Epilepsy Research News: March 2023

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


Epilepsy-Causing Neural “Hubs” in Children

A new method of determining which brain cells lead to seizures in children has been developed. The team used noninvasive techniques and advanced computational methods to measure the electric and magnetic signals generated by neural cells to identify brain “hubs” responsible for the generation of seizures in children with epilepsy. This team retrospectively analyzed electroencephalography (EEG) and magnetoencephalography data recorded from 37 children and young adults with drug-resistant epilepsy who had neurosurgery. They then created a virtual model of the brain and virtually implanted sensors at locations where invasive EEG contacts had been placed during neurosurgery. The researchers found that the virtual sensors could non-invasively identify highly connected hubs in patients with drug-resistant epilepsy. The authors stated that the discovery could help to identify areas of the brain that generate epileptic activity in children with drug-resistant epilepsy in a non-invasive way.

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Potential Cause of Infantile and Epileptic Spasms Syndrome

New research featuring the work of a former CURE Epilepsy grantee, Dr. Chris Dulla, and colleagues suggests that the timing of the death of a subset of neurons in the brain shortly after birth may be partly to blame for infantile and epileptic spasms syndrome (a form of which is also called infantile spasms (IS) or West syndrome), a childhood epilepsy with poor outcomes. These neurons are responsible for providing inhibitory input to the brain; the lack of these neurons may lead to too much excitation and epileptic spasms. The research suggests that it may be the timing of inhibitory neuron cell death which is important, not just the fact that it occurs. This research may suggest a potential target for the future development of treatments for infantile and epileptic spasms.

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Underreported Symptoms in Patients with Genetic Epilepsy

A new study increases our understanding of symptoms associated with changes in the STXBP1 gene, one of the most common genetic causes of childhood epilepsies and neurodevelopmental disorders. By systematically mapping symptoms and assessing their impacts on patients and their caregivers, the researchers identified previously underreported symptoms beyond just neurological symptoms. To understand these symptoms, the researchers performed more than 24 hours of interviews among 19 caregivers of 16 individuals with STXBP1-related disorders and seven healthcare professionals. In doing so, the researchers created a so-called “disease concept model,” which is meant to determine which outcomes are relevant in everyday clinical practice. These results may serve as an important foundation for future trials assessing the effectiveness of therapeutic interventions for all related symptoms.

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How Cannabidiol Counters Epileptic Seizures

A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in many treatment-resistant forms of pediatric epilepsy. The new study found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). Found in brain cells called neurons, LPI is thought to amplify nerve signals as part of normal function but can also be hijacked by disease to promote seizures. The work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings suggest for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment. “Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches,” stated a study author. “The study also clarified, not just how CBD counters seizures, but more broadly how neural circuits are balanced in the brain.”

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How the Brain’s Immune System Response Worsens Epilepsy

In a new study using a fruit fly model of epilepsy, researchers describe a chain of events that link the brain’s immune system response to worsening seizures. The researchers used flies with a mutation in a gene known as the prickle gene, similar to the mutation in the PRICKLE gene found in humans with progressive myoclonus epilepsy with ataxia, and found that this particular mutation can lead to increases in a condition called oxidative stress. The researchers found that oxidative stress can activate the brain’s resident immune cells (called glia), which in turn triggers more severe seizures. “We have provided genetic proof that both oxidative stress and activation of the brain immune system make epilepsy worse,” stated a study author. “This is hugely significant because our data suggest that we can now repurpose exceedingly well-tolerated anti-inflammatory compounds as well as perhaps antioxidants to help control epilepsy progression.”

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CURE Epilepsy Discovery: Implantable Devices Represent a Novel Way to Detect and Treat Epilepsy

Key Points:

  • Approximately one-third of people with epilepsy do not respond to anti-seizure medications and there are limited treatment options for these treatment-resistant cases.
  • Implantable epilepsy devices offer novel avenues to detect and treat seizures by recording seizure activity from neurons (brain cells) in high-resolution and stimulating these neurons in a way that halts seizures.
  • Brian Litt at the University of Pennsylvania was funded by CURE Epilepsy in 2011, and his work has led to the development of electrodes and technology that offer incredible precision in recording from and stimulating neurons.
  • Litt’s trainees, Dr. Jonathan Viventi at Duke University and Dr. Flavia Vitale at the University of Pennsylvania, are continuing their work to develop cutting-edge implantable devices to understand and treat epilepsy at their own laboratories.


