What is the best medicine for children with seizures?

This article discusses what is the best medication for children with seizures.

A recently published clinical study in the Journal of the American Medical Association has answered an urgent question that long puzzled ER pediatricians: Is the drug lorazepam really safer and more effective than diazepam – the U.S. Food and Drug Administration-approved medication as first line therapy most often used by emergency room doctors to control major epileptic seizures in children?

The answer to that question – based on a double-blind, randomized clinical trial that compared outcomes in 273 seizure patients, about half of whom were given lorazepam – is a clear-cut "no," said Prashant V. Mahajan, M.D., M.P.H., M.B.A, one of the authors of the study.

"The results of our clinical trial were very convincing, and they showed clearly that the two medications are just about equally effective and equally safe when it comes to treating status epilepticus [major epileptic brain seizures in children]," Dr. Mahajan said. "This is an important step forward for all of us who frequently treat kids in the ER for [epilepsy-related] seizures, since it answers the question about the best medication to use in ending the convulsions and getting these patients back to normal brain functioning."

Describing the brain convulsions that were targeted by the study, its authors pointed out that status epilepticus occurs when an epilepsy-related seizure lasts more than 30 minutes. Such seizures – which occur in more than 10,000 U.S. pediatric epilepsy patients every year – can cause permanent brain damage or even death, if allowed to persist.

Published in JAMA, the study, "Lorazepam vs Diazepam for Pediatric Status Epilepticus: A Randomized Clinical Trial," was designed to test earlier assertions by many clinicians that lorazepam was more effective at controlling pediatric seizures. The study-authors wrote, "Potential advantages proposed in some studies of lorazepam include improved effectiveness in terminating convulsions, longer duration of action compared with diazepam, and lower incidence of respiratory depression. Specific pediatric data comparing diazepam with lorazepam suggest that lorazepam might be superior, but they are limited to reports from single institutions or retrospective studies with small sample sizes, thus limiting generalizability."

Based on data collected over four years at 11 different U.S. pediatric emergency departments, the new study found that "treatment with lorazepam [among pediatric patients with convulsive status epilepticus] did not result in improved efficacy or safety, compared with diazepam."

That determination led the study authors to conclude: "These findings do not support the preferential use of lorazepam for this condition."

Dr. Mahajan, a nationally recognized researcher in pediatric emergency medicine and a Wayne State University School of Medicine pediatrics professor recently appointed chair of the American Academy of Pediatrics Executive Committee of the Section on Emergency Medicine, said the JAMA study provides "a compelling example of how effective research in pediatric medicine, based on treatment of patients right in the clinical setting, can play a major role in improving outcomes."

Children's Hospital of Michigan Chief of Pediatrics Steven E. Lipshultz, M.D., said this recent breakthrough will "undoubtedly result in better care for pediatric patients who present in the emergency room with seizures related to epilepsy.

"There's no doubt that combining excellent research with excellent treatment is the key to achieving the highest-quality outcomes for patients – and Dr. Mahajan's cutting-edge study is a terrific example of how kids are benefiting from the research that goes on here at Children's every single day," said Dr. Lipshultz.

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Study: Seizure medication may reduce risk for some cancers

A study shows that the seizure medication valproic acid may reduce the risk for certain head and neck cancers.

A drug used to treat seizures may reduce the risk of head and neck cancers, a new study suggests.

Valproic acid (Depakote) is prescribed to prevent seizures and also to control mood, but it is also being investigated for cancer prevention because it inhibits genetic changes that can lead to cancer.

The new study included nearly 440,000 U.S. veterans, including about 27,000 who were taking valproic acid for bipolar disorder, post-traumatic stress disorder (PTSD), migraines and seizures. Overall, veterans who took the drug for at least one year were 34 percent less likely to develop head and neck cancers than those who didn't take the drug, the investigators found.

The risk appeared to be even lower in those who took it in higher doses or for longer periods of time, according to the study published online March 24 in the journal Cancer.

Veterans who took valproic acid did not have a reduced risk for lung, bladder, colon or prostate cancers, said team leader Dr. Johann Christoph Brandes, of the Atlanta Veterans Affairs Medical Center and Emory University in Atlanta, and colleagues.

"A 34 percent risk reduction for the development of head and neck cancer with [valproic acid] use could result in the prevention of up to approximately 16,000 new cases and 3,000 to 4,000 annual deaths in the U.S. alone," Brandes said in a journal news release.

