News Topics: Treatments

Epilepsy Research News: August 2023

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

 

Brain Changes Associated with the Development of Post-Traumatic Epilepsy (PTE)

Research from the CURE Epilepsy PTE Initiative team at Virginia Tech has identified several changes in the brain that are associated with the development of PTE after a traumatic brain injury (TBI). The team examined changes in brain activity, cellular changes, and changes in the number of neurons in the brain after the development of PTE. The team found significant cellular and molecular changes in the dentate gyrus of the hippocampus, an area of the brain that has been implicated in seizure development. For example, the team found significant loss of neurons that inhibit brain activity, which may be important because seizures involve too much brain excitation, as well as changes in the structure of astroglia, which are cells that help regulate the transmission of signals between neurons in the brain. These findings suggest that changes in the dentate gyrus may contribute to the development of PTE following TBI.

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A New Brain Circuit Important in Epilepsy

Researchers have traced brain lesions (for example those caused by stroke, trauma, and tumors) that are associated with epilepsy to a shared brain circuit, indicating a unique role that deep brain circuits play in the origin and clinical management of epilepsy. The researchers found that lesions associated with epilepsy were connected to a common brain network located deep within the brain in regions called the basal ganglia and cerebellum. The researchers also examined a group of 30 individuals with drug-resistant epilepsy who underwent deep brain stimulation (DBS) to treat seizures and found that the individuals did better if the DBS site was connected to the same brain network implicated for epilepsy caused by brain lesions. The authors conclude that a lesion-related epilepsy network map could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

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MicroRNA as a Target to Treat Epilepsy

A recent study featuring the work of former CURE Epilepsy grantee Dr. David Henshall and colleagues investigated the role of the brain molecule micro-ribonucleic acid (miRNA) miR-335-5p as a potential therapeutic target for epilepsy. miRNAs can control levels of voltage-gated sodium channels, which are important in neuronal excitability, making them an attractive target of new treatments. Additionally, voltage-gated sodium channel function is decreased in some forms of epilepsy, like Dravet syndrome. The researchers found that miR-335-5p regulates voltage-gated sodium channels’ levels and neuronal excitability, supporting a role in epilepsy. The researchers concluded that targeting miR-335-5p could potentially lead to new treatments for epilepsy through its ability to influence voltage-gated sodium channels and neuronal excitability.

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Fetal Exposure to Antiseizure Medications and Long-Term Neurodevelopment in Children

A new study found that young children who were exposed to commonly prescribed antiseizure medications in utero do not score worse on several long-term neurodevelopmental outcomes (at age three) than children who were not exposed. This study recruited women who were treated for epilepsy at 20 medical centers across the United States and followed them and their babies over the course of pregnancy and several years postpartum. To assess the effects of fetal exposure to medications, children were tested for their vocabulary and verbal comprehension skills at the age of three. Children of women with epilepsy were as good at verbally describing simple objects and pictures as children of women without epilepsy, and their ability to understand language was also comparable. The researchers did find that a high dosage of levetiracetam (Keppra®) in the third trimester of pregnancy was correlated with certain negative neurodevelopmental effects in children and recommend especially careful monitoring of blood levels of this drug and thoughtful dosing strategies.

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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. 

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.

Single Target, Multiple Possibilities: MicroRNA Holds Promise for Epilepsy Treatment 

Article published by News Medical Life Sciences

Featuring the work of former CURE Epilepsy grantee Dr. David Henshall

 

In a recent study published in the PNAS Journal, a group of researchers investigated the role of micro-ribonucleic acid (miRNA) miR-335-5p as a potential therapeutic target for epilepsy by regulating neuronal excitability through the modulation of voltage-gated sodium channels (VGSCs). 

 

Epilepsy affects millions of individuals worldwide, and current antiseizure medications (ASMs) target VGSCs. However, some forms of epilepsy, like Dravet syndrome, are treatment-resistant due to loss of VGSC function. To develop better therapies, researchers are exploring miRNAs that regulate gene expression. 

 

MiRNAs can control VGSC expression, making them attractive therapeutic targets. Triangulating miRNA datasets and studying miRNA alterations caused by effective ASMs could reveal potential therapeutic miRNAs for epilepsy. 

 

Cannabidiol (CBD), approved for treatment-resistant epilepsy, is an example of an effective ASM with an unknown mechanism of action, arising the need for further investigation. 

 

The study focused on investigating epilepsy using animal models. Animals were kept in controlled conditions with a 12-hour light-dark cycle, proper temperature, and humidity, with food and water freely available. 