Deep dive

People with epilepsy are often prescribed anti-seizure medications (ASMs), and while they are effective in many people, about 30% of those with epilepsy continue to experience seizures. Resective surgery, where the part of the brain that generates seizures is removed, may be an option for some, but not all, people with treatment-resistant epilepsy (also called “refractory” epilepsy).[1] Devices for epilepsy represent an innovative treatment modality that has much to offer to those with treatment-resistant epilepsy.

Devices for epilepsy fall into two main categories: 1) wearable, seizure-alert devices, and 2) devices that are implanted in the body. Wearable devices can track seizures and alert a caregiver to the occurrence of a seizure. Wearable devices can have a positive impact on quality of life, and can contribute to the empowerment of the person with epilepsy by encouraging self-monitoring and self-management.[2,3] Implantable devices for epilepsy include neurostimulation devices. For example, responsive neurostimulation (RNS) devices) and deep brain stimulation (DBS) devices) reduce seizures by applying electrical stimulation to modulate brainwaves in specific areas of the brain.  The RNS device can be thought of as a pacemaker for the brain; it is implanted near the seizure focus and allow for insertion of wires that send electrical pulses to interfere with seizure activity in surface areas of the brain, whereas the DBS sends electrical pulses through wires to specific areas deep within the brain that are involved with seizures.

Implantable devices hold substantial promise for those with refractory epilepsies who have inadequate therapeutic alternatives. It has been suggested that implantable devices may even become alternatives to multiple ASMs and resective epilepsy surgery.[4] The promise that devices hold for epilepsy therapy aligns with CURE Epilepsy’s goal to identify and fund cutting-edge research, challenging scientists worldwide to collaborate and innovate in pursuit of a cure for epilepsy. To this end, this CURE Epilepsy Discovery features our grantee, Dr. Brian Litt who is jointly appointed at the Perelman School of Medicine and the School of Engineering and Applied Science at the University of Pennsylvania, positioning his work is at the nexus of neuroscience and engineering.

One of the first and most impactful grants that Dr. Litt received was from CURE Epilepsy, in 2011 through “Julie’s Hope,” one of three CURE Epilepsy grants funded by Jim and Susan Schneider in honor of their daughter Julie. As a neurologist, Dr. Litt saw first-hand the impact of epilepsy on people’s lives and the lack of options that were available for refractory epilepsies. Back in 2011, the field of implantable devices used standard, rigid clinical electrodes that did not conform to the brain’s surface. Each electrode was connected to a wire, and the device was cumbersome and lent itself to surgical complications and errors. Also, given the large number of wires, it was not possible to effectively cover large areas of the brain. In his project, Dr. Litt wanted to accelerate the development of devices and demonstrate relevance in human epilepsy. Specifically, he worked to develop and refine flexible, active, implantable electrodes to monitor and stimulate the brain with a goal to cure epilepsy. Work done for this grant led to the implantation of these flexible electrodes into experimental animals to record seizures and to stimulate the brain to control seizures.[5]

Over the years, Dr. Litt’s work has led to many other discoveries. Some of the most notable ones are the use of high-resolution, active, flexible surface electrode arrays to distinguish between seizures (“ictal” events) and in-between seizures (“interictal” events). By better visualizing brainwave patterns during these specific times, we can better understand the mechanisms by which seizures begin and discover opportunities for therapeutic interventions to stop them.[6] Another notable area of work is the development of a transparent, graphene-based electrode technology that can simultaneously record brainwaves and perform optical imaging. This innovative approach allows for specificity of the brain recordings coupled with the capacity to visualize the brain regions being recorded. By studying brain activity in this way, we can better understand how the brain processes information which has implications beyond epilepsy.[7]

