A new study published in the leading scientific journal Scientific Reports describes how cellular abnormalities caused by defects in a gene called GRIN2A may lead to epilepsy. Understanding the exact mechanism of how seizures develop at the cellular level could help scientists design better treatments against them in the future.
It was already known that mutations in the GRIN2A gene are associated with different types of childhood epilepsies. However the exact effect of the mutations on brain cells was not well understood.
In the present study, researchers led by Dr Daniel Ursu, at Eli Lilly Research Centre in Windlesham, Surrey showed that mutations in the GRIN2A gene lead to the GRIN2A protein being trapped inside nerve cells. The GRIN2A protein is normally found on the cell surface at the junctions between two nerve cells. There, it functions as a “channel” allowing the passage of electrical signals form one nerve cell to the other.
The researchers think that in the absence of GRIN2A protein, or if the GRIN2A protein does not function properly, the passage of electrical activity is affected, increasing the risk of epilepsy.
Importantly, the team showed that it was possible to restore the activity of the GRIN2A protein using a chemical compound in cells carrying the same mutations in the GRIN2A gene as in people with epilepsy. This is an exciting finding as it suggests that it may also be possible to restore the function of the GRIN2A in patients, offering a potentially treatment against seizures.
“This study is important as it shows that mutations in GRIN2A cause the protein produced to malfunction in different ways, leading to epilepsy,” said the first author of the study, Dr Laura Addis in a press release. “By understanding exactly what is going wrong in children with defects in GRIN2A, we can now try to work out what medicines target the pathways in the nerve cells that aren’t working properly”.
Professor Deb Pal at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London and a co-author of the study added: “Personalised medicine is the future of epilepsy treatment and will involve prescribing treatments based on the specific effects of a patient’s genetic defect”. He said that scientists need to develop methods to screen different medicines to see if they can restore the function of the defective GRIN2A protein. “As the mutations cause the protein to malfunction in different ways, we will need to work out strategies for the different types of effect,” he explained. “Some medicines will need to be able to get the protein to the cell surface, whereas others will need to make the protein work more, or less effectively, depending on the type of mutation.”
Author: Dr Özge Özkaya
A consensus panel of epilepsy specialists, experts in Dravet syndrome, and parents of children with Dravet syndrome came together to develop a set of recommendations for the better diagnosis and management of the condition. The recommendations were published in the journal Pediatric Neurology.
“We were able to identify areas where there was strong consensus that we hope will (1) inform health care providers on optimal diagnosis and management of patients with Dravet syndrome, (2) support reimbursement from insurance companies for genetic testing and Dravet syndrome-specific therapies, and (3) improve quality of life for patients with Dravet syndrome and their families by avoidance of unnecessary testing and provision of an early accurate diagnosis allowing optimal selection of therapeutic strategies,” the authors wrote.
The panel consisted of 13 physicians and five family members who had an enhanced experience and understanding of the condition through the active roles they were playing in Dravet syndrome associations. Three rounds of online questionnaires were conducted to identify areas of consensus and contention about the diagnosis and management of Dravet syndrome.
Strong consensus was reached among panelists in the following areas: typical clinical presentation of Dravet syndrome, range of EEG and MRI findings, need for genetic testing, critical information that should be conveyed to families at the time of diagnosis, priorities for seizure control, factors triggering seizures and recommendations to avoid these, first- and second-line therapies for seizures, requirement and indications for rescue therapy, specific recommendations for screening for other diseases that may co-occur at the same time as Dravet syndrome, and the need for family support.
Consensus was not as strong regarding later therapies, such as vagus nerve stimulation and surgery, and for specific therapies of associated diseases.
Apart from the initial treatment with drugs called benzodiazepines and the use of valproate, no consensus was reached on the best way to manage convulsive status epilepticus in a hospital setting.
Dravet syndrome is a type of childhood epilepsy affecting around one in 40,000 to one in 20.000 children. It is characterised by prolonged seizures that may require emergency intervention. It is usually managed with antiepileptic drugs (AEDs) but these may not be able to suppress seizures completely.
Author: Dr Özge Özkaya
What is Dravet Syndrome?
