Scientists Create Model to Assess Risk of Drug-Resistant Epilepsy in CP Children

Scientists Create Model to Assess Risk of Drug-Resistant Epilepsy in CP Children
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Based on clinical characteristics, researchers have developed a new, “simple to apply” model that has the capacity to accurately predict the risk that children with cerebral palsy (CP) have of developing drug-resistant epilepsy.

The model was described in the study, “Prediction of Drug-Resistant Epilepsy in Children With Cerebral Palsy,” published in the Journal of Child Neurology.

Epilepsy occurs in approximately 15-60% of children with CP, and is characterized by frequent bursts of electrical activity, or seizures, that can affect brain function temporarily.

In this patient population, epilepsy is associated with increased cognitive, motor, and behavioral difficulties, the researchers said.

Previous studies have shown that epilepsy that does not respond to anti-seizure medications — known as drug-resistant epilepsy — may be even more detrimental to the overall health of children with CP compared with other symptoms of the disorder, including motor impairments. However, the risk factors that predispose these children to drug-resistant epilepsy remain unknown.

Now, researchers sought to identify potential predictive clinical factors that could be used to assess the risk of drug-resistant epilepsy in children with CP. The team analyzed medical records from children with cerebral palsy who visited the pediatric neurology institute outpatient clinics at the Dana-Dwek Children’s Hospital, in Tel Aviv, from 2013 to 2018.

In total, 118 children with both CP and epilepsy — 66 with therapy-responsive epilepsy and 52 with the drug-resistant type — were included in the final analysis.

The most common type of CP observed in these children was spastic quadriplegia (42%), in which all four limbs are affected. This was followed by spastic hemiplegia (28%), which affects both the arm and leg on one side of the body, and spastic diplegia (13%), which impacts two limbs — usually the legs.  Children with mixed CP accounted for 8.5% of the cases, while 5% of the patients were observed to have spastic triplegia (5%), in which three limbs are affected. The remaining 2% were children with other types of CP, namely extra-pyramidal, ataxic, and hypotonic.

Among the main causes of CP for these children were premature birth, intracranial bleeding — bleeding occurring inside the skull — brain malformations, infection, trauma, and cerebral infarction. Cerebral infarction is severe damage — or infarct — caused by lack of blood flow to the brain.

The children’s first seizures occurred at a median age of 17 months. Generalized seizures occurred in 63 children (53%), focal seizures in 34 (29%), and combined generalized and focal seizures in 21 children (18%). Focal seizures start on one side of the brain, while generalized seizures start in both sides of the brain.

When investigators reviewed data from electroencephalograms (EEGs) — a test that records and analyzes patterns of electrical brain activity — they found that 104 of the 118 children (88%) included in the study had abnormal electrical brain activity.

After comparing clinical data of children with responsive and drug-resistant epilepsy, investigators came up with four different clinical features that, when combined in a model, could accurately distinguish children with both types of epilepsy and estimate the risk associated with drug-resistant epilepsy.

These features included having a low Apgar score (1-4) at five minutes after birth, having neonatal (newborn) seizures, having focal-onset epilepsy, and showing focal slowing — slower electrical activity on one side of the brain — on an EEG.

The Apgar test is performed on newborns shortly after birth to assess skin color (Appearance), heart rate (Pulse), reflexes (Grimace), muscle tone (Activity) and breathing rate (Respiration). Scores are between 10 and 0, where 10 is the highest score possible.

The researchers then focused on identifying other features that could arise as a consequence, rather than a cause, of drug-resistant epilepsy among the population with this type of epilepsy.

They found that intellectual disability and attendance in special education were more frequent among children with drug-resistant epilepsy. These children also much more commonly had a failure to respond to a large number of antiepileptic drugs (AEDs), and adherence or attempt to adhere to a ketogenic (very low-carb, high-fat) diet. Vagus nerve stimulation or surgery for epilepsy also was much more frequent among children with drug-resistant epilepsy. Vagal nerve stimulation is a method of employing a surgically fitted device that electrically stimulates the vagus nerve, one of the main nerves that runs from the abdomen to the brain, and controls several body functions.

“Based on our findings, we established a prediction model for drug-resistant epilepsy in children with cerebral palsy,” the researchers said, adding that their model is “simple to apply in clinical settings.”

This predictive model “may help health care providers complete a clinical picture of a ‘high-risk epilepsy’ and thereby further assist in the consideration of alternative therapeutic avenues in reaching the goal of reducing the burden of poor seizure control in children with cerebral palsy,” they concluded.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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