Emergency Departments Frequently Miss Signs of Epilepsy in Children

Article by NYU Langone Health

A subtle type of seizure goes undetected two-thirds of the time in pediatric emergency departments, a new study shows. The work focuses on “nonmotor” seizures, which cause children to ‘zone out’ and stare into space or fidget. Children may also feel sudden changes in emotions, thoughts, or sensations. According to the authors, improving recognition of nonmotor seizures may speed up the diagnosis and treatment of epilepsy in children, who often struggle to describe their symptoms to physicians, or are not asked to do so. Led by researchers at NYU Langone Health, the analysis involved 83 preteens and teens in treatment for epilepsy. Because seizures are easy to overlook or confuse for anxiety and panic attacks, the authors say it is critical that healthcare providers screen for signs of nonmotor seizures. To better understand how well such nonconvulsive episodes are spotted by physicians and patients alike, the researchers first explored how likely a child was to seek medical attention for their symptoms before they were aware that they had epilepsy. According to the findings, only 4 children went to the emergency department specifically for symptoms of a nonmotor seizure, although the study team later determined that 44 had a history of such issues. By contrast, 21 children visited the hospital for their first-ever motor seizure, out of 39 total. Even when treatment was sought, however, it was unlikely that their symptoms were properly diagnosed. The analysis showed that emergency department physicians correctly identified only 33 percent of first-time nonmotor seizures, compared with 81 percent of first-time motor seizures. Notably, the findings further revealed that while almost 40 percent of the teens turned out to have a history of nonmotor seizures, none were asked about them during their hospital visit. As a result, they were no more likely to be diagnosed and treated for epilepsy than those experiencing a motor seizure for the first time. The research team is now exploring ways to boost epilepsy recognition among members of the public as well, and hopes that symptoms become common knowledge, as the symptoms of heart attack and stroke are already.

Seizures Identified as Potential Cause of Sudden Unexplained Deaths in Children

Article published by NYU Langone Health

In a study designed to better understand sudden unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures accompanied by muscle convulsions as a potential cause. The study findings come from a registry of more than 300 cases of sudden unexplained death in children (SUDC) at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers that were potentially attributable to seizures. For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health. Published in the journal Neurology, the new study involved an analysis of the rare SUDC cases for which there were home video recordings. “Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep,” said study lead investigator Laura Gould, MSc, MA, PT, a research assistant professor at NYU Langone. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure. “These findings show that seizures are much more common than patients’ medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults,” said study senior investigator and neurologist Orrin Devinsky, MD.  

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial

Abstract found on PubMed


Objective: To test the hypothesis that early vigabatrin treatment in Tuberous Sclerosis Complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: Phase IIb multicenter randomized double-blind placebo-controlled trial of vigabatrin at first epileptiform EEG vs. vigabatrin at seizure onset in infants with TSC.

Primary outcome: Bayley-III cognitive assessment score at 24 months.

Secondary outcomes: prevalence of drug resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of eighty-four infants enrolled, 12 were screen failures, four went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). 56 were randomized to early vigabatrin (n=29) or placebo (n=27). 19 of 27 in the placebo arm transitioned to open label vigabatrin with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.

Interpretation: Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children; nor delay onset or lower the incidence of focal seizures and drug resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms.

Sleep Problems in Adolescents with Epilepsy and their Caregivers: Associations with Behavioral Difficulties

Abstract found on PubMed

Background: The aim of this study was to investigate the frequency of sleep problems in adolescents with epilepsy and their caregivers. We also examined the behavioural difficulties in adolescents with epilepsy and compared these behaviors with healthy controls.


Methods: This observational case-control study included 37 adolescents with epilepsy and their caregivers, and 43 healthy age-matched adolescents and their caregivers. The Children`s Sleep Habits Questionnaire (CSHQ), DSM-5 Level 2 Sleep Disorders Scale for Children, and Strengths & Difficulties Questionnaire (SDQ) were used to evaluate sleep habits, sleep problems, and behavioural difficulties in adolescents. The DSM-5 sleep disorder scale for adults was used to evaluate the caregivers` sleep problems.


