Diacomit Safe and Effective as Add-On Therapy in Dravet Infants 

Article published by Dravet Syndrome News

Diacomit (stiripentol) was safe and clinically effective at reducing seizures when given to infants with Dravet syndrome, ages 2 or younger, according to a 30-year real world study. It also reduced emergency hospitalizations due to long-lasting seizures.

“This 30-year, real-world experience shows that initiating stiripentol before the age of 2 years is highly beneficial for patients with Dravet syndrome,” researchers wrote in “Initiating stiripentol before 2 years of age in patients with Dravet syndrome is safe and beneficial against status epilepticus,” which was published in Developmental Medicine & Child Neurology.

Long-lasting seizures and status epilepticus are hallmark symptoms of Dravet syndrome’s onset and usually begin in the first year of life. They remain at high risk of occurrence during infancy and middle childhood. The seizures are life-threatening and interfere with development, affecting “quality of life, medical needs,” and families’ economic well-being.

Treatments focus on reducing seizures frequency and duration, and helping prevent and manage status epilepticus. For infants younger than 2, therapies remain limited, however, mainly due to the low frequency of seizures and their severity.

Diacomit, an antiseizure medication marketed by Biocodex, is administered as an add-on therapy to children with Dravet, including infants. Data on its effectiveness in infants younger than 2 is scarce, however, and individual efficacy or safety data are “often incomplete or pooled with those from older children,” the researchers wrote.

In this study, French researchers retrospectively analyzed real-world data of Dravet patients who began Diacomit before they were 2 and were followed for 30 years (1991-2021). Data from 131 patients (59 women, 72 men) collected over four patient databases in France were analyzed.

Pharmacological Aspects of Antiseizure Medications: From Basic Mechanisms to Clinical Considerations of Drug Interactions and Use of Therapeutic Drug Monitoring

Abstract published by PubMed

Antiseizure medications (ASMs) are the cornerstone of treatment for patients with epilepsy. Several new ASMs have recently been introduced to the market, making it possible to better tailor the treatment of epilepsy, as well as other indications (psychiatry and pain disorders). For this group of drugs there are numerous pharmacological challenges, and updated knowledge on their pharmacodynamic and pharmacokinetic properties is, therefore, crucial for an optimal treatment outcome. This review focuses on educational approaches to the following learning outcomes as described by the International League Against Epilepsy (ILAE): To demonstrate knowledge of pharmacokinetics and pharmacodynamics, drug interactions with ASMs and with concomitant medications, and appropriate monitoring of ASM serum levels (therapeutic drug monitoring, TDM). Basic principles in pharmacology, pharmacokinetic variability, and clinically relevant approaches to manage drug interactions are discussed. Furthermore, recent improvements in analytical technology and sampling are described. Future directions point to the combined implementation of TDM with genetic panels for proper diagnosis, pharmacogenetic tests where relevant, and the use of biochemical markers that will all contribute to personalized treatment. These approaches are clinically relevant for an optimal treatment outcome with ASMs in various patient groups.

1 in 4 Patients with Epilepsy May Stop Epidiolex Due to Side Effects 

Article published by Dravet Syndrome News

Up to 1 in 4 people with hard-to-treat epilepsy, including those with Dravet syndrome, were found to stop taking Epidiolex (cannabidiol) shortly after starting treatment, primarily due to side effects or a lack of efficacy, according to a real-world study.

“Epidiolex is generally well-tolerated and the majority continued long-term treatment,” researchers wrote, but noted that the data suggest that most patients who discontinued the therapy did so “within the first several months of treatment.”

“Further studies designed to evaluate early identification and potential mitigation of adverse [side] effects … are warranted,” the team wrote, adding that more research is needed to confirm these findings.

The study, “Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex (cannabidiol) in patients with refractory epilepsy,” was published in the journal Epilepsy & Behavior.

In people with epilepsy, problems in the functioning of the brain cause bursts of uncontrolled electrical activity called seizures. These events can lead to a wide range of mild to severe symptoms that in Dravet patients may present as developmental and cognitive delays, movement problems, and difficulties speaking and sleeping.

Previous trial data suggested Epidiolex can cause several potential therapy-limiting adverse effects or side effects, such as diarrhea, liver enzyme increases (a sign of liver damage), decreased appetite, somnolence or sleepiness, and sleep problems. The results also indicated that treatment interactions with certain medications may be therapy-limiting for some patients.

