Intellectual and behavioral issues in children with epilepsy

This article discusses behavioral and intellectual disabilities in children who have epilepsy.

Children with epilepsy can face greater intellectual and behavioral problems compared to their peers. New research presented at the American Epilepsy Society's (AES) 68th Annual Meeting explores the complex emotional, behavioral and intellectual disabilities associated with childhood epilepsy and their effect on development.

The first of three studies (Platform Session A.04) presents a culmination of 20-30 years of research that sought out to understand if intellectual disability (ID) predicts a low chance of remission and a high risk of intractability in epilepsy. Researchers of this study focused on examining the severity of ID to predict epilepsy outcome.

A cohort of children from Nova Scotia who developed epilepsy between 1977 and 1985 and had ID was followed for an average of 21 years following diagnosis. The initial study followed 692 children with incident epilepsy, of which 147 (21%) had intellectual disability. The degree of intellectual disability was established by standard psychometric testing around 5 years of age, and confirmed by subsequent academic achievements.

Researchers at Dalhousie University found that the degree of intellectual disability in children with epilepsy did predict seizure outcome. Mild intellectual disability was associated with a substantially better prognosis for remission and absence of intractability than moderate or severe/profound ID. Focal epilepsy and mild intellectual disability had the same rate of remission and intractability as focal epilepsy with normal intelligence. While mild ID seriously affects social outcome, it is not an important prognostic factor for seizure outcome, particularly if the epilepsy is focal.

The level of ID varied by the type of epilepsy present, with focal epilepsy apparent in 70% with mild ID, 38% with moderate and 29% with severe/profound ID. Generalized symptomatic epilepsies were most common with moderate (53%) and severe/profound ID (65%) than with mild ID (13%). Participants with mild ID were more likely to be in remission at the end of the twenty-year follow up (50%) than moderate (34%) or severe/profound ID (28%). Intractable epilepsy was more common with moderate (35%) and severe/profound (59%) than with mild ID (17%).

"Mild intellectual disability has a profound effect on a child's adaptation to adult life," said Dr. Peter Camfield, M.D., Professor Emeritus, Department of Pediatrics, Dalhousie University. "However, it is not particularly associated with severe epilepsy. Moderate to severe ID has ominous implications for seizure control."

A second study (Poster 1.097) explores the relationship between behavioral/psychiatric disorders and childhood epilepsy. Researchers at Northwestern University's Feinberg School of Medicine referenced children with the Connecticut Study of Epilepsy (CSE) that were recruited between 1993 and 1997, and underwent comprehensive reassessments between 2002 and 2006, 8 to 9 years after they were diagnosed with epilepsy. Within those 16 years, cognitive testing was conducted with a Wechsler IQ test and behavioral assessment with the parent-reported Child Behavior Check List (CBCL). Controls of this study were similar-aged siblings without epilepsy who received the same assessment instruments.

"Further analyses suggest the findings based on parent-reported behavior largely reflect parental emotional impact," said Dr. Soong Eom, Ph.D., Northwestern University Feinberg School of Medicine.

Researchers analyzed the CBCL and Wechsler IQ test results of 301 children with epilepsy (CWE) and 156 controls. The average age of CWE cases was 12.5, and 13.2 for controls. The cases of CWE were divided into two groups, "complicated" indicating a clear brain insult or abnormal exam, and "uncomplicated" indicating all normal exams. The case group was comprised after excluding complicated cases and those who were not seizure-free and on medication.

In an initial comparison, children with epilepsy across the board had worse behavioral problem scores and a lower social competency score than controls. After excluding complicated cases and those who were not seizure-free and off medication, there was a persistent difference between children with epilepsy and controls on parental reports of behavioral problems.

In a third study (Poster 2.023) presented by the University of Wisconsin Madison, a standardized psychiatric interview was conducted to determine whether children with recent-onset epilepsy would have higher rates of any psychological disorder than controls.

The study followed 178 children between the ages of 8 and 18, consisting of 105 children with epilepsy and 73 controls. The inclusion criteria for CWE were diagnosis of epilepsy in the past 12 months, no developmental disabilities or neurological disorders, normal neurological examinations and clinical imaging. Controls in this study were first-degree cousins of CWE with no history of seizures, early initial precipitating injuries, developmental or neurological diseases, or loss of consciousness greater than 5 minutes. Information was gathered through separate interviews with parents and participants at baseline and at a 2 year follow-up.

"This study indicates that rates of psychological disorders are higher in children with epilepsy compared to children without seizures," said Dr. Jana Jones, Ph.D., University of Wisconsin. "This study also indicates that there may be differences in the course of psychological disorders in children with epilepsy associated with focal and generalized seizures."

