epilepsy, the researchers suspect that in human brains as well, elevated miR-211 may act as a protective mechanism to reduce the risk of epileptic seizures.

“It is important to discover how only some people’s brains present a susceptibility to seizures, while others do not, even when subjected to these same stressors,” said Prof. Soreq. In searching for the physiological mechanisms that allow some people’s brains to avoid epilepsy, we found that increased levels of micro-RNA 211 could have a protective effect.”

According to the researchers, recognizing the importance of miR-211 could open new avenues for diagnosing and interfering with epilepsy. By understanding how miR-211 affects seizure thresholds, scientists could potentially develop therapeutics that lead to greater miR-211-production.

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Pinpointing where seizures are coming from, by looking between the seizures

A computational approach developed at Boston Children’s Hospital, described in the journal Neurosurgery, published online May 2, 2017, could enable more patients with epilepsy to benefit from surgery when medications do not help. The approach streamlines the seizure monitoring process required for surgical planning, making surgery a more feasible and less risky option for patients.

Currently, for some patients, pinpointing the diseased brain areas where their seizures originate requires invasive surgery to place grids of electrodes on the brain’s surface. This is followed by long-term electroencephalography (EEG) monitoring — typically for a week — while doctors wait for a seizure to happen. Then, patients must undergo a second brain operation to remove the diseased tissue.

The new technology, developed by Joseph Madsen, MD, Director of Epilepsy Surgery at Boston Children’s Hospital, and Eun-Hyoung Park, PhD, a computational biophysicist in the Department of Neurosurgery, could allow patients to be monitored in one short session, without the need to observe an actual seizure. Patients could then proceed directly to surgery, avoiding a second operation.

Effective use of this technology could cut the cost and risk by more than half by reducing the current two-stage procedure to one-stage, the researchers say.

“We know that the diseased brain network responsible for the seizures is there all along,” says Madsen. “So rather than wait for the patient to have a seizure, we set out to find patterns of interaction between various points in the brain that might predict where seizures would eventually start.”

Looking between the seizures

To identify the brain areas causing the seizures, Madsen and Park applied a special algorithm to analyze patients’ interictal EEG data — data captured between their seizures. They randomly selected 25 patients with hard-to-treat epilepsy who previously had long-term EEG monitoring at Boston Children’s, and analyzed data from the first 20 seizure-free minutes of the patients’ EEGs.

Their algorithm, known as Granger causality analysis, is based on a statistical approach developed Sir Clive Granger (for which he won the Nobel Prize in Economics in 2003). Madsen and Park adapted the Granger method, originally used for economic forecasting, to calculate the probability that activity at one brain location predicts subsequent activity at other brain locations strongly enough to be considered causative. Their analysis generated a map of the causal relations in each patient’s epileptogenic network, which Park and Madsen superimposed over images of the brain.

They then showed that the brain regions predicted to be causing seizures strongly correlated with actual causative regions on seizure EEGs — as read by ten board-certified epileptologists, usually many days later.

Madsen and Park have shown that their calculations can be done quickly enough to allow data obtained in the operating room to potentially influence surgical decision-making. They now are investigating how the Granger causality method can best augment readings of EEGs by trained neurophysiologists.

“We still need to validate and refine our approach before it can be used clinically,” notes Madsen. “But we are hopeful that these advanced computer applications can help us treat more children with epilepsy — with less risk and lower cost.”

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New analysis of brain network activity offers unique insight into epileptic seizures

Epilepsy is a complex neurological disorder that afflicts approximately 50 million people worldwide. Although this disease has been known to exist for centuries, the exact mechanism of its cardinal symptom, the epileptic seizure, remains poorly understood. In fact, roughly 25 percent of epileptic seizures can’t be controlled by any of the therapies available today.

Recent advances have led to a conceptualization of epilepsy as a “network disease” exhibiting connections within the brain. This large-scale epileptic network comprises various areas of the brain involved in normal brain activity during both seizure-free intervals and those involved in so-called pathophysiological activities such as seizures.

