Review: Status Epilepticus and Early Development: Neuronal Injury, Neurodegeneration, and Their Consequences

Abstract found in Wiley Online Library

Evidence showing that the immature brain is vulnerable to seizure-induced damage has been accumulating for decades. Clinical data have always suggested that some early life seizures are associated with negative sequellae, but clinical observations are frequently obscured by multiple uncontrolled contributing factors and can rarely establish causality. Determining with certainty that seizures, per se, can cause neuronal death, and can irreversibly disrupt critical developmental processes, required the development of suitable model systems. Several experimental seizure models clearly show that the immature brain can sustain neuronal injury as a result of uncontrolled seizure activity, and that even in the absence of observable neuronal death, the developing brain is selectively vulnerable to interruptions of required growth programs. Severe early-life seizures inhibit DNA, RNA, and protein synthesis, and they can reduce the accumulation of myelin and synaptic markers in the developing nervous system, leading to functional delays in development. Depending on the seizure pathway involved, and the developmental period under study, classic neurodegeneration, excitotoxicity and apoptosis, can result in permanent damage to critical neural networks in the temporal lobe and in many other brain regions. This conclusion is further supported by recent clinical studies showing that prolonged febrile status epilepticus can lead to hippocampal injury, which evolves into hippocampal atrophy and hippocampal sclerosis. A growing body of experimental data demonstrates that the metabolic compromise and cellular loss produced by seizures during critical phases of brain development, negatively affect later hippocampal physiology including learning and memory functions in maturity.

Late-Onset Epilepsy and the Risk of Dementia: a Systematic Review and Meta-Analysis

Abstract found in PubMed

Background: Patients with dementia have higher risk of epilepsy. However, it remains not comprehensively evaluated if late-onset epilepsy (LOE) is associated with higher risk of dementia. We, therefore, performed a meta-analysis to systematically evaluate the association.

Methods: Relevant cohort studies were identified by search of electronic databases including PubMed, Embase, and Web of Science. A randomized-effect model incorporating the possible between-study heterogeneity was used to pool the results.

Results: Overall, seven cohort studies including 873,438 adults were included, and 16,036 (1.8%) of them had LOE. With a mean follow-up duration of 8.7 years, 33,727 of them were diagnosed as dementia. Pooled results showed that LOE was associated with a higher risk of dementia (risk ratio [RR] 2.39, 95% confidence interval [CI] 2.04-2.81, p < 0.001, I2 = 67%). Results of subgroup analysis showed that the association between LOE and the risk of dementia was stronger in hospital-derived participants (RR 4.23, 95% CI 2.67-6.70, p < 0.001) than that in community-derived population (RR 2.25, 95% CI 1.93-2.63, p < 0.001; p for subgroup difference = 0.01). Pooled results of three studies showed that LOE was associated with a higher risk of Alzheimer’s disease (RR 2.35, 95% CI 1.08-5.08, p = 0.03, I2 = 85%). One study suggested a significant association between LOE and risk of vascular dementia (RR 2.0, 95% CI 1.77-2.26, p < 0.001).

Conclusions: Evidence from cohort studies suggests that LOE may be a risk factor of dementia.

Ambient Air Pollution and Epileptic Seizures: A Panel Study in Australia

Abstract found in Wiley Online Library

Objective: Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures.

Methods: This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista dataset, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010-2012. In the seizure diary dataset, 3419 self-reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018-2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matter ?10 ?m in diameter (PM10), and sulfur dioxide (SO2) were retrieved from the Environment Protection Authority (EPA) based on participants’ postcodes. A patient-time-stratified case-crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures.

Results: A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01-1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), while no significant associations were found for the other four air pollutants in the whole study population. Females had a significantly increased risk of seizures when exposing to elevated CO and NO2, with RR of 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.01-1.16), respectively. Additionally, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12-1.28).

Significance: Daily exposure to elevated CO concentrations may be associated with the increased risk of epileptic seizures, especially for subclinical seizures.

