News Topics: Pediatric Epilepsy

Design and Implementation of Electronic Health Record Common Data Elements for Pediatric Epilepsy: Foundations for a Learning Health Care System

Abstract, originally published in Epilepsia

Objective: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy.

Methods: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types.

Results: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center.

Significance: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.

Are You Tuned In? The Challenges of Seizure Identification in Children with Intellectual Disability: A Potential for Video-Based Care-Pathway

Abstract, originally published in Epilepsy & Behavior

This qualitative study explores the challenges parents/carers face in seizure identification in children with coexisting epilepsy and intellectual disability (ID).

Semi-structured interviews with parents/carers provided ten hours of data, transcribed verbatim for data analysis. Themes and subthemes were identified and grouped to reflect the findings. The importance of knowing the child’s usual behavior and recognizing changes to this was a consistent theme. All participants reported that being ‘in tune’ with their child helped in seizure recognition. Participants felt that the healthcare professionals (HCP) were poor at recognizing seizures in their children at times. They had mixed thoughts on the difficulty the presence of an ID contributes to seizure recognition. The severity of ID and the seizure type were the two main variables discussed.

The study concludes that knowing the child well and understanding the usual behavior of the child is crucial to seizure recognition. A video-based care pathway with videos of both usual behavior and seizure activity available to the HCP to classify the events correctly may be potentially beneficial to improve patient care.

Epilepsy Research News: December 2020

This month’s research news includes announcements about the Curing the Epilepsies 2021 Conference, and a reminder about the Cure Epilepsy and Taking Flight grant letters of intent (LOIs).

We also share that the Health Disparities Research Institute will be accepting applications, and that the TESS Research Foundation is hiring.

These news items are summarized below.

Research Highlights

Curing the Epilepsies 2021 Conference–January 4-6, 2021

Please join the epilepsy community from around the world to discuss the progress made in understanding the biological mechanisms underlying the epilepsies, and the inroads being made towards potential cures.

The main outcome and priority of the meeting will be to identify transformative research priorities that will accelerate development of cures and improve outcomes for people with epilepsy. The meeting takes place from January 4-6, 2021. It will be open to the public and freely available via livestream.

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Understanding & Treating Temporal Lobe Epilepsy
A team of researchers has found that an amino acid produced by the brain could play a crucial role in preventing cell loss and seizures associated with temporal lobe epilepsy. Utilizing an animal model of temporal lobe epilepsy, the research team found that administration of the amino acid D-serine prevented cell loss characteristic of temporal lobe epilepsy and reduced the number and severity of seizures.

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CURE Epilepsy and Taking Flight Grant Timeline–Letter of Intent (LOI) due January 11, 2021 9 PM EST
Reminder, CURE Epilepsy is accepting LOIs for both the CURE Epilepsy and Taking Flight grant awards now through Monday, January 11, 2021 at 9 PM ET. Don’t miss your opportunity to be considered!

  • CURE Epilepsy Award, $250,000 over two years: This award reflects CURE Epilepsy’s continued focus on scientific advances that have potential to truly transform the lives of those affected by epilepsy.
  • Taking Flight Award, $100,000 for one year: This award seeks to promote the careers of young epilepsy investigators, allowing them to develop a research focus independent of their mentors.
  • Research areas: Sudden unexpected death in epilepsy (SUDEP), acquired epilepsy, treatment-resistant epilepsy, pediatric epilepsy, and sleep and epilepsy

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2021 Health Disparities Research Institute–Accepting Applications February 1-March 8, 2021The next Health Disparities Research Institute–featuring lectures on minority health and health disparities research, mock grant review, seminars and more–will be held virtually August 9-13, 2021.

The program’s intent is to support early-career minority health/health disparities research scientists and stimulate research in the disciplines supported by health disparities science. Admission to this program is by application only. The application cycle is open February 1-March 8, 2021.

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Job Opportunity: Research Program Manager Position with TESS Research Foundation
Looking for an opportunity to make a difference in the area of rare epilepsies? The TESS Research Foundation is seeking a Research Program Manager to oversee all scientific research focused on SLC13A5 Epilepsy, including research coordination, grant program oversight, community outreach, and scientific communication and cultivation.

