News Category: Publication

The Seizure Severity Score: A Quantitative Tool for Comparing Seizures and Their Response to Therapy

Abstract found on PubMed

Epilepsy is a neurological disorder characterized by recurrent seizures which vary widely in severity, from clinically silent to prolonged convulsions. Measuring severity is crucial for guiding therapy, particularly when complete control is not possible. Seizure diaries, the current standard for guiding therapy, are insensitive to the duration of events or the propagation of seizure activity across the brain. We present a quantitative seizure severity score that incorporates EEG and clinical data and demonstrate how it can guide epilepsy therapies.

Approach: We collected intracranial EEG and clinical semiology data from 54 epilepsy patients who had 256 seizures during invasive, in-hospital presurgical evaluation. We applied an absolute slope algorithm to EEG recordings to identify seizing channels. From this data, we developed a seizure severity score that combines seizure duration, spread, and semiology using non-negative matrix factorization. For validation, we assessed its correlation with independent measures of epilepsy burden: seizure types, epilepsy duration, a pharmacokinetic model of medication load, and response to epilepsy surgery. We investigated the association between the seizure severity score and pre-ictal network features.

Main results: The seizure severity score augmented clinical classification by objectively delineating seizure duration and spread from recordings in available electrodes. Lower preictal medication loads were associated with higher seizure severity scores (p = 0.018, 97.5% CI = [-1.242, -0.116]) and lower pre-surgical severity was associated with better surgical outcome (p = 0.042). In 85% of patients with multiple seizure types, greater preictal change from baseline was associated with higher severity.

Significance: We present a quantitative measure of seizure severity that includes EEG and clinical features, validated on gold standard in-patient recordings. We provide a framework for extending our tool’s utility to ambulatory EEG devices, for linking it to seizure semiology measured by wearable sensors, and as a tool to advance data-driven epilepsy care.

CURE Epilepsy Update August 2023

Greetings Epilepsy Community,

We as a collective are painfully aware of how little the general public knows about epilepsy and how the lack of discourse about the disorder likely contributes to epilepsy research being underfunded by the government relative to other neurological conditions. One of the ways to tackle this problem is to increase awareness of epilepsy, seizures, and the impact upon individuals’ daily lives. By taking epilepsy out of the shadows and talking about it, we raise the profile, increase understanding, and build a sense of urgency around the need for cures. The recent opportunity for CURE Epilepsy to air a public service announcement (PSA) on ESPN this past month during 12 games of The Basketball Tournament is one example of how we can drive awareness. We hope this PSA helped increase understanding of epilepsy and that people exposed will seek to learn more about the condition.

Though TV provides a large audience for our message, there are many ways to increase awareness in our respective communities. Share a Seizing Life® episode with a friend. Wear CURE Epilepsy merchandise out and about. Tell coworkers about a relative’s diagnosis. Suggest seizure first aid training in the PTA meeting. All of these methods of raising awareness might not reach millions like the PSA did, but each step moves us forward toward a world with less stigma against epilepsy and more support for the epilepsy community.

Do you have other creative ideas? We would love to hear from you!

With a commitment to inspire hope and deliver impact.


In this CURE Epilepsy Update, please find information on:

Save the Date for UNITE to CURE Epilepsy 2023

Save the Date for UNITE to CURE Epilepsy 2023! This will be a three-day virtual experience from Wednesday, September 6 through Friday, September 8 culminating in a Day of Giving on the final day, which marks 25 years since CURE Epilepsy’s incorporation date. Stream live educational content, engage with community members, and come together with other CURE Epilepsy advocates to raise funds for critical epilepsy research. Only by joining together will we achieve our vision of a world without epilepsy.

Stay tuned for more information and a registration email landing in your inbox soon!

 

 

Watch the CURE Epilepsy PSA that Aired on ESPN

Though yesterday was the final day our PSA aired on ESPN during The Basketball Tournament, you can still watch the video online. The PSA features photos and video footage of 15 people living with epilepsy or who have tragically lost their lives to the disorder. The intent of the thirty-second ad is to highlight the heterogeneity of epilepsy, inspire urgency to advance science, and raise awareness of CURE Epilepsy by showing real people impacted by this common neurological disorder.

