Photosensitivity in children with epilepsy alone is reported to range from 2 – 14%. A pilot study to determine the incidence of photosensitivity in children with ASD has found a significant and unexpected higher rate of nearly 30% photosensitivity in adolescents with epilepsy and autism comorbidity. (Abstract 3.109) The study, presented at the American Epilepsy Society’s 65th annual meeting, is the first report of this marked difference in response to intermittent photic stimulation.

Investigators at Children’s Hospital Boston reviewed the records of children diagnosed with ASD between December 2010 and May 2011. Those given an EEG prior to or during the search period were included in the study. The EEG reports were examined to determine the presence or absence of a photoparoxysmal response (PPR) to intermittent photic stimulation.

“Our study found a high overall incidence of photosensitivity in 25 percent of children over 15 years of age with autism spectrum disorder, and an even higher rate of 29.4 percent in that age group of children who had both epilepsy and autism,” says lead author Jill Miller-Horn. “This finding has not been previously reported.”

Dr. Miller-Horn noted the relatively small size of the study. “Larger scale prospective studies are needed to confirm this trend,” she said. “Further study is also needed to identify the importance of these findings in the pathophysiology of epilepsy in children with autism spectrum disorder.”

Material adapted from American Epilepsy Society (AES).

More than 75% of the children screened positive for developmental delay, 41% of them with autism. Although many of the cases had been previously diagnosed, more than one-third of the children did not have a prior DD or autism diagnosis and were referred for further confirmatory evaluation.

According to Anne Berg and Breanne Fisher of the investigative team, “The yield of screening in the EMU setting for developmental and behavioral comorbidities is sufficiently high to support routine screening of both new onset and established cases of pediatric epilepsy. Our findings also suggest that all children seen in the epilepsy clinic should be screened for these comorbidities.”

The study was conducted among children under age five seen between November 1, 2010 and May 15, 2011. Parents were asked to complete the developmental screening instrument (Ages and Stages Questionnaire, ASQ) and one of two autism screening instruments used in the study. No child screened positive for autism alone.

The investigators have now focused the program on evaluating the prospective use of a more extensive battery of screening tools with new-onset patients followed over time.

Material adapted from American Epilepsy Society (AES).

In the first reported study of 3D-TV and children with epilepsy, researchers at the University of Munich, Germany and the University of Salzburg, Austria, exposed 140 consecutive young patients (median age 12) to a standard test for photosensitivity, called photo-paroxysmal stimulation, and to 15 minutes of 3D-TV viewing. The viewing was on a 50” 3D-Plasma TV with 3D shutter glasses at a distance of about two meters (approx. six and one-half feet). Responses to the two forms of stimulation were recorded on an EEG and evaluated by two independent professionals.

“In our cohort of children with a risk of epilepsy or with known epilepsy fifteen minutes of 3D television viewing did not increase epileptiform activity on EEG, nor were there any apparent seizures,” says lead author Herbert Plischke. “We conclude that the chance for people with undiagnosed epilepsy to have an epileptic seizure provoked by 3D-TV is unlikely.”

Seizures that are provoked by television appear not to be a matter of technology, according to the investigators, but a matter of content, for example, color, contrast, pattern, and flicker, independent of whether the viewing medium is a 2D- or 3D-TV. A significant number of patients (20%) did present with other symptoms like nausea, headache and dizziness.

Material adapted from American Epilepsy Society (AES).

“We found a strong connection between preterm birth and risk of epilepsy and the risk appears to increase dramatically the earlier the birth occurs during pregnancy,” said study author Casey Crump, MD, PhD, of Stanford University in Stanford, California. “More effective prevention of preterm birth is urgently needed to reduce the burden of epilepsy later in life.”

For the study, 630,090 adults in Sweden ages 25 to 37 were followed for four years. Participants who developed epilepsy were identified through hospital records as well as monitoring prescriptions for drugs that treat epilepsy. Of the participants, 27,953 had been born prematurely and 922, or 0.15 percent of the total study participants, had been hospitalized for epilepsy during the study.

The study found adults who were born very preterm (23-31 weeks gestational age) were five times more likely to be hospitalized for epilepsy as an adult compared to those adults who were born full-term (37-42 weeks gestational age). Adults who were born between 32-34 weeks of pregnancy were almost twice as likely to be hospitalized for epilepsy and adults who were born between 35 and 36 weeks were one-and-a-half times as likely to be hospitalized for epilepsy compared to those born full-term. The results remained the same regardless of fetal growth, birth order or related disorders that may be associated with preterm birth.

“Other disorders were also more common in people born preterm, including cerebral palsy and other diseases of the central nervous system,” said Crump. “It’s possible that the association between preterm birth and epilepsy may be explained by a decreased flow of oxygen to the brain in the uterus during pregnancy that leads to preterm birth or abnormal brain development resulting from preterm birth itself.”

This study was conducted at the Center for Primary Health Care Research at Lund University in Sweden and was supported by the National Institute of Child Health and Human Development, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the ALF project grant.

Material adapted from American Academy of Neurology (AAN).