Link Between Epilepsy and Multiple Sclerosis Uncovered, Could Help Scientists Develop New Treatments for Both Conditions
Researchers at the University of California uncovered a potential new link between epilepsy and multiple sclerosis (MS), an auto-immune disease where the immune system attacks the myelin sheath that covers nerve fibres. This new finding could lead to potential new treatments against epilepsy as well as MS.
The study that was published in the journal Neuroscience, showed that people with MS were three to six times more likely to develop epilepsy than the general population. When nerve cells loose their myelin, they are not able to function properly. When this happens in a subset of nerve cells called parvalbumin interneurons, whose role is to prevent hyperactivity, seizures occur.
To test whether it is really the loss of myelin that cause seizures in MS, researchers led by Dr Seema Tiwari-Woodruff fed mice a compound called cuprizone, which is known to damage the myelin-producing cells in the nervous system. They saw that after nine weeks, the mice started having seizures. “Without myelin, axons are vulnerable,” explained Dr Tiwari-Woodruff in a press release. “In both MS and our mouse model, parvalbumin interneurons are more vulnerable and likely to die. This causes the inhibition to be removed and induce seizures.”
When the researchers stopped feeding cuprizone to the mice, the nerve fibres started becoming myelinated again. However it is not know if this decreases seizures.
“Does remyelination affect seizure activity? Could we accelerate the remyelination with drugs? …We are interested in addressing these questions,” Dr Tiwari-Woodruff said. She added that they now have a mouse model with which they can work to test and suggest some therapeutic cures. Such drugs aimed at reducing neuronal hyperactivity could reduce the incidence of seizures and could help both epilepsy and MS patients.
Author: Dr Özge Özkaya
What is Myelin?
Myelin is a fatty white substance that surrounds the axon of some nerve cells, forming an electrically insulating layer. It is essential for the proper functioning of the nervous system. It is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination or myelinogenesis.
The International League Against Epilepsy (ILAE) recently updated the system used to classify different types of epilepsy. It is hoped that the new system will pave the way to better research, diagnosis, and treatments in epilepsy.
In a press release, Professor Ingrid Scheffer, a paediatric nephrologist and professor at The University of Melbourne said: “The new classification will help clinicians to think more deeply about each patient so that they can improve their care with optimised treatment and understanding of their disease. It will also be used for research into the epilepsies and to frame collaborative approaches that will lead to greater insights into this important group of diseases.”
It is important to have a thorough classification system as “applying the right therapy often depends upon knowing the precise type of seizure,” according to Dr Robert Fisher, the director of the Stanford Epilepsy Center. The last classification related to epilepsy was published in the 1980s and failed to capture many types of seizures.
According to Dr Fisher, the new classification system may also help patients and families better understand the name of their seizures. “[F]or example, a ‘focal aware seizure’ is more understandable than is the old term ‘simple partial seizure’,” he said.
The 2017 ILAE seizure classification includes the whole clinical picture of epilepsy underlining the potential causes of the condition. Groupings the different types of seizures in this way could lead to the advancement of research and the development of potential new treatments.
Three research articles outlining the changes in the new classification and providing guidance on how to use it in clinical practice have been published back to back in the scientific journal Epilepsia. They are titled “Operational Classification of Seizure Types by the International League Against Epilepsy”, “ILAE classification of the epilepsies. Position paper of the ILAE Commission for Classification and Terminology”, and “Instruction Manual for the ILAE 2017 Operational Classification of Seizure Types”.
Author: Dr Özge Özkaya
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Brain connectivity in people with epilepsy and those without are different showed a study published in the journal Human Brain Mapping. According to the researchers this finding could lead to a better understanding of epilepsy and help scientists develop new therapies in the future.
The team led by Professor Marina Vannucci, Noah Harding Professor and Chair of Statistics at Rice University in Houston, Texas found that while in people without epilepsy there seem to be structures that plan and then activate movement in one direction, people with epilepsy harbour abnormal bidirectional interactions between brain structures.
The team used a novel statistical approach to analyse the brain of people with and without epilepsy to reveal how different areas of the brain interact with each other. First they conducted functional magnetic resonance imaging (fMRI), which produces maps of the brain based on blood flow and highlights areas of high activity. Then, they conducted standard MRI to obtain information about detailed structural connections in the brain thought to be necessary for effective communication. Combining both data sets, statisticians modelled links between structures in the brains of people with epilepsy and compared these with each other and with the brains of people without epilepsy.