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Educational Interventions Improving Knowledge About Epilepsy in Preschool Children

Abstract, originally published in Epilepsy & Behavior

Objective: Sufficient public knowledge about epilepsy is a starting point for reducing epilepsy-related stigma and improving quality of life of people with this condition. Thus, interventions aimed at improving such knowledge are greatly needed. However, there is a significant lack of such interventions and none have been applied to preschool children. We aimed to develop effective interventions using the educational board game Action Zone! and a technique known as educational story, and by focusing on the acquisition of knowledge about epilepsy in children aged 5-6 years with no previous knowledge of epilepsy.

Methods: Knowledge about epilepsy was measured using a 20-item test consisting of questions selected from educational game and an 11-item test used successfully in our previous intervention study focused on children aged 9-11 years. Both measures exhibited acceptable internal consistency with Cronbach’s alpha of 0.72 and 0.67. In total, 296 children participated in three intervention studies (educational game, educational story, and a revised version of educational story). Level of knowledge was assessed immediately after each intervention and again one month later.

Results: We found that all interventions were effective (p = 0.001) in comparison of retest results with baseline of zero level of knowledge based on the statements of children before intervention. Intervention based on educational game resulted in a higher percentage of correct responses in comparison with educational story (p = 0.020). However, the revised version of educational story developed using participatory action research was superior in comparison with the original version (p < 0.001) and fully comparable with educational game (p = 0.864).

Conclusions: The results showed the aforesaid interventions were significant and effective ways to establish basic knowledge about epilepsy in the given age group.

Usefulness, Limitations, and Parental Opinion about Teleconsultation for Rare Pediatric Epilepsies

Abstract, originally published in Epilepsy & Behavior

Aim: Evaluation of the usefulness and the parental opinion about teleconsultation (TC) for rare pediatric epilepsies.

Method: One-month prospective survey of consecutive TCs. All clinics on site have been turned into TC in the context of COVID-19 pandemic. The physicians quoted all TCs while the parents expressed their opinion though an invitation for an online questionnaire.

Results: We included 151 TCs (145 patients) among the 259 epilepsy TCs done during the study period. The parental questionnaire has been answered 105 times. The physicians felt confident to organize a TC for the next visit of 74.8% of the children, but some limits were identified such as the absence of physical examination, weight, and psychomotor development evaluation. The physicians felt more confident for a new TC in older patients (9.5 ± 5.5 years versus 5.3 ± 4.3 years) and in stable patients (73.8% confident for instable, 82.8% for stable). Parents were satisfied with TC feeling that it answered health issues in a better manner than a clinic pinpointing the gain of time and the absence of travel. However, half of them would prefer a clinic for the next appointment.

Interpretation: Teleconsultation seems useful answering the patients’ needs according to both physicians and families. Despite some limitations, it is most likely that TCs become a new part of the clinical activities in rare pediatric epilepsy centers.

Epilepsy Research News: December 2020

In this month’s news, we spotlight a publication describing CURE Epilepsy’s Infantile Spasms (IS) Initiative, a collaborative research program that brought a team science approach to understanding the causes and potential treatments for IS. Running from 2013-2016, this program led to numerous advances in understanding the pathways in the brain involved in IS. 

Also, this month we feature news from the EPISTOP study showing that preventative treatment with the drug vigabatrin decreased the number of days with seizures as well as the severity of epilepsy in infants with tuberous sclerosis complex. We also highlight recent work from CURE Epilepsy Grantee Dr. Jeffrey Loeb, whose team identified a protein found in healthy brain tissue that may work to prevent the spread of seizures. 

These studies and more are summarized below. 

Research Highlights

Infantile Spasms
This recent publication highlights CURE Epilepsy’s Infantile Spasms (IS) Initiative, established in 2013 to support a collaborative, team science-based and milestone-driven effort to advance the understanding of causes of and potential treatments for IS. The combined efforts of the research team led to numerous advances in understanding the causes of IS. It also brought together a diverse group of investigators–who otherwise would not have collaborated–to study therapies for IS.