Little is known, however, about which specific areas of the brain contribute to a patient’s epileptic network or the roles these different areas play. As a group of researchers in Germany now reports this week in Chaos, from AIP Publishing, one way to get closer to the complex wiring of the human brain is by merging concepts from a timed-based synchronization theory and space-based network theory to construct functional brain networks.

Until now, the “seizure-generating area” of the brain — in which the earliest signs of seizure activity can be observed — was considered the most important of these regions. This finding was based on very limited data and it was unclear whether its importance changes with time.

With this new analytical approach, Professor Klaus Lehnertz, head of the Neurophysics Group in the Department of Epileptology at the University of Bonn, and his group explored the temporal and spatial variability of the importance of the brain’s different regions.

“New developments in network theory are providing powerful tools to construct so-called ‘functional networks’ from observations of brain activities such as the electroencephalogram (EEG), and helping to identify the important nodes and links within such networks,” Lehnertz said.

By associating network nodes with individually sampled brain regions, Lehnertz’s group can define a link between a pair of nodes by assessing the degree of synchrony between neuronal signals from all pairs of nodes; the higher the degree, the stronger the link.

“Applying these analysis concepts to multichannel long-term EEG recordings from 17 epilepsy patients with high temporal resolution allowed us to derive a sequence of functional brain networks spanning several days in duration,” said Christian Geier, a doctoral student working with Lehnertz. “For each network, we assess various aspects of the importance of individual brain regions with different centrality indices that were developed earlier for the social sciences. Then, we explore how the importance of network nodes fluctuates over time.”

The group’s work is particularly significant because they showed for the first time how the importance of individual nodes within functional brain networks fluctuates on timescales spanning tens of seconds up to days. They further showed that these fluctuations can be largely attributed to the normal, daily rhythms of a patient, yet only minimally attributed to phenomena directly related to the disease.

Perhaps their most intriguing finding is that in general, according to Geier, there isn’t a constant importance hierarchy between brain regions.

“Rather, they take turns in importance on various time scales,” Geier said. “And, depending on which aspect of importance is assessed, the seizure-generating area isn’t — as commonly believed — the most important node within a large-scale epileptic network.”

The understandings gained from this research are part of the necessary foundation for developing treatments related to the causes and symptoms of epilepsy.

“When different brain regions assume the highest importance within a functional brain network is the key to improving both prediction and control of epileptic seizures,” Lehnertz said. “In the long run, this improved understanding may enable the development of better treatment options for patients suffering from epilepsy. And understanding the importance of the nodes and links of functional brain networks may also be relevant for other neurological diseases.”

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Young adults with uncomplicated epilepsy fare as well as their siblings

A 15-year follow-up study of young adults with epilepsy found that those with uncomplicated epilepsy who were seizure-free for five years or more did as well as their siblings without epilepsy in measures of education, employment, family arrangements and driving status. Youth with complicated epilepsy had worse social outcomes and were less likely to drive, even if living without seizures. Results were published in the journal Epilepsia.

“So far there has been conflicting data on whether adults with uncomplicated childhood-onset epilepsy have worse social outcomes compared to people without epilepsy,” said senior author Anne T. Berg, PhD, from Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago. “Our study provides further evidence that children growing up with uncomplicated epilepsy who stay seizure-free have a favorable prognosis. However, if they do not achieve five-year seizure remission, young adults with uncomplicated epilepsy are less likely to drive and graduate high school. They also tend to be less productively engaged and not live independently. These results show how critically important it is to control seizures.”

In the study, patients with epilepsy were designated as having “uncomplicated” disease if they had no other neurologic impairments, no intellectual disability and no history of conditions such as meningitis or stroke that might have caused epilepsy. Researchers conducted structured interviews with 361 individuals with epilepsy and 173 siblings without epilepsy to compare their social outcomes. Participants were enrolled in the Connecticut Study of Epilepsy, a community-based study of individuals with childhood-onset epilepsy who were followed since diagnosis.