In a press release Prof Vannucci said: ”The statistical approach has advantages. One is that we use data from multiple subjects. Rather than estimating networks from individuals and then averaging them, we estimate networks at the epileptic and control group levels by using all the data at once. Then we can look for differences between the two networks and across time. We take into account what we call heterogeneity, accounting for variations between one individual and another. It allows us to get better estimations. At the end of the day we have fewer false positives, so the network we are able to construct is more reliable. Ultimately, we want to understand what is different about that connectivity and the effect of epilepsy on the connections across the whole brain”.
Results obtained from fMRI data confirmed the presence of several previously known connections but also revealed novel connections in the brain of people with epilepsy, including two-way communications between different areas of the brain.
The first author of the study, Sharon Chiang added: ”Currently, surgical resection is the treatment of choice for some patients with medically refractory epilepsy. However, if drivers in these networks can be identified and possibly stimulated, rather than completely resected, this may potentially allow a more targeted treatment.”
Researchers at the University of Helsinki showed that a change in the function of GABA, the main neurotransmitter in the brain, can cause the formation of incorrect connections between brain cells. These connections may cause epileptic seizures that are difficult to control with drugs.
“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,” explained in a press release, Dr Claudio Rivera, the senior author of the study that was published in the scientific journal Annals of Neurology.
According to the authors, the same harmful rewiring could be happening after a traumatic brain injury. This would explain why brain injury sometimes results in the onset of epilepsy.
When the researchers blocked the activity of GABA with a drug called bumetanide soon after a seizure in a rat model, they saw that the number of convulsive seizures were decreased. Moreover, they saw that the number of harmful connections in the brain was significantly reduced, two months after the seizure.
Bumetanide is a diuretic, or a drug that increases the passing of urine, which is already approved to be used in patients. Clinical research has shown that butenamide is also able to reduce or prevent convulsions. However, this is the first study showing that bumetanide has a long-term effect on the structure of the brain.
“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,” Dr Rivera concluded.
Author: Dr Özge Özkaya
A new small molecule that can be taken orally, called ADX71149, could have antiepileptic effects on its own or when used in combination with the widely available anti-seizure drug levetiracetam according to experiments conducted in a mouse model of epilepsy, the results of which were published in the scientific journal Epilepsia.
Robert Lütjens, Head of Discovery of Addex Therapeutics that co-developed ADX71149, said in a press release: “These studies performed by our collaborator Janssen Pharmaceuticals, Inc. suggest there is a positive pharmacodynamic relationship or strong synergistic effect for ADX71149 and levetiracetam when given in combination”. He added that if this effect can be translated into the clinic, it could offer a potential treatment option for people with epilepsy.
ADX71149 is a molecule that binds to a receptor called metabotropic glutamate receptor 2 or mGluR2, which is involved in most aspects of normal brain function. In order to test the efficacy of the compound, researchers led Professor Steve White at the University of Utah used an approach called the 6 Hz psychomotor seizure test. The test assesses the ability of new compounds to block a psychomotor seizure, which is induced by long-duration, low frequency (6 Hz) stimulation, a model of therapy-resistant complex partial seizures.
The results showed that ADX71149 is able to reduce seizures on its own and in combination with LEV. Importantly, the use of ADX71149 enables the reduction of the dose of levetiracetam necessary to obtain a full response. This is important because high doses of levetiracetam are associated with adverse side effects, such as aggression, nervousness, anxiety, somnolence, and fatigue, which limits its use.
When scientists used a fixed dose of ADX71149, they saw that the effect of levetiracetam was increased almost 35 fold. When they kept the dose of levetiracetam constant and used different doses of ADX71149, they found that the efficacy of ADX71149 was increased 14 fold. These results suggest that ADX71149 and levetiracetam increase each others efficacy and a combination of the two compounds could potentially be a therapeutic option for people with drug-resistant epilepsy.
“Treatment-resistant epilepsy remains a high unmet medical need, with new avenues of treatment urgently needed,” said Tim Dyer, the chief executive officer of Addex Therapeutics. “We are continuing to explore with Janssen how best to move ADX71149 into a Phase 2a proof of concept study,”
Author: Dr Özge Özkaya
“I would like to introduce myself as the newly appointed Chief Executive of Epilepsy Research UK. It is a real honour to have been given the opportunity to lead a charity that my family and I had already been supporting and I am looking forward to working with all of you, the incredibly hard working staff here, and the Board of Trustees to further the ambitions of the charity.