Results: Adolescents with epilepsy had higher sleep problem scores such as daytime sleepiness and overall sleep problems compared with healthy controls. The psychopathological symptoms such as conduct problems, hyperactivity/inattention, and total behavior were also more frequent in adolescents with epilepsy. There was a nonsignificant increase in DSM-5 sleep disturbance score in caregivers of adolescents with epilepsy. Sleep onset delay had a significant negative correlation with total behavioral difficulties (r = -0.44, p < 0.01), and emotional problems (r = -0.47, p < 0.05) in adolescents with epilepsy. Sleep duration was negatively correlated with conduct problems (r = -0.33, p < 0.05), but positively correlated with prosocial score (r = 0.46, p < 0.01) in adolescents with epilepsy. Night waking was positively correlated with total behavioral difficulties (r = 0.35, p < 0.05) and hyperactivity score (r = 0.38, p < 0.05) in adolescents with epilepsy.


Conclusions: Adolescents with epilepsy have more frequent sleep disturbances and maladaptive behaviors such as hyperactivity/inattention, and conduct problems compared with healthy controls, and their caregivers are more vulnerable to sleep problems. Moreover, we also demonstrated a strong association between sleep disturbances and behavioral problems in adolescents with epilepsy.

Surgical Outcomes of Open and Laser Interstitial Thermal Therapy (LITT) Approaches for Corpus Callosotomy in Pediatric Epilepsy

Abstract found on Wiley Online Library

Objective: Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less invasive alternative with the use of laser interstitial thermal therapy (LITT). LITT works by heating a stereotactically placed laser fiber to ablative temperatures under real-time MRI thermometry. This study aims to 1) describe the surgical outcomes of CC in a large cohort of children with medically refractory epilepsy, 2) compare anterior and complete CC, and 3) review LITT as a surgical alternative to open craniotomy for corpus callosotomy.

Methods: This retrospective cohortcohort study included 103 patients <21 years old with at least 1 year follow-up at a single institution between 2003 and 2021. Surgical outcomes and the comparative effectiveness of anterior versus complete and open versus LITT surgical approaches were assessed.

Results: Complete callosotomy was the most common surgical disconnection (65%, n=67) followed by anterior two-thirds (35%, n=36), with a portion proceeding to posterior completion (28%, n=10). The overall surgical complication rate was 6% (n=6/103). Open craniotomy was the most common approach (87%, n=90), with LITT used increasingly in recent years (13%, n=13). Compared to open, LITT had shorter hospital stay (3  days [IQR 2-5] vs. 5 days [IQR 3-7]; p<0.05). Modified Engel I, II, III, and IV outcomes at last follow-up were 19.8% (n=17/86), 19.8% (n=17/86), 40.2% (n=35/86), and 19.8% (n=17/86). Of the 70 patients with preoperative drop seizures, 75% resolved postoperatively (n=52/69).

Significance: No significant differences in seizure outcome between patients who underwent only anterior corpus callosotomy and complete corpus callosotomy were observed. LITT is a less invasive surgical alternative to open craniotomy for corpus callosotomy, associated with similar seizure outcomes, lower blood loss, shorter hospital stays, and lower complication rates, but with longer operative times, when compared with the open craniotomy approach.

Epilepsy Research News: May 2023

This issue of Epilepsy Research News includes summaries of articles on:


Epilepsy with Eyelid Myoclonia (EEM)

A newly published article, written by a steering committee convened by CURE Epilepsy, provides a comprehensive review of the characteristics of EEM, also known as Jeavons syndrome. EEM is a type of epilepsy?that occurs in childhood, with seizures often continuing into adulthood. It is more common in females and its hallmark traits consist of eyelid myoclonia (brief jerks of the eyelids) with or without absence seizures, eye closure-induced seizures, and photosensitivity. Individuals with EEM are often misdiagnosed and anti-seizure medication resistance is common, highlighting the need for further studies to understand more about this epilepsy and possible interventions to treat it.  

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A Computer Model of Epilepsy Brain Used in Clinical Trial for Epilepsy Surgery

Scientists in France are looking at how a computer model of the brain can improve the localization of the seizure zone before epilepsy surgery. The models are created using the Virtual Epileptic Patient (VEP), which employs brain scans and brainwave-recording data from individuals with epilepsy to build a personalized model to improve the understanding of where their seizures originate. The study authors said that VEP showed a 60% precision in identifying the epileptogenic zones in 53 patients with drug-resistant focal epilepsy. VEP is being evaluated in an ongoing clinical trial called EPINOV. If the trial results are promising, this computer model may become a new, personalized tool used in epilepsy surgical evaluations to improve surgical outcomes.  