"Head and neck cancer is an important global health crisis, and low cost and low toxicity prevention strategies like [valproic acid] use have a high potential impact on pain, suffering, costs, and [death] associated with this disease," he added.

Although the study found an association between valproic acid use and reduced risk of certain cancers, it did not prove cause-and-effect.

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Researchers find a new way that epilepsy spreads

Researchers found a new way that epileptic activity spreads through the brain, which has implications for seizure treatment.

Researchers in the biomedical engineering department at Case Western Reserve University have found that epileptic activity can spread through a part of the brain in a new way, suggesting a possible novel target for seizure-blocking medicines.

Evidence from a series of experiments and computer modeling strongly suggests individual cells in a part of the brain, known as the hippocampus, use a small electrical field to stimulate and synchronize neighboring cells, spreading the activity layer by layer.

The scientists report the discovery in theJournal of Neuroscience this week.

"We know there are several ways for neurons to talk with one another: chemical and electrical synaptic transmission and diffusion of ions," said Dominique Durand, professor ofbiomedical engineering at Case Western Reserve and the study's senior author. "But this shows a new mechanism. Neurons talk to each other cell to cell using electrical fields, propagating a wave of activity."

Durand worked with graduate students from Case Western Reserve's Neural Engineering Center: Mingming Zhang, Chen Qiu, Rajat J. Shrivacharan and Thomas P. Ladas; and Senior Research Associate Luis E. Gonzales-Reyes to investigate how epileptic seizure activity starts and spreads in the brain.

They inserted a 64-channel microelectrode array in the unfolded hippocampus of a mouse model to monitor its activity. They then injected the hippocampus, which is known to be involved in the most common form of epilepsy, with a drug to make the hippocampus epileptic.

They blocked chemical synapses from transmitting signals between neurons by reducing the calcium ion concentration below the level typically involved in signaling. They then blocked what are called "gap junctions," which electrically transmit signals across synapses, by injecting the antimalarial drug mefloquine, known to hamper the process.

Their tests showed that epileptic activity continued to spread at a speed of about 0.1 meter per second with or without synaptic transmission.

The propagation speed eliminated the third known route of epileptic propagation—signaling by diffusion of sodium and potassium ions across brain cell membranes. Diffusion is too slow to be the method of transmission.

The researchers were left with the fourth known way that neurons communicate: electrical fields. When a group of cells fire together, they can generate currents and electric fields that can be large enough to excite their neighbors.

Computer simulations with a large set of neurons confirmed that a weak electrical field could, by itself, spread epileptic signals at the speed that matched their experimental results. The computer model also predicted that signal transmission would change speeds depending on the distance between neurons.

The researchers verified the prediction by injecting drugs that would either expand or decrease the space between cells. The closer the cells, the faster the transmission. The more distant the cells, the slower the transmission until—at a certain distance—the signal failed to propagate.

For some time, doctors have used diuretics to treat some types of epilepsy.Diuretics are known remove water from cells and but their anticonvulsant properties are not known, Durand said.

As water is removed from cells and enters the extracellular space, it increases the space between cells and may be pushing them beyond the reach of the weak electrical field, he said.

The researchers say that this finding does not diminish the importance of synaptic transmission in epilepsy but points to another synchronizing and propagation mechanism.

But "this discovery has implications for epilepsy," Durand said. "If cells in an excited state can talk to or influence each other, they can synchronize to a seizure-like state, propagate to neighbors thereby generating a full-blown seizure."

The electrical fields and the process of synchronization and propagation may be new targets for medicines or other treatments to prevent or limit seizures.

The researchers are now investigating a way to directly test the effect of electric field on seizure generation and propagation.

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Type of epilepsy medication during pregnancy affected children differently

 A study shows that different types of epilepsy medication, when taken during pregnancy, affect children differently than the other types of medication.

Women with epilepsy usually need to take medications to treat the condition even while they are pregnant. But how do those medications affect their developing babies?

A recent study found that one epilepsy medication appeared to affect children's development less than another when the children were preschoolers.

The two medications studied were levetiracetam (brand name Keppra) and valproate sodium (brand name Depacon, Depakene or Depakote).

Children whose mothers took levetiracetam during pregnancy scored similarly to children not exposed to medications in the womb.

Children whose mothers took valproate sodium scored lower with motor skills and language skills.