In findings published on-line on Sept. 11, 2011, in Nature Medicine, the UAB team shows that malignant glioma cells release a tremendous amount of a neurotransmitter called glutamate into healthy neurons surrounding the tumor site. Neurons normally use glutamate to communicate with one another, but not in the staggering amounts released by the glioma cells.

“These tumor cells produce an enormous amount of glutamate, 100-fold beyond normal,” said Harald Sontheimer, Ph.D., professor of neurobiology at UAB and lead investigator. “This leads to a state of hyper-excitability that overwhelms healthy neurons and leads to their death.”

Sontheimer says the death of neurons in proximity to the glioma gives the malignant cell room to grow and expand into the space previously occupied by the neurons.

“The brain is a dense, closely packed space,” said Sontheimer, who directs the UAB Center for Glial Biology in Medicine. “For the glioma to grow, it has to make room for itself, which it does by clearing out surrounding neurons with this blast of glutamate.”

Excess glutamate can also cause abnormal electrical activity in the brain, which is the basis for epileptic seizures. Sontheimer’s team found that mice with human glial cells developed abnormal brain activity and behavioral signs consistent with seizures.

The good news, Sontheimer says, is that sulfasalazine, a drug used to treat Crohn’s disease, irritable bowel disease and some types of arthritis, seems to inhibit the glioma from releasing the large amount of glutamate. In mice, sulfasalazine stopped the release of glutamate and prohibited seizures.

Without the abnormal glutamate release, the nearby neurons are unaffected by the glioma, and its growth is compromised. Sontheimer says evidence suggests that tumor cells that cannot grow tend to die.

But sulfasalazine, as formulated to treat Crohn’s disease and other conditions, is not an efficient way to treat gliomas; because it is designed to break apart in the intestines, only about 20 percent of the drug gets into the blood stream where it can be carried to a glioma site in the brain. Sontheimer says, however, that the drug could be re-formulated to make it more efficient and effective.

“The drug could be re-designed so that it does not cleave apart in the intestine, keeping more of it in the blood stream for a longer period of time,” he said.

Sontheimer thinks a clinical trial of sulfasalazine in humans is warranted, and sulfasalazine should be considered an adjutant therapy to inhibit seizures in patients with glioma in the meantime.

“While we are waiting for the development of a new drug, the existing one will work to some degree. It’s nice to have a sharp knife, but a dull one will work,” Sontheimer said.

Sontheimer says the drug might be especially valuable in the early stages of the glioma, when the tumor is small, potentially to slow the progression of the disease and provide for a better quality of life.

About 18,000 Americans develop gliomas each year, and about half will die within 12 months of diagnosis, according to the Society for Neuroscience.

The study was funded by the National Institutes of Health, the UAB Brain Tumor SPORE grant, the Neuroscience Blueprint Core grant and the National Coalition for Cancer Research.

Material adapted from University of Alabama at Birmingham.

In his talk at the Antiepileptic Drug Trials XI Conference in Miami, Fla., DeGiorgio reported the results of a Phase 2 clinical trial of a new treatment called trigeminal nerve stimulation (TNS). He noted that 40 percent of the patients receiving TNS treatment experienced a significant improvement in seizure reduction.

The external stimulator, which is about the size of a large cell phone, attaches to a belt or can slip into a pocket. Wires from the stimulator are passed under the clothing and connected to conductive pads attached to the forehead. The electrodes, which can be covered by a cap or scarf, transmit a signal to the trigeminal nerve, which extends into the brain from the face and forehead and is known to play a role in seizure inhibition.

An illustration of trigeminal nerve stimulation (TNS).

The clinical trial showed that at the end of the 18-week study, 40 percent of patients receiving TNS experienced a significant improvement in seizure reduction, which is defined as a 50 percent or greater decrease in the frequency of seizures.

“We showed that TNS works well under stringent clinical-trial conditions. The fact that 40 percent showed a clinically-meaningful response is exciting,” DeGiorgio said.

These results confirm and extend the findings of DeGiorgio’s positive Phase 1 trial in epilepsy that was reported in 2009 in the journal Neurology.

In addition, the researchers found that the TNS treatment also improved the mood of the participants. Since depression is a common problem in people with epilepsy, this finding could have significant impact on the quality of life of people who suffer from the disorder.

DeGiorgio, lead inventor of TNS, was the principal investigator for the Phase 2 study, which was conducted at Olive View–UCLA Medical Center and the University of Southern California.

“I’m encouraged to see that our non-invasive and safe approach to neuromodulation compares favorably to pharmaceutical and surgically implanted–device therapies of drug-resistant epilepsy,” he said.

The research was funded by the Epilepsy Therapy Project; the Epilepsy Foundation; Boston Scientific; and the Milken Family Foundation. UCLA’s Office of Intellectual Property executed an exclusive worldwide license for TNS with NeuroSigma, Inc., a Los Angeles–based medical technology company. DeGiorgio is a consultant with NeuroSigma but has no equity interest in the company.

Material adapted from University of California, Los Angeles (UCLA), Health Sciences.

The report is available in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy (ILAE).