New-Onset Seizure at High Altitude Among Healthy Males

Abstract found in PubMed

Objectives: The risk of developing new-onset seizure following ascent to high-altitude areas is currently unknown. We undertook a prospective study to quantify this risk.

Methods: The study was conducted at a tertiary care hospital in India between July 2015 and December 2017. It included apparently healthy males of age ?18 years who ascended to an altitude of ? 2500 m and stayed there for > 30 continuous days. Individuals with a history of seizure in the past two years, those who had not undergone acclimatization protocol, and those who had a history of any chronic systemic illness were excluded.

Results: The 39,213 individuals included in the study together had 39,848.6 person-years of high-altitude exposure. New-onset seizure after ascent occurred in 41 of them, indicating a seizure incidence rate of 102.9 per 100,000 person-years (95% CI = 75.8-139.7). The incidence per 100,000 person-years (95% CI) at altitudes of 2,500-3,500 m, 3,500-5,800 m, and > 5,800 m was 82.3 (53.6-126.1), 134.6 (84.9-213.6), and 210.8 (52.8-841.4), respectively. Seizure was secondary to cerebral venous thrombosis in 12 (29.3%) individuals. No etiology could be determined in the remaining 29 (70.7%) individuals.

Conclusions: Our findings suggest that when subjects living at sea level are exposed to high altitudes, they will be at a higher risk for new-onset seizure in the immediate few months of exposure, and that this risk increases with increasing altitude.

Artificial Intelligence for Medical Image Analysis in Epilepsy

Abstract found in PubMed

Given improvements in computing power, artificial intelligence (AI) with deep learning has emerged as the state-of-the art method for the analysis of medical imaging data and will increasingly be used in the clinical setting. Recent work in epilepsy research has aimed to use AI methods to improve diagnosis, prognosis, and treatment, with the ultimate goal of developing highly accurate and reliable tools to aid clinical decision making. Here, we review how researchers are currently using AI methods in the analysis of neuroimaging data in epilepsy, focusing on challenges unique to each imaging modality with an emphasis on clinical significance. We further provide critical analyses of existing techniques and recommend areas for future work. We call for: (1) a multimodal approach that leverages the strengths of different modalities while compensating for their individual weaknesses, and (2) widespread implementation of generalizability testing of proposed models, a needed step before their introduction into clinical workflows. To achieve both goals, more collaborations among research groups and institutions in this field will be required.

CURE Epilepsy Update: April 2022

Greetings Epilepsy Community,

I am beyond thrilled and excited to share with you that CURE Epilepsy’s in-person Annual Benefit is officially returning this year! We will be back, live at Navy Pier in Chicago celebrating the progress we have made in advancing science to find a cure for epilepsy, sharing powerful stories from the community, and rocking out to music by our special guest. If you can wait just “One Week” more, we will reveal who our entertainment will be for the evening. They are sure to make a “Big Bang” at the benefit! This event is one of my favorite times of the year. It is a time when we can come together as a community with a shared vision and convert our passion into action by raising dollars to fund research. I can’t wait to share this special evening with so many of you.

Speaking of special days, Siblings Day – a day dedicated to recognizing the impact siblings can have on one another – is this Sunday. At CURE Epilepsy, we know that if a child has seizures, the impact is felt by the entire family, including their siblings. Watching a loved one experience epilepsy can be heartbreaking, and there are added elements of support, care, and advocacy that come with that heartbreak. We view Siblings Day as an opportunity to honor the brothers and sisters of those living with epilepsy and spotlight their stories. Visit the Siblings Day page on our website to learn about siblings of children with epilepsy, including CURE Epilepsy Board Members, Marilynn Gardner and Michael Axelrod.

Through research there is hope.

