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Scientists uncover how rare gene mutation affects brain development and memory

Researchers from the University of California, Irvine School of Medicine, have found that a rare gene mutation alters brain development in mice, impairing memory and disrupting the communication between nerve cells. They also show memory problems could be improved by transplanting a specific type of nerve cell into the brain. The findings were published today in Neuron.   “Mutations in hundreds of genes have been linked to neurodevelopmental disorders, many of which have devastating behavioral consequences that cannot be managed with available treatment options,” explained Robert Hunt, Ph.D., assistant professor of Anatomy & Neurobiology, who led the study with Young Kim, Ph.D., a postdoctoral fellow. “Now, a major challenge in the field is to identify the underlying cause for each of these rare genetic disorders so that new, disease-specific therapies can be developed.” The UCI team focused on the gene CHD2, which scientists believe modifies the structure of chromatin—the coiled complex of DNA and proteins—and controls expression of hundreds of other genes. Normally, humans have two copies of the CHD2 gene. However, in some cases, one copy is lost, which can lead to developmental disorders such as intellectual disability, epilepsy or autism. To mimic the human disorder and better understand how CHD2 is involved in brain development, Hunt and his colleagues created mice that possess only one functioning copy of the CHD2 gene. Remarkably, the mice had severe memory problems and an increase in electrical oscillations in the brain, features similar to the condition in people. A closer look at the animals’ brains revealed an abnormal development of brain circuitry, including changes in the way neurons communicate with each other, and fewer inhibitory interneurons, which control the activity of brain circuits. The mouse neurons also showed differences in the expression of more than 100 other genes associated with neurodevelopmental disorders. In the embryo, many of the altered genes are involved in critical biological processes like neurogenesis, but in adult animals, genes associated with neuronal activity and synapse function were changed. That insight indicated CHD2 may play different roles in early brain development and adulthood. The findings prompted Hunt’s team to transplant embryonic progenitor cells capable of generating inhibitory internerneurons into the brains of the mutant mice. They targeted the hippocampus, a brain region critical for learning and memory, for cell transplantation. “Inhibitory neurons regulate oscillatory rhythms that are required for memory functions,” Hunt said. “We’ve been developing a similar interneuron cell therapy for epilepsy, so we naturally thought of trying this approach in mice with CHD2 mutation.” In the UCI study, the transplanted inhibitory cells migrated throughout the hippocampus and generated new interneurons, in effect replacing the brain cells that were missing in the mutant mice. In addition to having more inhibitory nerve cells, the treated mice showed a dramatic improvement in hippocampal-dependent memory. “At least in principle, it should be possible to develop targeted therapies for genetic disorders like CHD2 mutation,” Hunt said. “That would be great, because in many cases, the medications that are currently available offer no therapeutic value at all.” While the new research offers an important step toward understanding the role of CHD2 in brain development and function, further studies are necessary before interneuron progenitors can be used for cell therapy in the clinic. The Hunt lab next aims to evaluate brain wiring in the mouse model more closely and to explore how CHD2 mutations affect different neuronal pathways.   Journal reference: Neuron   Provided by: University of California, Irvine Related posts: Researchers Identify New Link Between Gene Expression and Brain Memory Processing How an autism gene mutation alters brain development Scientists discover mutation limited to brain tissue that causes HMG Scientists Uncover a Difference Between the Sexes

