Posts tagged epilepsy
Articles and news from the latest research reports.
Discovery of genetic defect which triggers epilepsy
Researchers at the University Department of Neurology at the MedUni Vienna have identified a gene behind an epilepsy syndrome, which could also play an important role in other idiopathic (genetically caused) epilepsies. With the so-called “next generation sequencing”, with which genetic changes can be identified within a few days, it was ascertained that the CNTN2 gene is defective in this type of epilepsy.
This was investigated by a team led by Elisabeth Stögmann in collaboration with Cairo’s Ain Shams University and the Helmholtz Centre Munich with reference to a particular Egyptian family, in which five sick children have resulted from the marriage of one healthy cousin to his, likewise healthy, second cousin. The children affected suffer from a specific epilepsy syndrome, in which different types of epileptic attacks occur. This constellation has the “advantage”, according to Stögmann, that both alleles of the gene, which is how one designates different forms of the gene, demonstrate this defect: “As a result the defect becomes symptomatic and identifiable.
"20,000 to 25,000 genes, including all the "protein coding" ones, were sequenced for this. When this was done a mutation was found in the CNTN2 gene. CNTN2 undertakes an important function in the anchoring of potassium channels to the synapses. The mutation makes it no longer possible to generate this protein and, as a consequence, the potassium channels no longer remain affixed to the synapses. The researchers suspect that the epilepsy in this family is triggered by the altered function of the potassium channels.
This discovery, which has now been published in the top journal “Brain”, is providing the stimulus for further research to investigate this particular gene in other epilepsy patients as well. Approximately one percent of the population suffers from active epilepsy in which regular epileptic fits occur. The danger of suffering from an epileptic fit once in your life lies at approximately four to five percent. Genetic factors play a major part in the occurrence of epilepsies.
(Source: meduniwien.ac.at)
Tapeworm-Linked Seizures May Be Rising in U.S.
Tapeworm infection in the brain that can trigger seizures is a growing health concern, doctors say.
But the infection, which leads to swelling in the brain, is usually treatable with medication, according to a leading association of neurologists.
Estimated cases of neurocysticercosis, as the tapeworm infection is called, range from 40,000 to 160,000 each year in the United States, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston. “It’s been around a long time, affecting people living in severe poverty, but the disease is not well-studied or understood,” Hotez said.
Texas is one area of the country with many cases. “The disease has now become a leading cause of epilepsy in Houston,” Hotez said. “Every [week], we have patients come into our tropical medicine clinic with it.”
Concerns about an apparent increase of neurocysticercosis within the United States led the American Academy of Neurology to issue treatment guidelines for doctors and patients in the April 9 issue of the journal Neurology.
The recommendations are based on a review of 10 studies published between 1980 and 2010 that evaluated so-called cysticidal drugs for treatment of tapeworm infections. The infection involves infestation of the brain with the larvae of the Taenia solium tapeworm. In severe cases, it can cause death.
Tapeworm infection is common in Third World countries because of inadequate sanitation and hygiene, and an estimated 2 million people worldwide have epilepsy as a result. The good news is that good hygiene and food preparation can prevent it.
People develop the tapeworm infection when they consume improperly cooked meat, such as pork, or any food or drink that contains the tapeworm eggs or larvae (also known as cysts). Touching the fecal matter of an infected person is another means of transmission. The larvae then transform into full-sized tapeworms, which can grow to several feet, Hotez said.
In pigs, tapeworm larvae travel to the brain and await transmission to another animal (a human, for instance) when the pigs are eaten, he said. The parasites do the same thing in humans, but there’s nowhere to go from the human brain. Ultimately, the larvae die, and that’s when the trouble begins.
As the larvae die, they lose the ability to hide from the body’s immune system. The immune system responds by causing inflammation, which leads to epileptic seizures and brain swelling, Hotez said.
The guidelines for children and adults recommend using the medication albendazole to kill the cysts if they’re alive and treating brain swelling with corticosteroid drugs that dampen the immune system. The study found that albendazole (Albenza), used with or without the corticosteroids, reduced seizure frequency and the number of brain lesions seen in imaging scans. Not enough data was available to evaluate another drug, praziquantel, the researchers said.