 

Watch

 

Get Your Tickets for Epilepsy Awareness Night at Chicago White Sox Game

Join the CURE Epilepsy community for a very special night at the ballpark: Epilepsy Awareness Night with the Chicago White Sox on Saturday, September 2! Come celebrate CURE Epilepsy’s 25th Anniversary with a specially discounted ticket offer, plus, $5 of each ticket purchased for our selected sections will go towards epilepsy research. See the White Sox in a matchup against the Detroit Tigers, sit with other community members, and raise money for epilepsy

 

Get Tickets

 

Become a Sponsor for our Hamilton Unplugged Event in New York

CURE Epilepsy will host Hamilton Unplugged in New York City on October 23 with the longest-running star of Hamilton, Miguel Cervantes, who has performed this role since 2016. This will be an intimate evening of conversation and songs with an exclusive performance from Miguel and his Broadway friends. Sponsorships are available now starting at $2,500 and general admission tickets will be available later this summer.

 

 

Become a Sponsor

 

CURE Epilepsy Discovery: CURE Epilepsy Grantee Makes Strides in the Understanding of Acquired Epilepsies by Investigating Inflammation in the Brain

Status epilepticus (SE) is a medical emergency characterized by unrelenting seizures lasting more than five minutes and that can be associated with negative cognitive impacts, an eventual epilepsy diagnosis, and even death. Dr. Nicholas Varvel’s team found that using a drug to reduce the invasion of monocytes from the blood into the brain minimized the harmful effects of SE, such as a loss in functional impairment and inflammation. This work provides yet another clue to our understanding of acquired epilepsies; with more experiments and evidence, drugs that block monocyte invasion could become a therapy for the prevention and cure of acquired epilepsies.

 

Read the Discovery

 

 

What’s New from the Seizing Life® Podcast

A Teen Uncovers the Emotional Impacts of Childhood Seizures

 

Hailey Yoon talks about the emotional and psychological impacts that childhood epilepsy may have even years after seizures subside.

Watch or Listen

 

 

Comprehensive Epilepsy Centers: An Insider’s Guide

 

Dr. Dave Clarke, pediatric neurologist, Chief of the Comprehensive Pediatric Epilepsy Program within UT Health Austin Pediatric Neurosciences at Dell Children’s, and board member at the National Association of Epilepsy Centers (NAEC), gives us a thorough overview of the specialists and services available at comprehensive epilepsy centers and offers advice about when and how to access these centers.

Watch or Listen

 

 

 

Watch these and all of our upcoming Seizing Life episodes here.

The CURE Epilepsy Store

 

Need apparel or accessories to raise epilepsy awareness? Check out the CURE Epilepsy Store!

 

 

 

 

Shop Now

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

  • January 1 – December 31, 2023 – CURE Epilepsy’s 25th Anniversary
  • September 6-8 – UNITE to CURE Epilepsy
  • October 18 – SUDEP Action Day
  • October 31- November 1 – Epilepsy Awareness Day at Disneyland
  • November – Epilepsy Awareness Month
  • December 1-7 – Infantile Spasms Awareness Week

 

1 in 26 individuals will be impacted by epilepsy in their lifetime.
Each person has their own story.

Read Anu’s Story

 

STK-001 Lowers Seizures, Aids Cognition and Behavior, Trials Finding 

Article published by Dravet Syndrome News

Treatment with STK-001 led to a marked reduction in seizure frequency, and aided cognition and behavior, among children and adolescents with Dravet syndrome in early clinical trials, according to new findings announced by the therapy’s developer Stoke Therapeutics. 

 

“Together these data support the potential for STK-001 to address the underlying cause of Dravet syndrome by treating both seizures and the cognitive and behavioral issues that make this disease so complex and devastating,” Edward M. Kaye, MD, CEO of Stoke, said in a company press release. 

 

Stoke is conducting two parallel, open-label Phase 1/2a clinical trials of STK-001 in young people with Dravet syndrome: MONARCH (NCT04442295), being run at sites in the U.S., and ADMIRAL (ISRCTN99651026), which is being conducted in the U.K. Both studies mainly are evaluating the safety profile and pharmacological properties of the experimental therapy, with secondary goals looking into its efficacy. 