This work on implantable devices for epilepsy led to a large amount of data. Dr. Litt has been organizing and investigating this ‘big neuro data” by sharing it and collaborating with the international research community, using techniques such as cloud-based platforms and open data ecosystems.[8,9] On a broader level, Dr. Litt’s work with implantable electrodes has also led to the assembly of brain activity data across different epilepsy centers to be combined to create a “map” that may help guide epilepsy surgery.[10] Dr. Litt’s scientific contributions have led him to receive the NIH Director’s Pioneer Award in 2020,[11] awarded to “exceptionally creative scientists proposing pioneering approaches.” His work has also led to several patents.[12,13]

Dr. Litt is also passionate about mentoring scientists. Over the years, has trained over 50 scientists and clinician-engineers.  Two of Dr. Litt’s trainees, Drs. Jonathan Viventi and Flavia Vitale are now established scientists carrying on the work to develop implantable electrodes to understand seizure dynamics and treat epilepsy. Dr. Viventi was awarded the Taking Flight Award by CURE Epilepsy in 2012 and is currently an Assistant Professor in the Department of Biomedical Engineering at Duke University. The focus of Dr. Viventi’s work is to create new technology to understand the workings of the brain at hundreds of times the resolution of current devices. By mapping the brain and its abnormal circuitry, Dr. Viventi hopes to use precision stimulation to stop seizures. His technology consists of thin-film electrode arrays that have hundreds of microelectrodes to precisely map seizure activity in the human brain. This device was tested in nine people with epilepsy, and Dr. Viventi’s team was able to precisely localize the brain areas where seizures were generated. In the future, this technology can be used to plan epilepsy surgery or target brain stimulation.[14]

Dr. Vitale is an Assistant Professor of Neurology at the University of Pennsylvania, and was awarded a Taking Flight Award by CURE Epilepsy in 2017. In this project, she wanted to focus on the concept that seizures begin in a specific region of the brain, the seizure onset zone (SOZ). Brainwaves travel or propagate to surrounding areas, ultimately resulting in seizures. The thought is that to achieve seizure freedom, the SOZ and the surrounding epileptogenic zone must be removed. However, the differentiation of these zones has been challenging using current modalities. Dr. Vitale proposed a technology to precisely map epileptic networks to understand what exact neurons were involved in seizure generation. By using tiny, flexible electrodes that can be independently controlled, she aims to understand seizures at a scale that had never been done before. Building on the work with graphene electrodes with Dr. Litt, Dr. Vitale has developed a technique to accurately map the spread of seizures by using transparent microelectrode arrays.[15] Her team is also working on the next generation of soft electrodes and techniques for safe and precise insertion of electrodes into brain structures.[16]

Thanks to Dr. Litt’s deep interest and investment in training of new scientists, he received the Landis Award for Outstanding Mentorship in 2022.  Through his efforts, Dr. Litt has created a collaborative and nurturing environment in his lab, where trainees are selected not only on scientific merit but also on qualities such as thoughtfulness and real-world experience, and most importantly, the desire to use scientific knowledge for public betterment. Ever the champion of the trainees in his lab, Dr. Litt is actively equipping the next generation of brain scientists in the cross-disciplinary fields of neuroscience, surgery, engineering, computing, electronics, and device development.[17]

In conclusion, the funding that CURE Epilepsy provided to Dr. Litt in 2011 was the beginning of not only his scientific discoveries in the field of implantable devices but also an opportunity to deeply invest in the future and the next generation of scientists. While basic research can take decades to come to fruition, the rewards are great as it helps to build knowledge about how and why the brain generates seizures, and also provides insights into how the brain works in general. By funding basic research for epilepsy devices through Drs. Litt, Viventi, and Vitale, CURE Epilepsy positions the community to find a cure for epilepsy within our lifetime.