Epilepsy is characterized by recurrent seizures that range from mild staring spells to major convulsions, and frequently develops in early childhood. Studies have found that in the U.S. alone there are more than 325,000 children under the age of 15 who are diagnosed with epilepsy, with 45,000 new cases diagnosed each year. Medical evidence further suggests that early onset of seizures is a significant factor contributing to cognitive impairment in children.

For the present study, researchers reviewed medical data and psychological evaluations for 64 preschool children (3 to 6.11 years old) with active epilepsy in order to determine the frequency of cognitive impairment and the epilepsy-related factors contributing to the impairment. Children in the study group had a mean age of five with seizure onset between 0 and 75 months.

“Our study is the first to examine cognitive performance in preschool children with epilepsy,” said lead researcher Kati Rantanen, a PhD candidate at the University of Tampere in Finland.

The study showed that the prevalence of epilepsy was roughly 3 per 1,000 children, which is consistent with prior studies in Finland and other developed countries. The team identified 27 children with focal seizures, 31 with generalized seizures, and 6 with unclassified seizure types. More than half of the children (64%) were receiving monotherapy of an anti-epileptic drug for seizure control. The seizures were well-controlled in 37% of children, partially controlled in 16%, and poorly controlled in the remaining 47% of participants.

Researchers determined cognitive function based on psychological evaluation, parental reports, and observations from daycare. The intelligence quotient (IQ) was used to measure cognitive function; children were classified as having normal IQ (IQ over 70) or with mild (50-69), moderate (35-49), or profound (less than 34) intellectual disability. In the preschool cohort, 50% of the children displayed normal cognitive function, 22% had mild cognitive impairment, and 28% showed moderate to severe intellectual disability.

The study found that early onset epilepsy is a risk factor for cognitive impairment. The authors caution that lower (IQ) test scores in young children with epilepsy may be partly a reflection of development delay rather than mental disability.

“Early intervention programs may help to improve cognitive and psychological outcomes in preschoolers with epilepsy,” Rantanen concluded. “Further prospective research is needed to explore the developmental course of children with epilepsy.”

Material adapted from Wiley-Blackwell.

Reference / Abstract
“Cognitive Impairment in Preschool Children with Epilepsy.” Kati Rantanen, Kai Eriksson and Pirkko Nieminen. Epilepsia; Published Online: May 13, 2011 (DOI: 10.1111/j.1528-1167.2011.03092.x).

“Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on first-trimester use of newer-generation antiepileptic drugs and birth defects are limited,” according to background information in the article.

Ditte Molgaard-Nielsen, M.Sc., and Anders Hviid, M.Sc., Dr.Med.Sci., of the Statens Serum Institut, Copenhagen, Denmark, conducted a study to analyze the association between the use of lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam (newer-generation antiepileptic drugs) during the first trimester of pregnancy and the risk of any major birth defects. The study included data on 837,795 live-born infants in Denmark from January 1996 through September 2008. Individual-level information on dispensed antiepileptic drugs to mothers, birth defect diagnoses, and potential confounders (factors that can influence outcomes) were ascertained from nationwide health registries.

Among the live births included in the study (837,795), 19,960 were diagnosed with a major birth defect (2.4 percent) during the first year of life. Among 1,532 pregnancies exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester, 49 infants were diagnosed with a major birth defect (3.2 percent) compared with 19,911 infants (2.4 percent) among 836,263 unexposed pregnancies. After adjusting for various factors, the authors found that exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester was not associated with an increased risk of major birth defects. Gabapentin and levetiracetam exposure during the first trimester was uncommon.

The prevalence odds ratios for any major birth defects after exposure to any newer-generation antiepileptic drugs during the first trimester were not statistically different for mothers with epilepsy, mood affective disorder, or migraine, or without a diagnosis.

“Our study, to our knowledge, is the largest analytic cohort study on this topic and provides comprehensive safety information on a class of drugs commonly used during pregnancy. The use of lamotrigine and oxcarbazepine during the first trimester was not associated with moderate or greater risks of major birth defects like the older-generation antiepileptic drugs, but our study cannot exclude a minor excess in risk of major birth defects or risks of specific birth defects. Topiramate, gabapentin, and levetiracetam do not appear to be major teratogens [an agent that can cause malformations in an embryo or fetus], but our study cannot exclude minor to moderate risks of major birth defects,” the authors conclude.

Material adapted from JAMA.

Reference
JAMA. 2011;305[19]1996-2002.

“Because of epilepsy’s common occurrence, the narrow therapeutic and safety margins of antiepileptic medications, and the recognized complications of medication non-adherence in adults with epilepsy, identifying the rates, patterns, and predictors of non-adherence in children with epilepsy is imperative. The onset and evolution of antiepileptic drug nonadherence in children with newly diagnosed epilepsy remains unknown,” according to background information in the article.

Avani C. Modi, Ph.D., of Cincinnati Children’s Hospital Medical Center, Cincinnati, and colleagues conducted a study to identify and characterize medication adherence trajectories over the first 6 months of therapy for children with new-onset epilepsy using electronic monitors and to identify sociodemographic and epilepsy-specific predictors of adherence trajectories.