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Preventing the Spread of Seizures
New research may explain what prevents seizures in certain areas of the brain from spreading to other areas of the brain. In a study funded by the National Institutes of Health/American Epilepsy Society, CURE Epilepsy Grantee Dr. Jeffrey Loeb and his colleagues found that a protein called DUSP4 was increased in healthy brain tissue directly next to epileptic brain tissue. The research suggests that DUSP4 may work to prevent the spread of epilepsy in the brain and that boosting levels of DUSP4 could be a novel way of preventing or treating epilepsy.

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Tuberous Sclerosis Complex Treatment
Preventive treatment with vigabatrin effectively decreased the risk and severity of epilepsy in infants with tuberous sclerosis complex who were enrolled in the EPISTOP multi-center study. Vigabatrin resulted in a significantly longer time to first clinical seizure compared with conventional treatment as well as a lower proportion of days with seizures until age 2, according to the study findings. The “EPISTOP study has shown that it may be possible to change the natural history of severe infantile epilepsy through early intervention with antiepileptic therapy,” the researchers wrote.

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Epilepsy and Dementia
Late-onset epilepsy has been linked to a substantially increased risk of subsequent dementia. Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy. “We are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other on-going studies are finding similar results,” she added.

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Epilepsy Treatment Expansion Approval
The FDA expanded its approval of lacosamide, marketed as Vimpat, to include add-on therapy for primary generalized tonic-clonic seizures as well as an IV formulation for patients aged 4 years and older.

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FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Abstract, originally published in Epilepsia

Chromosome 1q41-q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41-q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41-q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41-q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41-q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug-resistant epilepsy, and hyperkinetic movement disorders.

Proposal to Optimize Evaluation and Treatment of Febrile Infection Related Epilepsy Syndrome (FIRES): A Report from FIRES Workshop

Summary, originally published in Epilepsia

Febrile infection related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019.

An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course.

FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL 1 receptor antagonist that blocks biologic activity of IL1 ) are recommended.

Epilepsy Research News: November 2020

This month’s research news includes a study that highlights the importance of adherence to antiepileptic drug regimens and controlling seizures to reduce the risk of sudden unexplained death in epilepsy (SUDEP). We also highlight an advancement in understanding and preventing temporal lobe epilepsy, utilizing an animal model.

Additionally, we share a study that highlights the difficulty that can be faced in diagnosing sometimes subtle seizures associated with focal epilepsy, and we present findings on the development of a new tool to help ease what can be a challenging transition from pediatric/adolescent to adult care for individuals with epilepsy.

In other news, a new FDA alert was issued to avoid the use of lamotrigine/Lamictal in people with cardiac conduction disorders, ventricular arrhythmias, or cardiac disease or abnormality.

These studies and the FDA alert are summarized below.

Research Highlights

Preventing SUDEP
Polytherapy, especially the use of three or more antiepileptic drugs, is correlated with a substantially decreased risk for SUDEP according to a nationwide study conducted in Sweden. The study also demonstrated a link between statin use and a decreased risk for SUDEP. “These results provide support for the importance of medication adherence and intensified anti-epileptic drug treatment for patients with poorly controlled generalized tonic-conic seizures in the efforts to reduce SUDEP risks and suggest that comedication with statins may reduce risks,” the researchers wrote.

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Understanding & Treating Temporal Lobe Epilepsy
A team of researchers has found that an amino acid produced by the brain could play a crucial role in preventing cell loss and seizures associated with temporal lobe epilepsy. Utilizing an animal model of temporal lobe epilepsy, the research team found that administration of the amino acid D-serine prevented cell loss characteristic of temporal lobe epilepsy and reduced the number and severity of seizures.

Learn More

Focal Epilepsy & Delayed Diagnosis
A new study shows that it can take on average two years for physicians to recognize the early signs of focal epilepsy, particularly in patients with seizures that do not involve uncontrolled movements of their arms and legs. Subtler cases are often not diagnosed until they have progressed to disruptive “motor” seizures, say the study authors, which can cause the unrestrained, whole-body spasms often portrayed in popular culture. Researchers believe the impact of earlier diagnosis in focal epilepsy patients goes beyond more timely treatment of patients; some study participants reported having one or more car accidents before their diagnosis. The researchers estimate that for every 13 early diagnoses, one car accident, equating to an estimated 1,816 annually worldwide, could be prevented.