Without you we would not be able to fund the valuable research that we all know is needed. Your activity and fundraising is the lifeblood of the charity and after 25 successful years, we are keen to get your opinions on how the charity should now develop into the future.
We are setting ambitious targets. £1m into research by the end of 2018 and £2m by the end of 2020. With your support we can achieve these targets.
We also want to make more people aware of the importance of epilepsy research and the impact that it can have on this potentially debilitating condition. Research not only improves the life of people right now, but will also improve the lives of the many people who will develop epilepsy in the future. We believe that research is essential if we are going to find a cure, new treatments, or greater understanding of the condition that may lead to those things. At Epilepsy Research UK we aim to provide the funding for the research that will help change lives. This is something we can all do together.
Over the next couple of months I am keen to speak to as many people as possible about how you think we can realise our ambition. I would like to know what more we could do to help your fundraising, things you think we should focus on and even, maybe things that you do not think we should do.
I aim to speak to supporters, researchers and anyone else with an interest in epilepsy research and I want people to be honest about what we are doing well and what we are not doing so well. I have put aside time to speak to people directly and you can click here to book me to call you at your convenience for a longer discussion.
Over the past 25 years in our various guises as the British Epilepsy Research Foundation, the Epilepsy Research Foundation, the Fund for Epilepsy and now as Epilepsy Research UK, we have raised millions of pounds for epilepsy research. I am determined to work with you to continue that proud tradition.”
Mike Rich, Chief Executive, Epilepsy Research UK
March contains much good news. Spring starts to break, for the more somnolent of us it is National Bed month and it is also National Free Wills month. This is an ideal time to tackle one of those things that many of us put off, and off, and off. Due to our membership of the Free Wills Network it is possible for you to get a simple Will written, or your existing Will changed, by a local solicitor at no cost to you.
There is absolutely no obligation on you to leave a gift to Epilepsy Research UK in your Will but, obviously, we hope that you do as gifts in Wills are a major source of our research funding every year.
It is a very simple process. Call us on 020 8747 5024, or email us your name and address with reply code ‘Free Wills’, and we will arrange for the National Free Wills Network to send you the names and addresses of at least two local firms of solicitors taking part in the scheme. The solicitor will then draw up your Will and you won’t have to pay the bill.
So, this March, forget National Bed Month and do something you may well have been putting off. Exercise your free Will.
This is a limited offer without any obligation on those who take up the offer to include a bequest to Epilepsy Research UK.
Children whose mothers used antiepileptic drugs (AEDs) while pregnant are not more likely to visit their GP during their childhood, according to a population-based study by Danish scientists.
It is important to note that the study only analyzed the frequency of primary healthcare visits and did not take into account complications such as malformations at birth and neurological and psychiatric disorders later in life, found to be associated with the use of AEDs by the mother, in previous studies.
Instead, the present study only looked at the general health of children whose mothers used AEDs while they were pregnant and compared this to that of children who were not exposed to AEDs before birth.
The team of researchers led by Dr Bodil Hammer Bech, at Aarhus University in Denmark identified all babies born in Denmark between 1997 and 2012 and followed them until 31 December 2013, through the Danish National Patient Register. They found that 963,010 babies were born in this period of time.
The researchers obtained information on whether or not the babies were exposed to AEDs before birth from the Danish Register of Medicinal Product Statistics. This revealed that 4,478 children (0.46%) were exposed to AEDs before birth.
The team then analyzed the number of GP visits for reasons other than routine checks and vaccinations. They found that children who were exposed to AEDs before birth had 3% more GP contacts during the study period compared to children who were not exposed to AEDs before birth. This was primarily in the form of phone contacts. The researchers did not find any difference between children who were exposed to AEDs before birth and those who were not, in terms of specific services provided by the GP.
The first author of the study Anne Mette Lund Würtz said in a press release: ”Our results are generally reassuring for women who need to take anti-epilepsy medicine during their pregnancy”.
The analysis took into account factors such as the child’s gender and date of birth, the mother’s age, the family’s income level, education status, the presence of any mental illnesses, the use of psychiatric medicines and insulin, and substance abuse.
The results were published in the scientific journal BMJ Open.