Literature Cited:

  1. Mesraoua B, Deleu D, Kullmann DM, Shetty AK, Boon P, Perucca E, et al. Novel therapies for epilepsy in the pipeline Epilepsy Behav. 2019 Aug;97:282-290.
  2. Verdru J, Van Paesschen W. Wearable seizure detection devices in refractory epilepsy Acta Neurol Belg. 2020 Dec;120:1271-1281.
  3. Esmaeili B, Vieluf S, Dworetzky BA, Reinsberger C. The Potential of Wearable Devices and Mobile Health Applications in the Evaluation and Treatment of Epilepsy Neurol Clin. 2022 Nov;40:729-739.
  4. Litt B. Evaluating devices for treating epilepsy Epilepsia. 2003;44 Suppl 7:30-37.
  5. Viventi J, Kim DH, Vigeland L, Frechette ES, Blanco JA, Kim YS, et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo Nat Neurosci. 2011 Nov 13;14:1599-1605.
  6. Vanleer AC, Blanco JA, Wagenaar JB, Viventi J, Contreras D, Litt B. Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures J Neural Eng. 2016 Apr;13:026015.
  7. Kuzum D, Takano H, Shim E, Reed JC, Juul H, Richardson AG, et al. Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging Nat Commun. 2014 Oct 20;5:5259.
  8. Wagenaar JB, Worrell GA, Ives Z, Dümpelmann M, Litt B, Schulze-Bonhage A. Collaborating and sharing data in epilepsy research J Clin Neurophysiol. 2015 Jun;32:235-239.
  9. Wiener M, Sommer FT, Ives ZG, Poldrack RA, Litt B. Enabling an Open Data Ecosystem for the Neurosciences Neuron. 2016 Nov 2;92:617-621.
  10. Bernabei JM, Sinha N, Arnold TC, Conrad E, Ong I, Pattnaik AR, et al. Normative intracranial EEG maps epileptogenic tissues in focal epilepsy Brain. 2022 Jun 30;145:1949-1961.
  11. NIH Director’s Pioneer Award Recipients: 2020 Awardees. Available at: https://commonfund.nih.gov/pioneer/AwardRecipients20. Accessed February 7.
  12. Echuaz JR WG, Litt B inventor; Active control of epileptic seizures and diagnosis based on critical systems-like behavior2012.
  13. Vitale F ND, Nicholas A, Litt B, inventor; Rapid manufacturing of absorbent substates for soft, comformable sensors and conductors 2022.
  14. Sun J, Barth K, Qiao S, Chiang CH, Wang C, Rahimpour S, et al. Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array Brain Commun. 2022;4:fcac122.
  15. Driscoll N, Rosch RE, Murphy BB, Ashourvan A, Vishnubhotla R, Dickens OO, et al. Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale Commun Biol. 2021 Jan 29;4:136.
  16. Apollo NV, Murphy B, Prezelski K, Driscoll N, Richardson AG, Lucas TH, et al. Gels, jets, mosquitoes, and magnets: a review of implantation strategies for soft neural probes J Neural Eng. 2020 Sep 11;17:041002.
  17. Litt B. Engineering the next generation of brain scientists Neuron. 2015 Apr 8;86:16-20.

New Method Finds Epilepsy-Causing Neural “Hubs” in Children

Article published by Inside Precision Medicine

A new, very precise, method of determining which brain cells lead to epileptic episodes in children has been developed by a team at University of Texas at Arlington and collaborators. Currently, epilepsy surgery is the safest and most effective treatment for these patients and offers a 50% chance of eliminating seizures.

The team used noninvasive techniques and advanced computational methods to measure the electric and magnetic signals generated by neural cells and identify functional networks responsible for the generation of seizures in children with epilepsy.

“This could benefit so many children who can’t control epilepsy with drugs, which represents between 20 and 30% of children suffering from epilepsy,” said Christos Papadelis, senior author, who also serves as the director of research in the Jane and John Justin Neurosciences Center at Cook Children’s Health Care System.

The paper was published in Brain, and the lead author is Ludovica Corona. It was produced in collaboration with Boston Children’s Hospital, Massachusetts General Hospital, and Harvard Medical School.

