Folate Fortification of Food: Insufficient for Women with Epilepsy

Abstract, originally published in Epilepsy & Behavior

Objective: Folic acid supplementation during the periconceptual period has been shown to improve cognitive outcomes in children of women with epilepsy taking anti-seizure medications (ASMs). The dose of folic acid necessary to provide positive cognitive outcomes is unclear. In many countries including the United States, food is fortified with folic acid, but no data exist on how food fortification may affect cognition in children with fetal-ASM exposure. This study evaluated the effect of dietary folate from natural folates plus folic acid fortification, separate from folic acid vitamin supplements, on age-6 year IQ in children with fetal-ASM exposure.

Methods: Data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study were retrospectively analyzed for this investigation. Assessment of nutrient intake was conducted using the Block Food Frequency Questionnaire-98. The primary outcome of the present study was to assess association of maternal pre-pregnancy nutrient levels to child age-6 IQ.

Results: Folate from food alone without supplement was not associated with improvement of age-6 IQ in children with fetal ASM exposure (95% CI: -11.7-2.3, p = 0.187). Periconceptual folate supplement use was associated with a 10.1-point higher age-6 IQ (95% CI: 5.2-15.0, p < .001). Total combined folate from food plus supplement also showed that higher intake of folate was associated with higher age-6 IQ (Coefficient: 4.5, 95% CI: 2.0-6.9, p < .001). Six other nutrients from food and supplements were analyzed (Vitamin C, Vitamin D, Vitamin E, Omega 3, Gamma Tocopherol, and Vitamin B12) and had no significant association with age 6-IQ.

Significance: Dietary content of folate, even in a country where food is fortified with folic acid, is not sufficient to provide improved cognitive outcomes for children of women taking anti-seizure medication during pregnancy. Folate supplementation is needed for significant improvement in cognitive outcomes, specifically age-6 IQ.

Patient, Caregiver, and Healthcare Professional Perspectives on Seizure Control and Treatment Goals

Abstract, originally published in Epilepsy & Behavior

Objective: To examine perspectives of adult patients with epilepsy, caregivers, and healthcare professionals (HCPs) on seizure freedom, seizure control, communication, and treatment goals.

Methods: Participants were recruited from online M3 panel and by Rare Patient Voice, and completed the self-administered online STEP Survey (Seize the Truth of Epilepsy Perceptions). Group comparisons used analysis of variance and chi-square tests.

Results: The STEP Survey was completed by 400 adult patients with epilepsy, 201 caregivers, and 258 HCPs (112 general neurologists, 96 epileptologists, 50 nurse practitioners/physician assistants). Significantly more patients (61%) and caregivers (66%) than HCPs (45%) agreed that seizure freedom is always a reasonable goal (P < 0.05). On average, patients considered 3.6 seizures/year to be “in control.” Of their patients with focal seizures, HCPs reported 47% were seizure-free and 33% were “in control” (63% were having 1-12 seizures/year), and 20% were with “uncontrolled” seizures. Among patients, caregivers, and HCPs, ?60% agreed that a defining characteristic indicating seizure control was having good quality of life. Patients, caregivers, and HCPs agreed that the emotional, psychological, and relational impact of seizures were least discussed (<50% of each group reporting discussion), but disagreed in their top priority for greater discussion (patients: sudden unexplained death in epilepsy [SUDEP]; HCPs: relational impact of seizures). Although ?80% of patients and caregivers selected multiple patient life goals as very or extremely important, 49% of patients said they do not share life goals with their HCP. HCPs agreed that patients are not telling them everything they should about their epilepsy (73% of HCPs) or their life goals (81% of HCPs).

Conclusions: Differing perspectives on seizure freedom, seizure control, communication priorities, and treatment goals that were identified in the STEP Survey provide opportunities to improve patient care and outcomes through more effective two-way communication and alignment of goals among patients with epilepsy, caregivers, and health care professionals.

Early Warning for Seizures Could be a Game Changer for Epilepsy Patients

Summary, originally published by the University of Southern California

Epilepsy is one of the most common neurological conditions, affecting more than 65 million worldwide. For those dealing with epilepsy, the advent of a seizure can feel like a ticking time bomb. It could happen at any time or any place, potentially posing a fatal risk when a seizure strikes during risky situations, such as while driving.

A research team at USC Viterbi School of Engineering and Keck Medicine of USC is tackling this dangerous problem with a powerful new seizure predicting mathematical model that will give epilepsy patients an accurate warning five minutes to one hour before they are likely to experience a seizure, offering enhanced freedom for the patient and cutting the need for medical intervention.

The research, published in the Journal of Neural Engineering, is led by corresponding authors Dong Song, research associate professor of biomedical engineering at USC Viterbi School of Engineering and Pen-Ning Yu, former PhD researcher in Song’s lab, in collaboration with Charles Liu, professor of clinical neurological surgery and director of the USC Neurorestoration Center. The other authors are David Packard Chair in Engineering and professor of biomedical engineering, Ted Berger, and medical director of the USC Comprehensive Epilepsy Program at the Keck Medical Center, Christianne Heck.

