Sudden Unexpected Death in Epilepsy During Cenobamate Clinical Development

Abstract found on PubMed

Objective: We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program.

Methods: We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic-clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic-clonic (PGTC) seizures who received ?1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days a patient received cenobamate during completed studies or up to June 1, 2022 for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years.

Results: A total of 2132 patients (n=2018 focal epilepsy; n=114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic-clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of 0.88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130-620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% CI 0.84-2.0), which was not significantly different from the general population.

Significance: These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.

Multimodal Nocturnal Seizure Detection in Children with Epilepsy: A Prospective, Multicenter, Long-Term, In-Home Trial

Abstract found on Wiley Online Library

Objective: There is a pressing need for reliable automated seizure detection in epilepsy care. Performance evidence on ambulatory non-EEG-based seizure detection devices is low and evidence on their effect on caregiver’s stress, sleep and quality of life (QoL) is still lacking. We aimed to determine the performance of NightWatch, a wearable nocturnal seizure detection device, in children with epilepsy in the family home setting and to assess its impact on caregiver burden.

Methods: We conducted a phase 4, multicenter, prospective, video-controlled, in-home NightWatch implementation study (NCT03909984). We included children aged 4-16 years, with 1 weekly nocturnal major motor seizure, living at home. We compared a two-month baseline period with a two-month NightWatch intervention. The primary outcome was the detection performance of NightWatch for major motor seizures (focal to bilateral or generalized tonic-clonic (TC) seizures, focal to bilateral or generalized tonic seizures lasting >30 seconds, hyperkinetic seizures, and a rest category of focal to bilateral or generalized clonic seizures and ‘TC-like’ seizures). Secondary outcomes included caregivers’ stress (Caregiver Strain Index, CSI), sleep (Pittsburgh Quality of Sleep Index), and quality of life (QoL, EQ-5D-5L).

Results: We included 53 children (55% male, mean age 9.7 ±3.6years, 68% learning disability) and analyzed 2310 nights (28,173 hours), including 552 major motor seizures. Nineteen participants did not experience any episode of interest during the trial. The median detection sensitivity per participant was 100% (range 46–100%), and the median individual false alarm rate was 0.04 per hour (range 0–0.53). Caregiver’s stress decreased significantly (mean total CSI score 8.0 vs. 7.1; p=0.032), while caregiver’s sleep and QoL did not change significantly during the trial.

Significance: The NightWatch system demonstrated high sensitivity for detecting nocturnal major motor seizures in children in a family home setting and reduced caregiver stress.

A Team Science Approach for the Preclinical and Clinical Characterization and Biomarker Development for Post-Traumatic Epilepsy

A Report of CURE Epilepsy’s Post-Traumatic Epilepsy Initiative

Abstract found on Wiley Online Library

Objective: Post-traumatic epilepsy (PTE) is an acquired epilepsy that develops in the months or years following a traumatic brain injury (TBI) and can lead to substantial personal, financial, and societal burden. To date, PTE is rarely curable; current treatments are partially effective and often accompanied by adverse side effects. While research on PTE has expanded significantly in the last several years, there remain numerous challenges to identifying effective prevention and treatment strategies. In this paper, we describe advances from the CURE Epilepsy PTE Initiative, including its implementation and the emphasis on team science.

Methods: The CURE Epilepsy PTE Initiative funded six research teams to link preclinical and clinical studies to engage in the validation of experimental models, characterization of pathophysiology and biological pathways, and identification of risk factors associated with PTE. Three teams had projects with both a preclinical and a clinical component; these teams focused on: targeting the epileptogenic effects of subarachnoid blood, exploring the neuropathological mechanisms of epileptogenesis, and defining the role of extracellular matrix injury. Two teams undertook entirely preclinical projects: exploring the role of vascular injury, gliosis, and neurogenesis as drivers for PTE, and identifying genetic, proteomic, metabolomic, and microRNA biosignatures to improve the prediction of PTE. One team’s project was entirely clinical and investigated genetic and protein biomarkers to improve the prediction of PTE.