The Impact of Parent Treatment Preference and Other Factors on Recruitment: Lessons Learned from a Paediatric Epilepsy Randomised Controlled Trial

Abstract found on Trails Journal

Background: In paediatric epilepsy, the evidence of effectiveness of antiseizure treatment is inconclusive for some types of epilepsy. As with other paediatric clinical trials, researchers undertaking paediatric epilepsy clinical trials face a range of challenges that may compromise external validity.

Main body: In this paper, we critically reflect upon the factors which impacted recruitment to the pilot phase of a phase IV unblinded, randomised controlled 3×2 factorial trial examining the effectiveness of two antiseizure medications (ASMs) and a sleep behaviour intervention in children with Rolandic epilepsy. We consider the processes established to support recruitment, public and patient involvement and engagement (PPIE), site induction, our oversight of recruitment targets and figures, and the actions we took to help us understand why we failed to recruit sufficient children to continue to the substantive trial phase.

The key lessons learned were about parent preference, children’s involvement and collaboration in decision-making, potential and alternative trial designs, and elicitation of stated preferences pre-trial design.

Despite pre-funding PPIE during the trial design phase, we failed to anticipate the scale of parental treatment preference for or against antiseizure medication (ASMs) and consequent unwillingness to be randomised. Future studies should ensure more detailed and in-depth consultation to ascertain parent and/or patient preferences. More intense engagement with parents and children exploring their ideas about treatment preferences could, perhaps, have helped predict some recruitment issues. Infrequent seizures or screening children close to natural remission were possible explanations for non-consent. It is possible some clinicians were unintentionally unable to convey clinical equipoise influencing parental decision against participation. We wanted children to be involved in decisions about trial participation. However, despite having tailored written and video information to explain the trial to children we do not know whether these materials were viewed in each consent conversation or how much input children had towards parents’ decisions to participate. Novel methods such as parent/patient preference trials and/or discrete choice experiments may be the way forward.

Conclusion: The importance of diligent consultation, the consideration of novel methods such as parent/patient preference trials and/or discrete choice experiments in studies examining the effectiveness of ASMs versus no-ASMs cannot be overemphasised even in the presence of widespread clinician equipoise.

New Method Provides Important Insights into the Development of Epilepsy

Article published by News Medical Life Sciences

In epilepsy research, it has long been assumed that a leaky blood-brain barrier is a cause of inflammation in the brain. Using a novel method, researchers from Bonn University Hospital (UKB) and the University of Bonn have demonstrated that the barrier between the blood and the central nervous system remains largely intact. The approach of their study provides important insights into the development of epilepsy and could significantly optimize drug development in the pharmaceutical industry. The study results have recently been published in the renowned journal “Nature Communications”.

500 kilometers of vessels in the human brain are lined with ten square meters of thin cell layer – the blood-brain barrier (BBB). This barrier protects the brain against harmful substances as well as pathogens. It also links the brain to the other organs in the body. If this selective barrier is leaky, diseases such as Parkinson’s, multiple sclerosis, Alzheimer’s could develop. Malfunctions of the BBB also play an important role in brain tumors. Researchers at the UKB and the University of Bonn want to get to the bottom of these interactions. To study BBB transport at the cellular level, they developed micropipette-based local perfusion of capillaries, i.e. finest blood vessels, in acute brain slices and combined it with multiphoton microscopy.

Prof. Dirk Dietrich, head of the experimental neurosurgery section at the Clinic of Neurosurgery at the UKB, compares the new analysis technique of the blood-brain barrier investigated in the study to a flat bicycle tire: “If the tire loses air, you don’t know where the leak is. That’s why you hold the inflated bicycle tube under water to identify the leak. This principle also underlies our method.” The researchers use a micropipette to fill the microscopic blood vessels with a liquid from the inside. Leaks are then visible to them under the multiphoton microscope.

Microbot Development Could Help Treat Seizures

Article published by The Hippocratic Post

University of Glasgow researchers are part of a new project which is setting out to develop tiny injectable robots capable of predicting and mitigating epileptic seizures.

The project, called CROSSBRAIN, is led by Tor Vergata University of Rome in Italy and is funded by the European Innovation Council.