The study included 124 children (2-12 years old) with final data collection through September 2009. Adherence was measured electronically with a system in which the cap of the medication bottle contained a microelectronic circuit to register the dates and times the bottle was opened and closed.

Of the children in the study, 58 percent demonstrated persistent nonadherence during the first 6 months of therapy. The researchers identified 5 different adherence patterns with group-based trajectory models. The 5 groups, based on severity and course of non-adherence, were severe early nonadherence (n= 16; 13 percent), severe delayed nonadherence (n = 8; 7 percent), moderate nonadherence (n= 16; 13 percent), mild nonadherence (n = 32; 26 percent), and near-perfect adherence (n = 52; 42 percent).

“The adherence pattern of most patients was established by the first month of therapy. Socioeconomic status was the sole predictor of adherence trajectory group status with lower socioeconomic status associated with higher non-adherence,” the authors write.

“Socioeconomic status was the only significant predictor of nonadherence and may help identify patients at highest risk. Given that nonadherence is frequent, may compromise the benefits of drug therapy, may complicate interpretation of clinical response, and can be addressed through evidence-based interventions, clinicians should consider routinely assessing adherence to antiepileptic drug therapy in all children with epilepsy.”

“…the rate of nonadherence over the course of the first 6 months of therapy is concerning and suggests a need for intervention studies that aim to optimize adherence early in the course of therapy,” the researchers conclude.

Material adapted from American Medical Association (AMA).

Reference
JAMA. 2011;305[16]1669-1676.

Epilepsy is associated with high rates of psychiatric disorder and one form of epilepsy, known as temporal lobe epilepsy (TLE), in particular, shows increased rates of psychosis. Until now, little was known about the underlying biological mechanisms behind this type of psychiatric disorder.

The study, which used advanced neuroimaging techniques, found that a lower density of cells (grey and white matter) was widespread across many regions of the brain in people who had both TLE and psychosis. This pattern of a low density of cells in parts of the brain was similar to those observed in schizophrenia.

These brain differences are potentially relevant to both psychiatric disorders in temporal lobe epilepsy (TLE) and to schizophrenia in the general population.

Dr. Frederick Sundram, Senior Registrar and Honorary Lecturer in Psychiatry at RCSI commented: “This research gives new insights into the overlap between physical and psychiatric disorders such as epilepsy and schizophrenia respectively. In future, this may inform on potential treatments for psychiatric disorders associated with temporal lobe epilepsy as well as schizophrenia which affects over 10,000 people in Ireland (1). Our findings show that there is a low density of cells in TLE related psychosis which resembles schizophrenia. Patients with these conditions may benefit in future from treatments that target these abnormal brain regions.”

Epilepsy is one of the most common and debilitating neurological disorders which affects an estimated 35,000 of people in Ireland (2).

Dr. Sundram, lead author of the study worked with a team from the Department of Psychiatry, RCSI and Beaumont Hospital including Professor Mary Cannon and Professor David Cotter in collaboration with Dr Colin Doherty, St. James’ Hospital, Dublin; Professor Gareth Barker, Institute of Psychiatry at King’s College, London; and Ms Mary Fitzsimons and Dr Norman Delanty, Beaumont Hospital.

The research was published in the British Journal of Psychiatry(3) and the research group was funded by the Health Research Board and The Brain and Behavior Research Foundation, NARSAD (USA).

Material adapted from Royal College of Surgeons in Ireland (RCSI).

References
(1) Behan C, Kennelly B, O’Callaghan E, The economic cost of schizophrenia in Ireland: a cost of illness study. Ir J Psych Med 2008; 25(3): 80-87.
(2) Source: Brainwave – The Irish Epilepsy Association.
(3) Sundram F, Cannon M, Doherty CP, Barker GJ, Fitzsimons M, Delanty N, Cotter D. Neuroanatomical correlates of psychosis in temporal lobe epilepsy: voxel-based morphometry study. British Journal of Psychiatry. 2010 Dec;197:482-92.

According to the Centers for Disease Control and Prevention (CDC), autism spectrum disorders (ASDs) are a group of developmental disabilities that can significantly impact social interaction, communication, and behavior. The CDC estimates that on average, 1 in 110 U.S. children has an ASD (which is four times more likely to develop in boys than in girls). Medical evidence suggests that the prevalence of epilepsy in autism ranges from 7% to 46%.

Researchers on the present study team, led by Orrin Devinsky, M.D., Professor of Neurology, Neurosurgery, and Psychiatry at NYU School of Medicine and Director of the NYU Comprehensive Epilepsy Center in New York, reviewed clinical and laboratory data for patients with idiopathic autism evaluated at the Center during a 20-year period. Seizures were classified using ILAE criteria with treatment resistance defined as failure of adequate trials of two tolerated AED regimens. “Treatment-resistant epilepsy is common among patients with autism, and more than one-third of patients in our study group had TRE,” said Dr. Devinsky. “Among patients for whom we had complete AED and seizure control data, 55% had TRE.”