Results of the study found that compared to controls, children with epilepsy have higher rates of psychological disorders at baseline and 2-year follow-up (59.0% vs. 23.3%). At baseline, children with epilepsy were more likely to have depression (15.2% vs. 2.7%), anxiety (34.3% vs. 15.1%) and ADHD (22.9% vs. 6.8%). These differences remained at the two-year follow-up with one exception; rates of depression were no longer significantly different (7.6% vs. 2.7%) between the CWE and the controls. At baseline, children with focal seizures and generalized seizures had similar rates of psychological disorders (67.3% vs. 51.0%). At 2-year follow-up children with focal seizures had higher rates of psychological disorders (65.5% vs. 36.7%). Children with focal seizures also had higher rates of anxiety disorders (43.6% vs. 20.4%) and ADHD (25.5% vs. 8.2%) but not depression (7.3% vs. 8.2%) when compared to children with generalized seizures.

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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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Zebrafish help find model to treat childhood epilepsy

A study by the National Institute of Health (NIH) shows that zebrafish may help model a treatment for Dravet syndrome, a severe childhood epilepsy.

According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.

Scott C. Baraban, Ph.D., and his colleagues at the University of California, San Francisco (UCSF), carefully assessed whether the mutated zebrafish could serve as a model for DS, and then developed a new screening method to quickly identify potential treatments for DS using these fish. This study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health and builds on pioneering epilepsy zebrafish models first described by the Baraban laboratory in 2005.

Dravet syndrome is commonly caused by a mutation in the Scn1a gene, which encodes for Nav1.1, a specific sodium ion channel found in the brain. Sodium ion channels are critical for communication between brain cells and proper brain functioning.

The researchers found that the zebrafish that were engineered to have the Scn1a mutation that causes DS in humans exhibited some of the same characteristics, such as spontaneous seizures, commonly seen in children with DS. Unprovoked seizure activity in the mutant fish resulted in hyperactivity and whole-body convulsions associated with very fast swimming. These types of behaviors are not seen in normal healthy zebrafish.

“We were also surprised at how similar the mutant zebrafish drug profile was to that of Dravet patients,” said Dr. Baraban. “Antiepileptic drugs shown to have some benefits in patients (such as benzodiazepines or stiripentol) also exhibited some antiepileptic activity in these mutants. Conversely, many of the antiepileptic drugs that do not reduce seizures in these patients showed no effect in the mutant zebrafish.”

In this study, the researchers developed a fast and automated drug screen to quickly test the effectiveness of various compounds in mutant zebrafish. The researchers tracked behavior and measured brain activity in the mutant zebrafish to determine if the compounds had an impact on seizures.

“Scn1a mutants seize often, so it is relatively easy to monitor their seizure behavior at baseline and then again after a drug application,” said Dr. Baraban. “Using zebrafish placed individually in a 96-part petri dish we can accurately quantify this seizure behavior. In this way, we can test almost 100 fish at one time and quickly determine whether a drug candidate has any effect on these spontaneous seizures.”

In the first such application of this approach, UCSF researchers screened 320 compounds and found that clemizole was most effective in inhibiting seizure activity. Clemizole is approved by the U.S. Food and Drug Administration and has a safe toxicology profile. “This finding was completely unexpected. Based on what is currently known about clemizole, we did not predict that it would have antiepileptic effects,” said Dr. Baraban.

These findings suggest that Scn1a mutant zebrafish may serve as a good model of DS and that the drug screen may be effective in quickly identifying novel therapies for epilepsy.

Dr. Baraban also noted that someday these experiments can be “personalized,” by looking at mutated zebrafish that use genetic information from individual patients.

This research was funded by the Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) program at NIH that supports innovative research with the potential for big impact in biomedical science.

“The goal of the EUREKA program is to provide a means to test high-risk ideas to see if they are worth pursuing further. These kinds of ideas often come from left field and are very creative. Since they are so unique, however, there may not be any existing preliminary data to support the hypothesis or demonstrate feasibility. EUREKA grants provide an opportunity to gather this information,” said Brandy Fureman, Ph.D., program director at NINDS.

This particular study was chosen in response to a request by NINDS to help spur novel research on epilepsy. “This research was selected for a EUREKA grant because it proposed a well-designed, inventive model of genetic epilepsy that could accelerate the pace of drug-screening for this devastating form of pediatric epilepsy” said Dr. Fureman.

Dr. Fureman noted that these findings not only describe a novel model of Dravet syndrome, but the positive results with an unexpected FDA-approved drug may lead to new therapeutic avenues. “There is more work to be done, but I am very pleased to see these initial results. These kinds of new directions are exactly what we hoped to stimulate with the EUREKA program,” she said.