New causative gene found in severe childhood epilepsy

A large international research team has discovered a new genetic cause for a severe, difficult-to-treat childhood epilepsy syndrome. Spontaneous mutations in one gene disrupt the flow of calcium in brain cells, resulting in epileptic overactivity. The team’s research in patients also found clues to potential medical treatments for the rare condition. “Even though variants in this gene were only just discovered to cause disease, we already have a good understanding of how changes in the gene’s associated protein affect brain function—causing neural overactivity in epilepsy,” said first author Katherine L. Helbig, MS, CGC, a research genetic counselor in the Neurogenetics Program in the Division of Neurology at Children’s Hospital of Philadelphia (CHOP). “Furthermore, although much follow-up research remains to be done, we found that there is a possibility that specific anti-seizure medications could reduce this overactivity in some patients.” The senior authors of this large international study, published online today in the American Journal of Human Genetics, were Heather C. Mefford, MD, Ph.D., of the University of Washington, and Holger Lerche, MD, of the University of Tuebingen, Germany. The full research team included nearly 100 scientists, from Europe, Canada, China, Australia, New Zealand and the United States. Katherine L. Helbig, MS, LCGC, is a genetic counselor in the Division of Neurology at Children’s Hospital of Philadelphia. Credit: Children’s Hospital of Philadelphia The research team focused on disease-causing changes in the CACNAIE gene, long suspected to play a key role in how neurons regulate their electrical activity, but not previously known to cause human disease. This study was the first to link the gene to human epilepsy. By doing next-generation sequencing in 30 infants and young children with severe epilepsy, the team pinpointed disease-causing variants in CACNA1E. In most cases, the gene variants were de novo—present in the affected children, but not found in their parents. De novo variants are being increasingly found in severe childhood epilepsies. “The fact that we were able to identify 30 patients at this stage of research indicates that we could be looking at a more common cause of genetic epilepsy than we would have initially assumed,” said Helbig. She added, “This research enables us to give some families an answer as to why their child has severe epilepsy. It also offers the potential that we can build on this knowledge to find new strategies for treatment.” In addition to having difficult-to-treat epilepsy, most of the affected children had severe developmental delays, low muscle tone, contractures starting at birth and movement disorder. “Many of the children were initially thought to have a severe muscular condition because of their contractures,” said Helbig. “We were surprised to find that a genetic epilepsy had such severe symptoms.” Helbig is a specialist genetic counselor in CHOP Neurology, which has deep experience in investigating and treating genetic epilepsies. The de novo mutations disrupt a calcium channel in brain cells, causing the channel to activate too easily or to inactivate too slowly, and giving rise to epilepsy. In some cases, the study team found the increase in calcium current was too high to measure. Most of the 30 patients did not respond to any anti-epileptic medications, except for a few who responded to the medication topiramate, known to target the CACNA1E channel. Further systematic work, said Helbig, will investigate this finding and other aspects of their research, with the aim of translating their knowledge into targeted precision therapies for children with severe genetic epilepsy. Provided by: Children’s Hospital of Philadelphia Related posts: Research reveals new insights into severe childhood epilepsy Researchers exploit gene discovery in severe epilepsy to identify precision treatment Severe Forms Of Childhood Epilepsy Caused By Gene Mutations European epilepsy consortium uses novel combination of technologies to identify new gene for severe childhood epilepsy

Childhood Seizures After Phototherapy

A follow-up study of Danish babies with neonatal hyperbilirubinaemia* who had been treated with phototherapy discovered a modest increase in the risk of childhood epilepsy. The finding has now been replicated in a large database analysis from the United States. Phototherapy is associated with an increase in the likelihood of epilepsy by 30% to 40% and the risk seems to be greater in boys than girls. Phototherapy (light treatment) is the process of using light to eliminate bilirubin in the blood, many time used on newborn babies with jaundice. * A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME**, is normally excreted in the BILE or further catabolized before excretion in the urine. **An iron-containing compound of the porphyrin class that forms the nonprotein part of hemoglobin and some other biological molecules. Related posts: Study: Infants’ jaundice treatment may increase risk of developing epilepsy A Chronic Childhood Illness Like Epilepsy Could Increase Risk of Adult Depression, Study Reports Severe Forms Of Childhood Epilepsy Caused By Gene Mutations Maternal linked to childhood epilepsy