The mathematical model works by learning from large amounts of brain signal data collected from an electrical implant in the patient. Liu and his team have already been working with epilepsy patients with implantable devices, which are able to offer ongoing real-time monitoring of the brain’s electrical signals in the same way that an electroencephalogram (EEG) uses external electrodes to measure signals. The new mathematical model can take this data and learn each patient’s unique brain signals, looking out for precursors, or patterns of brain activity that show a “pre-ictal” state, in which a patient is at risk of seizure onset.

World-Leading Children’s Hospitals Partner to Find New Treatments for Pediatric Diseases

Summary, originally published by University College London

Four leading children’s research institutions on three continents are joining forces to decipher pediatric illnesses, including rare diseases, and find better treatments.

The four pediatric hospitals — Boston Children’s Hospital; UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital (London); the Murdoch Children’s Research Institute with The Royal Children’s Hospital (Melbourne); and The Hospital for Sick Children (SickKids) in Toronto — are working together to evaluate genomic data, clinical data from patients, and scientific and medical expertise to accelerate discovery and therapeutic development.

The partnership, known as the International Precision Child Health Partnership (IPCHiP), is the first major global collaboration around genomics and child health. The founding partners anticipate that additional institutions will join the collaboration in the future.

IPCHiP’s first project will involve epilepsy in infants, bringing together efforts already underway at the four hospitals.

Investigators at each site will enroll babies under age one with epilepsy, sequence their genomes, change treatment based on the findings when appropriate, and follow the children’s development long term. No patient will be identifiable from the data used, and no patient data will be shared across international borders.

Elevated Blood Purine Levels as a Biomarker of Seizures and Epilepsy

Abstract, originally published in Epilepsia

Objective: There is a major unmet need for a molecular biomarker of seizures or epilepsy that lends itself to fast, affordable detection in an easy-to-use point-of-care device. Purines such as adenosine triphosphate and adenosine are potent neuromodulators released during excessive neuronal activity that are also present in biofluids. Their biomarker potential for seizures and epilepsy in peripheral blood has, however, not yet been investigated. The aim of the present study was to determine whether blood purine nucleoside measurements can serve as a biomarker for the recent occurrence of seizures and to support the diagnosis of epilepsy.

Methods: Blood purine concentrations were measured via a point-of-care diagnostic technology based on the summated electrochemical detection of adenosine and adenosine breakdown products (inosine, hypoxanthine, and xanthine; SMARTChip). Measurements of blood purine concentrations were carried out using samples from mice subjected to intra-amygdala kainic acid-induced status epilepticus and in video-electroencephalogram (EEG)-monitored adult patients with epilepsy.

Results: In mice, blood purine concentrations were rapidly increased approximately two? to threefold after status epilepticus (2.32 ± .40 µmol·L–1 [control] vs. 8.93 ± 1.03 µmol·L–1 [after status epilepticus]), and levels correlated with seizure burden and post-seizure neurodegeneration in the hippocampus. Blood purine concentrations were also elevated in patients with video-EEG-diagnosed epilepsy (2.39 ± .34 µmol·L–1 [control, n = 13] vs. 4.35 ± .38 µmol·L–1 [epilepsy, n = 26]).

Significance: Our data provide proof of concept that the measurement of blood purine concentrations may offer a rapid, low-volume bedside test to support the diagnosis of seizures and epilepsy.

New EBRAINS-Enabled Tool to Help Guide Surgery in Drug-Resistant Epilepsy Patients

Summary, originally published on EIN Newswire

Scientists of the Human Brain Project have developed a computational tool to locate the areas in a patient’s brain where epilepsy seizures emerge. Now, the team is using EBRAINS to further boost the accuracy with high resolution brain atlas data. With a clinical trial ongoing, the approach aims to give surgeons an increasingly powerful and precise tool to support targeted surgery decisions for each patient.

“Surgery success depends on locating these areas as precisely as possible. But in clinical practice this often proves very difficult, and the average surgery success rate remains at only around 60%”, says Viktor Jirsa. Any improvement would have major impact for many patients.”

The scientist has developed a computational tool, called “The Virtual Brain” (TVB), to model and predict activity in an individual patient brain. In collaboration with the neurologist Fabrice Bartolomei, they adapted the model to epilepsy, simulating the spread of individual seizure activity. The model thus can become an additional advisory tool for neurosurgeons to help target surgeries more precisely.

Relation Between Coffee Consumption and Risk of Seizure-Related Respiratory Dysfunction in Patients With Drug-Resistant Focal Epilepsy

Abstract, originally published in Epilepsia

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown.

Methods: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon’s epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with 1 or more focal seizure (FS), valid pulse oximetry (SpO2) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (3 or fewer cups/week), moderate (4 cups/week to 3 cups/day), and high (4 or more cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both.

Results: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07–.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04–.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042).

Significance: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.