Now, a team of researchers at the University of Wisconsin-Madison, in the U.S., evaluated the long-term effectiveness of Epidiolex. The focus was on a combination of efficacy and tolerability in people with refractory epilepsy in a real-world setting.

The study included 108 patients seen at the researchers’ center and who took Epidiolex for at least two weeks between December 2018 and December 2020.

Soft Robot Brain Implant Designed to Treat Epilepsy 

Article published by Informa


A new small-scale, soft robotic implant has been designed to help treat epilepsy.  


The flexible robot is inserted into a patient’s skull and sits between the skull and the surface of the brain.


Created by a team from Switzerland’s Ecole Polytechnique Fédérale de Lausanne (EPFL), the robot is a tiny, foldable electrode array that can be unfurled once inserted through a hole in a patient’s skull, applying consistent pressure to certain parts of the brain. 


This electrode array stimulates and monitors electrical activity in the brain for patients who suffer from neurological conditions such as epilepsy. 


“Minimally invasive neurotechnologies are essential approaches to offer efficient, patient-tailored therapies,” says Stéphanie Lacour, EPFL’s neurotechnology expert. “We needed to design a miniaturized electrode array capable of folding, passing through a small hole in the skull and then deploying in a flat surface resting over the cortex. We then combined concepts from soft bioelectronics and soft robotics.” 


The first prototype consists of an electrode array that fits through a hole 0.7 inches in diameter but can expand to cover a surface of the brain double the size. 


According to the team, the robot’s folding and expanding capabilities are achieved by the device being turned inside out and then extended once deployed in the brain using a pressurized liquid, a method known as eversion.

Epilepsy Research News: May 2023

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


Epilepsy with Eyelid Myoclonia (EEM)

A newly published article, written by a steering committee convened by CURE Epilepsy, provides a comprehensive review of the characteristics of EEM, also known as Jeavons syndrome. EEM is a type of epilepsy?that occurs in childhood, with seizures often continuing into adulthood. It is more common in females and its hallmark traits consist of eyelid myoclonia (brief jerks of the eyelids) with or without absence seizures, eye closure-induced seizures, and photosensitivity. Individuals with EEM are often misdiagnosed and anti-seizure medication resistance is common, highlighting the need for further studies to understand more about this epilepsy and possible interventions to treat it.  

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A Computer Model of Epilepsy Brain Used in Clinical Trial for Epilepsy Surgery

Scientists in France are looking at how a computer model of the brain can improve the localization of the seizure zone before epilepsy surgery. The models are created using the Virtual Epileptic Patient (VEP), which employs brain scans and brainwave-recording data from individuals with epilepsy to build a personalized model to improve the understanding of where their seizures originate. The study authors said that VEP showed a 60% precision in identifying the epileptogenic zones in 53 patients with drug-resistant focal epilepsy. VEP is being evaluated in an ongoing clinical trial called EPINOV. If the trial results are promising, this computer model may become a new, personalized tool used in epilepsy surgical evaluations to improve surgical outcomes.  

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Worsened Perinatal Outcomes in Women with Epilepsy

Recently published findings showed that women with epilepsy have worse perinatal outcomes compared with women without epilepsy, including a 5-fold increase in the odds of maternal death. Combining the results of 76 already-published papers, investigators found that relative to women without epilepsy, those with epilepsy had increased odds of gestational hypertension, preeclampsia, intrauterine growth restriction, miscarriage, preterm birth, induced labor, stillbirth, cesarean delivery, and maternal death. “When counseling pregnant women with epilepsy and those of childbearing age, clinicians should consider these findings,” a lead investigator concluded. “In addition, clinicians and women with epilepsy should bear in mind the increased odds of negative adverse maternal and neonatal outcomes.”  

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Early-Life Meningitis Associated with Risk of Developing Epilepsy in Later Childhood

Infants exposed to invasive Group B Streptococcus (iGBS) meningitis during their first three months of life could have a greater risk of developing epilepsy in later childhood compared to infants who were not exposed, according to a recent study. Investigators evaluated the cumulative risk (CR) of an infant diagnosed with iGBS sepsis or meningitis during the first three months of age developing epilepsy. Examining a group of 1,432 children with iGBS and 14,211 without iGBS, the team found that the overall CR of developing epilepsy into later childhood was 3.6% among children with iGBS disease, whereas the CR of later-adulthood epilepsy was 2.3% in the group without iGBS. The study authors noted that the data have implications for affected individuals and underline the need for better long-term follow-up and care. 