Only limited evidence exists to support specific treatment approaches, however, and the treatments may produce side effects, such as abdominal complaints, according to the guidelines. It’s also unclear whether anti-epileptic medications may help prevent the seizures caused by the inflammation.
For now, the key is physician awareness, said Dr. Karen Roos, a professor of neurology at the Indiana University School of Medicine and lead author of the guidelines. “Physicians from areas of the world where this infection is endemic are very knowledgeable about this infection,” she said. “They know more than U.S. physicians.”
Infection with the tapeworm is preventable through proper sanitation, good hygiene and thorough cooking of meat.
(Source: nlm.nih.gov)
Non-Invasive Mapping Helps to Localize Language Centers Before Brain Surgery
A new functional magnetic resonance imaging (fMRI) technique may provide neurosurgeons with a non-invasive tool to help in mapping critical areas of the brain before surgery, reports a study in the April issue of Neurosurgery, official journal of the Congress of Neurological Surgeons. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
Evaluating brain fMRI responses to a “single, short auditory language task” can reliably localize critical language areas of the brain—in healthy people as well as patients requiring brain surgery for epilepsy or tumors, according to the new research by Melanie Genetti, PhD, and colleagues of Geneva University Hospitals, Switzerland.
Brief fMRI Task for Functional Brain Mapping
The researchers designed and evaluated a quick and simple fMRI task for use in functional brain mapping. Functional MRI can show brain activity in response to stimuli (in contrast to conventional brain MRI, which shows anatomy only). Before neurosurgery for severe epilepsy or brain tumors, functional brain mapping provides essential information on the location of critical brain areas governing speech and other functions.
The standard approach to brain mapping is direct electrocortical stimulation (ECS)—recording brain activity from electrodes placed on the brain surface. However, this requires several hours of testing and may not be applicable in all patients. Previous studies have compared fMRI techniques with ECS, but mainly for determining the side of language function (lateralization) rather than the precise location (localization).
The new fMRI task was developed and evaluated in 28 healthy volunteers and in 35 patients undergoing surgery for brain tumors or epilepsy. The test used a brief (eight minutes) auditory language stimulus in which the patients heard a series of sense and nonsense sentences.
Functional MRI scans were obtained to localize the brain areas activated by the language task—activated areas would “light up,” reflecting increased oxygenation. A subgroup of patients also underwent ECS, the results of which were compared to fMRI.
Non-invasive Test Accurately Localizes Critical Brain Areas
Based on responses to the language stimulus, fMRI showed activation of the anterior and posterior (front and rear) language areas of the brain in about 90 percent of subjects—neurosurgery patients as well as healthy volunteers. Functional MRI activation was weaker and the language centers more spread-out in the patient group. These differences may have reflected brain adaptations to slow-growing tumors or longstanding epilepsy.
Five of the epilepsy patients also underwent ECS using brain electrodes, the results of which agreed well with the fMRI findings. Two patients had temporary problems with language function after surgery. In both cases, the deficits were related to surgery or complications (bleeding) in the language area identified by fMRI.
Functional brain mapping is important for planning for complex neurosurgery procedures. It provides a guide for the neurosurgeon to navigate safely to the tumor or other diseased area, while avoiding damage to critical areas of the brain. An accurate, non-invasive approach to brain mapping would provide a valuable alternative to the time-consuming ECS procedure.
"The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects," Dr. Genetti and colleagues conclude. In its current state, the new test probably isn’t suitable as the only approach to planning surgery—too many areas "light up" with fMRI, which may limit the surgeon’s ability to perform more extensive surgery with necessary confidence. The researchers add, "Rather than a substitute, our current fMRI protocol can be considered as a valuable complementary tool that can reliably guide ECS in the surgical planning of epileptogenic foci and of brain tumors."