Just the right dose: antiepileptic drug clearance changes during pregnancy

Study finds significant changes in how seizure medications are metabolized during the different trimesters of pregnancy BRIGHAM AND WOMEN’S HOSPITAL During pregnancy, the numerous physiological changes a woman’s body undergoes can alter the way medications are metabolized, the rate at which they are cleared, and their overall effectiveness. Many women continue taking antiepileptic drugs (AEDs) during pregnancy, but while many studies address their safety, it has been unclear if the drug’s effectiveness may be altered during pregnancy. A new study by investigators from Brigham and Women’s Hospital examined whether pregnancy-related changes may influence how effectively five common AEDs prevent seizures and found that AED clearance significantly changes by the first trimester for the most commonly used medication and by the second trimester for two others. Their results are published in Neurology. “We want to be able to give the exact dose of a drug that keeps a woman seizure-free and keeps her and her baby safe, but there are relatively few studies that have examined pregnancy-related changes in AED metabolism for us to know how to adjust this dose,” said lead author P. Emanuela Voinescu, MD, PhD, associate neurologist in the Department of Neurology at BWH. “We sought to fill that gap about changes in AED metabolism during the different trimesters of pregnancy.” The team investigated five commonly used drugs, including levetiracetam – one of the most widely used medications during pregnancy – oxcarbazepine, topiramate, phenytoin, and valproate. The prospective, observational study, started by senior author Page Pennell, MD, while at Emory University, consisted of 40 women with epilepsy who were planning to conceive or were less than 16 weeks pregnant, and who chose to continue their AEDs during pregnancy. Study visits occurred every one to three months and for the first postpartum year. Drug clearance values, the dose required to maintain a certain blood serum concentration, were obtained via blood draw at baseline and during pregnancy. Seizure occurrence and frequency were recorded throughout the study. Researchers found that the metabolic changes affecting levetiracetam started early, in the first trimester, and drug clearance remained elevated during the second and third trimesters. In contrast, they found that oxcarbazepine and topiramate had elevated clearance starting in the second trimester. This is important because if drug clearance increases, patients may need to be prescribed a higher or more frequent dose of their antiepileptic medication. “It is already a challenge to be pregnant and our patients have to deal with epilepsy on top of it. It requires a little more work because of all the frequent blood draws and medication adjustments” said Voinescu. “It would be nice to be able to simplify their management by having more scientific guidelines in place regarding how to adjust medication doses during pregnancy to keep them seizure-free and to keep their babies safe.” Funding for this work was supported by an NIH Specialized Center of Research (P50MH 68036) NCRR M01-RR00039, NINDS and NICHD (U01 NS038455), the American Brain Foundation, American Epilepsy Society and the Epilepsy Foundation as the Susan Spencer Clinical Research Training Fellowship and the Karger Fund. Paper cited: Voinescu, E et al. “Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy” Neurology DOI:10.1212/WNL.0000000000006240 Related posts: Study identifies genetic variants associated with severe skin reactions to commonly used antiepileptic drug Safety of Antiepileptic Drugs During Pregnancy High dose of Topiramate during pregnancy can up the risk of cleft lip or cleft palate in babies Antiepileptic drugs during pregnancy: Folic acid could help to prevent autism