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Improving Seizure Freedom After Epilepsy Surgery

Article published by Epilepsy Action

A network of connections in the brain could be the key to improving frontal lobe epilepsy surgery, according to new research from the UCL Queen Square Institute of Neurology.

The research, published in the journal Brain, suggests that disconnecting certain pathways in the frontal lobe could lead to longer-lasting seizure freedom after brain surgery.

Some people with epilepsy can have brain surgery to try to stop their seizures when epilepsy medicines don’t work. But in people with frontal lobe epilepsy, only around a third (30%) remain seizure free in the long term after surgery.

The networks of connections that the researchers identified link the frontal lobe to brain structures deep in the brain, including the thalamus and striatum. These control things like sensory and motor signals, motor control and emotion.

In their research, 47 people with damage in the frontal lobe of their brain had these networks disconnected. The results showed nearly nine in 10 people stayed seizure free three years after the surgery, and between seven and eight in 10 were seizure free after five years.

The research found that this surgery also did not have negative effects on language or on executive functions like planning, self-control and focus. However, other functions, such as mood or emotions, still need to be studied.

Robot-Assisted Stereoencephalography Versus Subdural Electrodes in the Evaluation of Temporal Lobe Epilepsy

Abstract found on Wiley Online Library


Objective: Invasive video-electroencephalography (iVEEG) is the gold standard for evaluation of refractory temporal lobe epilepsy before second stage resective surgery (SSRS). Traditionally, the presumed seizure onset zone (SOZ) has been covered with subdural electrodes (SDE), a very invasive procedure prone to complications. Temporal stereoelectroencephalography (SEEG) with conventional frame-based stereotaxy is time-consuming and impeded by the geometry of the frame. The introduction of robotic assistance promised a simplification of temporal SEEG implantation. However, the efficacy of temporal SEEG in iVEEG remains unclear. The aim of the present study was therefore to describe the efficiency and efficacy of SEEG in iVEEG of temporal lobe epilepsy.

Methods: This retrospective study enrolled 60 consecutive patients with medically intractable epilepsy who underwent iVEEG of a potential temporal SOZ by SDE (n=40) or SEEG (n=20). Surgical time efficiency was analyzed by the skin-to-skin time (STS) and the total procedure time (TPT) and compared between groups (SDE vs. SEEG). Surgical risk was depicted by the 90-day complication rate. Temporal SOZ were treated by second stage resective surgery (SSRS). Favorable outcome (Engel°1) was assessed after one year of follow-up.

Results: Robot-assisted SEEG significantly reduced the duration of surgery (STS and TPT) compared to SDE implantations. There was no significant difference in complication rates. Notably, all surgical revisions in this study were attributed to SDE. Unilateral temporal SOZ was detected in 34/60 cases. 30/34 patients underwent second stage SSRS. Both SDE and SEEG had a good predictive value for the outcome of temporal SSRS with no significant group difference.

Significance: Robot-assisted stereoelectroencephalography (SEEG) improves the accessibility of the temporal lobe for iVEEG by increasing surgical time efficiency and by simplifying trajectory selection without losing its predictive value for second stage resective surgery (SSRS).

The Impact of Epilepsy Surgery on Quality of Life: Systematic Review and Meta-Analysis

Abstract found on Wiley Online Library

Objectives: Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes.

Methods: We conducted a systematic review and meta-analysis using Medline, EMBASE, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the post-surgery change in QoL. Meta-regression assessed the effect of post-operative seizure outcomes on post-operative QoL as well as change in pre- and post-operative QoL scores.

Results: 3,774 titles and abstracts were reviewed and ultimately 16 studies, comprising 1182 unique patients, were included. QOLIE-31 (Quality of Life in Epilepsy Inventory- 31 item) meta-analysis included six studies and QOLIE-89 meta-analysis included four studies. Post-operative change in raw score was 20.5 for QOLIE-31 (95% CI: 10.9–30.1, I2=?95.5) and 12.1 for QOLIE-89 (95% CI: 8.0–16.1, I2=?55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher post-operative QOLIE-31 score as well as change in pre- and post-operative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, pre-operative absence of mood disorders, better pre-operative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved post-operative QoL.