Researcher Update: February 2021 

In this month’s Researcher Update you’ll find information on:

CURE Epilepsy Virtual Seminar Series

Please join CURE Epilepsy for our upcoming virtual seminars series. Seminar topics include:

Virtual seminars are part of the Frontiers in Research Seminar Series sponsored by the Nussenbaum-Vogelstein Family.

NIH launches database to track neurological symptoms associated with COVID-19

A new database will collect information from clinicians about COVID-19-related neurological symptoms, complications, and outcomes as well as COVID-19 effects on pre-existing neurological conditions. The COVID-19 Neuro Databank/Biobank (NeuroCOVID), which was created and will be maintained by NYU Langone Health, New York City, will be a resource of clinical information as well as biospecimens from people of all ages who have experienced neurological problems associated with SARS-CoV-2 infection.

Learn more

Cures Within Reach Funding Opportunity – Proposal Submissions Due March 17

Cures Within Reach has two new funding opportunities for up to $50,000 available for clinical repurposing trials: one to address high priority medical needs of veterans including those with brain injuries, and one for any rare pediatric disease. Projects repurposing approved drugs, devices, nutraceuticals and/or diagnostics are eligible. There’s no limit to the number of submissions from any institution or primary investigator (PI), and PIs at any career stage are welcome to apply.

Learn more

NINDS Post-Traumatic Epilepsy Workshop Sessions – First Session is March 18

The National Institute of Neurological Disorders and Stroke (NINDS) is sponsoring a series of workshops related to post-traumatic epilepsy. The workshops will set the stage to optimize preclinical and clinical research to prevent epileptogenesis following TBI. The results will help improve biomedical research in PTE. The workshops are tuition-free, but participation is limited, so early registration is suggested.

Learn More

Job Opportunities

  • Faculty Position: Center for Pediatric Neurological Disease Research, St. Jude Translational Neuroscience Initiative: Seeking an exceptional and creative scientist to lead an innovative laboratory-based research program using cutting-edge approaches to elucidate mechanisms and/or therapeutic strategies relevant to understanding and treating pediatric neurological disease. Learn more
  • Postdoctoral Research Associate, St. Jude Children’s Research Hospital: Seeking a postdoctoral fellow in translational neuroscience to study genomic and epigenomic causes of pediatric epilepsy and related disorders. Learn more.
  • Postdoctoral Fellow – Neurology Epilepsy, Emory University: Looking for a creative, productive, and motivated postdoctoral fellow to join a funded project examining the phenomenology and circuit basis of interactions between sleep-wake and seizures/epilepsy that will include expansion of observations from animal models to a large trove of scalp and intracranial human EEG data. Learn More.

Addressing Neuropsychological Diagnostics in Adults with Epilepsy: Introducing the International Classification of Cognitive Disorders in Epilepsy (IC-Code)

Abstract, originally published in Epilepsia Open

This paper addresses the absence of an international diagnostic taxonomy for cognitive disorders in patients with epilepsy. Initiated through the 2020 Memorandum of Understanding between the International League Against Epilepsy and the International Neuropsychological Society, neuropsychological representatives from both organizations met to address the problem and consequences of the absence of an international diagnostic taxonomy for cognitive disorders in epilepsy, overview potential solutions, and propose specific solutions going forward. The group concluded that a classification of cognitive disorders in epilepsy, including an overall taxonomy and associated operational criteria, was clearly lacking and sorely needed.

This paper reviews the advantages and shortcomings of four existing cognitive diagnostic approaches, including taxonomies derived from the US National Neuropsychology Network, DSM?V Neurocognitive Disorders, the Mild Cognitive Impairment classification from the aging/preclinical dementia literature and the Research Domain Criteria Initiative. We propose a framework to develop a consensus-based classification system for cognitive disorders in epilepsy that will be international in scope and be applicable for clinical practice and research globally and introduce the International Classification of Cognitive Disorders in Epilepsy (IC-CODE) project.

Molecular Blueprint of Receptor Could Help To Design New Drugs for Epilepsy

Summary, originally published on

In order for a drug to be effective at the right places in the body, it helps if scientists can predict as accurately as possible how the molecules of that drug will interact with human cells. In a joint research project, scientists from Collaborative Research Centre 1423 at Leipzig University and the Chinese Academy of Sciences in Shanghai have succeeded in elucidating such a structure, namely that of the neuropeptide Y receptor Y2 with one of its ligands. This is the first time that a molecular blueprint for this receptor is available, which will enable the development of tailor-made new drugs, for example to treat epilepsy or cardiovascular diseases. The researchers’ findings have now been published in Nature Communications.

The Y2 receptor plays an important role, especially in the peripheral nervous system and in the brain, as it is considered one of the “satiety receptors”. It also plays a role in epilepsy as well as in cardiovascular diseases. If these diseases are to be treated with drugs that block the Y2 receptor, it is important to ensure that the drug can target this receptor precisely and exclusively, because some closely related receptors would have exactly the opposite effect. When developing novel drugs, it is therefore essential to obtain highly targeted compounds and to have precise knowledge of their molecular properties.