Nocturnal Monitoring May Reduce SUDEP in Severe Epilepsy

Monitoring patients with severe epilepsy in residential care facilities during the night was associated with a much lower rate of sudden unexplained death in epilepsy (SUDEP), a new study found. “Our study was conducted in patients with severe epilepsy and learning difficulties in a residential care institution,” senior author Roland D. Thijs, MD, Stichting Epilepsie Instellingen Nederland, commented to Medscape Medical News. Nocturnal monitoring of such patients varies “hugely” between different institutions, he noted. “There are no guidelines on this, so each center makes their own decisions on monitoring within their budgets. “Our results now provide enough evidence for some initial guidance on this — that these patients should receive nocturnal monitoring, probably with an acoustic listening device as the first step,” he added. In an accompanying editorial, Orrin Devinsky, MD, Daniel Friedman, MD, New York University Langone Medical Center, New York City, and Frank M. C. Besag, FRCP, East London National Health Services Foundation Trust, Bedford, United Kingdom, say the study provides additional evidence that certain populations of patients with epilepsy should be monitored during sleep to prevent SUDEP. They suggest that better SUDEP prevention could be brought about by “focused monitoring…at high-risk times for individual patients (when their convulsive seizures are most likely) and when SUDEP is most common (sleep). “Because 85% – 90% of SUDEPs are unwitnessed, it seems as if witnesses can prevent SUDEP. Observations in epilepsy units suggest that peri-ictal intervention could mitigate deleterious consequences of seizures,” they add. “For instance, earlier stimulation and oxygen application by a nurse is associated with shorter postictal coma and EEG suppression. An untrained caregiver, who simply turns a postictal patient on their side and frees the airway and stimulates the patient by calling their name, may prevent SUDEP.” In their article, Thijs and colleagues note that SUDEP is mostly a sleep-related, unwitnessed event, and although the incidence of SUDEP is substantial, at 3.6 to 3.8 per 1000 person-years, recommendations for nocturnal supervision are lacking. For this nested case-control study, the researchers reviewed records of all people who died during a 25-year period at two residential care facilities (one in the Netherlands and one in the United Kingdom). Participants were adults with severe epilepsy; >90% had convulsive seizures, and 50% were receiving three or more antiepileptic drugs. The patients also had intellectual disabilities. The Dutch center had the most intensive nocturnal monitoring. This included a central acoustic detection system that covered all residents, as well as bed motion sensors and video monitoring for those suspected of having had unwitnessed nocturnal events during the study period. The UK center had no central nocturnal seizure detection system, but the institutional protocol recommended that all residents be physically checked once every 15 or 30 minutes. The researchers identified 60 patients who died of SUDEP and 198 matched control persons from the same institutions. Results showed that people who died of SUDEP were more likely to have had nocturnal convulsive seizures in general (77% of patients vs 33% of control persons; P< .001). In addition, the frequency of nocturnal convulsive seizures was higher among patients who died by SUDEP. The total SUDEP incidence was 3.53 per 1000 patient-years, although the incidence differed widely between the two centers. At the UK center, which was the center with less intensive nocturnal monitoring, the incidence of SUDEP was nearly threefold higher (6.12 vs 2.21 per 1,000 patient-years). This difference was not explained by other factors, such as seizure severity. The authors point out that this study has five times more person-years of data than previous studies. They write that the results confirm that the occurrence of nocturnal convulsive seizures, as well as a high frequency of such seizures, are independent risk factors for SUDEP. They say the strong association between SUDEP and sleep is explained by two factors: prone position, and the absence of a witness. “Most SUDEP cases are found in the prone position, which is remarkable as people seldom are prone after nonfatal convulsive seizures,” they write. “When an individual is in the prone position after a seizure, respiratory dysfunction may lead to apnea and asystole, which should normally evoke an arousal response. Postictal coma might, however, prevent arousal and thus the resumption of ventilation, consequently leading to SUDEP.” Nursing interventions, including repositioning and oxygen administration, have been reported to significantly shorten the duration of respiratory dysfunction after a convulsive seizure, they add. “Further study of the mechanisms involving nursing interventions (other than cardiopulmonary resuscitation) may help prevent postictal coma or even SUDEP,” the authors note. They conclude that this study and two previous reports “suggest that nocturnal supervision is protective for SUDEP.” Of the two previous reports, the first was a case-control study in which patients who died by SUDEP were less likely to have had a roommate or to have been given a listening device compared with the control patients. The second was a cohort study of children with severe epilepsy and intellectual disabilities. In this study, all 14 SUDEP deaths occurred while the students were not under the supervision of the boarding school because they had left the school or were on leave. The authors point out that the variation in nocturnal supervision among the two sites in the current study were predominantly explained by the implementation of an acoustic detection system in the Dutch center. “Acoustic detection systems are often useful, as in 85% of tonic-clonic seizures, an ictal cry is heard,” they add. To Medscape Medical News, Thijs said acoustic listening devices “would be a good first step. Other measures could be added if it is thought seizures are being missed with the acoustic device.” He said the study results could not be extrapolated to patients living at home. “Our population was made up of patients with severe epilepsy and learning disabilities in residential care. This is a very specialized set of circumstances. We need to study the home setting separately.” In their editorial, Devinsky, Friedman, and Besag agree that the data from the study fall far short of establishing a mandate that all patients with epilepsy be monitored. They note that more research is needed on night-time monitoring strategies and SUDEP prevention. They also write of “the relative value of different strategies, the absolute value of any strategy, which populations are most important to monitor, and which populations may be least important to monitor. “Worldwide, there are around 60 million people with epilepsy and 80,000 SUDEPs per year,” they write. “If we monitor every person with epilepsy every night, how many false alarms will we create, with lost sleep and anxiety for the patient and caregiver? How many SUDEPs will we prevent? How much guilt will result from not responding quickly to an alarm?” They conclude that SUDEP research “should move from observational and retrospective case-control studies to prospective preventive studies.” Source: MedScape by S. Hughes from Neurology. Published online September 21, 2018. Related posts: Could antidepressants help reduce the risk of sudden unexpected death in epilepsy? What is the Brain Sentinel® Monitoring and Alerting System? SUDEP: Sleeping Position Linked to Risk of SUDEP RAISING SUDEP AWARENESS IN PEDIATRIC EPILEPSY