 

“Our ongoing studies are providing a better understanding of a dose and dosing regimen that may generate substantial and sustained benefits for patients, while continuing to be generally well tolerated,” Kaye said. 

 

Most cases of Dravet syndrome are caused by mutations that disrupt the production of the protein NaV1.1. STK-001 is designed to increase NaV1.1 protein production; the therapy is administered via injection into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. 

 

New trial data show that patients experienced a reduction in seizure frequency following treatment with STK-001. 

 

The most profound reductions were seen among the 11 patients in the ADMIRAL study who were given two or three injections of STK-001 at a high dose of 70 mg. Data from five evaluable patients showed a drop in seizure frequency of 80% at three months after the last dose. At six months after the last dose, seizure frequency was reduced by 89% for the three patients with evaluable data. 

Scientists Uncover New Brain Circuit for Epilepsy 

Article published by SciTechDaily

 

Researchers from Brigham have traced lesions associated with epilepsy to a shared brain circuit, indicating a unique role that deep brain circuits play in the origin and management of epilepsy. These innovative findings underscore the potential to leverage this specific brain circuit as a directional guide for brain stimulation treatments aimed at managing epilepsy. 

 

Over 30 million individuals around the globe are affected by focal epilepsy, often linked to brain lesions caused by conditions like stroke. Yet, it remains unclear why certain lesion locations trigger epilepsy while others don’t. A recent study conducted by scientists from the Brigham and Women’s Hospital, a key contributor to the Mass General Brigham healthcare system, discovered a usual brain circuit that might connect diverse lesion locations leading to epilepsy. 

 

In a paper published in JAMA Neurology, the researchers used a technique called lesion network mapping to identify this brain circuit with findings that point to potential targets for brain stimulation. 

 

“We’re learning more and more about where in the brain epilepsy comes from and what brain circuits we need to modulate to treat patients with epilepsy,” said lead author Frederic Schaper, MD, Ph.D., an Instructor of Neurology at Harvard Medical School and scientist at the Brigham and Women’s Center for Brain Circuit Therapeutics. “Using a wiring diagram of the human brain, lesion network mapping allows us to look beyond the individual lesion location and map its connected brain circuit.” 

 

Schaper and the team studied 5 datasets of over 1,500 patients with brain lesions. Participating centers across the US and Europe included the Brigham and Women’s Hospital, Massachusetts General Hospital, Boston Children’s Hospital, Northwestern University, and University Hospitals of Turku in Finland, Maastricht in the Netherlands, and Barcelona in Spain. They studied a variety of brain lesions such as stroke, trauma, and tumors, which allowed them to search for common network connections associated with epilepsy across different regions and types of brain damage. 

Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy

Featuring the work of CURE Epilepsy PTE Initiative’s Virginia Tech Team

 

Abstract found on MDPI

 

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under investigation. The dentate gyrus—a structure that is highly susceptible to injury—has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2–4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by unbiased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching, and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-Seq were performed to determine differential gene expression in animals that developed post-traumatic epilepsy (PTE+) vs. those animals that did not (PTE-), which may be associated with epileptogenesis. Results: CCI injury resulted in 37% PTE incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions, which showed increased astroglial expression in the PTE+ hilus. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

Identification of Drug Resistance in a Validated Cohort of Incident Epilepsy Patients in the Danish National Patient Register

Abstract found on PubMed

 

Objective: The main purposes of this study were to validate the epilepsy diagnosis in incident epilepsy cases in the Danish National Patient Registry (DNPR), containing information on nearly 9,000,000 individuals; and identify persons in the validated cohort who fulfilled the International League Against Epilepsy (ILAE) criteria for drug resistant epilepsy (DRE).

 

Methods: We reviewed a random sample of medical records from all individuals registered with a first diagnosis of epilepsy (ICD-10: G40) or seizures (ICD-10: G41, R56, or F445) in Central Denmark Region from 2010-2019. In persons with a validated incident epilepsy diagnosis, we determined the proportion with DRE at the latest contact. We performed logistic regression analyses to identify clinical factors that correlated with risk of DRE.