Over the course of the next four years, the CROSSBRAIN collaborators will develop implantable ‘microbots’, about a tenth of a millimetre in size, made from advanced nanomaterials with specially-tailored physical properties.

Once implanted in the brain, they will be controlled by a small, wearable central control unit capable of monitoring electrical activity to detect the onset of a seizure and modulate its effect through targeted neurostimulation.

The microbots will be able to deliver genetic material on command, enabling cell- and microcircuit-level neuromodulation in rodent brains during the later stages of the project’s development.

Professor Hadi Heidari, of the University of Glasgow’s James Watt School of Engineering, is leading the UK contribution to CROSSBRAIN. Professor Heidari’s Microelectronics Lab conducts pioneering research on integrated micro and nanoelectronics design for medical and industrial applications. In this project, the Microelectronics Lab will help to design and develop the microbots’ wireless power and data management and delivery systems.

The CROSSBRAIN team will develop a cutting-edge FBAR magnetoelectric antenna at the world-class cleanroom facilities of the University’s James Watt Nanofabrication Centre.

Professor Heidari said: “We’re pleased to be part of this ambitious project, which has the potential to pave the way for transformative treatments for pathological brain conditions like epilepsy.

Adjunctive Cenobamate (XCOPRI ®) in Highly Active and Ultra-Refractory Focal Epilepsy: A ‘Real-World’ Retrospective Study

Abstract found on Wiley Online Library

Objective: Recent clinical trials showed that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy. However, little is known about cenobamate’s performance in highly active (?20 seizures/month) and ultra-refractory focal epilepsy (?6 failed epilepsy treatments, including anti-seizure medications [ASM], epilepsy surgery and vagus nerve stimulation). Here, we studied cenobamate’s efficacy and tolerability in a ‘real-world’ severe DRE cohort.

Methods: We conducted a single-centre retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analysed.

Results: Fifty-seven patients received cenobamate for at least three months (median duration, 11 months). The median cenobamate dose was 250mg/day (range 75-350mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75-99% reduction in seizures (42.1% of cohort), and 16 had a 50-74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic-clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ?250mg/day. Three-quarters of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ?250mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine and perampanel.

Significance: Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.

Differential Diagnosis of Familial Adult Myoclonic Epilepsy

Abstract found on Wiley Online Library

Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA and TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease; whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. The EEG may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder.

Recognition of familial adult myoclonic epilepsy (FAME) will inform prognostic and genetic counseling, and diagnosis of the insidious progression which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow identification of the underlying aetiology.

Epilepsy Research News: February 2023

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


Combining Diet with Drugs to Reduce Seizures

Following a modified Atkins diet that is high in fat and low in carbohydrates in addition to taking antiseizure medication(s) may reduce seizures in people with tough-to-treat epilepsy, according to a recently published study. The study involved 160 adults and adolescents who had epilepsy for more than 10 years on average and had at least 27 seizures per month, despite trying an average of four antiseizure medications at the maximum tolerated dose. After six months, researchers found that 26% of people who used drug therapy and followed the modified Atkins diet had more than a 50% reduction in seizures, compared to only 3% of the people who had drug therapy alone. Four people in the diet group were seizure free by the end of the study, while no one in the medication-only group was seizure free. A limitation of the study is that seizures were self-reported or reported by caregivers, so some seizures may not have been reported. Despite this important consideration, “for people with drug-resistant epilepsy, or those who have been unable to find effective treatment to reduce seizures, it’s encouraging to see that there are lifestyle changes that can be combined with standard drug therapy to reduce the number of seizures,” stated a study author.

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Parents Need Guidance Managing Sleep Issues in Children with Epilepsy

According to a new qualitative study that included interviews with nine mothers, sleep and epilepsy have a complex and bidirectional relationship. The aim of the study was to capture parental perceptions and experiences related to their child’s sleep habits and management, the impact of sleep difficulties on the child and their family, and available support. According to the study, epilepsy exacerbated the struggle to initiate sleep (settling and falling asleep), maintenance of sleep (experiencing night or early morning wakings), duration of sleep, daytime sleepiness, and sleep anxiety. Study authors noted that mothers were aware of the links between sleep and seizures yet felt that they lacked guidance about how to address or improve their child’s sleep, including from their healthcare teams. The authors also stated that the finding emphasizes the need to ensure adequate help is available to support healthy sleep in children with epilepsy.