This study, led by R. Shallcross, PhD, of the Department of Clinical Psychology at the University of Liverpool in the United Kingdom, looked at the development of children whose mothers took epilepsy medications while pregnant.

The researchers compared the children of 97 women who took either levetiracetam or valproate sodium while pregnant to the children of 131 women without epilepsy, who took no prescription medications during pregnancy.

The children were aged 3 to 4.5, and their cognitive skills and language development were tested with established scales.

After taking into account other characteristics that differed among the children and/or their mothers, the 53 children whose mothers took levetiracetam did not score any differently than children not exposed to medications during pregnancy.

Differences were seen, however, among the children whose mothers took valproate sodium during pregnancy.

The 44 children exposed to valproate sodium in the womb scored an average 15.8 points lower on gross motor skills than children exposed to levetiracetam in the womb.

The scale used is calculated similarly to an IQ scale, with 100 representing the average for children.

Children of mothers who took valproate sodium also scored an average 6.4 points lower on language comprehension and 9.5 points lower on expressive language skills, compared to children of mothers who took levetiracetam during pregnancy.

The researchers therefore concluded that children whose mothers used levetiracetam to treat their epilepsy during pregnancy fared better in motor skills and language development than children whose mothers used valproate sodium.

However, the researchers cautioned that their findings do not mean that valproate sodium should never be used during pregnancy.

Because this medication is used to treat seizures, which can also be dangerous for an unborn baby, some women may still need to take it while pregnant.

This study was published January 8 in the journal Neurology.

The research was funded by UCB Pharma Ltd., the Epilepsy Research Foundtion, GlaxoSmithKline, Sanofi Aventis, Janssen-Cilag, Novartis, Pfizer, Eisai and Epilepsy Research UK.

Five authors have received travel funds or advisory board honorariums from various pharmaceutical companies, including Sanofi Aventis and UCB Pharma Ltd.

Three of these authors have also given expert testimony in legal cases related to fetal anticonvulsant syndrome or the safety of anticonvulsants during pregnancy.

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Epilepsy drug may help adults learn pitch

Results from a study shows that an epilepsy drug can help adults learn the rare skill of having perfect pitch.

Perfect pitch, also called absolute pitch, is the ability to accurately name any pitch you hear. People with perfect pitch can sing any note of the chromatic scale without hearing reference pitches first.

Until recently, perfect pitch was thought to be an innate ability that very few children possessed. The American Psychological Association estimates that only one in 10,000 Americans have the gift.

But according to a research report published last week, scientists have discovered that Valproate, a drug used to treat epilepsy, can help adults develop perfect pitch.

Research had shown that the drug enabled adult mice to learn habits that were previously only possible for mice to learn during youth.

Harvard researcher Takao Hensch and an international team of scientists, then, decided to give Valproate to a group of adult men who had no prior musical training. They asked the group to complete an online ear-training course that lasted for two weeks.

At the end of the trial, those who took Valproate were significantly better at identifying pitches than those taking a placebo.

Hensch, who is a professor of molecular and cellular biology at Harvard, recently discussed the research team's findings with Linda Wertheimer of NPR. "It's a mood-stabilizing drug, but we found that it also restores the plasticity of the brain to a juvenile state," Hensch said.

In other words, the drug seems to restore the ability to learn certain tasks that were once thought impossible to learn outside of childhood.

Of course, the implications of such a drug are enormous. It could help adults learn a new language and speak that language without an accent, abilities which are thought to peak in early childhood.

For a long time, perfect pitch was thought to be a result of nature, not nurture.

In the NPR interview, Hensch acknowledges that there is a genetic component. But he and many other researchers believe that perfect pitch can be acquired, through early musical training before age seven.

Other researchers disagree, saying that the ability to develop perfect pitch is genetic and can't be taught.

However, there is one point on which researchers tend to agree: It is impossible for adults to develop perfect pitch.

Many musicians regard perfect pitch as the holy grail, the ultimate musical gift. Mozart had perfect pitch, and many experts think Beethoven had it also.

The ability to instantly identify whether any pitch is sharp or flat can help string players play in tune. The ability to sing any pitch can help singers navigate densely chromatic music.

And perfect pitch can help any musician sight-read a difficult score. A drug that could aid adults in developing this ability would probably prove extremely popular among musicians.

But Hensch warns that scientists are only beginning to understand how Valproate affects the brain's ability to learn new things. And the drug is known to have side effects.