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Transitioning to Adulthood with Epilepsy
Clinicians at Michigan Medicine have developed an assessment tool to help doctors ensure adolescents and young adults with epilepsy have the skills and confidence they need to take control of seizures and health care. Through a customized screening tool for 16 to 26-year-olds, doctors are effectively able to monitor their patients’ development of knowledge and self-management skills regarding their condition. This tool allows providers to proactively address gaps in readiness that may impact long term health outcomes.

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FDA Alert for Lamotrigine
The FDA has issued a new warning advising against the use of lamotrigine/Lamictal in people with cardiac conduction disorders, ventricular arrhythmias, or cardiac disease or abnormality. People currently taking lamotrigine should consult their healthcare provider. Do not stop taking lamotrigine without talking to your healthcare provider as doing so can cause serious problems.

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Epilepsy Research News: October 2020

This month’s research news features two studies advancing Dravet syndrome research, both utilizing mouse models mimicking the disorder. One study, featuring the work of former CURE Grantee Dr. Lori Isom, tested a new type of drug and found that it decreased the frequency of Sudden Unexplained Death in Epilepsy (SUDEP) in these mice.

In other news, a recent study has increased our understanding of the unique way epilepsy can affect women, showing that women who have seizures that increase in frequency during their menstrual cycle are also more likely to have drug-resistant epilepsy.

Finally, research has helped pinpoint individuals with epilepsy who may be at risk for obstructive sleep apnea, a finding that may help physicians identify who is most at risk and who would likely benefit from treatment.

Summaries of these research discoveries and more are below.

Research Discoveries

Dravet Syndrome (Featuring the work of former CURE Grantee, Dr. Lori Isom)
A new treatment curbs deadly seizures in a mouse model of Dravet syndrome, a severe form of epilepsy, according to a new study. This new drug counteracts the effects of mutations in a gene known as SCN1A, which cause Dravet syndrome. In this study, the drug significantly decreased the overall frequency of SUDEP, lowering the likelihood of a fatal seizure. A clinical trial is evaluating the drug’s safety in children with the syndrome.

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Dravet Syndrome
A study has utilized a gene therapy technique to reduce seizures and improve behaviors in a mouse model of Dravet syndrome. Researchers used the technique to activate the SCN1A gene, a gene with decreased activity in individuals with Dravet syndrome. The authors note that although more work must be done before the technique can be tested in people, the study supports a potential new approach to treating this cause of epilepsy.

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Epilepsy Genetics
Researchers have identified a critical new step in how brain cells function in people with one of the most common forms of epilepsy. Using mice, researchers found certain changes in gene activity and regulation in an area of the brain important in temporal lobe epilepsy. The researchers note that the study could eventually lead to targeted treatments that prevent a person from developing epilepsy.

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Epilepsy and Fetal Alcohol Spectrum Disorder
A study has found a much higher prevalence of epilepsy or history of seizures in individuals with fetal alcohol spectrum disorder (FASD), a disorder that refers to a range of developmental problems that result from maternal drinking during pregnancy. Although more research is needed to establish a direct cause-effect relationship between FASD and epilepsy, the study, which examined the medical histories of individuals from two FASD clinics, supports the link between maternal drinking during pregnancy and a wide array of health impacts to the child.

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Drug Resistant Epilepsy and Women
More frequent seizures during the menstrual cycle in women with genetic generalized epilepsy have been linked for the first time to drug-resistant epilepsy. Women with catamenial epilepsy, a generalized epilepsy characterized by increased seizure frequency during the menstrual cycle, were nearly four times more likely to have drug-resistant epilepsy than women who experience no changes in frequency.

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Epilepsy and Sleep Apnea
People with generalized epilepsy who have seizures arising from both sides of the brain simultaneously have a higher risk of obstructive sleep apnea than those who have focal epilepsy where seizures emanate from one area of the brain, according to a new study. These findings may help physicians better understand who is most at risk for obstructive sleep apnea and, therefore, who will benefit most from treatment.

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