Unplanned Pregnancy May Double Miscarriage Risk in Epilepsy Patients

The rate of miscarriage was doubled in women with epilepsy whose pregnancies were unplanned, a survey of Epilepsy Birth Control Registry participants found. Among women with epilepsy, spontaneous fetal loss occurred in 35% of unplanned versus 16% of planned pregnancies, reported Andrew Herzog, MD, MSc, of Beth Israel Medical Center in Boston, and colleagues in JAMA Neurology. “This is important because unplanned pregnancy is very common among women with epilepsy, more common than in the general population,” Herzog told MedPage Today. About 65% of pregnancies in women with epilepsy are unplanned, despite epilepsy practice guidelinesthat suggest these women “plan pregnancies to occur when they have achieved optimal seizure control on the minimum effective dosage of antiepileptic drugs and take folic acid supplement before conception to achieve optimal maternal and fetal outcomes,” Herzog added. Reasons behind these practice guidelines have been evident for years: prenatal exposure to valproate (Depakote) has been tied to autism and impaired cognitive development in children, prompting FDA warnings about using the drug during pregnancy. And while research indicates that newer anti-epileptic drugs like levetiracetam (Keppra) or topiramate (Topamax) during pregnancy are not linked to reduced cognitive abilities in children, a recent study showed that women on anti-seizure medications who did not take folic acid supplements before conceiving had a substantially increased risk of children with autistic traits. “Discussion about the importance of planned pregnancies should be part of standard care by neurologists carrying for teens and women with epilepsy,” said Page Pennell, MD, of Brigham and Women’s Hospital in Boston, who was not involved with the study. “To increase the likelihood of a planned pregnancy, the neurologist should also be directly engaged in education of the patient and her other healthcare providers if the anti-seizure medicine prescribed interacts with hormonal contraceptives and lowers their efficacy,” Pennell told MedPage Today. “In those situations, long-acting reversible contraceptives such as intrauterine devices should be encouraged.” In this study, researchers conducted a web-based retrospective survey from 2010 to 2014 on women with epilepsy from the Epilepsy Birth Control Registry. The average age of survey respondents was 28.5 years; nearly 4 in 10 had household incomes of $25,000 or less, and minority women represented 8.7% of participants. Respondents reported that 794 pregnancies had occurred: 530 were unplanned (66.8%) and 264 were planned (33.2%). Among 653 unaborted pregnancies, the risk for spontaneous fetal loss was greater for unplanned (n=137 of 391, 35.0%) than planned (n=43 of 262, 16.4%) pregnancies (RR 2.14, 95% CI 1.59-2.90, P<0.001). Regression analysis identified an interpregnancy interval of less than 1 year and conception age under 18 or over 37 years as predictors of spontaneous fetal loss. Miscarriage frequencies were comparable among women who did and did not use antiepileptic drugs during pregnancy. “The Epilepsy Birth Control Registry has previously published that a substantial minority of women with epilepsy do not use highly effective contraception despite their increased risk for having offspring with major congenital malformations,” Herzog said. “The current findings strengthen the need for the education of patients and healthcare providers in this regard.” The researchers listed several important limitations to the study, including its reliance on self-reported information not verified by medical records. Stigmatized health information tends to be underreported, they pointed out, and it’s possible women reported fewer induced abortions in favor of miscarriage, despite survey anonymity and the option to not answer questions about pregnancy outcome. Minority women also were underrepresented in the sample. This study was funded by the Epilepsy Foundation and Lundbeck. Researchers reported relationships with the Epilepsy Foundation and Lundbeck. Source: By J. George MedPage Today Related posts: Epilepsy and pregnancy Could dietary supplement in pregnancy reduce autism risk? Understanding Stroke Risk in Pregnancy High dose of Topiramate during pregnancy can up the risk of cleft lip or cleft palate in babies

What are the health effects of chronic stress?

