Epilepsy is one of the most common neurological diseases globally. According to WHO estimates, around 50 million people worldwide have epilepsy and nearly 80% of these people live in low and middle-income countries with an estimated 12 million in India. It is the most common brain disorder in children. Ahead of the International Epilepsy Day on February 13, a well-known pediatric neurologist warns that symptoms of epilepsy in children often go unrecognised as their manifestation can be very different from the popular perception of how an epileptic seizure looks like. This can cause life-long cognitive and motor impairment. The HEALTH PIONEER brings forth several aspects of childhood epilepsy.
Late diagnosis of epileptic children is a major area of concern. Their brain is still developing, and recurring seizures at this stage can lead to life-long impairment. Seizures in young children often remain undiagnosed as they do not look like typical seizures, which people think essentially involve involuntary jerking and loss of consciousnessm” says Dr. Pratibha Singh, Head, Department of Pediatric Neurology, Amrita Hospital, Faridabad.
However, she adds, this does not necessarily apply to all children who have epilepsy and seizures. Symptoms of seizures in young patients can range from staring and rapid eye blinking to breathing difficulties, sudden jerks (which are mistaken as child getting afraid), going blank and not responding to words, twitching, loss of bladder control, falling suddenly without any cause, nodding head rhythmically, and appearing confused or in a haze. “People, and even many doctors, are simply not aware that these are also signs of epileptic attack in children.”
Dr Singh added: “Seizures and their manifestations differ greatly in young children compared to adults. Childhood epilepsy is extremely important because of the developing brain. If seizures are not taken care of in time, they can cause epileptic encephalopathy, which depresses the child’s development and causes severe cognitive and motor disabilities.
“So, it’s very important to recognize seizures in children early and start treatment without loss of time. However, even after treatment starts, compliance becomes another issue. For most children whose seizures get controlled, the parents stop their medication, thinking that the child has become fine. People should realize that anti-seizure medication (ASM) should never be stopped or decreased without consulting the doctor, otherwise the child may get bad seizures again.”
Cause for mysterious cases of epilepsy in children identified: Study
Modern medicine can prevent most seizure recurrences, but approximately 20% of patients do not respond to treatment.
In these cases, the reason may originate in patches of damaged or abnormal brain tissue known as “malformations of cortical development” (MCD), which results in a diverse group of neurodevelopmental disorders. Surgical resection or removal of the patch can cure seizures, and epilepsy surgery to improve neurological outcomes is now a key part of the modern medical armamentarium, but what causes the patches has largely remained a mystery.
The study is published in Nature Genetics. The researchers at University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine had collaborated with an international consortium of more than 20 children’s hospitals worldwide which helped them report a significant breakthrough in understanding the genetic causes of MCD.
Members of the Focal Cortical Dysplasia Neurogenetics Consortium investigated 283 brain resections from children across a range of MCD types, with parental consent, looking for potential genetic causes. Because most brain tissue in these children is normal, the scientists focused on mutations present in a small subset of brain cells, a phenomenon termed genetic somatic mosaicism.
“This was a decade-long journey, bringing specialists together from around the world, to recruit patients for this study,” said senior study author Joseph Gleeson, MD, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine. “Until recently, most hospitals did not study resected brain tissue for genetic causes. The consortium organized a biobank to store tissue for high-throughput mosaicism analysis.”
Previous research by Gleeson and colleagues had shown that genetic somatic mosaicism in the mTOR signaling pathway was a contributing factor, said co-first author Changuk Chung, PhD, a postdoctoral fellow in the Gleeson lab.
“But most patients remain undiagnosed, which hinders treatment. We tested for hidden mutations, detectable only by greatly expanding the cohort size and improving methods so that the results could be meaningful. We collaborated to solve technical and logistical bottlenecks. The pieces fell into place, but it took 10 years.”
The team conducted intensive genomic discovery using state-of-art somatic mosaic algorithms developed by the National Institutes of Health-sponsored Brain Somatic Mosaicism Network, of which UC San Diego is a member.
“We tried our best to detect mutations in as little as 1 percent of cells,” said co-first author Xiaoxu Yang, PhD, a postdoctoral scholar in Gleeson’s lab. “Initially we failed. To solve these problems, we needed to develop novel artificial intelligence methods to overcome barriers in sensitivity and specificity.”
The team ultimately identified 69 different genes carrying somatic brain mutations, the majority of which have never previously reported in MCD.
“We can draw parallels with the cancer field because these mutations disrupt cellular function and need to be resected,” said co-first author Chung. “However, unlike cancer cells, brain cells mostly do not divide so these cells misbehave by stimulating epileptic seizures. The question that arose was whether the newly found gene mutations were sufficient to cause MCD disease.”
Gleeson said the scientists found that the genes converged on calcium signaling, gene expression and synaptic functions, and noted that when the mutations were introduced into a mouse model, abnormalities similar to those seen in patients were observed. The study authors suggest the findings could be used to improve diagnosis and develop cures for MCD disease.
“The MCD genes in patient brains have demonstrated critical roles during cortical development,” said Gleeson. “These findings could lead to new molecular classifications for MCD, and ultimately to personalized therapies for epilepsy.”
FACTFILE
l Epilepsy is commonly diagnosed in children and can be confused with other conditions. An accurate diagnosis is essential.
l Seizures usually respond well to medication and most children with epilepsy will enjoy a normal and active childhood.
l The impact of epilepsy will vary for each child. Try to keep epilepsy in perspective for your child and your family.
l Remember to keep a balance between protecting your child and encouraging their independence.
COMMON SIGNS OF A SEIZURE INCLUDE
l Blank staring/Confused speech/Loss of consciousness/Uncontrollable shaking or jerking movements/Wandering
HOW TO HANDLE KIDS LIVING WITH
EPILEPSY/ SEIZURE
l Avoid tub baths; showers are safer than baths
l Make sure the bathroom door is not locked
l No swimming without constant adult supervision
l Wear a life jacket at all times when boating or on a jet ski
l No climbing higher than 10 feet including ladders, trees and bunk beds
l Wear a helmet at all times when bike riding and horseback riding
l For children with frequent seizures, avoid bike riding on streets
l No cooking over an open stove (use microwave instead) or using an iron
l Teenagers with uncontrolled seizures shouldn't drive, including ATVs, mini-motor cycles, 4-wheelers
l Do not allow the handling of firearms