Results: In addition to scientific discoveries including characterization of a variety of animal models and progress towards the understanding of biological underpinnings and biomarkers for PTE, significant programmatic and personnel-related processes were incorporated, including standardized, rigorous policies and procedures to ensure quality and accountability between and within groups.

Significance: We propose CURE Epilepsy’s team science approach as an effective way to bring together a diverse set of investigators to explore biological mechanisms that may lead to cures for the epilepsies.

Influence of Weather Regime and Local Geomagnetic Activity on the Occurrence of Epileptic Seizures

Abstract found on PubMed

Epilepsy is a common neurologic disease and presents a major public health problem. Patients with epilepsy have unexpected occurrence of seizures with many triggered by existing triggering factors such as alcohol, stress etc. Other potential triggers include certain weather or atmospheric parameters and local geomagnetic activity. We have analyzed the impact of atmospheric parameters grouped in 6 grouped weather types or weather regimes and the local geomagnetic activity through the K – index. In the prospective study, we analyzed a total of 431 seizures over a 17-month period. In the results obtained, we found that the most severely common weather regime grouped type of weather was radiation and then precipitation regime. It was also found that grouped weather types of weather regimes had more impact on generalized than focal epileptic seizures. Local geomagnetic activity had no direct effect on the occurrence of epileptic seizures. Those results confirm the thesis how the impact of certain external factors is complex and that the further study is required in that respect.


CURE Epilepsy Update May 2023

Greetings Epilepsy Community,

I am so excited to share that this past weekend, thanks to our generous donors and sponsors, CURE Epilepsy raised $3.1 million for epilepsy research at our 25th Anniversary Gala in Chicago. It was wonderful to share an evening with our community of people living with epilepsy, family members and friends, researchers, past and present board members and other volunteers and supporters who have helped to shape CURE Epilepsy over the last 25 years. We also toasted our founder Susan Axelrod, without whom none of our progress would be possible, and awarded our inaugural Founders Award to our first research chair Barb Kelly.

Though we still have a long way to go, epilepsy diagnostics, treatments, and therapies have come incredibly far in the past 25 years, giving hope to so many who were previously left with extremely limited options. Our search is unrelenting, and we remain committed to funding the most innovative science until we reach a world without seizures or side effects. The epilepsy journey can be lonely and isolating, and, especially during this Mental Health Awareness month, the value of this community and the support we give each other cannot be overstated.

With a commitment to inspire hope and deliver impact.

In this CURE Epilepsy Update, please find information on:

$3.1 Million Raised for Epilepsy Research at CURE Epilepsy’s 25th Anniversary Gala

Thanks to the generous and committed members of our CURE Epilepsy community, we raised $3.1 million for epilepsy research at our 25th Anniversary Gala in Chicago last weekend. It was an incredible evening celebrating inspiring stories from the community and promising advancements in research. Thank you again to our Host Committee, sponsors, donors, and volunteers. If you would still like to make a gift to help find a cure for epilepsy, you can visit the event page.



Donate Today

May is Mental Health Awareness Month

May is Mental Health Awareness Month, an opportunity for the epilepsy community to raise awareness and challenge stigma about mental health concerns specific to people with epilepsy.

Epilepsy is not a mental health disorder. However, one-third of people with epilepsy have a psychiatric disorder as well. While some may experience few mental health issues, others experience debilitating anxiety, depression, or mood disorders. This is why it is important for the epilepsy community to continue to raise awareness about both epilepsy and mental health.