 

Results: Of 20,723 persons with a first diagnosis of epilepsy (n=11,812) or seizures (n=8,911), we reviewed the medical records of n=1,067 with incident epilepsy and n=610 with incident seizures. Among those with a register diagnosis of epilepsy, the diagnosis was confirmed in 838 cases (45% females, mean age at onset = 42.4 years), providing a positive predictive value (PPV) of 79% (95% CI: 76-81%). The PPV of focal epilepsy was 86% (95% CI: 82-89%), and the PPV of generalized epilepsy was 71% (95% CI: 61-80%). Of 740 patients with confirmed incident epilepsy and ? 1 year of follow-up, 103 (14%) fulfilled the definition of DRE, 476 (64%) were drug responsive, and 161 (22%) had undefined responsiveness. In multivariable logistic regression analysis, early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were associated with DRE.

 

Significance: In the Danish National Patient Registry, we found a positive predictive value of the epilepsy diagnosis of 79%. Among persons with confirmed epilepsy, 14% fulfilled ILAE criteria of drug resistant epilepsy. Early age at epilepsy onset, cognitive impairment, and a history of status epilepticus were independently associated with drug resistance.

Ketogenic Dietary Therapies in Epilepsy: Recommendations of the Italian League Against Epilepsy Dietary Therapy Study Group

 Abstract found on PubMed

 

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients’ associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

Natural Language Processing Identifies Patients Who May be Good Candidates for Epilepsy Surgery 

Article published by AJMC

 

A review of 6 studies found natural language processing (NLP) showed moderate-to-high performance levels in identifying suitable candidates to undergo epilepsy surgery, an effective, but oftentimes underutilized treatment, in which approximately 50% to 60% of patients became seizure-free after surgery. 

 

“This study has found that there is evidence, using multiple algorithms, that NLP may aid in the identification of candidates who may benefit from referral for epilepsy surgery evaluation,” wrote the researchers of the study. “It is noteworthy that these studies have shown that the NLP approaches may identify suitable candidates prior to the time that treating neurologists refer their patients.” 

 

The systemic review is published in the Journal of Clinical Neuroscience. 

 

Similar to machine learning, NLP uses computers to analyze or interact with human language and has various uses in health care, including information extraction, information retrieval, document categorization, and text summarization. Furthermore, NLP can aid in generating meaningful information, such as diagnosis or prognosis from electric health record data. 

 

Previous research has suggested that NLP may be useful in identifying patients with drug-resistant focal epilepsy, who account for about 30% of individuals with epilepsy. In the current review, researchers aimed to examine previous studies using NLP to identify patients for epilepsy surgery. 

 

A data search identified 1369 publication results from PubMed (n = 324), EMBASE (n = 94) and Cochrane library (n = 951), in which 58 full-text articles were identified for review. 

 

After exclusion, 6 studies were selected for analysis. Most studies were conducted in a single study center, with 1 study utilizing data from 2 centers, and 1 study from 6 centers. Study characteristics included were the number of participants, age, gender, and NLP information, such as task assigned, ground truth (gold standard), and the type of NLP algorithms used. 

 

Five of the 6 studies used support vector machines and 1 study used NLP strategies, such as random forest models and gradient boosted machines. Furthermore, all studies showed moderate-to-to-high levels of performance. 

 

Some of the studies showed that NLP could identify patients 1 to 2 years prior to the treating clinicians initial referral. However, none of the studies identified evaluated the influence of implementing these algorithms on health care systems or patient outcomes. 

“NLP is a promising technology for the identification of patients who may benefit from epilepsy surgery referral,” wrote the researchers. 

Fetal Exposure to Epilepsy Medications Does Not Affect Neurodevelopment in Children

Article published by News Medical Life Sciences

 

Most mothers who took prescription antiseizure medications during pregnancy can breathe a sigh of relief: A new study published today in Lancet Neurology found that young children who were exposed to commonly-prescribed medications in utero do not have worse neurodevelopmental outcomes than children of healthy women. 

 

Commonly used antiseizure medications such as lamotrigine and levetiracetam are generally considered effective and safe, especially compared to many first-generation epilepsy treatments that carried profound risks to the unborn child. But while epilepsy may no longer be the reason that prevents someone from starting a family, there is still not enough information about how drugs taken by the mother affect maternal and child outcomes after delivery. 