For more information about Dravet syndrome and epilepsy, please visit:

• http://www.ninds.nih.gov/disorders/dravet_syndrome/dravet_syndrome.htm
• http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm

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Link found between epilepsy and obstructive sleep apnea

Doctors find key link between epilepsy and obstructive sleep apnea

By medical reporter Sophie Scott

Updated Sun Jun 2, 2013 11:01pm AEST

PHOTO: In the general population, the prevalence of sleep-disordered breathing is 3 to 7 per cent. ()

Australian doctors have found a new link between epilepsy and obstructive sleep apnoea, a condition where patients stop breathing at night.

Professor Terry O'Brien from the Royal Melbourne Hospital says there has been some evidence from other studies that patients with epilepsy may have an increased incidence of sleep-disordered breathing.

Professor O'Brien says there are similar symptoms of daytime sleepiness and fatigue between the two conditions.

He says patients with epilepsy can gain weight as a result of their medications, something that increases their risk of sleep-disordered breathing.

"We put two and two together and thought we should look into this," he said.

Doctors recruited 87 patients with epilepsy and monitored them in a sleep unit.

They found 25 per cent had significant sleep-disordered breathing that was severe enough to require treatment.

In the general population, the prevalence of sleep-disordered breathing is 3 to 7 per cent.

Awake for up to three days straight

Thirty-six-year-old Daniel Goldstein had always had strange sleeping habits, which included rocking back and forth during the night while he slept.

Eventually, he was diagnosed with epilepsy but it was hard to stop seizures.

To identify the issue, Mr Goldstein undertook a sleep study at the Royal Melbourne Hospital and was found to have severe sleep apnoea.

He said at times he would be awake for up to three days straight.

Since being treated for sleep apnoea, Mr Goldstein has also been able to reduce his epilepsy medications.

Mr Goldstein was also given a CPAP machine which he says helps him soundly throughout the night.

"Now I've got energy in a way I didn't have before. It's like learning to walk again," he said. "I feel just phenomenal."

Well-established treatment for sleep-disordered breathing

Professor O'Brien says the beauty of this recent research is that there is a well-established treatment for sleep-disordered breathing.

He says when epilepsy patients were given a CPAP machine, there was a significant improvement.

http://www.abc.net.au/news/2013-06-02/link-between-epilepsy-and-obstructive-sleep-apnoea/4728076

Early diagnosis of pediatric epilepsy necessary for optimal brain function

This article discusses pediatric epilepsy and how important early diagnosis is to ensure optimal brain function.

Seizure and epilepsy are words that are often used interchangeably and both are frequently misunderstood. A seizure is an action that may or may not occur again; epilepsy, on the other hand, is a medical condition where multiple seizures take place over a period of time. Infants and toddlers who suffer from epilepsy experience repeated seizures, with the frequency varying from patient to patient. Most of the time, these episodes can be avoided or lessened with medication. It is imperative for these children to receive prompt medical assessment because with early and accurate diagnosis, most pediatric cases can be successfully controlled and some cases can eventually be cured. In the most severe situations, surgery can also be a successful treatment solution.

The onset of epilepsy is most common during early childhood and after age 65. Each year 150,000 children and adolescents in the United States will have a newly occurring single seizure and 30,000 will be diagnosed with epilepsy after subsequent seizures occur.The highest incidence of epilepsy is during the first year of life, which is why new parents can often miss or misinterpret physical symptoms. Common misconceptions As a specialist in pediatric epilepsy, I’ve encountered frequent misinformation about this condition and the children who live with it. Let me dispel the most common misconceptions:A large percentage of patients have normal IQ scores, some even above normal intelligence. The majority of children will develop normal motor skills, show positive progress in school and maintain normal social relationships. Unlike other chronic diseases, many children with epilepsy will eventually outgrow the condition. It has been known for some time that prolonged seizures can injure the brain; more recently, we learned that even short seizures, if frequent or repetitive, can harm the brain as well.This is why early diagnosis and treatment is so critical.

Symptoms in infants and children

Epilepsy is caused by abnormal activity in brain cells and seizures can affect any process the brain coordinates. During development, infants often exhibit a variety of physical movements and mannerisms that may not cause immediate concern.As a result, parents and caregivers can mistake a seizure for typical baby behavior. In most cases, a child with epilepsy will tend to have the same type of seizure each time, so symptoms will be similar from episode to episode such as:

 a staring spell

 uncontrollable jerking movements of the arms and legs

 lack of response to verbal stimulation

 shaking, falling or smacking of the lips

Specialty care for children with epilepsy

If you suspect that your child may have experienced even one seizure, contact your pediatrician immediately for an evaluation.Take notes about the duration and symptoms your child exhibited and share this with your doctor. Failure to properly diagnose epilepsy early on can lead to learning and speech disabilities. 

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