Author: Özge Özkaya
An international team of researchers identified a new candidate gene linked to myoclonic epilepsy in people while examining dogs with generalised myoclonic epilepsy syndrome. The findings were published in the leading scientific journal Proceedings of the National Academy of Sciences (PNAS). This discovery might not only help doctors better diagnose myoclonic epilepsy but could also lead to the development of new therapies to treat this type of epilepsy. Moreover, the dog model could help scientists better understand the condition.
The senior author of the study, Professor Hannes Lohi said in a press release: “The genetic backgrounds of myoclonic epilepsies are not well known yet, and our study provides a new candidate gene, which helps to further characterise the underlying pathophysiology in future studies. This would be important for the development of new treatment scenarios.”
The co-first author Riika Sarviaho added: “We found a novel epilepsy gene, DIRAS1, which has not been linked to any neurological diseases before. The gene is poorly characterised 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.”
Cholinergic neurotransmission is the passage of information from one nerve cell to the other via a chemical called acetylcholine, Acetylcholine also plays an important role at the neuromuscular junction, where nerve cells connect with muscle cells controlling their contraction, hence the muscle jerks observed in myoclonic epilepsy.
DIRAS1 is widely expressed in the brain and previous works suggests that it may be regulating the release of acetylcholine and play a role in development of the nervous system. Further research is needed to better understand the role of DIRAS1 in neurotransmission.
Myoclonic epilepsy is one of the most common forms of epilepsy characterised by shock-like jerks in a muscle or groups of muscles. The myoclonic epilepsy observed in the dogs is very similar to human juvenile myoclonic syndrome in many aspects and the study might have meaningful implications for epilepsy research both in dogs and in humans, according to the authors.
Author: Dr Özge Özkaya
Researchers in the U.S. developed a new scoring system that can help doctors prioritise which patients should receive long-term video-EEG monitoring to evaluate whether staring spells are epileptic seizures.
Staring spells are episodes where children appear to stare into space and do not respond if spoken to or touched. These spells are the main symptom in patients with absence seizures and account for 10-17% of childhood-onset epilepsy. They are a common reason for a child to be referred to neurology services for overnight epilepsy monitoring. However overnight monitoring is time-consuming, expensive, and can cause distress to both children and their families.
Researchers led by Dr Jack Stevens at Nationwide Children’s Hospital and Ohio State University in Columbus performed a four-year chart review of all children who received long-term monitoring in one centre to characterise staring.
“The two goals were a) assess how often [a long-term monitoring] admission captured a staring spell that was diagnosed as a seizure and b) determine if any baseline factors predicted this particular positive result,” the researchers wrote.
Long-term monitoring was able to capture only 29 staring spells in all 276 patients who were referred for monitoring, and diagnose it as seizures. This is just a little more than 10% of all cases. Importantly, the researchers were able to predict whether or not staring spells would be diagnosed as seizures before the long-term monitoring. This was thanks to the scoring system they developed based on the following criteria: most recent EEG results, parental reports of the duration, frequency, and breakability of the staring events. Factors such as the mental status of the children following seizures, the presence or absence of automatisms, previous neurological and psychiatric diagnoses and medications, and family history of epilepsy were also considered.
The score of a child was calculated as follows: − 3 points if the previous EEG was normal, − 1 point if the child took any drugs for a psychiatric condition, + 1 point if the child took an antiepileptic drug (AED) for epilepsy, and + 1 point if the spells lasted less than one minute. If the total score was zero or less, staring spells were rarely diagnosed (in less than 5% of cases) during long-term monitoring.
“Our scoring system shows how consideration of prior EEG findings, medication history, and staring spell duration can help prioritise patients for [long-term monitoring admission] to evaluate if staring spells are epileptic seizures,” the authors concluded.
They added that the scoring system can only be an addition to clinical judgment on when children should be referred for long-term monitoring, and cannot replace it. It is important to note that factors predicting the outcome of the prediction may be different from one patient group to the other and across different centres. Therefore a comprehensive approach should be adopted when evaluating patients before admission to long-term monitoring. Further research in more than one centre is needed to evaluate the validity of the scoring system proposed in the present study.
The study was published in the journal Epilepsy and Behavior.