We share this article since we all know stress is a trigger for seizures. EpilepsyU Short-lived feelings of stress are a regular part of daily life. When these feelings become chronic, or long-lasting, they can severely impact a person’s health. In this article, we look at what chronic stress is, how to identify it, and the medical consequences it can have. We also describe ways to manage stress, including medical treatments, and when to see a doctor. What is chronic stress? Signs of chronic stress can include headaches, fatigue, and low self-esteem. Stress is a biological response to demanding situations. It causes the body to release hormones, such as cortisol and adrenaline. These hormones help prepare the body to take action, for example by increasing the heart and breath rates. When this occurs, a doctor might describe a person as being in a state of heightened alertness or arousal. Many factors can trigger a stress response, including dangerous situations and psychological pressures, such as work deadlines, exams, and sporting events. The physical effects of stress usually do not last long. However, some people find themselves in a nearly constant state of heightened alertness. This is chronic stress. Some potential causes of chronic stress include: high-pressure jobs financial difficulties challenging relationships Chronic stress puts pressure on the body for an extended period. This can cause a range of symptoms and increase the risk of developing certain illnesses.   Signs and symptoms Chronic stress affects the whole body. It can have several physical or psychological symptoms, which can make functioning on a daily basis more challenging. The type and severity of symptoms vary considerably from person to person. Signs and symptoms of chronic stress can include: irritability, which can be extreme fatigue headaches difficulty concentrating, or an inability to do so rapid, disorganized thoughts difficulty sleeping digestive problems changes in appetite feeling helpless a perceived loss of control low self-esteem loss of sexual desire nervousness frequent infections or illnesses   Health consequences Over long periods, chronic stress can contribute to the development of a range of physical and mental disorders, including: Chronic stress can contribute to high blood pressure. heart disease high blood pressure diabetes obesity a weakened immune system sexual dysfunction gastrointestinal disorders skin irritation respiratory infections autoimmune diseases insomnia burnout depression anxiety disorders post-traumatic stress disorder, or PTSD schizophrenia   Managing stress Chronic stress can seem overwhelming, and a person may feel unable to regain control over their life. However, a number of strategies can help to reduce stress levels and improve well-being. Some methods for managing stress include: Understanding the signs and symptoms. These indications can vary, but if a person can recognize their own signals of stress, they will be better able to manage them. Speaking to friends and family. They can provide emotional support and the motivation to take action. Identifying triggers. It is not always possible to avoid triggers of stress. However, taking note of specific triggers can help a person to develop coping and management strategies, which may involve reducing exposure. Exercising regularly. Physical activity increases the body’s production of endorphins, which are chemicals that boost the mood and reduce stress. Exercise can involve walking, cycling, running, working out, or playing sports. Trying mindfulness. People who practice this form of meditation use breathing and thought techniques to create an awareness of their body and surroundings. Research suggests that mindfulness can have a positive impact on stress, anxiety, and depression. Improving sleep quality. Getting too little sleep or sleep of poor quality can contribute to stress. Try to get at least 7 hours every night, and set regular times for going to sleep and waking up. Avoid caffeine, eating, and intense physical activity in the hours before bed. It can also help to unwind before sleeping, by listening to music, reading a book, taking a warm bath, or meditating, for example. Treatment If strategies such as those listed above are not helping, it is important to see a healthcare professional for advice and support. A doctor may recommend psychological therapy, such as cognitive behavioral therapy (CBT). One established aim of CBT is to help people deal with chronic stress. In structured sessions, a therapist works to enable a person to modify their behaviors, thoughts, and feelings concerning stressors. CBT can also help a person develop tools and coping mechanisms to manage stress responses. Sometimes, a doctor recommends medications to help treat some symptoms of chronic stress. For example, they may prescribe antidepressants to treat anxiety or depression. For people with trouble sleeping, doctors may prescribe sedatives.   When to see a doctor Do not try to deal with chronic stress alone. If self-help strategies are not working, a doctor can provide support and advice about treatment options. They can also refer a person to a more specialized healthcare provider, such as a psychologist or psychiatrist. Anyone feeling overwhelmed by stress should see a doctor as soon as possible, especially if they are having suicidal thoughts or using drugs or alcohol to cope.   Takeaway Stress is a regular part of daily life. Short-lived stress is generally harmless, but when it lasts and becomes chronic, it can cause a range of symptoms. It can also contribute to the development of physical and mental disorders. Self-help techniques include identifying triggers, developing coping and avoidance strategies, reaching out to friends and family, and practicing mindfulness. If these techniques are not working, or if stress is becoming overwhelming, a person should speak to a healthcare professional. Source: Article by A. Kandola Reviewed by T. Legg, PhD, CRNP Related posts: Activation of MMP-9 enzyme (Involved in ALS, Epilepsy) leads to behavioral problems connected to chronic stress Epilepsy Neurology / Neuroscience Pediatrics / Children’s Health Childhood-onset epilepsy has long-term effects on patients’ health and social status HOW TO BE A “FRIEND” TO SOMEONE WITH A CHRONIC HEALTH CONDITION What are Barbiturates? Uses, Side Effects and Health Risks