Among the 127 patients with autism and at least one epileptic seizure, 34% had TRE and 28% were seizure-free. The remaining 39% of patients with autism and epilepsy had infrequent seizures or insufficient data to properly categorize them. In patients with TRE, researchers found that seizure onset was at an earlier age than in patients who were seizure free. TRE patients also had more developmental regression, as well as motor and language delays, than seizure-free participants.

Three patients had surgical resection and one underwent anterior callosotomy; these surgical treatments provided little or no improvement in seizure status. In nine patients with vagus nerve stimulator (VNS) implantation, limited improvement of seizures was noted in two patients and no improvement in seven patients. “In patients with autism, we found that surgical and VNS outcomes were less favorable, providing a lower rate of seizure freedom, than in other TRE populations,” concluded Dr. Devinsky. “Further studies are needed to explore the association between chronic epilepsy and autism.”

Material adapted from Wiley-Blackwell.

Reference
“Medically Refractory Epilepsy in Autism.” Gemma Sansa, Chad Carlson, Werner Doyle, Howard Weiner, Judith Bluvstein, William Barr and Orrin Devinsky. Epilepsia; Published Online: April 19, 2011 (DOI: 10.1111/j.1528-1167.2011.03069.x).

“For about one-third of people with epilepsy, the drugs either don’t stop their seizures or the side effects are not tolerable,” said study author Jacqueline French, MD, with New York University in New York. French is also a Fellow of the American Academy of Neurology. “If this drug is approved by the Food and Drug Administration (FDA), it will be another tool in our arsenal for combating or reducing seizures in people with difficult to treat epilepsy.”

The study involved 387 people in the United States and Latin America who had uncontrolled epilepsy and were currently taking one to three other anti-seizure drugs. Participants were assigned to receive either eight or 12 milligrams of perampanel or a placebo pill once daily for 19 weeks in addition to their regular treatment.

Patients who took the 12 milligram dose of perampanel had a 14-percent reduction in seizures in a 28-day period compared to those who took the placebo. Those who took the eight milligram dose cut their seizure frequency by nearly six percent compared to those who took the placebo.

The most common side effects of the drug were dizziness, drowsiness, irritability, headache, falls, and ataxia, which is a lack of muscle coordination.

“These findings provide further evidence of the effectiveness and safety of perampanel as an added treatment option to reduce seizures,” said French. “Plans are to submit the drug for FDA approval this year.”

The study was supported by Eisai Inc.

Material adapted from American Academy of Neurology (AAN).

Previous studies have shown that children with epilepsy are at increased risk of developing behavioral problems and psychiatric disorders including anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD). In a 2003 population-based study, psychiatric disorders were reported in 37% of children with epilepsy, while children with diabetes and those in the healthy control group were much lower at 11% and 9%, respectively (Davies et al., 2003). Medical evidence, however, has not clearly established when children or teens with epilepsy may be vulnerable to developing psychiatric issues or how gender influences psychopathology in epilepsy.

The current study used data collected by the Norwegian Health Services Research Centre in a 2002 health profile questionnaire. For children in the 8-13 years of age group, there were 14,699 (response rate of 78%) parents who completed the questionnaire which included questions on topics such as sociodemographic conditions, physical and mental health, and psychosocial conditions. To assess psychiatric symptoms, researchers used the parent report of the Strengths and Difficulties Questionnaire (SDQ) which included questions covering four problem domains – emotional symptoms, conduct problems, hyperactivity-inattention, and peer problems – and prosocial behavior. The SDQ scores were classified as normal, borderline, or abnormal.

Based upon parent’s response to the health questionnaire, 111 children were identified with epilepsy (a frequency of 0.8%) of whom 110 completed the questions included in the SDQ (64 boys and 46 girls). Researchers found that children with epilepsy had a significantly higher frequency of psychiatric symptoms (38%) compared with healthy controls (17%). Boys had a higher risk of psychiatric symptoms than girls in both the epilepsy population and in controls.

Additional risk factors were low socioeconomic status (living in a single family home, family income below poverty limit), having another chronic disease (asthma/diabetes), and epilepsy. However, these independent risk factors contributed with different prominence (odds ratio) to psychiatric problems in boys and girls in the epilepsy population. Having or having had epilepsy was a much stronger risk factor of developing psychiatric problems in girls, whereas boys with epilepsy seemed almost as affected by low socioeconomic status as having epilepsy. The authors say the reason for this remains unclear, however a previous study found a more negative attitude towards having epilepsy in girls than in boys.

Further results showed that 33% of children with epilepsy who were 8-9 years had a borderline/abnormal SDQ score compared with 18% of healthy children of the same age; 41% compared to 16% in the 10-13 year age group. “We chose to divide the groups at the age of ten years as this is the start of preadolescence. The wish ‘to be like the others’ and to participate in different activities as an equal may be issues of particular importance for children with epilepsy,” said Dr. Kristin Alfstad of the National Centre for Epilepsy at Oslo University Hospital in Norway, and lead study author. Analysis also showed an increased risk of psychiatric problems for girls with epilepsy in the 10-13 year age group.