Epileptic Seizures Can Propagate Using Functional Brain Networks
The seizures that affect people with temporal-lobe epilepsy usually start in a region of the brain called the hippocampus. But they are often able to involve other areas outside the temporal lobe, propagating via anatomically and functionally connected networks in the brain. New research findings that link decreased brain cell concentration to altered functional connectivity in temporal-lobe epilepsy are reported in an article in Brain Connectivity, a bimonthly peer-reviewed publication from Mary Ann Liebert, Inc., publishers. The article is available on the Brain Connectivity website.
Martha Holmes and colleagues from Vanderbilt University, Nashville, TN, identified regions in the brains of patients with temporal-lobe epilepsy that had reduced gray-matter concentrations. Greater reductions in gray-matter concentration correlated with either decreased or increased signaling and communication between brain regions connected through known functional networks.
The authors present their findings in the article “Functional Networks in Temporal-Lobe Epilepsy: A Voxel-Wise Study of Resting-State Functional Connectivity and Gray-Matter Concentration.”
“This is one of the first studies to actually correlate both functional and structural brain changes in epilepsy,” says Christopher Pawela, PhD, Co-Editor-in-Chief and Assistant Professor, Medical College of Wisconsin. “This is an exciting finding and may have impact in other brain disorders in which both the structure and function of the brain are involved.”
Epilepsy sends differentiated neurons on the run
The smooth operation of the brain requires a certain robustness to fluctuations in its home within the body. At the same time, its extraordinary power derives from an activity structure poised at criticality. In other words, it is highly responsive to many low-threshold events. When forced beyond its comfort zone in parameter space—its operating temperature, electrolytes, sugars, blood gas or even sensory input— the direct result is seizure, coma, or both. It would appear that anything rendered too hot or cold, too concentrated or scarce, precipitates seizure. In those genetically predisposed, or compromised by head trauma, the seizing tends toward full-blown epilepsy. A group in Hamburg, led by Michael Frotscher has been chipping away at the causes of common form a epilepsy, temporal lobe epilepsy (TLE). Their latest research published in the journal, Cerebral Cortex, takes a closer at differentiated neurons in the dentate gyrus of mouse hippocampus. Once thought to be completely immobilized by virtue of their broadly integrated dendritic trees, these neurons are now shown to become migratory once again in direct response to seizure activity.
Genetic predisposition to seizure can come in the form of ongoing chemical or metabolic imbalance due to defects in enzymes, ion channels or receptors. Alternatively it manifests through direct structural defect as a result of a developmental flaw. In slice preparations, Frotscher looked at a particular form of TLE, where the granule cell layer (GCL) in the dentate gyrus is disrupted. The cells there have either failed to migrate along glial scaffolds into a compact layer with clearly defined margins, or aberrant clumps of cells congregate in the wrong places. Seizures secondary to fever have been known to cause this aberrant migration of granule cells, as has a particular kind of mouse mutant known as the reeler mouse.
The catalog of mouse mutants is expansive; it is a veritable library of hopeless monsters. The reeler mutant, known since 1951, has a unique set of issues wherein cells fail to migrate to the right spots in the cerebellum, cortex, and hippocampus. The protein, reelin was later discovered as one of the causes of this particular phenotype. Reelin is an extracellular matrix protein which initially provides scaffolding for neuron migration, and later a fence to fix neurons in place. In mice with mutated reelin protein, cells in all parts of the hippocampus, not just the dentate gyrus are spread out into a broad and diffuse layer.
By injecting kainate (KA), an excitotoxin that predictably results in seizures, into the dentate gyrus, Frotscher biased the granule cells into entering a phase of bursting activity. With their glutamate receptors fully activated by KA, the granule cells fire rapid volleys of spikes followed by deep depolarization periods. Cells that had been fluorescently labeled with GFP and observed with real time video microscopy were also seen to become motile and dispersed. The normal band of granule cells doubled, or tripled, in thickness. Next, Frostcher looked for a link between this response to KA and the reelin protein. Both reelin mRNA and reelin immunoreactivity were found to be reduced in the dentate granule cells that had been dispersed by KA.