So, it may be a long time before Valproate is available to consumers for this purpose. And those who take such a medication may find that perfect pitch has its downside.

Those who have it might not enjoy listening to an orchestra that tunes to a concert "A" that is a little sharp or flat, as some orchestras do. And hearing the out-of-tune pitches of electric appliances, train whistles and other background noises in our environment could become annoying for a whole new reason.

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The effect of anti-epileptic drugs on children's growth

A recent study looked into how the use of anti-epilepsy drugs effects children's growth and health, and results showed that the use of certain drugs to impair the growth of children with epilepsy.

This study investigated whether long–term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA.

Methods

• Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1year were selected.
• The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13years.
• Patients with a history of febrile convulsions were selected as the controls.

Results

• One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p<0.005) compared with the control group.
• The underlying mechanism may have been due to the direct effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium.

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Inflammation can be caused by anti-epilepsy drugs

A report claims that anti-epilepsy drugs can cause inflammation and thus may have roots in the immune system.

Physicians at the Ruhr-Universität Bochum (RUB) have been investigating if established anti-epilepsy drugs have anti-inflammatory or pro-inflammatory properties -- an effect for which these pharmaceutical agents are not usually tested. One of the substances tested caused stronger inflammations, while another one inhibited them. As inflammatory reactions in the brain may be the underlying cause for epileptic disorders, it is vital to take the trigger for the disorder under consideration when selecting drugs for treatment, as the researchers concluded. They published their report in the journal Epilepsia.

Glial cells play a crucial role in the nervous system

Hannes Dambach from the Department for Neuroanatomy and Molecular Brain Research, together with a team of colleagues, studied how anti-epilepsy drugs affect the survival of glial cells in cultures. Glial cells are the largest cell group in the brain; they are crucial for supplying neurons with nutrients and affect immune and inflammatory responses. The question of how glial cells are affected by anti-epilepsy drugs had previously not been studied in depth. The RUB work group Clinical Neuroanatomy, headed by Prof Dr Pedro Faustmann, analysed four substances: valproic acid, gabapentin, phenytoin and carbamazepine.

Four anti-epilepsy drugs affect glial cells in different ways

Glial cells treated by the researchers with valproic adic and gabapentin had better survival chances than those treated with phenytoin and carbamazepine. However, carbamazepine had a positive effect, too: it reduced inflammatory responses. Valproic acid, on the other hand, turned out to be pro-inflammatory. In how far the anti-epilepsy drugs affected inflammations was also determined by the applied dose. Consequently, different drugs affected glial cells -- and hence indirectly the neurons -- in different ways.

Inflammatory responses should be taken under consideration in clinical studies

"Clinical studies should focus not only on the question in how far anti-epilepsy drugs affect the severity and frequency of epileptic seizures," says Pedro Faustmann. "It is also necessary to test them with regard to the role they play in inflammatory responses in the central nervous system." Thus, doctors could take the underlying inflammatory condition under consideration when selecting the right anti-epilepsy drug.

Epilepsy may have different causes

In Germany, between 0.5 and 1 percent of the population suffer from epilepsy that requires drug treatment. The disease may have many causes: genetic predisposition, disorders of the central nervous system after meningitis, traumatic brain injury and stroke. Inflammatory responses may also be caused by damage to the brain.

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Research on women, pregnancy, and the effects of epilepsy

Research looks into women, pregnancy and folic acid supplementation, and how valproate, an antiepileptic drug, effects them.

New research pertaining to the latest findings on the effects of epilepsy on both the mother and child were presented at the American Epilepsy Society's 67th Annual Meeting in Washington DC. These studies explore folic acid use, the effect of surgery with intractable focal epilepsy, and antiepileptic drug exposure during breastfeeding.

Researchers from the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Boston, Massachusetts investigated the frequency of folic acidsupplement use by women with epilepsy in the community and factors that may predict its use (Platform B.04 / Abstract 1722353). Folic acid deficiency in early pregnancy is known to cause birth defects and increase the risk of miscarriages, which can occur most with enzyme-inducing antiepileptic drugs (AED). Neural tube malformations are most common with the use of Valproate, a folic acid antagonist.

Data for this study was collected through the Epilepsy Birth Control Registry (EBCR), a web-based survey and educational site used to gather key information from 626 women with epilepsy in the community. The study found that 44% of respondents took folic acid.