In this CURE Epilepsy Update, please find information on:

CURE Epilepsy’s 2022 Annual Benefit
Learn More

We are back live at Navy Pier! We are excited to welcome back our supporters and the epilepsy community to celebrate the progress we have made in advancing science to find a cure for epilepsy, share powerful stories from the community, convert our passion to action by raising critical dollars to fund innovative research, and inspire our researchers and clinicians to keep driving forward on behalf of the community. Your support has helped launch amazing progress in epilepsy research and will continue to drive science forward until our mission is accomplished. And if you can wait just “One Week” more, we will reveal our entertainment! Learn more and get tickets

Webinar: Mental Health & Epilepsy: Improving Quality of Life

Join us for a free webinar on Thursday, May 5, where we will discuss the prevalence of anxiety and depression among people with epilepsy. Viewers will learn about the various ways that anxiety and depression impact people with epilepsy, and the tools that neurologists have at their disposal to help alleviate these comorbid conditions.

CURE Epilepsy Discovery
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With funding from his CURE Epilepsy Taking Flight Award, Dr. Stuart Cain sought to explore the basic biological mechanisms underlying Sudden Unexpected Death in Epilepsy (SUDEP) in a laboratory model system. He and his team investigated spreading depolarization, a phenomenon known to contribute to respiratory arrest, in the areas of the brain called the superior and inferior colliculus. Their research showed the specific role of the superior colliculus in spreading depolarization which may contribute to SUDEP. This research furthers our understanding of the potential brain circuits involved in SUDEP and provides a foundation for continued study to help develop preventative approaches for SUDEP.

Join Team CURE Epilepsy at the NYC Marathon
Learn More

Looking to run one of the major world marathon races for a good cause? General registration is now closed, but you can still join Team CURE Epilepsy at the TSC New York City Marathon on Sunday, November 6. Race to raise funds for epilepsy research and knock this race off your list. Limited spots remain. We’ll be there cheering you on!

Join Team CURE Epilepsy at the Chicago Triathlon
Learn More

Not a marathoner, but looking for a challenge? Help us raise funds, as we proudly partner with the 2022 Life Time Chicago Triathlon being held Saturday, August 27 – Sunday, August 28. No matter what distance you want to go (international or sprint), we have secured 15 charity spots for individuals who want to swim, bike, and run for research through the most iconic spots in our hometown.

World Autism Awareness Day
Learn More

World Autism Awareness Day is recognized internationally on April 2 every year. Epilepsy and autism are often interconnected, and it is estimated that over 30% of people with epilepsy also meet the diagnostic criteria for autism spectrum disorder. Visit our website to learn more about epilepsy and autism.

Siblings Day
Learn More

Siblings Day is April 10. When a child has epilepsy, it affects the entire family including the child’s siblings. Visit our Siblings Day page to see poignant Seizing Life episodes with siblings of individuals with epilepsy (including CURE Epilepsy Board Members Marilynn Gardner and Michael Axelrod) and a webinar on the impact seizures can have on a family.

CURE Epilepsy Promotes Dr. Lauren Harte-Hargrove to Director, Research

CURE Epilepsy is proud to announce that Dr. Lauren Harte-Hargrove has been promoted to Director, Research. In her time at CURE Epilepsy, Dr. Harte-Hargrove has contributed significantly to CURE Epilepsy’s overall research program, communications, and especially our efforts to drive research on post-traumatic epilepsy (PTE). Her leadership of CURE Epilepsy’s ongoing PTE Initiative has been critical to its success. As a recognized expert in the field of PTE research and patient advocacy, Dr. Harte-Hargrove is also driving greater awareness of the challenges faced by people with traumatic brain injury and PTE. See the entire CURE Epilepsy Team

What’s New from the Seizing Life® Podcast
Watch or Listen

Catch up on the latest episodes of our Seizing Life podcast, where you will hear:

  • College student Kiara Mowat shares stories from her epilepsy journey as a young adult from diagnosis in 2018 at age 14 to her first year in college. Tune in to this inspiring epilepsy story from an amazing young woman who is determined not to let seizures overwhelm her goals and ambitions. Listen or watch
  • Channing Seideman shares her epilepsy story and discusses the social, emotional, and physical impacts of drug-resistant epilepsy as well as the side effects of the numerous antiseizure medications that have so far failed to provide seizure freedom. Listen or watch

CURE Epilepsy Store
Shop here

Looking to show your CURE Epilepsy pride? Visit our CURE Epilepsy Store for exciting merchandise that will help raise awareness about the need to find a cure for epilepsy and the importance of research and look cool doing it!