Significance: This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies, and high risk of bias.

CURE Epilepsy Discovery: CURE Epilepsy Funds Research to Investigate Mechanisms of Genetic Epilepsies

Key Points:

  •  As part of its quest to find a cure for the epilepsies, CURE Epilepsy has led initiatives, including one focused on genetic epilepsies.
  • The impact of CURE Epilepsy on epilepsy genetics over the years has been broad, ranging from the discovery of individual genes that are associated with epilepsy, to contributions in rare epilepsies, to the Epilepsy Genetics Initiative (EGI).
  • In this CURE Epilepsy Discovery, we highlight the efforts of EGI and the centralized database to store and analyze genetic signatures associated with epilepsy; we also summarize its impact on people living with genetic epilepsies and the epilepsy research community.
  • We then feature three recent CURE Epilepsy grants awardees who have contributed to numerous aspects of genetic epilepsies ranging from the development and application of new technology to study epilepsy genetics, to studying specific genes and their contributions to epilepsy, to exploring the epigenomic pattern associated with epilepsy.
  • The three CURE Epilepsy grants awardees are Dr. Heather Mefford at St. Jude Children’s Research Hospital, and Drs. Gemma Carvill and Jeff Calhoun, both at Northwestern University.
  • Adding to this work is a recent endeavor, the Rare Epilepsy Partnership Award to find cures for rare forms of epilepsies.


Deep Dive

Epilepsy occurs when the normal electrical signaling between brain cells (neurons) is disrupted; however, the exact causes of epilepsy are not fully understood. Broadly speaking, epilepsy can have several potential causes, and one of these causes is genetic. Epilepsy is said to have a genetic cause if the seizures are caused as a result of a genetic defect or mutation.[1] These epilepsies are very diverse and the underlying gene or genes involved are not always known. Having a genetic cause for the epilepsies does not necessarily mean that the gene mutation was inherited; sometimes, the genetic variant or mutation may occur spontaneously in a child without being present in either parent; these are called “de novo” mutations.[2] Some epilepsies that have a genetic cause may have additional environmental causes as well.

With the emergence of novel technologies, our knowledge about the genes impacting the epilepsies has grown substantially in the last several years. The increased availability and steadily decreasing costs of genetic technology to analyze one’s entire genetic makeup has meant that scientists can identify many more genes that may be associated with epilepsy. By identifying particular genes associated with epilepsy, we can create animal models to simulate epilepsy in the lab and answer questions regarding the mechanisms by which a particular genetic mutation gives rise to seizures. The ultimate goal of identifying genes associated with epilepsy is to develop targeted therapies for a particular gene.[3] An even more exciting prospect of understanding the genes associated with epilepsy is the prospect of targeting the genes to potentially stop the onset of seizures before it even begins! Understanding the genetic mechanisms of epilepsy is helped by continued advances in genetic technologies, sophisticated ways to store and analyze huge datasets, and the capability to perform experiments in animals and translate findings to the human condition, thus setting the scene for precision medicine in genetic epilepsy.[4]

CURE Epilepsy’s Epilepsy Genetics Initiative (EGI) was formed in 2015 and was instrumental in creating a centralized database that holds the genetic (whole exome sequence) data of people with epilepsy. Whole exome sequencing is a way to analyze a person’s unique DNA fingerprint pattern. By analyzing and re-analyzing genetic data as techniques advance, EGI aimed to advance our understanding of the genetic causes of epilepsy so that clinicians could better and more effectively diagnose, treat, and even prevent genetic epilepsies. Thanks to GI, new genes underlying epilepsy have been found; re-analysis of patient genetic materials has led to new diagnoses for those with genetic epilepsy. Additionally, there have been benefits to the epilepsy community as well. EGI is a community resource, and the whole exome data within the database is available to the research community. All the genetic data are de-identified; hence, there is no way for information to be linked back to a patient or the patient’s family.

In addition to the formation of a centralized database, CURE Epilepsy is also intently focused on identifying and funding cutting-edge research in epilepsy curing the epilepsies. This CURE Epilepsy Discovery article will also outline the work of three CURE Epilepsy grants awardees: Dr. Heather Mefford, her mentee Dr. Gemma Carvill, and Dr. Carvill’s mentee Dr. Jeff Calhoun. By funding these outstanding researchers investigating mechanisms underlying genetic epilepsies, CURE Epilepsy is actively supporting the development of the future generation of epilepsy researchers and scientists.