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Worsened Perinatal Outcomes in Women with Epilepsy

Recently published findings showed that women with epilepsy have worse perinatal outcomes compared with women without epilepsy, including a 5-fold increase in the odds of maternal death. Combining the results of 76 already-published papers, investigators found that relative to women without epilepsy, those with epilepsy had increased odds of gestational hypertension, preeclampsia, intrauterine growth restriction, miscarriage, preterm birth, induced labor, stillbirth, cesarean delivery, and maternal death. “When counseling pregnant women with epilepsy and those of childbearing age, clinicians should consider these findings,” a lead investigator concluded. “In addition, clinicians and women with epilepsy should bear in mind the increased odds of negative adverse maternal and neonatal outcomes.”  

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Early-Life Meningitis Associated with Risk of Developing Epilepsy in Later Childhood

Infants exposed to invasive Group B Streptococcus (iGBS) meningitis during their first three months of life could have a greater risk of developing epilepsy in later childhood compared to infants who were not exposed, according to a recent study. Investigators evaluated the cumulative risk (CR) of an infant diagnosed with iGBS sepsis or meningitis during the first three months of age developing epilepsy. Examining a group of 1,432 children with iGBS and 14,211 without iGBS, the team found that the overall CR of developing epilepsy into later childhood was 3.6% among children with iGBS disease, whereas the CR of later-adulthood epilepsy was 2.3% in the group without iGBS. The study authors noted that the data have implications for affected individuals and underline the need for better long-term follow-up and care. 

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A Comprehensive Narrative Review of Epilepsy with Eyelid Myoclonia

Article published by Epilepsy Research

Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy. Recently, specific genetic mutations have been recognized in a minority patients, including in SYNGAP1, NEXMIF, RORB, and CHD2 genes. There are no randomized controlled trials in EEM, and the management literature is largely restricted to small retrospective studies. Broad-spectrum antiseizure medications such as valproate, levetiracetam, lamotrigine, and benzodiazepines are typically used. Seizures typically persist into adulthood, and drug-resistant epilepsy is reported in over 50%.

Early-Life Meningitis Associated with Risk of Developing Epilepsy in Later Childhood

Article published by Pharmacy Times

Infants exposed to invasive Group B Streptococcus (iGBS) meningitis during their first 3 months of life could have a greater risk of developing epilepsy in later childhood compared to infants who were not exposed, according to a 20-year study conducted from Denmark that was recently published in JAMA Network Open. iGBS is a leading cause of neonatal/young infant mortality. It is also associated with maternal death, stillbirth, and neurodevelopmental impairment (NDI) in the surviving neonates. NDIs include stroke, encephalopathy, cerebral palsy, intellectual and/or motor, vision, hearing impairment, sepsis, and meningitis. Among the limited and small studies that analyze NDI outcomes, most focus on meningitis.

Meningitis may cause epilepsy following neonatal iGBS disease. However, more research is needed to understand iGBS disease on the risk of long-term epilepsy, and the risk among patients with neonatal iGBS sepsis. Investigators evaluated the cumulative risk (CR) of an infant diagnosed with iGBS sepsis or meningitis during the first 3 months of age developing epilepsy. The team accounted for sex, prematurity, and maternal socioeconomic position (SEP) as effect modification factors.

Epilepsy Research News: April 2023

This issue of Epilepsy Research News includes summaries of articles on:


Predicting Seizures in Temporal Lobe Epilepsy

Seizures can be predicted more than 30 minutes before they occur in patients with temporal lobe epilepsy, possibly opening the door to preventing seizures from happening, according to a new study. Researchers used electroencephalography (EEG), which measures electrical activity in the brain, to examine periods of potentially heightened risk for seizures known as “pro-ictal states.” The researchers were able to detect pro-ictal states in patients with temporal lobe epilepsy approximately 30 minutes or more before seizure onset. This information could lead to the development of electrical stimulation or drug therapies aimed at preventing seizures in people with this type of epilepsy. “The ability to predict seizures before they occur is a major step forward in the field of epilepsy research,” a study author stated.