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New Understanding of the Cause of Post-Traumatic Epilepsy (PTE)

A research team has uncovered information about changes that occur in the brain following a traumatic brain injury (TBI) that could help advance future preventative treatments for PTE, a type of epilepsy caused by a TBI. The findings show that activation of a subset of neurons within an area of the brain called the hippocampus plays a key role in the changes that occur during the development of PTE. For this study, the team looked at neurons called dentate granule cells, which continuously regenerate in areas of the brain that are crucial for learning and memory and are also commonly impacted by epilepsy. The team found that when the dentate granule cells were activated, the activity of other brain cells involved in epilepsy was inhibited. They also found that the cells that were formed just prior to a were much more likely to activate this circuit than those generated at other points in time. The team noted that being able to get to a point of understanding the changes that occur in the development of epilepsy may lead to the ability to prevent or reverse epilepsy.

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Links Between Parental Factors, Emotional, and Behavioral Issues Found in Pediatric Epilepsy

Adolescents with epilepsy commonly experience emotional and behavioral problems, which vary depending on demographic, clinical, and parental factors, according to a new study. The parental factors included how parents perceived that others treated their child. The study included 289 adolescents aged between 11 and 18 years. The study found 18.3% of adolescents with epilepsy had at least one emotional or behavioral problem in the clinical range. Additionally, consistent with findings of prior studies, this study showed one in four parents of adolescents with epilepsy perceived that other people felt uncomfortable with their child, treated their child as inferior, or preferred to avoid their child because of their epilepsy. Due to these findings, the study’s authors emphasized it is crucial to identify and properly manage these problems early to decrease comorbid psychopathology in adolescents with epilepsy.

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Use of Newer Antiseizure Medications for Epilepsy Differs by Race, Ethnicity

Racial and ethnic minority groups are less likely to be taking newer-generation antiseizure medications for their epilepsy, an analysis of Medicaid data showed. Compared with white patients, Black, Hispanic, and Native Hawaiian/Pacific Islander patients had lower odds of being on newer antiseizure medications, the study found. Of note, taking a second-generation antiseizure medication was associated with better treatment adherence, and those seeing a neurologist had higher odds of being on newer antiseizure medications. The study authors stated that being on a newer, second and third-generation antiseizure medication may represent an important marker of quality of care for people with epilepsy and that differences appear to reflect racial and ethnic inequities in epilepsy care.

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Perampanel (FYCOMPA®) as Precision Therapy in Rare Genetic Epilepsies

Abstract found on 

Objective: Perampanel, an antiseizure drug with AMPA-receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Special interest holds epilepsies with loss of GABA inhibition (e.g. SCN1A), overactive excitatory neurons (e.g. SCN2ASCN8A ), and variants in glutamate receptors (e.g. GRIN2A). We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy.

Methods: A multicenter project based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel was collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified.

Results: 137 patients, with 79 different etiologies, aged 2 months-61?years (mean 15.48±9.9) were enrolled. The mean dosage was 6.45±2.47 mg, and treatment period was 2.0±1.78?years (1.5 months-8?years). 62 patients (44.9%) were treated for >2?years. 98 patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61±34.36%. 60 patients (43.5%) sustained over 75% reduction in seizure frequency, including 38 (27.5%) with >?90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, NEU1. 11/17 (64.7%) of patients with SCN1A, 35.3% of which had over 90% seizure reduction. Other etiologies remarkable for over 90% reduction in seizures were GNAO1 and PIGA. 14 patients had a CSWS EEG pattern and in 6 subjects perampanel reduced epileptiform activity.

Significance: Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1 and POLG, suggesting a targeted effect related to glutamate transmission.