Author: Dr Özge Özkaya
Some Forms of Epilepsy Could Be Autoimmune in Nature, Suggests Study Linking Parasitic Infection and Nodding Syndrome
Some forms of epilepsy such as nodding syndrome, could be autoimmune in nature according to a study published in the journal Science Translational Medicine.
“The findings … suggest that therapies targeting the immune system may be effective treatments against this disorder and possibly other forms of epilepsy,” said the senior author of the study Dr Avindra Nath who is also the clinical director of the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), in a press release.
Nodding syndrome is a form of childhood epilepsy seen in certain areas of East Africa. It is characterised by head nodding, seizures, severe impairment in thinking ability and restricted growth.
The cause of the condition remained a mystery until now. The present study suggests that the condition might be caused by an immune response triggered by a parasitic worm called Onchocerca volvulus, which then attacks the body’s own nervous system.
For the study, Dr Nath and colleagues compared blood samples from children with nodding syndrome and children without, who all lived in the same village in Uganda. They found antibodies in the blood of children with nodding syndrome, which recognised proteins from the parasitic worm as well as a protein called leiomodin-1. Leiomodin-1 antibodies were also present in the fluid covering the brain and the spinal chord of the children with nodding syndrome.
Leiomodin-1 is highly expressed in human nerve cells grown in the laboratory and is also found in certain areas of the mouse brain. These areas of the brains are the counterparts of the areas in the children’s brain that were affected by nodding syndrome.
When the researchers treated normal nerve cells grown in the laboratory with serum from nodding syndrome patients, they saw that the nerve cells died suggesting that the serum of the children contains a factor that was toxic for nerve cells. In order to test whether this factor could be leiomodin-1 antibodies, the researchers treated the nerve cells with the antibody directly and obtained the same results: the nerve cells died. And when they treated the nerve cells with serum from which the leiomodin-1 antibodies had been removed, the nerve cells survived
The researchers concluded that nodding syndrome may be an auto-immune epileptic disorders triggered by infection with a parasitic worm. The antibodies that the body produces to fight off the parasite wrongly recognise a protein found in the nerve cells and attacks them.
According to the authors, more research is needed to better understand the role of leiomodin-1 in healthy people and people with epilepsy.
Author: Dr Özge Özkaya
What is Nodding Syndrome? This information is from the WHO website
Nodding syndrome (NS) is a neurological condition with unknown etiology. It was first documented in the United Republic of Tanzania (URT) in the 1960s, then later in the Republic of South Sudan in the 1990s and in northern Uganda in 2007. Typically, NS affects children between the ages of 5 and 15 years old, causing progressive cognitive dysfunction, neurological deterioration, stunted growth and a characteristic nodding of the head. Despite numerous and extensive investigations in all three countries, very little is known about the cause of the disease.
To date, Nodding Syndrome is known to occur in the southern region of the United Republic of Tanzania (URT) (Mahenge mountains, Ulanga District), South Sudan (Western Equatoria State, Eastern Equatoria State, Central Equatoria State, and Lakes State) and northern Uganda (Pader, Kitgum and Lamwo districts, with new cases starting to present in Gulu, Amuru, Oyam and Lira districts).
Jilek et al (1962) first described several children with attacks of “head nodding” in Mahenge, a region in URT. The current burden of NS in URT is unknown but observations during case control studies in 2005 and 2009 in the Mahenge region do not suggest a notable increase in the number of cases relative to those detected in the late 1950s and early 1960s.
Samaritan Purse, a local NGO, described observations of head nodding among several children in southern Sudan in the Lui and Amadi villages of East Mundri County in the mid-1990s. A physician from Samaritan Purse reported the outbreak to WHO in 1997. The 2001-2002 investigations by WHO and partners estimated the prevalence of NS at 4.6% among a small population in Western Equatoria State, which appeared to have the highest burden of the illness. By 2003, an estimated 300 cases had been reported from this region. The Ministry of Health of South Sudan estimates the current burden of NS at between six and seven thousand cases, but no systematic large-scale prevalence study has been conducted. The Mundri region in the northeast of Western Equatoria is the presumed epicentre for the disease.
In 2008 and 2009, an illness consistent with NS was reported from Kitgum and Pader Districts in northern Uganda. As of February 2012, Uganda has reported over 3 000 cases of NS from the three districts of Kitgum, Lamwo and Pader. A community survey is underway in Uganda to determine the real burden of NS in the affected districts. Kaiser et al (2009) referred to a phenomenon of head nodding observed in the Kabarole District in Western Uganda as possibly constituting a feature of an epileptic syndrome caused by Onchocerca volvulus (O. volvulus).