“The fact that teens with uncomplicated epilepsy who were seizure free finished high school at rates comparable to their siblings might be a reflection of the special education services many of them have received,” said Berg, who is also a Research Professor of Neurology at Northwestern University Feinberg School of Medicine. “These services can have tremendous impact.”

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Genetic basis for drug response in childhood absence epilepsy

Consider two children who have childhood absence epilepsy (CAE), the most common form of pediatric epilepsy. They both take the same drug — one child sees an improvement in their seizures, but the other does not. A new study in the Annals of Neurology identified the genes that may underlie this difference in treatment outcomes, suggesting there may be potential for using a precision medicine approach to help predict which drugs will be most effective to help children with CAE. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of the National Institutes of Health.

“A better understanding of genetic factors underlying a disease and the way that people respond to treatments may help healthcare providers select the best therapies for children with CAE,” said Vicky Whittemore, Ph.D., program director at NINDS.

A team led by Tracy A. Glauser, M.D., director of the Comprehensive Epilepsy Center at Cincinnati Children’s Hospital Medical Center and professor of pediatrics in the University of Cincinnati College of Medicine, investigated whether there may be a genetic basis for different responses to three drugs used for CAE (ethosuximide, valproic acid, and lamotrigine). The experiments focused on three genes that code for T-type calcium channels that are involved in CAE and one gene that codes for a transporter that shuttles the drugs out of the brain. T-type calcium channels help control the firing rate of brain cells.

The current study is part of a 32-center, randomized, controlled clinical trial that compared the effects of the three most commonly used drugs in 446 children who were recently diagnosed with CAE.

These results suggest knowledge of specific gene variants in children with CAE may help predict what drugs would work best for them. For example, two specific forms of the calcium channel genes appeared more often in children for whom ethosuximide did not work. Two other variants of the calcium channel genes were found in children for whom lamotrigine did work, but one form of the drug transporter gene was associated with a continuation of seizures.

Dr. Glauser and his colleagues conducted additional experiments using the form of calcium channel gene that was associated with ethosuximide failure in patients. When cells in a dish containing this calcium channel variant were treated with ethosuximide, the drug had less effect on inhibiting the channel, suggesting that the genetic form of calcium channel may determine patients’ response to the drug.

“We identified a potential link between genes and the children’s’ responses to certain treatments. We were also able to clearly show that one variant caused a change in how a key calcium channel responded to ethosuximide, confirming what was found in the clinical trial,” said Dr. Glauser.

CAE is characterized by absence seizures, in which children stare into space, unaware of their surroundings. The seizures are brief, often lasting less than 20 seconds, although children may have up to 100 of them per day. The disease usually begins in children who are between 4 and 8 years old. About one third of children with CAE also have problems with attention. Many children will stop experiencing absence seizures by the time they reach adolescence, although others go on to develop more severe seizures.

More research is needed to learn about the specific genes involved in CAE and the ways that they influence the effect of anti-epileptic drugs. In addition, researchers need to determine which factors, other than genetics, may play a role in treatment response.

 

Brain cell simulations show critical tipping point for swelling

When brain cells don’t get enough energy, caused by a stroke or trauma, they can start swelling rapidly. New mathematical models of this mechanism, developed by Koen Dijkstra of the University of Twente in The Netherlands, show a critical tipping point: at lower energy levels, there is no way back.

Brain cells that suffer from oxygen shortage, run the risk of swelling: they take up fluid that normally is in between the cells. This fluid overload is dangerous: even if the energy balance is restored, the damage can be permanent. Dijkstra looked into this mechanism in detail, using mathematical models describing the biophysics of a single cell.

No way back

His simulations show a tipping point in the energy levels: from that point on, rapid swelling occurs. At the moment a brain scan clearly shows areas with low energy levels, in most cases this point has been passed and there is no way back. Earlier intervention, however, makes sense. Dijkstra’s simulations show that a temporary blockage of the sodium channels – this is also done in epilepsy treatment – can have an effect.