Against this tableau of complex responses to KA, is the fact that adult neurogenesis of dentate granule cells occurs within many mammalian species. A narrowly-defined rostral migratory stream normally delivers fresh cells to both the dentate gyrus and olfactory bulb. Application of BrdU, a marker of newly born cells, labeled microglial and astrocytes near the site of injection, but only a few of the granule cells. As an excitotoxin, KA may be expected to kill at least some cells outright, and cause significant dendritic degeneration in many more. An interesting question to ask, is how does KA induce granule cell dispersion despite the dense interconnections with their neighbors?
During KA induced motility, the nucleus was typically observed to translocate within the cell into one of the dendrites, pulling the soma along with it. This process is believed to involve a myosin-dependant forward flow of actin structural protein within the cell. Outside the cell, changes to the reelin matrix appear to be involved as well. One potential mechanism that has emerged is that reelin induces serine phosporylation of cofilin, an actin-associated protein involved in depolymerization. The authors conclude reelin-induced cofilin phosphorylation controls neuronal migration during development, and prevents abnormal motility in the mature brain.
Undoubtedly many mechanisms are involved in the KA-induced seizure and reelin story. Other cell types in the dentate gyrus need to be looked at in closer detail. For example, how reelin expression is regulated, and which cells manufacture it are current areas of study. It is important as well to differentiate between the causes of seizure, and its consequences. On paper they can be neatly packaged concepts but in the real tissue, and in intact animals, they can be anything but.
(Source: medicalxpress.com)
Cats and humans suffer from similar forms of epilepsy
Epilepsy arises when the brain is temporarily swamped by uncoordinated signals from nerve cells. Research at the Vetmeduni Vienna has now uncovered a cause of a particular type of epilepsy in cats. Surprisingly, an incorrectly channelled immune response seems to be responsible for the condition, which closely resembles a form of epilepsy in humans. The work is published in the current issue of the Journal of Veterinary Internal Medicine.
There is something sinister about epilepsy: the disease affects the very core of our being, our brain. Epileptic attacks can lead to seizures throughout the body or in parts of it. Clouding of consciousness or memory lapses are also possible. The causes are still only partially understood but in some cases brain tumours, infections, inflammations of the brain or metabolic diseases have been implicated.
Epilepsy is not confined to humans and many animals also suffer from it. Together with partners in Oxford and Budapest, Akos Pakozdy and his colleagues at the University of Veterinary Medicine, Vienna have managed to identify the cause of a certain form of epilepsy in cats, in which the body’s own immune system attacks particular proteins in the cell membranes of nerve cells. The symptoms include twitching facial muscles, a fixed stare, chewing motions and heavy dribbling. Based on their clinical experience, the researchers believe that this form of epilepsy is fairly widespread in cats. Interestingly, a highly similar type of epilepsy occurs in humans: an inflammation in the brain, known as limbic encephalitis, leads to epileptic seizures that generally manifest themselves in the arm and the facial muscles on only one side of the body.
Pakozdy and his colleagues have found antibodies in the blood of epileptic cats that react to proteins in the cell membranes of nerve cells. The proteins form the building blocks of ion channels that are involved in the production of nerve signals. The same ion channels are affected in the corresponding human form of epilepsy. They control the membrane’s permeability to potassium ions based on the electric potential across the membrane, thereby helping generate the rapid nerve signals of the so-called action potential.
Immunotherapy for cats?
If the immune system attacks components of these ion channels, the production of nerve signals is disrupted. There is an increased release of neurotransmitters, which leads directly to the symptoms of epilepsy. Previous work – in another group – on human patients has shown that normal anti-epilepsy medication has hardly any effect on this form of epilepsy. However, immunotherapy has proven to be relatively effective. Pakozdy’s work now shows that “limbic encephalitis in cats has the same cause as it does in humans, where the origins have been known for years. It is important that cats with epilepsy are diagnosed early, so that the correct form of therapy can be started. We believe this will dramatically increase the chances of a successful treatment. It seems as though epileptic cats might benefit from treatment with immune preparations.”
(Image: Thinkstock)
Parasites and poor antenatal care are the main causes of epilepsy in sub-Saharan Africa
Epilepsy is one of the most common neurological conditions worldwide, and it is well known that it is significantly more prevalent in poorer countries and rural areas. The study of more than half a million people in five countries of sub-Saharan Africa is the first to reveal the true extent of the problem and the impact of different risk factors.