The prevalence of both onchocerciasis and epilepsy in the areas affected by NS is high. The affected populations are impoverished and experience regular and prolonged periods of severe food shortages. In South Sudan and in northern Uganda, affected populations have a history of internal displacement and living in internally displaced persons (IDPs) camps.
Familial clustering has been observed in some families with NS patients, with more than one sibling with NS and/or siblings or relatives with other forms of epilepsy.
The age of onset in the vast majority of cases ranges between 5 and 15 years old, but cases have been reported in children as young as 2 years old and in adults up to 32 years old. There is no observed significant difference in the proportion of males to females among the affected, nor is there an observed seasonal variation.
The formation of a specific type of brain cell during the progression of brain tumours is also linked to the development of epileptic seizures, according to a study conducted on mice and published in the leading scientific journal Nature Neuroscience. This knowledge can help scientists better understand how brain tumours cause epilepsy and potentially help them develop new approaches that can prevent or even treat the condition.
“We do not understand exactly how malignant cells cause seizures, or why seizures persist after tumor surgery,” said one of the senior authors of the study, Dr Jeffrey Noebels, professor of neurology, neuroscience, and molecular and human genetics at Baylor College of Medicine in Texas, in a press release.
Dr Noebels and colleagues were studying normal brain cells and in particular a type of brain cell called astrocytes. These are start-shaped cells that fulfil a broad range of roles including biochemically supporting other cell types in the brain cells, providing nutrients to the brain, and repairing the nervous tissue following injury. They are also crucial for the formation of synapses or connections between neurons.
Astrocytes are often considered to be just one type of cell, but researchers identified five distinct sub-types of astrocytes based on the molecules found on their surface. They thought that the different sub-types may be responsible of fulfilling different roles in the brain.
They then looked at the brain of a mouse model of glioma, or brain cancer. They saw that as the tumor grew, neighbouring cells became more excitable, and eventually the mice started to have seizures. This correlated with the emergence of one of the five sub-populations of astrocytes. Strikingly, this sub-population expressed a significant number of genes linked to epilepsy.
Dr Benjamin Deneen, associate professor at Baylor explained: “[A]s the tumor evolves, different subpopulations of astrocyte-like cells develop within the tumor and execute distinct functions that are related to two important tumor characteristics, synaptic imbalance that can lead to seizures, and tumor migration that can lead to tumor invasion of other tissues”.
Dr Noebels added he is excited that for the first time, it is possible to study the earliest effects of tumours on the brain before seizures even start. “These studies would be a major advance in patient care, allowing clinicians to bypass precious months spent searching for effective therapy to stop seizures. Because seizures themselves damage brain tissue, timely effective therapy is of the essence,” he concluded.
Author: Dr Özge Özkaya
What is an Astrocyte
The video below from the Khan Academy gives a good and accessible overview of astrocytes.
A new study published in the leading scientific journal PNAS may shed light onto why people with the same type of epilepsy-causing mutation may have symptoms that vary so dramatically in severity.
Previous research has shown that mutations in a gene called SCN2A, which encodes for sodium channels found on the surface of cells, are the most common cause of genetic epilepsy. However people with the same mutation in the SCN2A gene may experience seizures of very different severity and frequency.
Researchers think that this might be due to the effect of other genes known as genetic modifiers, which may be different between people.
In the present study, a team led by Dr Alfred George Jr. at Northwest University in Chicago studied the variability in seizure severity using a mouse model of epilepsy. They compared mice that had different degrees of epilepsy severity even though they had the same mutation in the SCN2a gene. Importantly, the animals came from different laboratory strains and had different genetic backgrounds.
When they analysed the properties of the animals’ brain cells, the researchers found that the brain cells of the animals more severely affected by epilepsy were more excitable than those of animals less severely affected.
On further analysis, the researchers uncovered that sodium channels on the surface of these cells were behaving differently in more and less severely affected animals. This different “behaviour” was modulated by an enzyme called calcium/calmodulin protein kinase II (CaMKII).
When they blocked the activity of the CaMKII enzyme, the researchers saw that the hyper excitability of the nerve cells was suppressed.