Modelling energy in the brain is very complicated because of the many interactions between cells. Neurons that don’t get enough oxygen, however, first start ‘cutting down’ on communication. The models can therefore be simplified down to the cell level, for accurate simulation.

Epilepsy

Apart from these single cell models, Dijkstra also developed models including connections. He used these to simulate what happens in different parts of the brain, during epileptic seizure. Around a ‘core’ area where neurons fire at high frequencies, another large area with low frequency activity can be seen.

The new models, on various scales, give neurologists valuable new information on the underlying processes in the brain. This can also lead to new treatment strategies.

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Research team develops first-of-a-kind model to research post-malaria epilepsy

A first-of-its-kind mouse model could lead to an understanding of how cerebral malaria infection leads to the development of epilepsy in children, and to the prevention of seizures. The model — a way for researchers to simulate the effects of malaria in children by using mice — was developed in a collaboration between researchers at Penn State’s colleges of medicine, engineering, science and agriculture.

Cerebral malaria is prevalent in children under 5 in developing countries with high malaria incidence. This form of malaria has a high mortality rate and also leads to epilepsy in survivors, with the rate of epilepsy in countries with malaria infections being up to six times higher than those in industrialized countries. There are no treatments during the infection that have been shown to reduce the development of epilepsy and it is not yet understood how malaria leads to epilepsy.

“I work in Africa and people tell me about the shockingly high incidence of epilepsy in children and adults,” said lead investigator Steven Schiff, professor of neurosurgery, Brush Chair Professor of Engineering Science and Mechanics and Mechanical Engineering and director of the Penn State Center for Neural Engineering.

Children with cerebral malaria often enter a coma and die from complications, and up to 17 percent of survivors develop epilepsy. As Schiff looked into how to approach the problem, he realized that not much science is available on post-malaria epilepsy, one of the leading causes of epilepsy on the planet.

“A group of us at Penn State decided to put together our expertise and develop an animal model to test what would be the best therapies for children, so they don’t get epilepsy after malaria,” he said.

To effectively study post-malarial epilepsy, the animal model must be as close to the human version of the disease as possible. The model must contract malaria, be cured and then have the potential to develop epilepsy in the same way that a child does. To mirror the natural environment, the model needs to be generalizable to a variety of situations and not be restricted to a particular type of parasite or infected host.

Having a model will allow researchers to perform pre-clinical testing to design therapies to prevent epilepsy if given during treatment of malaria infection. The model can also be used to study how malaria and similar infectious diseases cause epilepsy — a mystery at present.

The researchers developed four different variations, giving scientists a suite of tools to study malaria. They reported their results in Scientific Reports.

“It’s a suite of models, not just one strain of malaria,” Schiff said. “This helps protect against a model having a version of the disease that is irrelevant to humans. It’s our best shot at developing treatments because there are four different parasite-mouse models to use.”

The model can also be used to study sudden unexplained death from epilepsy (SUDEP). In certain cases, epileptic seizures can lead to a person not breathing and their heart stopping. Until now, researchers did not have a way to study SUDEP. The model they developed also shows instances of SUDEP, giving scientists an important tool to learn what causes the sudden death. By understanding how epilepsy causes SUDEP, researchers can better develop preventative treatments.

This research was a collaboration between Penn State colleges and departments, bringing together experts in malaria and infectious disease, neurosciences, mechanical engineering, electrical engineering, experimental physics, biology, public health sciences and more. The first author on the paper, Paddy Ssentongo, is an African physician with deep knowledge of the complexities of malaria in Africa. The College of Engineering faculty helped develop the technologies needed to conduct the research. Schiff said that the research could not have happened without the team effort.

“This was indeed a collaborative project between requiring a range of very different and critical expertise — from the identification of a critical clinical and human high-impact health problem, to the biology and physiology of malaria parasites, to experimental and instrumentation design,” said Bruce Gluckman, associate professor of engineering science and mechanics and biomedical engineering. “Equally important was the extensive effort — the long hours — put in by the assembled team to pursue this project to its end.”