FDA Expands Use of Epilepsy Drug Perampanel (Fycompa) to Younger Children

The US Food and Drug Administration (FDA) has granted expanded approval of perampanel (Fycompa, Esai Inc) for the treatment of “partial-onset seizures (POS) with or without secondary generalized seizures” in patients as young as 4 years, the manufacturer reports. The expanded indication is for both monotherapy and adjunctive use in patients 4 years of age and older. The drug was initially approved in 2012 as adjunctive treatment for POS. This was followed in 2015 by approval as adjunctive treatment for primary generalized tonic-clonic seizures in patients with epilepsy who were at least 12 years of age, and in 2017 as monotherapy for POS with or without secondary generalized seizures in the same age group. To date, the drug “is approved in 55 countries and has treated more than 200,000 patients worldwide across all indications,” the company reported in a press release. The new approval for the antiepileptic drug (AED) includes both film-coated tablet and oral suspension formulations. The former is available in 2-, 4-, 6-, 8-, 10-, and 12-mg doses; the latter is available at a dose of 0.5 mg/mL. “Taking an AED as prescribed every day is a critical part of reaching the goal of seizure freedom for pediatric patients,” Jesus Eric Piña-Garza, MD, pediatric neurologist at TriStar Medical Group Children’s Specialists, Nashville, Tennessee, said in the same release. “With Fycompa, children and their parents now have a once-daily dosing option with a long half-life that can fit into their increasingly busy lives,” added Piña-Garza. AMPA Receptor Antagonist It is currently estimated that approximately 470,000 US children have epilepsy. Of these, up to 40% will have uncontrolled seizures even with existing treatments. The company notes that “breakthrough seizures” can also occur because of a number of factors, including illness, loss of sleep, and missed medication doses. “Fycompa has a long half-life and in a pharmacokinetic study, it has been demonstrated that in the event of a missed dose, plasma levels remain relatively stable,” it adds. The drug is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. In addition to past phase 3 trials of adults with POS, two safety studies of children with epilepsy aged 4 to 11 years have been conducted. In the safety studies, 225 pediatric patients received the drug at baseline, 110 were exposed to the drug for at least 6 months, and 21 were exposed for at least a year. Adverse reactions “were similar to those seen in patients 12 years of age and older,” the company reports. It adds that final results of these studies will be presented at an upcoming medical meeting. The company notes that perampanel, “like other AEDs, may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.” It also may cause psychiatric problems, such as new or worse aggressive behavior or hostility, hallucinations, paranoia, confusion, extreme changes in mood, or memory difficulties. Other adverse events (AEs) may include dizziness, sleepiness, increased risk for falls, and serious allergic reactions. The most commonly reported AEs include dizziness, tiredness, irritability, falls, nausea and vomiting, and weight gain. The US Drug Enforcement Administration has designated the product as a federally controlled substance (CIII).   Related posts: Perampanel Distributes is Europe, Maker Eisai keeps Prices Low Eisai Launches New Oral Suspension Formulation for Antiepileptic Drug Fycompa (Perampanel) in the United States Study shows Fycompa® (perampanel) provides sustained seizure control for people living with epilepsy Pivotal global Phase III study data for Fycompa® (perampanel) in primary generalised tonic-clonic seizures now published in Neurology

Epilepsy drug (Gabapentin/Neuronton) linked to opioid misuse

A recent study conducted by Duquesne University professor John Tomko has linked high dosages of the epilepsy drug Gabapentin to opioid abuse. Based on the findings of the study, Tomko recommends prescribing and distributing Gabapentin with more scrutiny and oversight. Gabapentin, brand name Neurontin, has been formally approved by the Food and Drug Administration (FDA) to treat symptoms of epilepsy, such as seizures and post herpetic neuralgia, a type of pain caused by shingles. According to Tomko, however, Gabapentin has been used off-label (i.e., not approved by the FDA) to treat other ailments such as back pain, anxiety, bipolar disorder, migraines and more. Tomko’s study found that subjects in UPMC Mercy’s Behavioral Health units were twice as likely to test positive for illicit drug abuse and Hepatitis C when they were taking more than 1800 milligrams of Gabapentin a day. Courtesy of John Tomko  John Tomko is an associate professor at the university’s School of Pharmacy. Tomko noted that these off-label prescriptions of Gabapentin are often unclear. “Many of these off-label uses have little positive data supporting their use or may even have outcomes that do not support their use,” Tomko said. “Previous works have shown that patients may be using [Gabapentin] to enhance the effect of illicit opiates or opiate replacement treatments such as methadone or buprenorphine.” It is this link between Gabapentin and opiates with which Tomko’s study was concerned. The study was first prompted by a correlation between patients visiting UPMC Mercy’s mental health units who tested positive for drugs of abuse, and who had also been prescribed Gabapentin for off-label purposes. While other previous studies have shown that Gabapentin is often abused, Tomko’s study sought to provide a model that can predict opiate abuse when a patient requests a high dose of Gabapentin from his or her doctor. The study, which lasted from December 2015 to January 2017, focused on all patients admitted to UPMC Mercy Behavioral Health units. Tomko’s research found that, of the 23.3 percent of patients who were prescribed Gabapentin, only 6.7 percent were taking the drug for an FDA-approved purpose. This, combined with the fact that 67.2 percent of Gabapentin users were taking 1800 milligrams a day or more, suggested to researchers that there was a problem with the use of Gabapentin among patients. Of particular note was the fact that 9 percent of patients prescribed Gabapentin were doing so with an “undetermined reason for use,” according to Tomko. Tomko stressed that this study identifies Gabapentin as a drug used to enhance the effect of opioids, rather than as a gateway drug to opioid abuse itself. Being the first study of its kind to provide a predictive model for drug abuse, Tomko hopes that the findings of his study will cause doctors to consider prescribing Gabapentin with more scrutiny. “If a patient is persistent in their requests, a physician may wish to inquire more about the reasons for the request and perhaps even request a urine drug screen to rule out illicit substance use,” Tomko said. He believes that the findings of this study support potentially considering Gabapentin as a controlled substance by the Drug Enforcement Administration. Douglas J. Bricker, dean of the School of Pharmacy at Duquesne, praised Tomko and his study. “The research conducted by Tomko provides primary care physicians and other healthcare prescribers with pertinent information to recognize that patients who are prescribed or who ask for higher doses of Gabapentin should be aware of the association between this behavior and Substance Use Disorders,” Bricker said. “In this era of extensive opioid misuse, having predictive warning tools … can be very beneficial in combating the overuse and misuse of opioids.” Tomko’s study adds not only to the existing body of work surrounding Gabapentin and its potential for misuse, but also provides a clear indication that high doses of the drug — often prescribed for unclear or off-label purposes — is linked to abuse of opioids. Tomko and his team hope that this study will help physicians recognize more subtle signs of substance abuse and will raise awareness of substance use disorders. Source: dugsm.com Related posts: PAIN MANAGEMENT: AAN releases new position statement on opioids for chronic non-cancer pain Medical Marijuana Laws Linked to Fewer Opioid Deaths Drug warning: Epilepsy drug Potiga linked to skin and eye abnormalities (Video) Drug Used for Pain, Anxiety May Be Linked to Birth Defects