 

The researchers used two epilepsy models: the PPS model of temporal lobe epilepsy (TLE) in rats and the pentylenetetrazol (PTZ) model in mice. For the perforant path stimulation (PPS) model, electrodes were implanted, and seizures were induced using paired-pulse stimuli. For the PTZ model, mice received a convulsant dose of PTZ to trigger seizures. 

 

Various treatments were administered to investigate their effects on epilepsy. They modulated miRNA through antisense oligonucleotide “antimir” injections and viral particles expressing specific miRNAs. Additionally, they administered CBD, a compound derived from cannabis, to study its potential effects on epilepsy. 

 

The researchers analyzed miRNA and mRNA expression in the brain tissues of the animals. They also identified miRNA-target interactions and performed pathway enrichment analyses to understand the molecular mechanisms involved in epilepsy. 

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. 

Epilepsy Research News: July 2023

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

 

Beating Seizures by Jamming the Cellular Circuitry

Researchers have shown for the first time how the commonly prescribed antiseizure and pain medication gabapentin (Neurontin®) acts to affect cell function, potentially opening the door to new, more effective treatments for diseases like epilepsy. This research shows how gabapentin interacts with proteins called voltage-gated calcium channels, which are critical to the function of the brain. Voltage-gated calcium channels control the flow of calcium in and out of the cell and regulate brain excitation. By utilizing a technique called cryo-electron microscopy, the researchers confirmed the site where gabapentin binds to the channel to affect its function. The researchers also discovered that gabapentin interferes with the actions of a protein known as EMC. This interference could inhibit the actions of the ion channel, possibly decreasing the amount of calcium that gets into brain cells, in turn reducing brain activity and seizures. The study authors noted that by showing how gabapentin binds to calcium channels, there may be the opportunity to design a new generation of therapies.

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Identifying Seizures that Occur While Driving, Before Epilepsy Diagnosis

Five percent of people with focal epilepsy had a seizure while driving prior to being diagnosed with epilepsy, according to a new study. Researchers looked at clinical descriptions from study participants’ seizure diaries and medical records to classify types of seizures, seizure occurrence, and information about seizures while driving. They found 23 out of 447 participants, or 5% of participants, experienced one or more seizures while driving, for a total of 32 seizures while driving prior to diagnosis. Of these 23 people, seven people, or 30%, had more than one seizure while driving prior to diagnosis. The consequences of these seizures while driving included 19 motor vehicle accidents and 11 hospitalizations for injuries ranging from a tongue bite and a dislocated thumb to a near drowning. “From our study, we estimate nearly 6,500 people per year may experience pre-diagnosis seizures while driving in the United States alone, leading to nearly 4,000 possible motor vehicle accidents and over 2,200 hospitalizations,” stated the study authors. “Much of this may be preventable by earlier diagnosis.”

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Understanding Autism and Epilepsy

A study has increased our understanding and identified a possible treatment target for people with autism and epilepsy due to a lack of the ANK2 gene. This study showed that mice lacking the ANK2 gene in certain brain cells that contribute to brain excitation have autism spectrum disorder-like behaviors and juvenile seizure-related death. The researchers identified increased excitability of cortical neurons in these ANK2-deficient mice. These changes were accompanied by decreases in the function of a particular type of potassium channel in the brain. When the researchers used retigabine, an antiseizure medication, to enhance potassium channel function in the mice, they were able to restore neuronal excitability to normal levels and reduce seizure-induced deaths, suggesting that activation of potassium channels may be effective in treating epilepsy caused by ANK2 defects.

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Brain Inflammation and Drug-Resistant Epilepsy

New research investigated how inflammation contributes to the development of drug-resistant epilepsy. To study this, researchers examined brain tissue obtained during resective epileptic brain surgery. The researchers used a genetic sequencing technique called cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), which gathers information on RNA and surface proteins in single cells. They uncovered a proinflammatory microenvironment in drug-resistant epilepsy lesions that resembles brain autoimmune diseases, such as multiple sclerosis. They found that the drug-resistant epilepsy microenvironment includes activated microglia and other proinflammatory immune cells, and they captured cellular interactions with additional molecular analyses. The researchers noted that these results provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.