 

The new study provides reassurance to patients and offers guidance to neurologists who are faced with a challenge of maintaining fragile balance between prescribing drug dosages that suppress mother’s seizures but carry no increased risks of neurological complications for the baby. 

 

“A blanket saying that all antiseizure medications are bad is overly simplistic and doesn’t make sense biologically. Being able to say that no, taking these medications will not put their future child at a greater risk of autism or learning disabilities, has a huge impact for women with epilepsy who are considering pregnancy,” said Page Pennell, M.D., senior author, professor and chair of neurology at the University of Pittsburgh 

 

Epilepsy is a neurological disorder of abnormal electrical activity in the brain that affects over one million American women of childbearing age. With its sudden and debilitating seizures and limited number of medications, which caused significant risks to the developing fetus, the condition was considered incompatible with pregnancy for much of the 20th century, though that landscape is gradually changing. 

 

The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study was launched two decades ago with the goal of delivering high-quality information about how antiseizure medications affect both the mother and the child. The prospective observational study recruited women who were treated for epilepsy at twenty medical centers across the United States and followed them and their babies over the course of pregnancy and several years postpartum. 

 

Previous research that has come out from the study highlighted the need to carefully monitor and adjust the dosage of antiseizure medications to achieve adequate control of seizures without compromising the health of the fetus. The new study focused on determining whether exposure to these drugs causes long-term neurodevelopmental effects that negatively affect the child. 

 

To assess the effects of fetal exposure to medications, children at the age of three years old were tested for their vocabulary and verbal comprehension skills as well as ability to describe simple pictures. Children of women with epilepsy were as good at verbally describing simple objects and pictures as children of women without epilepsy. Their ability to understand language was also comparable to children of the same age who were born to women without epilepsy, highlighting that both lamotrigine and levetiracetam pose low risks for negatively affecting cognitive outcomes. 

A Novel Wearable Device for Automated Real-time Detection of Epileptic Seizures

 Abstract found on PubMed

 

Background: Epilepsy is a neurological disorder that has a variety of origins. It is caused by hyperexcitability and an imbalance between excitation and inhibition, which results in seizures. The World Health Organization (WHO) and its partners have classified epilepsy as a major public health concern. Over 50 million individuals globally are affected by epilepsy which shows that the patient’s family, social, educational, and vocational activities are severely limited if seizures are not controlled. Patients who suffer from epileptic seizures have emotional, behavioral, and neurological issues. Alerting systems using a wearable sensor are commonly used to detect epileptic seizures. However, most of the devices have no multimodal systems that increase sensitivity and lower the false discovery rate for screening and intervention of epileptic seizures. Therefore, the objective of this project was, to design and develop an efficient, economical, and automatically detecting epileptic seizure device in real-time.

Methods: Our design incorporates different sensors to assess the patient’s condition such as an accelerometer, pulsoxymeter and vibration sensor which process body movement, heart rate variability, oxygen denaturation, and jerky movement respectively. The algorithm for real-time detection of epileptic seizures is based on the following: acceleration increases to a higher value of 23.4 m/s2 or decreases to a lower value of 10 m/s2 as energy is absorbed by the body, the heart rate increases by 10 bpm from the normal heart rate, oxygen denaturation is below 90% and vibration should be out of the range of 3 Hz -17 Hz. Then, a pulsoxymeter device was used as a gold standard to compare the heart rate variability and oxygen saturation sensor readings. The accuracy of the accelerometer and vibration sensor was also tested by a fast-moving and vibrating normal person’s hand.

Results: The prototype was built and subjected to different tests and iterations. The proposed device was tested for accuracy, cost-effectiveness and ease of use. An acceptable accuracy was achieved for the accelerometer, pulsoxymeter, and vibration sensor measurements, and the prototype was built only with a component cost of less than 40 USD excluding design, manufacturing, and other costs. The design is tested to see if it fits the design criteria; the results of the tests reveal that a large portion of the scientific procedures utilized in this study to identify epileptic seizures is effective.

Conclusion: This project is objectively targeted to design a medical device with multimodal systems that enable us to accurately detect epileptic seizures by detecting symptoms commonly associated with an episode of epileptic seizure and notifying a caregiver for immediate assistance. The proposed device has a great impact on reducing epileptic seizer mortality, especially in low-resource settings where both expertise and treatment are scarce.