The current study findings confirm the psychiatric co-morbidity of epilepsy reported in prior studies. The authors noted that a lack of a standard age groups and methodology differences makes comparison of these studies difficult. “Multiple risk factors contribute to the high prevalence of psychiatric symptoms, differently in boys and girls, it seems,” concluded Dr. Alfstad. “Identifying high risk groups may help clinicians who can implement interventions that prevent more serious psychiatric problems.”

Material adapted from Wiley – Blackwell.

Reference
“Psychiatric Symptoms in Norwegian Children with Epilepsy Aged 8-13 Years: Effects of Age and Gender?” Kristin Alfstad, Jocelyne Clench-Aas, Betty Van Roy, Petter Mowinckel, Leif Gjerstad, Morten Lossius. Epilepsia; Published Online: March 25, 2011.

Dr. Sterman demonstrated that cats who received SMR-neurofeedback became resistant to seizures when exposed to jet fuel. He further hypothesized that SMR-neurofeedback might be able to produce a similar protective effect in humans.

Future studies would show that SMR-neurofeedback, which typically targets increased SMR (sensori-motor rhythm; 12 – 15 Hz on the sensori-motor strip) and decreased slow waves (often Theta or 4 – 8 hertz), did indeed reduce the number of seizures in those with seizure disorders, such as epilepsy. Moreover, these reduction in seizures occurred even in those with treatment resistant epilepsy.

The release of this classic study is a positive development for the field of neurofeedback. There is a strong push to disseminate neurofeedback research (as well as to conduct more studies) to the general public by the International Society for Neurofeedback and Research, the parent organization of the Journal of Neurotherapy, and the release of this free journal article this certainly helps to meet this important goal.

Download / Reference
M. B. Sterman, R. W. LoPresti, & M. D. Fairchild. Electroencephalographic and Behavioral Studies of Monomethyl Hydrazine Toxicity in the Cat. Journal of Neurotherapy, 14:293–300, 2010.

Citations
Tobias Egner and M Barry Sterman. Neurofeedback treatment of epilepsy: from basic rationale to practical application. Expert Review of Neurotherapeutics, February 2006, Vol. 6, No. 2, Pages 247-257 , DOI 10.1586/14737175.6.2.247

M. Barry Sterman and Tobias Egner. Foundation and Practice of Neurofeedback for the Treatment of Epilepsy. Applied Psychophysiology and Biofeedback, Volume 31, Number 1, 21-35, DOI: 10.1007/s10484-006-9002-x

The treatment called UPLIFT (Using Practice and Learning to Increase Favorable Thoughts) is a home-based depression prevention and treatment program. Based on mindfulness-based cognitive therapy, the weekly program was designed for group delivery via the phone or Web. It involves eight, hour-long sessions focused on increasing knowledge about depression, epilepsy, cognitive-behavioral therapy (CBT), and mindfulness.

Forty participants were randomly assigned to participate in the intervention or waitlist groups. Depressive symptoms and other outcomes were measured at baseline, after eight weeks, and after 16 weeks.

Depressive symptoms decreased by 64 percent in the intervention group but only by 15 percent in the waitlist group. There was no significant difference in results between participants who received the intervention via telephone or Internet.

“The Project UPLIFT intervention was effective in teaching people with epilepsy the knowledge and skills associated with reducing their symptoms of depression,” says lead study author Nancy Thompson, PhD, associate professor of behavioral science and health education at Emory’s Rollins School of Public Health. “Addressing the mental health needs of this population is important as many people with epilepsy – between 32 percent and 48 percent – report being depressed as well as feeling isolated and stigmatized.”

Future studies of the UPLIFT program will target other populations at risk of depression, such as caregivers or persons with disabilities, who may benefit from a home-based treatment. The U.S. Centers for Disease Control and Prevention funded the Project UPLIFT pilot study.

In addition to Thompson, study authors were Elizabeth Reisinger Walker, Natasha Obolensky, Ashley Winning, Christina Barmon, and Colleen Dilorio, of the Rollins School of Public Health; and Michael Compton of the Emory School of Medicine.

Material adapted from Emery University.

The team, led by BGU Prof. Ohad Birk of the National Institute for Biotechnology in the Negev determined that the defect is associated with the production of the 21st amino acid, selenocysteine (SEC), which leads to progressive brain atrophy.

According to Prof. Birk, “One out of every 40 Jews of both Moroccan and Iraqi ancestry may be carriers of this mutation. As the disease is both severe and common, testing for these mutations is expected to become a routine prenatal genetic screening test in these two populations, enabling prevention of future cases.”

It is believed that further research will identify other mutations in the same gene as the cause of mental retardation with epilepsy in other communities. As the disease is progressive, elucidation of its molecular mechanisms might open new venues to treatment, preventing disease progression.

The human genetic code, as deciphered some 50 years ago, encodes 20 amino acids which are the building blocks of all proteins in the human body. However, in recent years it became apparent that a 21st amino acid exists: selenium, entering the body in food, is incorporated in the human tissues into what is known as selenocysteine.