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Reducing Seizures After Brain Tumor Treatment

According to a recent study, inhibiting a mutated gene can reduce seizure activity in adult-type diffuse gliomas, which are the most common type of malignant tumors arising in the central nervous system and which commonly cause seizures that are difficult to control with medication. Previous research has shown that gliomas with mutations in the IDH (IDHMut) gene are more likely to cause seizures because the mutated gene produces D-2-hydroxyglutarate (D2HG), a chemical which excites neurons and leads to an increase in seizure activity. In the recent study, scientists found that AG881, a newly discovered small molecule inhibitor that can cross the blood-brain barrier, can reduce seizure activity in mice with IDHmut gliomas by more than 50 percent. IDHmut inhibition also inhibited the production of D2HG by IDHmut glioma cells. The researchers stated that these findings provide a potential basis for treating seizures in human glioma patients.

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Patterns of Psychotropic Drug Use in Veterans with Epilepsy: Do Drug Interactions Matter?

Abstract found on PubMed

Rationale: Patients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic drugs (PDs). While it is clear that CYP enzyme-inducing ASMs (EIASMs) can increase the oral clearance of multiple medications (thus lowering systemic exposure), it is less clear that all PK interactions are clinically meaningful (e.g. lower efficacy). As a first step in addressing this issue, this study sought to quantify the potential impact of ASM choice, whether EIASM or non-inducer (NIASM), on surrogate markers of suggestive of clinical use, including resultant antidepressant (AD) or antipsychotic (AP) dose, frequency of combination use of AD & AP, and number of multiple drug switches of PDs. Our hypothesis is that because of PK interactions, EIAED treatment would be associated with higher psychotropic drug doses, more frequent Rx adjustments and poly psychotropic comedication, all in order to optimize therapeutic response.

Methods: Using VA pharmacy and national encounter databases, veterans with epilepsy were identified based on having a seizure diagnosis and being prescribed concomitantly an ASM and a psychotropic drug for at least 365 days between 10/1/2010 and 9/30/2014. Patients for whom psychotropic drugs were prescribed any time between beginning and end prescriptions dates of ASMs were considered. Among those, patients receiving both an EIASM + NEIASM concomitantly were categorized with the EIASM group. Patients were evaluated for AD only, AP only and both (AD & AP). To compute average drug doses per day, averages for each patient were computed and averaged again. Multiple drug switches were defined to be for patients who had been prescribed more than three psychotropic drugs during the observation period. Pearson’s Chi-Square test was used to compare relative proportions of AD, AP and AD + AP in both groups.

Results: In all, 16,188 patients were identified (57.0% on EIASM, 43.0% on NIASM) with a mean age of 58.7 years (91.2% male). A larger proportion of patients on EIASM received mono treatment with any psychotropic drug, as compared to NIASM (42.0% vs 36.1%). Among all, 59.6% received AD only, 6.5% received AP only, and 33.8% received both concurrently. Of EIASM, 62.5% were on AD, 5.9% on AP, and 31.7% on both AP & AD. For NIASM, 55.9% received AD, 7.4% AP, and 36.7% on AD & AP.Chi-square showed that the distribution of PD was statistically different between EIASM and NIASM groups. Z tests showed that each difference (AD, AP and both) in proportions was statistically significant (p values (4 tests, one Chi-square, 3 Z tests <0.001) between EIASM vs NIASM. Interestingly, mean doses of AD or AP did not appear to differ between ASM groups.

Conclusions: Concurrent psychotropic drug use is quite common in the VA population with epilepsy, and a large number of patients still receive enzyme-inducing ASMs that may complicate other medical therapies. Interestingly, in seeming contradiction to our hypothesis, mean daily doses of either AD or AP did not appear to differ between inducers vs non-inducers. Similarly, use of polytherapy, and/or multiple trials of various psychotropic drugs did not appear increased in the CYP-induced group. In fact, combination therapy of AD + AP was higher in NIASM than EIASM. These data suggest that perhaps these types of PK interactions may not in fact result in meaningful clinical differences. Since the present analyses did not include clinical psychiatric measures, future analyses examining direct clinical outcomes are clearly warranted.

Medicated Oral Film for Epilepsy, Green Concrete Among Ideas Supported by NUS Innovation Programme 

Article published by The Straits Times 

 

Local start-up PharLyfe+ has developed medicated oral films which can be easily administered to treat epilepsy. 

The film, made of edible polymers, is stuck inside the patient’s cheek and medicine on the film is released directly into the bloodstream. 

 

PharLyfe+ was one of the 14 start-ups featured at the National University of Singapore’s (NUS) Graduate Research Innovation Programme (Grip) Lift-Off Day on Wednesday. 