Research that crosses the borders of engineering, biology and medicine is often complex and complicated.

“This research is a testament to the interdisciplinary collaboration that flourishes at the Penn State Center for Neural Engineering, the Penn State Neuroscience Institute and Penn State University,” said Robert Harbaugh, director of Penn State Neuroscience Institute and chair, Department of Neurosurgery.

Judith Todd, chair, engineering science and mechanics said, “Led by Dr. Steven Schiff, Penn State’s Center for Neural Engineering is truly a model for interdisciplinary collaboration. The common goals of identifying the mechanisms and prevention of post-malarial epilepsy and SUDEP have unified faculty, physicians and students from the engineering sciences, medicine, biomedical engineering, the sciences, and public health, with our global colleagues in Uganda, to achieve results far beyond those of any one group alone. Inspired by a vision of preventing post-malarial epilepsy in millions of sufferers per year, Dr. Schiff is showing how breakthrough research is found when multiple disciplines intersect.”

Cannabis use in people with epilepsy revealed: Australian survey

People with epilepsy resort to cannabis products when antiepileptic drug side-effects are intolerable and epilepsy uncontrolled.

The first Australian nationwide survey on the experiences and opinions of medicinal cannabis use in people with epilepsy has revealed that 14 per cent of people with epilepsy have used cannabis products as a way to manage seizures.

The study showed that of those with a history of cannabis product use, 90 per cent of adults and 71 per cent of parents of children with epilepsy reported success in managing seizures after commencing using cannabis products.

Published in Epilepsy & Behaviour, the Epilepsy Action Australia study, in partnership with The Lambert Initiative at the University of Sydney, surveyed 976 respondents to examine cannabis use in people with epilepsy, reasons for use, and any perceived benefits self-reported by consumers (or their carers).

The survey revealed:

      * 15 per cent of adults with epilepsy and 13 per cent of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy.

* Across all respondents, the main reasons for trying cannabis products were to manage treatment-resistant epilepsy and to obtain a more favourable side-effect profile compared to standard antiepileptic drugs.

* The number of past antiepileptic drugs was a significant predictor of medicinal cannabis use in both adults and children with epilepsy.

“This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community,” said lead author Anastasia Suraev from The Lambert Initiative.

“Despite the limitations of a retrospective online survey, we cannot ignore that a significant proportion of adults and children with epilepsy are using cannabis-based products in Australia, and many are self-reporting considerable benefits to their condition.

“More systematic clinical studies are urgently needed to help us better understand the role of cannabinoids in epilepsy,” she said.

Co-author of the paper Carol Ireland, CEO of Epilepsy Action Australia, who was recently appointed to the Australian Government’s new Australian Advisory Council on the Medicinal Use of Cannabis, said: “Cannabis products are often what people turn to when they have been unable to control their epilepsy with conventional medication.”

“This highlights a growing need to educate consumers and health professionals on the use of cannabis by people with epilepsy, and to provide safe and timely access to cannabinoid medicine in order to lessen people’s reliance on illicit black market products” she said.

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Researchers find neurological link between religious experiences and epilepsy

A relationship between epilepsy and heightened religious experiences has been recognized since at least the 19th century. In a recent study, researchers from the University of Missouri found a neurological relationship exists between religiosity — a disposition for spiritual experience and religious activity — and epilepsy. This finding sheds light on the connection between religion and neuropsychological processes within the human brain.

“Past research has indicated that humans might have a distinctive neurological tendency toward being spiritually oriented,” said Brick Johnstone, a neuropsychologist and professor of health psychology. “This research supports the notion that the human propensity for religious or spiritual experiences may be neurologically based.”

“The end goal of this research is to understand if some type of connection exists between the brain and spiritual experience,” said Daniel Cohen, co-author and assistant professor of religious studies. “If a connection exists, what does it mean for humans and their relationship with religion?”