This 21st amino acid is unique in that it is encoded by what is normally a stop codon – that is, a DNA sequence that normally instructs the protein building system to end the chain of amino acids, terminating the generated protein. In contrast with most genes, some 25 genes have a unique component that manipulates the stop codon so that instead of terminating the evolving protein chain, it inserts at that point an SEC building block.

Material adapted from American Associates, Ben-Gurion University of the Negev.

Professor Andreas Schulze-Bonhage, head of the Epilepsy Center at the University Hospital Freiburg: “Unfortunately, a considerable fraction of all epilepsy patients do not respond well to commonly used pharmaceuticals. For these patients, an automatic prediction of their suddenly occurring seizures would offer great benefit – they could prepare for the epileptic attack, for example by taking fast-acting medicine.”

The scientists work on possibilities to detect pre-seizure changes in the brain. “In recent years, several methods were developed to calculate predictive features from the electroencephalogram, which measures brain waves”, says Professor Jens Timmer, physicist at the Freiburg Institute for Advanced Studies (FRIAS). Yet, for individual prediction methods no satisfactory performances could be observed up to now. Within the framework of the European Union funded project “EPILEPSIAE”, the research team studied whether a combination of different prediction methods could help to improve prediction performances. To this aim, a warning is given only if two methods trigger alarms during a short interval of time.

The study was based on the registrations of the electroencephalogram from eight patients, measured directly at the cortex. On average for all patients, the combination of methods yielded an increase in prediction performance by more then 50%, proving the approach to be auspicious.

“In our study, about every second seizure could be predicted correctly”, says Hinnerk Feldwisch-Drentrup from the Bernstein Center Freiburg. “While it is better than a random prediction, in the current state it seems not just yet to be sufficient for real clinical applications.” In order to investigate further possible improvements, the scientists compiled an extensive database of EEG recordings from currently 200 patients together with partners in France and Portugal. Additionally, real-time applications of their methods are planned to be studied in the near future.

Material adapted from Albert-Ludwigs-Universität Freiburg.

Reference
H. Feldwisch-Drentrup, B. Schelter, M. Jachan, J. Nawrath, J. Timmer, A. Schulze-Bonhage. Joining the benefits: Combining epileptic seizures prediction methods. Epilepsia 51, 2010, 1598-1606.

Past studies have shown decreased levels of BDNF in the serum of patients with psychiatric disorders such as major depressive disorder and conversion disorders (a condition in which a patient displays neurological symptoms such as numbness or seizures when no neurological lesion or pathology is found). Children with epilepsy have been found to have increased levels of BDNF compared to healthy controls. Serum BDNF levels, however, have not been investigated in adult patients with epileptic seizures (ES). With this in mind, researchers from Rhode Island Hospital hypothesized that BDNF would differentiate between ES and PNES.

W. Curt LaFrance, Jr., MD, MPH, director of neuropsychiatry and behavioral neurology at Rhode Island Hospital, and assistant professor of psychiatry and neurology (research) at The Alpert Medical School of Brown University led the study of three groups of patients — one group with confirmed PNES, one group with ES and one healthy control group. The patients were also screened for comorbid depression as well, as past studies have suggested that chronic antidepressant use increases serum BDNF in patients with depression. More than half (8 of 13) of the patients in the PNES group were diagnosed with mild depression and were taking psychotropic (antidepressant) medication.

LaFrance and his fellow colleagues from Brown University found decreased levels of serum BDNF in both the PNES and ES groups when compared to the healthy control group. They believe these findings are significant in that it would be expected that the PNES patients taking antidepressant medications would have an increased level of serum BDNF. There were no significant differences in the levels of serum BDNF among all the patients in the PNES group, whether they were taking antidepressants or not. As a result, they believe that the reduced levels of BDNF may be a biomarker for PNES.

LaFrance says, “While BDNF may play a similar role in the pathophysiology of depression and PNES, the differential response of serum BDNF to antidepressants in patients with psychogenic nonepileptic seizures could highlight an important difference. The fact that antidepressants did not increase serum BDNF levels in our study and that there were no BDNF differences between patients with PNES who were depressed and those who did not have depression would suggest that serum BDNF might represent a trait marker of PNES. This could potentially be useful in understanding the pathophysiology of conversion disorders.”

The study also found decreased levels of BDNF in adult patients with epileptic seizures, unlike the elevated levels found in children with ES. LaFrance comments, “This result is unexpected given the findings of elevated serum BDNF levels in children and the studies investigating BDNF concentrations in adult patients with ES.”

LaFrance noted, “A model that may provide a unifying hypothesis on the decreased serum BDNF findings in both seizure groups may not be related to seizures – it may be related to stress. Stress has been shown to lower BDNF, and a shared characteristic of patients with epilepsy or with nonepileptic seizures is fear of the next seizure. There may be great potential for biomarkers for PNES and for treatment response.” Based on these findings, LaFrance and his colleagues propose that additional studies of BDNF levels take place to provide further insight into the role of BDNF in seizure disorders.

Material adapted from Lifespan.