 

Grip, now in its ninth run, is a three-month structured programme that guides participants to become deep-tech entrepreneurs, translating their research into start-ups. 

 

At the end of the programme, teams present their start-ups to venture capitalists, incubators and industry players to secure funding and support. 

 

Dr Tan Poh Leng, 37, co-founder of PharLyfe+, said: “As mothers, we have seen how difficult it is to get children to take injections. Some children also have difficulty swallowing tablets, especially big ones. So we feel that our films would address these problems as they are easy to take. It can be used for the elderly as well.” 

 

People with epilepsy have seizures. The most common form of medication to stop the seizure is an injection to the arm or a medicine inserted to the rectum, which may be distressing for the patient and difficult to administer. 

PharLyfe+’s innovation makes administering medicine to epileptics easier. 

 

The buccal films are also being specialised for end-of-life care with a different combination of medicines and polymers. 

PharLyfe+ is seeking regulatory approval for the films and is conducting human trials. 

Epilepsy Research News: June 2023

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

 

CURE Epilepsy’s Team Science Post-Traumatic Epilepsy (PTE) Initiative: Approach and Advances

CURE Epilepsy’s PTE Initiative united six preclinical and clinical research teams to form a consortium focused on improving ways to study PTE in a laboratory setting, understanding changes in the brain that occur after a traumatic brain injury (TBI) that lead to PTE, and uncovering risk factors associated with the development of PTE. PTE is a debilitating type of epilepsy that can develop in the months or even years following a TBI. Currently, there is no way to predict who will develop PTE or any way to prevent it. A recently published paper from the PTE Initiative describes scientific advances from CURE Epilepsy’s PTE Initiative, as well as its methods, implementation, and emphasis on team science and collaboration. Work on the PTE Initiative is ongoing, with the ultimate goal of understanding who is at risk for PTE, and laying the groundwork for the development of ways to prevent it from occurring. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Psychological Health and Traumatic Brain Injury Research Program under Award No. W81XWH-15-2-0069.

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Genetic Mutations Contributing to Adult Epilepsy

A recent study sheds new light on the role of changes in DNA known as somatic mutations in patients who develop mesial temporal lobe epilepsy (MTLE). Unlike inherited DNA mutations, which are passed down from a person’s parents, somatic mutations occur after a person is conceived. To examine the role of somatic mutations, researchers analyzed DNA from brain tissue samples collected from 105 patients with drug-resistant MTLE as well as 30 people who did not have epilepsy. The team pinpointed 11 somatic mutations that were enriched in the hippocampus (the region of the brain where seizures typically originate in MTLE) of 11 patients with drug-resistant MTLE. All but one of the 11 mutations were connected to a specific genetic pathway known as the RAS/MAPK pathway. The researchers noted that certain anti-cancer drugs target this pathway, opening a new avenue of therapeutic possibilities for MTLE patients that are resistant to antiseizure medications. In addition to suggesting a potential path to treatment, the findings could also be used to help inform treatment decisions for patients who harbor these somatic mutations.

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Improving Seizure Freedom After Epilepsy Surgery

A network of connections in the brain could be the key to improving frontal lobe epilepsy surgery, according to new research. This research suggests that disconnecting certain pathways in the frontal lobe could lead to longer-lasting seizure freedom after brain surgery. These pathways link the frontal lobe to brain structures deep in the brain, including areas called the thalamus and striatum. The researchers analyzed the cases of 47 people who underwent surgery for drug-resistant frontal lobe epilepsy and found that disconnection of these pathways was associated with seizure freedom after three and five years. The research found that this surgery also did not have negative effects on language or executive functions like planning, self-control, and focus. However, other functions, such as mood and emotions, still need to be studied. These findings provide hope that disconnection could lead to improved outcomes and long-term seizure freedom in people with frontal lobe epilepsy.

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Predictors of Epilepsy in Children with Complex Febrile Seizures

Four predictors of future epilepsy in children with complex febrile seizures (CFS) have been identified in a recently published study. These include experiencing more than three febrile seizures in 24 hours, a certain type of brain activity seen on a post-CFS electroencephalogram (EEG), a family history of seizures not associated with fever, and CFS onset at age three or later. The researchers retrospectively examined 621 children and found that having all four risk factors raised the risk of developing epilepsy to over 75%. The researchers noted that early identification of children who will develop epilepsy after a CFS is essential to future management and counseling for parents and caregivers.

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