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Altered Brain Signaling in People with Epilepsy Detected Through Non-Invasive Approach

New research has found that large-scale changes in the activation of neurons can be detected in the brains of people with temporal lobe epilepsy during a resting state (a state in which the brain is not stimulated by tasks or input), even when no seizure is occurring. The non-invasive approach uses EEG to detect changes in brain activity and could lead to a new method to aid in the diagnosis of epilepsy. While the brain is at rest, spontaneous waves of neuronal activation are constantly generated in a phenomenon called a “neuronal avalanche.” The researchers demonstrated that even during the resting state it is possible to detect a change in the neuronal avalanches in the brains of people with epilepsy. The researchers suggested that this method might be used as a preliminary diagnostic method, especially for difficult cases where standard scalp EEG fails to detect seizures, but additional investigations are necessary.

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Simple Blood Test Shows Potential Biomarker to Distinguish Epileptic from Non-Epileptic Psychogenic Seizures

Researchers have discovered higher levels of immune proteins in the blood before and after an epileptic seizure. In this study, researchers discovered that levels of five inflammation markers, or proteins, were elevated in people with temporal or frontal lobe epilepsy who had experienced a seizure. Among patients with psychogenic non-epileptic seizures (PNES), however, there was no change in the protein levels. These proteins, therefore, have the potential to be future biomarkers for a diagnosis of epilepsy. Diagnosing epilepsy from a simple blood draw would provide a significant advantage over the current diagnostic standards which may include admittance to a hospital for several days with constant video and EEG surveillance.

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Study Investigates Therapy for Treatment-Resistant Epilepsy

In a new study, researchers report that sodium selenate could be the first curative drug therapy for epilepsy. The study, conducted in an animal model of drug-resistant epilepsy, revealed sodium selenate to have a long-lasting effect (after months of stopping the medication) in reducing the frequency of seizures and in 30% of cases stopping them altogether. Sodium selenate also improved other aspects of epilepsy such as memory, learning, and sensor-motor functioning. The researchers will next begin a clinical trial of sodium selenate as a curative treatment in patients with drug-resistant epilepsy. “Despite the cost of the disease and the enormous amount of research into it, there has not been a single therapy developed to prevent the development of epilepsy,” stated a study author. “This Phase 2 clinical trial, if effective, has the potential to tackle a disease that is an enormous global burden as well as being truly transformative for people who are impacted by often daily seizures, with no respite.”

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Insights into the Drivers of Glioma-Related Epilepsy

Researchers at Baylor College of Medicine, including former CURE Epilepsy grantee Dr. Jeff Noebels, report that glioma tumors in the brain can interfere with the ability of surrounding neurons to handle potassium, an important ion in neuronal communication. The disruption of this normal neural function drives seizures and favors the progression of epilepsy. The team found that patients who have seizures have increased expression of genes involved in the formation of neuronal connections or synapses. In both humans with glioma and animal models, the researchers identified one of the genes, IGSF3, as the driver that mediated seizures in glioma-related epilepsy. The team found that IGSF3 suppresses the ability of these cells to take up potassium, which leads to its accumulation of this ion and then seizures. “Our studies reveal that tumor progression and seizures are triggered by disruption of potassium handling. The findings support further studies into novel strategies to control seizures and tumor growth,” stated one of the study’s authors.

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Researchers Identify Cause of Mysterious Cases of Childhood Epilepsy

Article published by  SciTechDaily

International research teams have uncovered a new cause for pediatric seizures: mosaicism, a condition in which cells within the same individual have different genetic compositions.

Approximately 4% of the population is affected by epilepsy, making it one of the most prevalent brain disorders among children. While modern medicine is effective in preventing seizures in the majority of patients, unfortunately, 20% of those with epilepsy do not respond to treatment.

In some cases, the cause of epilepsy may stem from patches of damaged or abnormal brain tissue known as “malformations of cortical development” (MCD). These MCDs result in a variety of neurodevelopment disorders. Surgical resection or removal of the patch can cure the 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.

In a recent paper published in Nature Genetics, researchers at the University of California San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine, collaborating with an international consortium of more than 20 children’s hospitals worldwide, 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.”