Dr. Heather Mefford is currently at St. Jude Children’s Hospital and received a CURE Epilepsy Award in 2019. As part of this grant, she investigated the causes of Developmental and Epileptic Encephalopathies (DEE). DEE are severe, early-onset epilepsy disorders that are associated with developmental delay and seizures that are resistant to treatment. A specific genetic cause can be correctly identified in about half of the cases of DEE, and this identification can be associated with a correct diagnosis and a favorable prognosis (course of the disease). Also, a proper diagnosis can help the clinician connect the family to appropriate support groups as well. However, about half of those with DEE are not accurately diagnosed, even with state-of-the-art genetic testing. Work done by Dr. Mefford’s team looked for a different cause in those with DEE that are not diagnosed. Her team looked at abnormal methylation – a type of chemical modification in the DNA structure – in individuals with DEE that did not have a diagnosis or cause. Methylation is considered an “epigenetic” modification – these modifications are not hardwired into one’s DNA, but turn genes “on” and “off.” [5]

Work done by Dr. Mefford’s team has led to the development of “methylation signature” analysis by which methylation patterns of individuals with DEE without a known diagnosis can be studied. Methylation patterns have been studied for other disorders, but not comprehensively for epilepsy. More work is needed to understand the precise methylation signature in DEE; however, the goal is that one day, by diagnosing methylation patterns, we will be able to improve the diagnosis of those with DEE. An accurate diagnosis could also improve the prognosis, and clinicians will be able to accurately offer genetic counseling services to patients and families. There is also the hope of being able to provide targeted precision therapies for these specific methylation patterns.

In addition to recognizing methylation patterns, Dr. Mefford’s team has also been instrumental in characterizing de novo mutations in a gene called PPP3CA and the role of these mutations in causing epilepsy. Since mutations in the PPP3CA gene are very rare, the scientists working on this gene pooled data from different sources including CURE Epilepsy’s EGI. By collecting and analyzing data in this way, Dr. Mefford and her collaborators were able to show that mutations in the PPP3CA gene were a lead factor in the development of specific childhood-onset epilepsy. Dr. Mefford and her collaborators were also able to understand how mutations in the PPP3CA gene cause epilepsy. This gene is responsible for the production of a protein in the brain known as calcineurin; this substance is responsible for key functions in the brain, including proper signaling between neurons. Mutations in PPP3CA interfere with the ability of calcineurin in electrical transmission in the brain leading to neurodevelopmental disorders and epilepsy.[6] Hence, Dr. Mefford’s work funded and supported by CURE Epilepsy is laying the foundation for the study of epigenetics, particularly methylation, in DEE.[7]

In addition to her work as a physician caring for pediatric patients living with severe epilepsy syndromes, and her work as an epilepsy genetics researcher (described above), Dr. Mefford is also passionate about supporting the next generation of epilepsy scientists. One of her trainees, Dr. Gemma Carvill is an independent epilepsy researcher and leads her research program at Northwestern University. Dr. Carvill received CURE Epilepsy’s Taking Flight Award in 2015. The Taking Flight Award was developed to foster and develop the careers of young epilepsy investigators by allowing them to develop a research focus independent of their mentor(s). The Taking Flight Award came at an opportune time in Dr. Carvill’s career and was instrumental in directing her scientific interests in the field of epilepsy genetics.

Dr. Carvill investigated the genetic causes of the most severe forms of epilepsy known as epileptic encephalopathy. Childhood epileptic encephalopathies are a group of epilepsy disorders that are profoundly treatment-resistant; children with this condition also have severe cognitive and neurological deficits.[8,9] Specifically, she was interested in exploring the epigenomic causes of epileptic encephalopathy, i.e., studying genes that turn the activity of other genes “on” or “off”. By using a new genome-editing technology called CRISPR-Cas9 to introduce mutations in a class of genes known as “chromatin remodelers”, she was able to study the mechanisms by which these genes cause seizures.