"Our findings show that only about half of the women surveyed are taking folic acid, despite their high risk of unintended pregnancies. Additionally, we found that many of the respondents who were not taking precaution of neural tube malformation were taking Valproate, a folic acid antagonist," said Andrew G. Herzog, MD, principal investigator of the study. "Overall the women at risk, regardless of antiepileptic drugs or contraceptive use, did not differ significantly from women not at risk and on no antiepileptic drugs."

In a related study, researchers from The Mayo Clinic-Rochester presented evidence to support the importance of early surgery in women with intractable focal epilepsylooking to get pregnant (Poster 3.250 / Abstract 1750307). One hundred and thirteen women were included in this study. An average of 0.93 pregnancies and 0.73 births were identified prior to surgery, compared to a significantly higher success rate of 1.27 pregnancies and 0.96 births post-surgery. A total of 17 women had a total of 35 pregnancies and 25 births after surgery. Those patients who received fewer medications prior to surgery were more likely to have additional children following surgery.

"While the significance of these findings is uncertain, we believe that they support a role for earlier surgical intervention in the management of intractable focal epilepsy and the relationship it has to conceiving and giving birth," said Rachel R. Fabris, MD, the lead author of this study.

A third study was presented as a follow up to previous research determining the effects of antiepileptic drug exposure via breast milk on IQ at age 3 years old. The new data collected was from a cohort of children at the age of 6, which the researchers deemed an age more predictive of school performance and adult abilities (Poster 2.213 / Abstract 1732174). While breastfeeding is known to have beneficial effects for both the child and the mother, there is concern regarding whether breastfeeding while taking antiepileptic drugs could be harmful to the cognitive development of the infant.

Results of the study were analyzed as a function of whether the children had been breastfed or not. Overall, 43% of the children were breastfed, but the results failed to show adverse effects of AED exposure: children who breastfed exhibited higher IQ and Verbal Index scores even though their mothers used AEDs.

"Our results are encouraging in that women with epilepsy can be less fearful of breastfeeding their baby," said the leader of this study, Kimford Meador, MD. "Nevertheless, this is a limited study and additional research is needed."

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What changes quality of life in a child with epilepsy? An action plan for families and neurologists.

This study looks at children recently diagnosed with epilepsy and determines their health-related quality of life which can be changed by medications, cognitive problems or behavior, parental depression and family demands.

The objectives of this study were to document trajectories of health–related quality of life (HRQL) and to identify predictors of the trajectory group in children with new–onset epilepsy. Results suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family–centered framework to improve HRQL of children with new–onset epilepsy.

Methods

• Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4–12 years old with new–onset epilepsy followed for 24 months.
• Health–related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire.
• Trajectories of HRQL were investigated using latent class trajectory modeling.
• Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories.

Results

• A total of 374 families responded at baseline and 283 (76%) completed the study.
• Five HRQL trajectories were observed: low–increasing (4%), moderate–decreasing (12%), moderate–increasing (22%), high–increasing (32%), and high–stable (30%).
• Many children in the low–increasing, moderate–increasing, high–increasing, and high–stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively.
• In contrast, the majority of children in the moderate–decreasing group (56%) experienced clinically meaningful declines in their HRQL.
• Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands.

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Mechanism that valproate uses to block seizures understood

The mechanism by which the anti-epileptic drug valproate works is finally understood 50 years after the discovery of the drug.

50 years after valproate was first discovered, research published today in the journalNeurobiology of Disease, reports how the drug works to block seizure progression.

Valproate (variously labelled worldwide as Epilim, Depacon, Depakene, Depakote, Orlept, Episenta, Orfiril, and Convulex) is one of the world's most highly prescribed treatments for epilepsy. It was first discovered to be an effective treatment for epilepsy, by accident, in 1963 by a group of French scientists. In thousands of subsequent experiments, animals have been used to investigate how valproate blocks seizures, without success. Scientists from Royal Holloway and University College London have now identified how valproate blocks seizures in the brain, by using a simple amoeba.

"The discovery of how valproate blocks seizures, initially using the social amoeba Dictyostelium, and then replicated using accepted seizure models, highlights the successful use of non-animal testing in biomedical research," said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.