Study: Infants’ jaundice treatment may increase risk of developing epilepsy

Treating newborns for jaundice with phototherapy could increase the child risk of developing epilepsy, especially in boys, according to a study. Researchers analyzed data from 499,642 children born between 1995 and 2011 in the Kaiser Permanente Northern California healthcare system and followed up for an average of 8 years. The findings were published in the September Pediatrics journal. Photo: A study found treating newborns for jaundice with phototherapy could increase the child risk of developing epilepsy. Photo by Dr. Hudson/Wikimedia Commons  “Phototherapy may have delayed adverse effects that should make us more cautious about using it, and not use it in babies who don’t need it,” first author Dr. Thomas Newman, professor emeritus of epidemiology and biostatistics and pediatrics at University of California San Francisco said in a press release. Neonatal jaundice affects up to 84 percent of term newborns, according to the American Academy of Family Physicians. Jaundice develops from the build-up of bilirubin, which is a yellow pigment in the bloodstream. Bilirubin normally is a byproduct of the breakdown of red blood cells, but at high levels the compound is toxic to brain cells and can cause permanent damage. The peak bilirubin levels are about three to seven days after birth. Then, livers mature and become capable of processing the compound. Also, mothers will begin producing higher-calorie mature milk, which helps increase bilirubin excretion. Phototherapy lowers bilirubin levels. Blue light is absorbed through their skin, and then changes the shape of the bilirubin molecules and renders them water-soluble. They are more easily excreted. In the study 37,683 of the children — or 7.6 percent — received phototherapy. In the treated group, about 1.24 children per 1,000 per year received at least one seizure diagnosis and at least one prescription for an antiepileptic drug. That compared with 0.76 per 1,000 per year in the untreated group. After statistical adjustment for factors that might lead to phototherapy and seizures, those exposed to the therapy had a 22 percent higher risk of experiencing these outcomes. “It looks like phototherapy increases the risk of seizures in boys, but we can’t say whether it does so in girls,” Newman said. Physicians sometimes will administer phototherapy even if a baby’s bilirubin levels likely will fall naturally, said Newman. “Phototherapy is sometimes done during the birth hospitalization to try to reduce the chances of having to draw more bilirubin levels and treat with phototherapy later,” he said. “That would make sense if we were sure phototherapy were harmless. But data like these suggest that we should treat only babies that really need phototherapy now, not those who might need it later.” The American Academy of Pediatrics recommends phototherapy based on gestational age, sex and time since delivery for the treatment as well as risk factors of significant bruising, exclusive breastfeeding, anemia and a sibling with a history of neonatal jaundice. Source: UPI.com By A. Cone Related posts: A Chronic Childhood Illness Like Epilepsy Could Increase Risk of Adult Depression, Study Reports New Study – Premature Birth May Increase Risk Of Epilepsy Later In Life Bad Weather May Increase Risk of Seizures in People with Epilepsy, Study Suggests TSC Infants at Risk of Seizures to Be Treated with Sabril as Preventive Measure in Study