To study the epigenomic causes of epilepsy, she studied de novo mutations in the CUX2 gene. In an international study done with Dr. Gaetan Lesca of the Lyon University Hospital, Dr. Carvill found mutations in the CUX2 gene in nine patients who started having seizures early in life, had treatment-resistant epilepsy, and severe developmental delay. Since mutations such as the one in the CUX2 gene are rare, several research teams must come together to provide statistical rigor. By identifying mutations in the CUX2 gene in epileptic encephalopathy, this gene can potentially be targeted to develop therapies.[10]

Another work done by Dr. Carvill and her team looked at another epilepsy-associated gene called SZT2. Earlier studies have shown an association between mutations in the SZT2 gene and some neurodevelopmental disorders,[11] but the full extent of the impact of mutations in this gene and its link to epilepsy was not yet known. It is also known that the SZT2 gene plays a critical role in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway which is essential in cell growth and proliferation. By using state-of-the-art genetic technologies, Dr. Carvill’s team determined that mutations in the SZT2 gene were likely pathogenic and that the mutation is more prevalent in individuals of Ashkenazi Jewish ancestry. The direct implication of these findings is the knowledge that this gene should be included in prenatal gene panels. Given that the SZT2 gene interacts with the mTORC1 pathway, and since the mTORC1 pathway is implicated in other neurodevelopmental diseases as well, there are also implications for potential treatment strategies involving the mtORC1 signaling pathway.[12]

Since receiving the Taking Flight Award, Dr. Carvill has been awarded other accolades also; notably the prestigious Innovator’s Award from the NIH. As part of this award, she will continue her work on genetic epilepsies, specifically exploring if cell-free DNA (cfDNA) could be used as a non-invasive avenue for epilepsy diagnosis and perhaps as a biomarker.[13] At Northwestern University, she too is mentoring a Taking Flight grantee, Dr. Jeffrey Calhoun.

Carrying on the tradition, Dr. Jeffrey Calhoun received the Taking Flight Award in 2022 and his research will look at genetic variants that are linked to the risk for epilepsy. He is developing methods to determine which genetic variants near SCN1A, a gene implicated in epilepsy, alter SCN1A gene expression. This technique eventually could also be used to study variants that impact other genes associated with epilepsy. By understanding the pattern of gene expression and the variants that may cause variable expression, Dr. Calhoun’s work aims to impact the diagnosis and care of those with genetic epilepsies. 

Hence, the work of Drs. Mefford, Carvill, and Calhoun together aim to develop new technologies to better understand genetic epilepsies, which many times, can be catastrophic. In addition to funding Dr. Mefford and her mentees, CURE Epilepsy is making an incredible impact on rare epilepsies, having inaugurated the Rare Epilepsy Partnership Award this year. With this partnership award providing funding for the rare and devasting epilepsies, we can not only provide hope but more understanding that will one day be translated into a cure.


Literature Cited:

  1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology Epilepsia. 2017 Apr;58:512-521.
  2. Steinlein OK. Genetics and epilepsy Dialogues Clin Neurosci. 2008;10:29-38.
  3. Szepetowski P. Genetics of human epilepsies: Continuing progress Presse Med. 2018 Mar;47:218-226.
  4. Knowles JK, Helbig I, Metcalf CS, Lubbers LS, Isom LL, Demarest S, et al. Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress Epilepsia. 2022 Oct;63:2461-2475.
  5. What is Epigenetics? Available at: https://www.cdc.gov/genomics/disease/epigenetics.htm. Accessed April 9, 2023.
  6. Myers CT, Stong N, Mountier EI, Helbig KL, Freytag S, Sullivan JE, et al. De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures Am J Hum Genet. 2017 Oct 5;101:516-524.
  7. Hebbar M, Mefford HC. Recent advances in epilepsy genomics and genetic testing F1000Res. 2020;9.
  8. Cross JH, Guerrini R. The epileptic encephalopathies Handb Clin Neurol. 2013;111:619-626.
  9. Jehi L, Wyllie E, Devinsky O. Epileptic encephalopathies: Optimizing seizure control and developmental outcome Epilepsia. 2015 Oct;56:1486-1489.
  10. Chatron N, Møller RS, Champaigne NL, Schneider AL, Kuechler A, Labalme A, et al. The epilepsy phenotypic spectrum associated with a recurrent CUX2 variant Ann Neurol. 2018 May;83:926-934.
  11. Kariminejad A, Yazdan H, Rahimian E, Kalhor Z, Fattahi Z, Zonooz MF, et al. SZT2 mutation in a boy with intellectual disability, seizures and autistic features European Journal of Medical Genetics. 2019 2019/09/01/;62:103556.
  12. Calhoun JD, Aziz MC, Happ HC, Gunti J, Gleason C, Mohamed N, et al. mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion Brain. 2022 Jun 30;145:1939-1948.
  13. Carvill GL. Cell-free DNA sequencing approaches to define the genetic etiology of unexplained epilepsy. Accessed April 9, 2023.