Please mark your calendar for some key dates in the epilepsy community:

  • April 2 – World Autism Awareness Day
  • April 10 – Siblings Day
  • June 1 – CURE Epilepsy’s 2022 Annual Event
  • June 23 – International Dravet Syndrome Awareness Day
  • August 1-31 – Seizure Dog Awareness Month
  • October 19 – SUDEP Action Day
  • November 1 – International LGS Awareness Day
  • November 1-30 – Epilepsy Awareness Month
  • December 1-7 – Infantile Spasms Awareness Week


Cost of Pre-Surgical Evaluation for Epilepsy Surgery: A Single-Center Experience

Abstract found in PubMed

Objective: To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery.

Methods: We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured. National Health Service tariffs applicable to our setting were used to estimate the total cost of evaluation for individuals following different routes through the pre-surgical pathway. After surgery, self-reported seizure freedom rates were obtained from each individual to assess the approximate cost of pre-surgical evaluation per additional person seizure-free.

Results: Of 100 individuals evaluated, 27 had surgery, 63 had a definitive decision not to have surgery, and ten were awaiting further investigations. The median duration of the pre-surgical evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9138 (IQR £6984-£14,868). Those who proceeded to Stage Two investigations (including fluorodeoxyglucose positron emission tomography, ictal single-photon emission computerized tomography and intracranial electroencephalography) had a higher cost and extended evaluation length. After a median of 3.1 (IQR 2.3-3.7) years, 15/27 people who had surgery were seizure-free. This equated to an approximate cost of £123,500 spent per additional person seizure-free.

Conclusion: Pre-surgical evaluation is long and costly, particularly for those who require icEEG. For those with drug-resistant focal epilepsy, surgery is, however, associated with a greater chance of seizure freedom. The suitability and risk-benefit ratio of surgery should be considered at each step of the pre-surgical pathway.

COVID-19 Vaccine in Patients with Dravet Syndrome: Observations and Real-World Experiences

Abstract found on Wiley Online Library

Objectives: Vaccination against SARS-CoV-2 virus is a primary tool to combat the COVID-19 pandemic. However, vaccination is a common seizure trigger in individuals with Dravet syndrome (DS). Information surrounding COVID-19 vaccines side-effects in patients with DS would aid caregivers and providers in decisions for and management of COVID-19 vaccination.

Methods: A survey was emailed to the Dravet Syndrome Foundation’s (DSF) Family Network and posted to the Dravet Parent & Caregiver Support Group on Facebook between May and August 2021. Deidentified information obtained included demographics and vaccination status for individuals with DS. Vaccine type, side effects, preventative measures, and changes in seizure activity following COVID-19 vaccination were recorded. For unvaccinated individuals, caregivers were asked about intent to vaccinate and reasons for their decision.

Results: Of 278 survey responses, 120 represented vaccinated individuals with DS (median age 19.5 years) with 50% reporting no side effects from COVID-19 vaccination. Increased seizures following COVID-19 vaccination were reported in 16 individuals, but none had status epilepticus. Of the 158 individuals who had not received a COVID-19 vaccination, 37 were over the age of 12 (i.e., eligible at time of study) and only six of these caregivers indicated intent to seek vaccination. The remaining 121 responses were caregivers to children under the age of 12, 60 of whom indicated they would not seek COVID-19 vaccination when their child with DS is eligible. Reasons for vaccine-hesitancy were fear of increased seizure activity and concerns about vaccine safety.

Significance: These results indicate COVID-19 vaccination is well-tolerated by individuals with DS. One main reason for vaccine hesitancy was fear of increased seizure activity, which only occurred in 13% of vaccinated individuals and none had status epilepticus. This study provides critical and reassuring insights for caregivers and healthcare providers making decisions about safety of COVID-19 vaccinations for individuals with DS.