Researchers have long suspected that abnormal ion channels in the brains of individuals that cause epilepsy also put them at risk for sudden unexplained death in epilepsy, or SUDEP, perhaps by harming the heart. An ion channel is a protein that lets charged particles enter or leave a cell to generate electrical signals, a basic process of nerve cell communication.

A team of neuroscientists, led by Jeffrey Noebels, MD, PhD, of the Department of Neurology, Baylor College of Medicine, used an animal model to study a particular type of potassium ion channel called Kv1.1, which helps regulate electrical signals in the brain. In humans, mutation of the gene for Kv1.1 has been associated with spontaneous seizures, abnormal muscle movements, and motor coordination problems. Now Noebels and his colleagues have found that these channels are also required for proper heart function.

(click to enlarge) The pair of traces shows 25 seconds of simultaneous brain and heart activity, as recorded by electroencephalography-electrocardiography, during a seizure in a mouse lacking Kv1.1 ion channels shortly before it suffered sudden death. As the seizure progresses, the regular cardiac rhythm disappears temporarily and the heart beats only intermittently. (Credit: Courtesy, with permission: Glasscock et al. The Journal of Neuroscience 2010.)

In this study, they focused on Kv1.1 because studies have shown that mice without these channels show signs of severe epilepsy and involuntary movement, and they die prematurely. Noebels and his team investigated why the mice die and whether Kv1.1, in particular, is a possible factor for SUDEP.

The authors recorded electrical signals from the brains and hearts of mice bred to lack the gene for Kv1.1 channels to determine where and how the lethal abnormalities originated. The results showed that the hearts of the mutated mice skipped beats intermittently. When the mice had epileptic seizures, their heart beats became even more erratic — suggesting the signals from their brains to their hearts were disordered. The mice soon died after several episodes of cardiac arrest.

The researchers determined that in healthy animals these specific potassium channels are present in the brain and the vagus nerve, a bundle of axons that helps regulate cardiac rhythms, but are barely detectable in the heart. In the mutant mice, the brain signals sent to the heart through the vagus nerve were crippled.

“In mice without Kv1.1 channels, we think the vagus nerve loses control and sends extra nerve impulses to the heart, telling it to slow down — and even stop beating — when it shouldn’t,” said Edward Glasscock, PhD, first author of the study.

This potassium ion channel gene is the second such gene found by the group to cause abnormal electrical activity leading to death in epilepsy. “Now that we are starting to grasp the genes and proteins underlying SUDEP, we can begin to predict and find ways to reduce the risk of death in patients with epilepsy,” Noebels said.

Philip Schwartzkroin, PhD, of the University of California at Davis, who studies epileptic seizures and was unaffiliated with the study, said this new finding could be of considerable significance. “The potential association of this deficit with SUDEP provides insights that could lead to better treatments for at-risk patients,” he said. “Such progress would be very important given that SUDEP accounts for a high proportion of deaths in epilepsy patients.”

Schwartzkroin also pointed out that similar tests have yet to be tried for humans, and there may be multiple genes that contribute to SUDEP in different people.

Material adapted from Society for Neuroscience by CFisher.

Published in the Proceedings of the National Academy of Sciences (PNAS), Dr Cunningham said the findings marked a huge step forward in our understanding of a disease which affects an estimated 45 million people worldwide. “Until now we have only been able to mimic epilepsy using experimental animal models but this can never give you a true picture of what is actually going on inside the human brain in epilepsy,” explained Dr Cunningham who is based in Newcastle University’s Institute of Neuroscience. “Our findings help us to understand what is going wrong and are an important step towards finding new epilepsy treatments in the future.”

The Study
The first line of treatment for patients with epilepsy uses anti-epileptic drugs to control seizures. However, in almost 30 per cent of patients the drugs don’t work. In this case, one course of action available to them is a neurosurgical procedure in which the brain tissue responsible for the epilepsy is removed from the patient. Working in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital and IBM Watson Research Centre in New York, the team – with permission from the patients – have taken this epileptic tissue into the lab and ‘fooled’ it into thinking it is still part of the living brain.

Supported by experts in the University’s School of Computing Science, Dr Cunningham and the team have then been able to record electrical signals from individual neurons and also networks of neurons. Comparing this with normal brain tissue activity they managed to record an underlying ‘noise’ – a particular type of brain wave, or oscillation, which occurs in the intact epileptic human brain and which scientists believe is a precursor to an epileptic seizure.

Using a combination of experimental techniques, the team have shown that rather than being controlled by chemical signals which most conventional anti-epileptic drugs target, this oscillation relies on direct electrical connections. “This may explain why the traditional drugs that target chemical connections don’t work for patients with this kind of epilepsy,” explains Dr Cunningham, who conducted the research with his colleague Professor Miles Whittington.

Implications Of The Study
“These findings have massively increased our understanding of epilepsy and offer real hope in terms of finding new ways of tackling the disease. “The next step is to understand what it is that triggers the transition between the underlying epileptic state of the brain cells and the fast oscillations that are responsible for causing a seizure.”

Adapted from Newcastle University by CFisher