The study - conducted at International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) demographic surveillance sites in Kenya, South Africa, Uganda, Tanzania and Ghana - screened 586 607 residents and identified 1711 who were diagnosed as having active convulsive epilepsy.
These individuals, along with 2033 who did not have epilepsy, were given a questionnaire to complete about their lifestyle habits. The team also took blood samples to test for exposure to malaria, HIV and four other parasitic diseases that are common in low-income countries.
The team found that adults who had been exposed to parasitic diseases were 1.5 to 3 times more likely to have epilepsy than those who had not. Epilepsy has previously been linked with various parasite infections, but this is the first study to reveal the extent of the problem.
Professor Charles Newton from the Wellcome Trust programme at the Kenyan Medical Research Institute (KEMRI) and the Department of Psychiatry at Oxford University, who led the study, said: “This study demonstrates that many cases of epilepsy could be entirely preventable with elimination of parasites in Africa, some of which - for example, onchocerciasis - have been controlled in some areas. In some areas the incidence of epilepsy could be reduced by 30-60 per cent with appropriate control measures.”
In children, the greatest risk factors for developing epilepsy were complications associated with delivery and head injury. Interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region, say the authors.
The study focused on people with convulsive epilepsies as they are the most reliably detected and reported and there remains a substantial stigma attached to patients with the disease.
“Facilities for diagnosis, treatment and ongoing management of epilepsy are virtually non-existent in many of the world’s poorest regions, so it’s vital that we take these simple steps to try and prevent as many cases of this debilitating disease as possible,” Professor Newton added.
The findings were published today in the journal ‘Lancet Neurology’. The study was funded by the Wellcome Trust, with support from the University of the Witwatersrand and the South African Medical Research Council.
(Source)
In the 19th century, a speechless patient wasted away in the Bicetre Hospital in France for 21 years. He was known as ‘Tan’ for the only word he could say, and for 150 years, his identity has remained a mystery. In 1861, as Tan lay dying, the famous physician Paul Broca encountered the patient. When the ill-fated patient died, Broca autopsied his brain. Broca noticed a lesion in a part of the brain tucked up behind the eyes. He concluded that the brain region was responsible for language processing. But despite Tan becoming one of the most famous medical patients in history, he was never identified until now.
A 2007 study in the journal Brain revealed the extent of the lesion using MRI imaging. A recent study identified the patient as a Monsieur Louis Leborgne, a craftsman who had suffered from epilepsy his whole life.
UCI neuroscientists create fiber-optic method of arresting epileptic seizures
UC Irvine neuroscientists have developed a way to stop epileptic seizures with fiber-optic light signals, heralding a novel opportunity to treat the most severe manifestations of the brain disorder.
Using a mouse model of temporal lobe epilepsy, Ivan Soltesz, Chancellor’s Professor and chair of anatomy & neurobiology, and colleagues created an EEG-based computer system that activates hair-thin optical strands implanted in the brain when it detects a real-time seizure.
These fibers subsequently “turn on” specially expressed, light-sensitive proteins called opsins, which can either stimulate or inhibit specific neurons in select brain regions during seizures, depending on the type of opsin.
The researchers found that this process was able to arrest ongoing electrical seizure activity and reduce the incidence of severe “tonic-clonic” events.
“This approach is useful for understanding how seizures occur and how they can be stopped experimentally,” Soltesz said. “In addition, clinical efforts that affect a minimum number of cells and only at the time of a seizure may someday overcome many of the side effects and limitations of currently available treatment options.”
Study results appear online in Nature Communications.
More than 3 million Americans suffer from epilepsy, a condition of recurrent spontaneous seizures that occur unpredictably, often cause changes in consciousness, and can preclude normal activities such as driving and working. In at least 40 percent of patients, seizures cannot be controlled with existing drugs, and even in those whose seizures are well controlled, the treatments can have major cognitive side effects.
Although the study was carried out in mice, not humans, Soltesz said the work could lead to a better alternative to the currently available electrical stimulation devices.