"Sodium valproate is one of the most effective antiepileptic drugs in many people with epilepsy, but its use has been limited by side-effects, in particular its effect in pregnant women on the unborn child," said Professor Matthew Walker from the Institute of Neurology at University College London. "Understanding valproate's mechanism of action is a first step to developing even more effective drugs that lack many of valproate's side-effects.

"Our study also found that the decrease of a specific chemical in the brain at the start of the seizure causes even more seizure activity. This holds important implications for identifying underlying causes," added Professor Williams.

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FDA approved marijuana-based CLINICAL TRIAL to treat Epilepsy

PLEASE NOTE: The FDA has recently approved a clinical trial  or an experiment with a marijuana-base to treat epileptic disorders. The agent has not been approved for clinical use. If interested call the study sponsors below.  JR

The US Federal Drug Association approved clinical studies that aim to determine whether purified cannabidiol (CBD) is a viable anti-seizure treatment. Physician investigators will be provided with Epidiolex, a new 98% CBD product made by GW Pharmaceuticals, and conduct Investigational New Drug studies involving epileptic children.

According to O’Shaughnessy, the clinical studies will be sponsored by Orrin Devinsky, MD, at the NYU School of Medicine, and Roberta Cilio, MD, PhD, at University of California, San Francisco. Both are expected to monitor the progress of 25 patients, but they may enroll more with approval from the FDA. Additionally, Cilio will conduct two individual studies as well.

GW Pharmaceuticals, the British company responsible for the cannabis-based spray Sativex, will provide researchers with their latest “pure CBD” product – Epidiolex. The drug will come in the form of a viscous liquid to be dispensed in syringe droppers. Additionally, there will be two strengths available: 25 milligrams per milliliter and 100 mg/ml.

According to GW, Epidiolex contains no tetrahydrocannabinol (THC), the psychotropic component in cannabis. It is said to contain more than 98% cannabidiol (CBD) and trace amounts of other cannabinoids. GW chairman Geoffrey Guy, MD, told O’Shaughnessy, “Our definition of pure is no THC.”

Guy believes the studies will help provide “better understanding and experience in what cannabidiol does in these different children groups, what benefit we can see, and how the results can best be measured.”

Considering anecdotal evidence that cannabis can help treat epileptic seizures, and nearly 5 years of pre-clinical trial data from GW Pharmaceuticals, Guy expects more studies to come in the future.

“In the coming months, if the FDA is comfortable about how things are going, there will be a number of senior epileptologists in major university centers throughout the U.S., each treating a couple of dozen patients with various epilepsies,” he explained.

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Epilepsy drugs used during pregnancy may be linked adverse outcomes!

This study looked at women who used certain epilepsy medications while pregnant and if there was an association with the drug and adverse outcomes.

Talk to your neurologist if you are planning pregnancy and have epilepsy. Certain medications may have less adverse effects than others. JR

Antiepileptic drugs may cause congenital malformations. Less is known about the effect on development in infancy and childhood. The aim of this study was to examine whether exposure to antiepileptic drugs during pregnancy has an effect on early child development. Exposure to antiepileptic drugs during pregnancy is associated with adverse development at 18 and 36 months of age, measured as low scores within key developmental domains rated by mothers.

 Exposures to valproate, lamotrigine, carbamazepine, or multiple antiepileptic drugs were associated with adverse outcome within different developmental domains.

Methods

• From mid-1999 through December 2008, children of mothers recruited at 13–17 weeks of pregnancy were studied in the ongoing prospective Norwegian Mother and Child Cohort Study.
• Information on birth outcomes were obtained from the Medical Birth Registry (108,264 children), and mothers reported on their child's motor development, language, social skills, and autistic traits using items from standardized screening tools at 18 months (61,351 children) and 36 months (44,147 children) of age.
• The relative risk of adverse outcomes in children according to maternal or paternal epilepsy with and without prenatal exposure to antiepileptic drugs was estimated as odds ratios (ORs), using logistic regression with adjustment for maternal age, parity, education, smoking, depression/anxiety, folate supplementation, and child congenital malformation or low birth weight.