In their study, the researchers asked individuals with epilepsy to take two surveys. The first survey assessed behavior characteristics specifically associated with epilepsy. The second survey measured religious activities and spiritual orientations. The average participant was 39 years old, with the majority of participants of Caucasian descent; 32 percent identified as Protestant, 10 percent as Catholic, 5 percent as Buddhist, 5 percent as atheist, 38 percent as other, and 10 percent did not indicate any religious affiliation.

“We found a strong correlation between philosophical religious thoughts and epilepsy, but no correlation between emotional thinking and epilepsy,” said Greyson Holliday, co-author and MU undergraduate student studying psychology. “This study suggests that people may have natural neurological predispositions to think about religion but not in a way that is necessarily associated with emotion.”

Based on the findings, future research from Johnstone, Holliday and Cohen will examine religious experiences before and after brain surgery to help determine the specific nature of religiously oriented neuropsychological processes.

“Heightened religiosity and epilepsy: evidence for religious-specific neuropsychological processes,” recently was published in the journal Mental Health, Religion and Culture. Future research from Johnstone, Holliday and Cohen will examine religious experiences before and after brain surgery. Johnstone is a professor of health psychology in the MU School of Health Professions. The psychology and religious studies departments are in the MU College of Arts and Sciences.

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New mech­an­ism un­der­ly­ing epi­lepsy found

Prolonged epileptic seizures may cause serious problems that will continue for the rest of a patient’s life. As a result of a seizure, neural connections of the brain may be rewired in an incorrect way. This may result in seizures that are difficult to control with medication. Mechanisms underlying this phenomenon are not entirely known, which makes current therapies ineffective in some patients.

A study conducted with a rat epilepsy model at the Neuroscience Center of the University of Helsinki showed that a change in the function of gamma-aminobutyric acid (GABA), a main neurotransmitter in the brain, is an underlying cause in the creation of harmful neural connections.

After a prolonged convulsive seizure, instead of the usual inhibitory effect of the transmitter, GABA accelerates brain activity. This, in turn, creates new, harmful neural connections, says Research Director Claudio Rivera.

The accelerating effect of GABA was blocked for three days with a drug called bumetanide given soon after a seizure. Two months after the seizure, the number of harmful connections detected in the brain was significantly lower.

“Most importantly, the number of convulsive seizures diminished markedly,” says Claudio Rivera.

In this study, new indications may be found for bumetanide in the treatment of epilepsy. Bumetanide is a diuretic already in clinical use. Extensive clinical studies have already been conducted with bumetanide regarding its ability to reduce the amount of convulsions or prevent them entirely in the acute phase of seizures. This, however, is the first time that bumetanide has been found to have a long-term effect on the neural network structure of the brain.

Further study of the newly found mechanism may eventually help limit the exacerbation of epilepsy and prevent the onset of permanent epilepsy after an individual serious seizure. It may also be possible that a similar mechanism is responsible for the onset of epilepsy after a traumatic brain injury.

“The next step is to study bumetanide both by itself and in combination with other clinically used drugs. We want to find out the ways in which it may offer additional benefits in the treatment of epilepsy in combination with and even in place of currently used antiepileptic drugs,” says Claudio Rivera.

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MRI-guided laser surgery proving effective for some epilepsy patients

Melanie Vandyke wasn’t exactly eager to have brain surgery.

“I was very nervous, afraid it might make things worse,” Vandyke said of the relatively new procedure that was being recommended to her by epilepsy specialists at Wake Forest Baptist Medical Center.

Even though the operation had the potential to relieve the seizures she had been experiencing for nearly 15 years by eradicating a lesion on her right medial temporal lobe, Vandyke said she was “ready to not have it.”

But discussions with her neurologist, Dr. Cormac O’Donovan, and other members of the team at Wake Forest Baptist’s Comprehensive Epilepsy Center eventually convinced Vandyke that “they were really dedicated to helping me, not setting me back,” so she agreed to the procedure.

That was almost four years ago. She has been seizure-free ever since.