Susceptibility to Epilepsy After Traumatic Brain Injury is Associated with Preexistent Gut Microbiome Profile

Abstract found in Wiley Online Library


Objective: We examined whether post-traumatic epilepsy (PTE) is associated with measurable perturbations in gut microbiome.

Methods: Adult Sprague-Dawley rats were subjected to Lateral Fluid Percussion Injury (LFPI). PTE was examined 7 months after LFPI, during a 4-week continuous video-EEG monitoring. 16S ribosomal ribonucleic acid gene sequencing was performed in fecal samples collected before LFPI/sham-LFPI and 1 week, 1 and 7 months thereafter. Longitudinal analyses of alpha diversity, beta diversity, and differential microbial abundance were performed. Short-chain fatty acids (SCFA) were measured in fecal samples collected before LFPI by Liquid Chromatography with Tandem Mass Spectrometry.

Results: Alpha diversity changed over time in both LFPI and sham-LFPI subjects; no association was observed between alpha diversity and LFPI, the severity of post-LFPI neuromotor impairments, and PTE. LFPI produced significant changes in beta diversity and selective changes in microbial abundances associated with the severity of neuromotor impairments. No association between LFPI-dependent microbial perturbations and PTE was detected. PTE was associated with beta diversity irrespective of timepoint vis-à-vis LFPI, including at baseline. Preexistent fecal microbial abundances of four amplicon sequence variants belonging to the Lachnospiraceae family (three enriched and one depleted) predicted the risk of PTE with area under the curve (AUC) of 0.73. Global SCFA content was associated with the increased risk of PTE with AUC of 0.722, and with 2-Methylbutyric (depleted), valeric (depleted), isobutyric (enriched) and isovaleric (enriched) acids being most important factors (AUC of 0.717). When the analyses of baseline microbial and SCFA compositions were combined, AUC to predict PTE increased to 0.78.

Significance: While lateral fluid percussion injury produces no perturbations in the gut microbiome that are associated with PTE, the risk of PTE can be stratified based on preexistent microbial abundances and short-chain fatty acid content.

Prevalence of Self-Reported Emotional, Physical, and Sexual Abuse and Association with Fear of Childbirth in Pregnant Women with Epilepsy – The Norwegian Mother, Father and Child Cohort Study

Abstract found on Wiley Online Library


Objective: To examine the prevalence of self-reported experiences with abuse in pregnant women with epilepsy and the association between having experienced abuse and childbirth expectations, particularly the fear of childbirth.

Methods: We performed a cross-sectional study of women with and without epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study 1999-2008. Data on epilepsy diagnosis; antiseizure medication (ASM) use; emotional, physical, and sexual abuse; and childbirth expectations were collected from questionnaires completed during gestational weeks 17-19 and 30.

Results: Our study population included 295 women with ASM-treated epilepsy, 318 women with ASM-untreated epilepsy, and 93,949 women without epilepsy. A total of 115 women (47%) with ASM-treated and 132 women (57%) with ASM-untreated epilepsy reported any emotional, physical, or sexual abuse, compared to 25,100 women (32%) without epilepsy. The adjusted odds ratios (aORs) for having experienced any abuse were 1.8 (95% confidence interval 1.4-2.3) and 1.8 (1.4-2.2) for ASM-treated and ASM-untreated epilepsy, respectively. A total of 29 women (11%) with ASM-treated and 34 women (11%) with ASM-untreated epilepsy reported having been raped, compared to 3088 women (4%) without epilepsy [aORs 2.8 (1.8-4.1) and 2.9 (2.0-4.2), respectively]. In nulliparous women with ASM-untreated epilepsy, having experienced abuse was associated with fear of childbirth; 22 women (31%) with abuse experiences reported fear of childbirth compared to 5 women (7%) with no experience of abuse [aOR 5.4 (1.7-17.2)]. This association was not seen in multiparous women or in women with ASM-treated epilepsy.

Significance: More women with epilepsy reported emotional, physical, and sexual abuse than women without epilepsy. Such experiences may be associated with childbirth expectations.