Results

• A total of 333 children were exposed to antiepileptic drugs in utero.
• At 18 months, the exposed children had increased risk of abnormal scores for gross motor skills (7.1% vs. 2.9%; OR 2.0, 95% confidence interval [CI] 1.1–3.7) and autistic traits (3.5% vs. 0.9%; OR 2.7, CI 1.1–6.7) compared to children of parents without epilepsy. At 36 months, the exposed children had increased risk of abnormal score for gross motor skills (7.5% vs. 3.3%; OR 2.2, CI 1.1–4.2), sentence skills (11.2% vs. 4.8%; OR 2.1, CI 1.2–3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6–7.0).
• The drug-exposed children also had increased risk of congenital malformations (6.1% vs. 2.9%; OR 2.1, CI 1.4–3.4), but exclusion of congenital malformations did not affect the risk of adverse development.
• Children born to women with epilepsy who did not use antiepileptic drugs had no increased risks.
• Children of fathers with epilepsy generally scored within the normal range.

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Risks of taking epilepsy drugs while pregnant

Keep in mind ...What does the WHO recommend

Recommendation(s)

• Women with epilepsy should have seizures controlled as well as possible with the minimum dose of antiepileptic drug taken in monotherapy, wherever possible. Antiepileptic drug polytherapy should be avoided. Valproic acid should be avoided if possible.  Strength of recommendation: STRONG
• Folic acid should routinely be taken by women with epilepsy of child bearing age who are on antiepileptic drugs.  Strength of recommendation: STRONG
• Standard breast feeding recommendations remain appropriate for women with epilepsy on the antiepileptic drugs included in this review (phenobarbital, phenytoin, carbamazepine and valproic acid). Strength of recommendation: STRONG
• JR

Risks of taking epilepsy drugs while pregnant

This article discusses the various risks associated with pregnant women taking drugs for epilepsy, such as having a child with developmental delays or showing signs of autism.

Women with epilepsy who take anti-seizure medication while they are pregnant are more likely to later report delays in their child's development and autism symptoms, according to a new study from Norway.

The findings probably won't change the conversation too much between women and their doctors in terms of managing epilepsy during pregnancy, because it's already understood that the medications carry some risks, said Dr. Lewis Holmes, director of the Antiepilepsy Drug Registry at Massachusetts General Hospital, who was not involved in the research.

However, studies like this are badly needed, he added, because women are often asking about risks to their children's development, and "it hasn't really been mapped out."

The researchers could not prove that the anti-epileptic drugs are to blame, but the findings add to other evidence linking the medications to effects on children's development.

Seizure medication taken during pregnancy is already tied to a higher risk of physical malformations in the baby, and the drugs are linked with a greater chance of complications during pregnancy and childbirth.

One study from Denmark earlier this year also found that women who took the epilepsy drug valproate during pregnancy were three times more likely to have a child with an autism spectrum disorder.

"The risk of other effects on fetal development, that is, development and behavior, is less clear," said Dr. Gyri Veiby, lead author of the new study and a researcher at the University of Bergen in Norway.

She said that among all pregnancies, about three to five women out of every 1,000 use anti-epileptic drugs during pregnancy.

"It is reasonable to assume that most (anti-epileptic drugs) have the potential to harm the developing fetus. On the other hand, seizures should also be avoided during pregnancy," Veiby wrote in an email.

"In order to assess whether antiepileptic drug treatment during pregnancy is justified, we need to know as much as possible about the potential risks for the fetus," she said.

Veiby and her colleagues examined data from a large survey of mothers across Norway.

More than 108,000 women filled out a questionnaire asking about the behavior and development of their children at 18 and 36 months of age.

The survey included questions about social, physical and verbal skills, mannerisms, aggression and other traits.

Among the women in the study, 634 had epilepsy and 333 of them took epilepsy medication while they were pregnant - that translated to about 46 percent of the children of epileptic mothers having been exposed to one or more of the medications.

Children whose mothers took epilepsy drugs while pregnant were more likely to score outside the normal range on several developmental measurements, the researchers report in the journal Epilepsia.

For instance, 3.3 percent of three-year-olds whose mothers did not have epilepsy did not meet milestones for physical skills, whereas 7.5 percent of kids exposed to epilepsy drugs in utero failed to meet these milestones.

In addition, 4.8 percent of three-year-olds whose mothers did not have epilepsy scored abnormally on their ability to form sentences, while 11.2 percent of the children whose mothers took anti-seizure medication were delayed in their sentence skills.

The kids whose mothers took epilepsy medication while pregnant were also more likely to have autistic traits - 6 percent - compared to just 1.8 percent of the kids who mothers did not have epilepsy.

A mother's epilepsy itself did not appear to contribute to the heightened risk. Mothers with the condition who did not take any medication were no more likely to have a child with delays than mothers without epilepsy.