The operation Vandyke underwent is called MRI-guided laser ablation surgery. It is a minimally invasive procedure that is proving to be a very effective treatment for people with medial temporal lobe epilepsy (MTLE), a common form of drug-resistant epilepsy.

“It’s a game-changer,” said Dr. Gautam “Vinnie” Popli, chief of the section on epilepsy at Wake Forest Baptist. “This type of surgery allows us to precisely target areas of seizure without added risk, and there’s a very short recovery time.”

Approximately 3 million people in the United States have epilepsy, a neurological disease in which abnormal electrical discharges in the brain produce sudden episodes of altered or diminished consciousness, involuntary movements or convulsions. Collectively known as seizures, these episodes can severely limit an individual’s range of activities and lead to a number of serious physical and cognitive problems.

In roughly 60 percent of all cases, epileptic seizures can be controlled by medication. For other patients, especially those identified through brain imaging and other tests as having MTLE, surgery is generally the sole treatment option.

Until rather recently that meant a craniotomy — a conventional, day-long operation involving removing part of the patient’s skull, cutting through healthy brain matter and physically taking out the problem tissue, followed by a weeklong hospital stay and a prolonged recovery period.

The MRI-guided laser ablation method is far less invasive and time-consuming. A thin laser-tipped applicator inserted through a tiny hole in the skull delivers heat to the target area in the brain and destroys the unwanted tissue with the neurosurgeon viewing and being guided by real-time MRI images throughout the operation.

The entire process can be completed in about four hours, the incision in the scalp can be closed with just one stitch and most patients can go home the next day and resume their normal activities without restrictions.

“The patient is not excessively inconvenienced or placed at extraordinary risk to get relief from their seizures,” Popli said. “There’s much less collateral damage and fewer adverse effects than conventional surgery, and better outcomes.”

Neurosurgeons performed the first MRI-guided laser ablation surgery for epilepsy at Wake Forest Baptist in 2012, using a technology called Visualase. Since then they have employed the system more than 45 times on patients ranging in age from under 18 months to over 60 years. The success rate of these operations, in terms of either eliminating seizures or reducing their frequency or severity, depending on the individual patient’s condition, has been above 75 percent.

Popli called that a marked improvement over the 60 percent success rate of conventional epilepsy surgery, which, he noted, has not been performed at the medical center since it adopted the Visualase technology.

Melanie Vandyke was among the first dozen people to undergo laser epilepsy surgery at Wake Forest Baptist, and although she was discharged from the hospital the following day it took much longer than that for her to regard the operation as a success.

“It was probably five or six months after the surgery before I felt that it really had helped me,” said the 40-year-old resident of Buchanan County in southwestern Virginia. “Now I know that it was definitely worth it.”

These days Vandyke is working full-time, driving, traveling, socializing and doing just about everything else the epileptic seizures had kept her from doing for most of her adult life.

“When I was having the seizures I was a different person than I was before. I was isolated, and felt as if I was a burden on everyone, especially my parents,” Vandyke said. “But now I’ve regained my independence. I’m back to being the old me, and thankful for that.”

Anti-epilepsy medicine taken by pregnant women does not harm the child's overall health

Children whose mothers have taken anti-epilepsy medicine during pregnancy, do not visit the doctor more often than children who have not been exposed to this medicine in utero. This is the result of a new study from Aarhus.

Previous studies have shown that anti-epilepsy medicine may lead to congenital malformations in the fetus and that the use of anti-epilepsy medicine during pregnancy affects the development of the brain among the children. There is still a lack of knowledge in the area about the general health of children who are exposed to anti-epilepsy medicine in foetallife. But this new study is generally reassuring for women who need to take anti-epilepsy medicine during their pregnancy.

Being born to a mother who has taken anti-epilepsy medicine during pregnancy appears not to harm the child’s health. These are the findings of the first Danish study of the correlation between anti-epilepsy medicine and the general health of the child which has been carried out by the Research Unit for General Practice, Aarhus University and Aarhus University Hospital.