Epilepsy Research News: April 2023

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


Predicting Seizures in Temporal Lobe Epilepsy

Seizures can be predicted more than 30 minutes before they occur in patients with temporal lobe epilepsy, possibly opening the door to preventing seizures from happening, according to a new study. Researchers used electroencephalography (EEG), which measures electrical activity in the brain, to examine periods of potentially heightened risk for seizures known as “pro-ictal states.” The researchers were able to detect pro-ictal states in patients with temporal lobe epilepsy approximately 30 minutes or more before seizure onset. This information could lead to the development of electrical stimulation or drug therapies aimed at preventing seizures in people with this type of epilepsy. “The ability to predict seizures before they occur is a major step forward in the field of epilepsy research,” a study author stated.

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Altered Brain Signaling in People with Epilepsy Detected Through Non-Invasive Approach

New research has found that large-scale changes in the activation of neurons can be detected in the brains of people with temporal lobe epilepsy during a resting state (a state in which the brain is not stimulated by tasks or input), even when no seizure is occurring. The non-invasive approach uses EEG to detect changes in brain activity and could lead to a new method to aid in the diagnosis of epilepsy. While the brain is at rest, spontaneous waves of neuronal activation are constantly generated in a phenomenon called a “neuronal avalanche.” The researchers demonstrated that even during the resting state it is possible to detect a change in the neuronal avalanches in the brains of people with epilepsy. The researchers suggested that this method might be used as a preliminary diagnostic method, especially for difficult cases where standard scalp EEG fails to detect seizures, but additional investigations are necessary.

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Simple Blood Test Shows Potential Biomarker to Distinguish Epileptic from Non-Epileptic Psychogenic Seizures

Researchers have discovered higher levels of immune proteins in the blood before and after an epileptic seizure. In this study, researchers discovered that levels of five inflammation markers, or proteins, were elevated in people with temporal or frontal lobe epilepsy who had experienced a seizure. Among patients with psychogenic non-epileptic seizures (PNES), however, there was no change in the protein levels. These proteins, therefore, have the potential to be future biomarkers for a diagnosis of epilepsy. Diagnosing epilepsy from a simple blood draw would provide a significant advantage over the current diagnostic standards which may include admittance to a hospital for several days with constant video and EEG surveillance.

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Study Investigates Therapy for Treatment-Resistant Epilepsy

In a new study, researchers report that sodium selenate could be the first curative drug therapy for epilepsy. The study, conducted in an animal model of drug-resistant epilepsy, revealed sodium selenate to have a long-lasting effect (after months of stopping the medication) in reducing the frequency of seizures and in 30% of cases stopping them altogether. Sodium selenate also improved other aspects of epilepsy such as memory, learning, and sensor-motor functioning. The researchers will next begin a clinical trial of sodium selenate as a curative treatment in patients with drug-resistant epilepsy. “Despite the cost of the disease and the enormous amount of research into it, there has not been a single therapy developed to prevent the development of epilepsy,” stated a study author. “This Phase 2 clinical trial, if effective, has the potential to tackle a disease that is an enormous global burden as well as being truly transformative for people who are impacted by often daily seizures, with no respite.”

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Insights into the Drivers of Glioma-Related Epilepsy

Researchers at Baylor College of Medicine, including former CURE Epilepsy grantee Dr. Jeff Noebels, report that glioma tumors in the brain can interfere with the ability of surrounding neurons to handle potassium, an important ion in neuronal communication. The disruption of this normal neural function drives seizures and favors the progression of epilepsy. The team found that patients who have seizures have increased expression of genes involved in the formation of neuronal connections or synapses. In both humans with glioma and animal models, the researchers identified one of the genes, IGSF3, as the driver that mediated seizures in glioma-related epilepsy. The team found that IGSF3 suppresses the ability of these cells to take up potassium, which leads to its accumulation of this ion and then seizures. “Our studies reveal that tumor progression and seizures are triggered by disruption of potassium handling. The findings support further studies into novel strategies to control seizures and tumor growth,” stated one of the study’s authors.

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