Dr. Cynthia Harden, a neurology professor at Hofstra-North Shore LIJ School of Medicine in Hempstead, New York, said it's possible the findings could be explained in part by something called "selection bias."

Mothers who take epilepsy medication while pregnant, for example, might be more concerned and therefore looking out for developmental delays, so they could be more likely to report them.

But Harden also said it's possible the drugs themselves have a negative effect on babies' development.

"There might be something real going on here, but it's possible that the magnitude of the effect is exaggerated by selection bias," said Harden, who is also the director of the Comprehensive Epilepsy Care Center at North Shore-LIJ Medical Group in Great Neck, NY.

Holmes said the findings support parents taking action on cues that their child might have a delay.

"Because there are concerns about subtle effects, I think it's smart to go ahead and think about obtaining some formal testing...as a way of making sure that everything is OK before first grade," Holmes said.

Harden agreed that the study doesn't change the discussion about epilepsy management during pregnancy too much.

Already, patients and physicians are aware of the potential hazards of the drugs, yet "seizures are dangerous, and we cannot permit our patients to have seizures during pregnancy," she said.

Physicians try to reduce the dose of the medication, trim back the treatment to one type of drug if possible, and avoid the use of valproate.

Veiby added that another way to minimize the risks during pregnancy is to plan ahead to figure out the safest treatment strategy, and to avoid unplanned pregnancies.

"Unfortunately, many women on (anti-epileptic drugs) do not receive the appropriate pre-pregnancy counseling," she said.

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People with epilepsy at elevated risk for some cancers

A study from Denmark reveals the elevated risk for some cancers that comes with epilepsy medications.

Here’s an interesting fact. Epilepsy is fairly common in Denmark. About 1.5 percent of the Danish population has this brain disorder that causes seizures. A recent study looked at cancer risks associated with the disease and its treatment.

Scientists have been debating for decades about whether or not the powerful medicines used to treat epilepsy increase an individual’s cancer risks.

After studying the entire Danish population, a new study found little or no association between epilepsy medications and increased cancer risks.

However, researchers did discover that the disease itself may increase the risk for certain cancers.

Jeanette Kaae and colleagues from the Department of Epidemiology Research at the Statens Serum Institut in Copenhagen, Denmark, gathered information on 4,803,613 Danish residents over the age of 16, of whom 97,318 had a known epilepsy diagnosis.

The aim of this study was to establish whether medications used to treat epilepsy increase the risk for cancer.

The researchers looked at the wide range of medications used to treat the convulsive disease. A total of 22 medications were part of this analysis, some of which are used to treat conditions other than epilepsy.

Some of the medications included Lamictal (lamotrigine), Keppra (levetiracetam), Lyrica (pregabalin) and Zonegran (zonisamide).

The researchers found small increased risks (4-11 percent) of esophageal, stomach, intestine, lymph system, male genital tract, skin and urinary tract cancers among non-epileptics taking anti-epileptic medications (any medication) compared to non-users of these medications.

Non-epileptics taking these anti-epileptic medications also had 23 to 59 percent greater risks of liver, mouth and throat and respiratory tract cancers than did people without epilepsy who didn’t take these medicines.

People with epilepsy who were not taking any medications for the condition had small to moderate increased risks (17-35 percent) of cancer of the digestive and respiratory organs, compared to people without the disease.

Epileptics not taking any medicines, however, had a two-fold risk of central nervous system cancers and a three-fold greater risk of cancers of the mouth and throat compared to non-epileptics.

Adding medications did not further increase the risks of oral, digestive or respiratory cancers. 

Epileptics taking medications did have a nearly four-fold increased risk of central nervous system cancers and a 41 percent increased risk of liver cancer.

“For epileptics both with and without a record of anti-epileptic medication use, we observed strong associations between having epilepsy and the risks of central nervous system (200-400 percent increased risk) and mouth and throat (200-300 percent increased risk) cancers, as well as a modest association (30-35 percent increased risk) between epilepsy and the risk of respiratory tract cancers,” the authors wrote.

“The fact that there were generally no differences in cancer risk for epileptics who were taking medication for their condition and those who were not suggests that it is not primarily anti-epileptic medications that are responsible for the increased cancer risk among epileptics but epilepsy itself or another aspect of epilepsy diagnosis or treatment,” the authors concluded.

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