They concluded that blocking CamKII activity could constitute a new approach to treat epilepsy.
In a press release, Dr George said: “Not only did the findings explain the varying severity of epilepsy, but they also revealed a previously under appreciated pathway by which brain sodium channels are regulated — something that could be exploited for therapy.”
The researchers are now working on finding out whether this result can be generalised to mutations on other genes and models of epilepsy.
Author: Dr Özge Özkaya
The side and site of epilepsy surgery affects its psychological outcome according to a new study published in the journal Epilepsy and Behavior.
This finding highlights the importance of considering psychological changes that may occur as a result of epilepsy surgery, on an individual patient basis.
According to the authors, further studies are needed to identify potential risk factors that may make the symptoms of surgery more severe. Further research could also help provide patients with counselling before surgery and identify those who may be most in need of psychological surveillance following surgery.
For the study, the team of researchers led by Dr Robyn Busch, a clinical psychologist at Cleveland Clinic Epilepsy Centre analysed 228 adults with epilepsy who underwent temporal lobe or frontal lobe brain surgery. The patients completed the Personality Assessment Inventory (PAI), which provides an objective assessment of adult psychological problems, both before and after surgery.
The researchers then compared the psychological outcome of the operation between people who had surgery on the left side of their brain versus those who had right-sided surgery.
They found that people with left temporal lobe epilepsy had higher PAI scores (i.e. more psychological problems) before the operation compared to those with left frontal lobe epilepsy. Following surgery, the psychological problems, which included anxiety and depression, usually improved although a small subset of patients reported that their symptoms became worse after surgery. The most frequent improvements were seen in those undergoing temporal lobe surgery.
The researchers concluded that the side and site of brain surgery in epilepsy are important factors in determining the psychological outcome of the operation in adults. They stress that it is important to identify the risk factors that may be associated with the worsening of the symptoms seen in a subset of patients after surgery.
It is estimated that 20 to 40% of people with epilepsy are diagnosed with at least one form of psychological disorder and this percentage can be as high as 70% in people with drug resistant epilepsy. Previous studies have shown that depression is more frequent in people with a seizure focus on the left side of the brain.
Author: Dr Özge Özkaya
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Young people with temporal lobe epilepsy are more likely to have mental health conditions than those with other types of epilepsy, a new study published in the scientific journal Epilepsy and Behavior suggests.
According to the authors Dr William Schraegle and Dr Jeffrey Titus, these findings reinforce the relationship between depression and temporal lobe epilepsy.
In order to determine whether the region of the brain causing the epilepsy (i.e. the seizure focus) had an impact on rates of psychiatric conditions, the researchers looked at data from 132 children and adolescents aged between six and 18 years with either generalised or partial epilepsy. Those with partial epilepsy had either frontal lobe epilepsy or temporal lobe epilepsy.
The researchers measured the rates of depression, anxiety and withdrawal behaviours using two questionnaires: the Behavior Assessment System for Children (BASC-2), a measure of a caregiver’s perceptions of a child’s emotional and behavioural functioning, and the Quality of Life in Childhood Epilepsy (QOLCE) scale.
The results showed that almost half of the children (41%) had evidence of a psychiatric condition. The rates of these conditions were similar between children with generalised epilepsy and those with partial epilepsy and did not differ depending on the side of the brain (i.e. left or right) from which the epilepsy arose.
However, when the researchers compared children with temporal lobe epilepsy against those with frontal lobe epilepsy, they found that those with temporal lobe epilepsy had higher rates of depression.
In addition, increased numbers of antiepileptic drugs used and higher depression scores, as assessed by their parents, were also associated with a reduction in health-related quality of life in children with temporal lobe epilepsy.
Children and young people with epilepsy often have additional psychiatric problems such as depression and anxiety associated with their epilepsy. It is important that these problems are examined carefully as they can reduce the patient’s overall quality of life.
Author: Dr Özge Özkaya
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This event is the first of its kind in Glasgow, held at the University of Glasgow, on the 28th February 2017. The day has a neurological / genetics theme with a number of local speakers with a specialism in epilepsy.
The event is open to the public and is free to attend but registration is essential. Policy makers, researchers, clinicians, charities or anyone with an interest in the area are also welcome.
Lunch, tea and coffee will be provided. Click here for more information.