The results have just been published in the international scientific journal BMJ Open.

The researchers have looked into whether children who have been exposed to the mother’s anti-epilepsy medicine have contact with their general practitioner (GP) more often than other children — and there are no significant differences.

No reason til worry

“Our results are generally reassuring for women who need to take anti-epilepsy medicine during their pregnancy, including women with epilepsy,” says Anne Mette Lund Würtz, who is one of the researchers behind the project.

The difference in the number of contacts to the general practitioner between exposed and non-exposed children is only three per cent.

“The small difference we found in the number of contacts is primarily due to a difference in the number of telephone contacts and not to actual visits to the GP. At the same time, we cannot rule out that the difference in the number of contacts is caused by a small group of children who have more frequent contact with their GP because of illness,” explains Anne Mette Lund Würtz.

Of the 963,010 children born between 1997 and 2012, who were included in the survey, anti-epilepsy medicine was used in 4,478 of the pregnancies that were studied.

Anti-epilepsy medicine is also used for the treatment of other diseases such as migraine and bipolar disorder. The study shows that there were no differences relating to whether the women who used anti-epilepsy medicine during pregnancy were diagnosed with epilepsy or not.

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Significant epilepsy gene discovery in dogs

A collaborative study describes a novel myoclonic epilepsy syndrome in dogs for the first time and discovers its genetic cause at DIRAS1 gene. The affected dogs developed myoclonic seizures at young age — on average 6 months old — and seizures occur typically at rest. In some of the dogs the seizures could be triggered by light.

A novel candidate gene for human myoclonic epilepsies

The canine myoclonic epilepsy resembles human juvenile myoclonic syndrome in many aspects and the study has therefore meaningful implications for epilepsy research across species, says Professor Hannes Lohi from the canine gene research group, University of Helsinki.

Myoclonic epilepsies are one of the most common forms of epilepsy in human and the canine findings will not only help in diagnostics but also provide a novel entry point to understand the pathophysiology of the disease. The identified DIRAS1 gene may play a role in cholinergic transmission in the brain and provides a novel target for the development of epilepsy treatments.

We found a novel epilepsy gene, DIRAS1, which has not been linked to any neurological diseases before. The gene is poorly characterized so far, but some studies suggest that it may play a role in cholinergic neurotransmission, which could be a highly relevant pathway for the myoclonic epilepsies, explains MSc Sarviaho, co-first author of the study.

The genetic backgrounds of myoclonic epilepsies are not well known yet, and our study provides a new candidate gene, which helps to further characterize the underlying pathophysiology in future studies. This would be important for the development of new treatment scenarios, summarizes Professor Lohi, senior author of the study.

The affected dogs continue to serve as preclinical models when new treatment options are sought in ongoing studies.

A genetic test helps breeding and diagnostics

The results have implications for both veterinary diagnostics and breeding programs.

We screened over 600 Rhodesian Ridgebacks and about 1000 epileptic dogs in other breeds and found that the DIRAS1 defect was specific for juvenile myoclonic epilepsy in Rhodesian Ridgebacks so far, says MSc Sarviaho.

With the help of the genetic test, veterinarians can diagnose this specific epilepsy in their canine patients while breeders will be able to identify carriers and revise the breeding plans to avoid future affected puppies. About 15% of the dogs in the breed carry the DIRAS1 mutation and dogs all over Europe and beyond are affected, says DVM Franziska Wieländer from LMU Munich.

Dogs don’t need to be sedated anymore for epilepsy research

To characterize the clinical features, researchers utilized a novel wireless video-EEG recording method. This allows a real-time monitoring of the electrical events prior, during and after the seizure episode in unsedated dogs.

All the wires from electrodes are attached to a small portable device on the dog’s back that transmits the data straight to our computers. Thus, the dog is free to move around and we can record the EEG for long periods at one go, explains Professor Fiona James.

She has been previously developing the method at the University of Guelph, Ontario, Canada.

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Materials provided by University of Helsinki. Note: Content may be edited for style and length.