Explore Mental Health Awareness Resources

Register for Our Webinar: Mental Health and Childhood Epilepsy

Join us for our webinar on Thursday, May 18 at 1 pm CT that will explore the complexities of childhood epilepsy and mental health. Mental health and behavioral problems are just a few of the concerns that can affect children with epilepsy, and these can vary greatly from one child to the next. The speaker for this webinar is Dr. Clemente Vega, a board-certified clinical neuropsychologist and a certified subspecialist in pediatric neuropsychology. He is employed in the Epilepsy Center at Boston Children’s Hospital, with clinical and academic efforts that focus on pediatric epilepsy syndromes, neurosurgical outcomes, and cross-cultural application of neuropsychological assessment.




New Resource for the Community: Medication Access

The health insurance and prescription benefit ecosystem in the United States is incredibly complex. It can be difficult to understand and navigate how prescription drugs get from the manufacturer to the pharmacy and what determines whether or not your insurance will cover the cost. And yet, access to medications prescribed by your physician is important to both control seizures and ensure the best possible outcome for your health.

This is why CURE Epilepsy has created an online Medication Access resource. This resource will provide you with a high-level description of the prescription process so that you can better understand the various players and how to overcome obstacles to obtaining your medicine.


Explore the New Medication Access Resource

Join Team CURE Epilepsy for the Marine Corps Marathon (MCM)

Join us on October 29 in Washington DC for the 2023 Marine Corps Marathon (MCM). CURE Epilepsy is proud to be a new partner of this annual marathon. You can join fellow Team CURE Epilepsy runners in our nation’s capital as we raise critical funds and awareness in our efforts to find a cure for epilepsy, by promoting and funding patient-focused research.





Watch Our Treatment Talk: Treatment of Focal Epilepsy: Advancement Toward Medical Remission


If you missed our latest Treatment Talk you can now access the recording. This Treatment Talk discusses focal epilepsy and the most recent treatments to help patients achieve medical remission. The talk features Dr. Michael Smith, Senior Attending Neurologist and Director of the Rush Epilepsy Center in Chicago, and Sarah Carlson, a patient of Dr. Smith’s who battled epilepsy and its corresponding stigma for many years before achieving seizure freedom. Viewers will learn about focal epilepsy, how a new medication called cenobamate can offer patients the hope of medical remission, and the benefits and risks identified in recent clinical trials of cenobamate.



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


In this CURE Epilepsy Discovery, we highlight the efforts of our Epilepsy Genetics Initiative (EGI), which created a centralized database to store and analyze genetic signatures associated with epilepsy. We also summarize EGI’s impact on people living with genetic epilepsies and the epilepsy research community. We then feature three recent CURE Epilepsy grant awardees who have contributed to numerous aspects of genetic epilepsies ranging from the development and application of new technology to studying specific genes and their contributions to epilepsy, to exploring the epigenomic pattern associated with epilepsy.


Read Discovery


What’s New from the Seizing Life® Podcast

Teen Tennis Player Remains on Court Despite Seizures and Stigma


Hear Reid’s story of a sudden onset of epilepsy that he experienced as a freshman in high school, his journey to controlling his tonic-clonic seizures, and how epilepsy and stigma have impacted his education and tennis career as one of the top young players in Oklahoma.

Watch or Listen



From LGS to Surgery to Just Being a Kid: A Mother Shares Her Son’s Epilepsy Journey


Mother and epilepsy advocate, Collen Jendreas, joins us to share her young son Owen’s epilepsy journey from initial onset to a diagnosis of Lennox-Gastaut syndrome (LGS), and discuss how two particular interventions have made a significant impact on Owen’s quality of life.



Watch or Listen

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

The CURE Epilepsy Store


Need apparel or accessories to spread epilepsy awareness and help support funding research to find a cure? Check out the CURE Epilepsy Store.





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

  • January 1 – December 31, 2023 – CURE Epilepsy’s 25th Anniversary
  • 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 Marc’s Story


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.

Characterizing the Treatment Gap in the U.S. Among Adult Patients with A New Diagnosis of Epilepsy

Abstract found on Wiley Online Library

Objective: Epilepsy is largely a treatable condition with antiseizure medication (ASM). Recent national administrative claims data suggest one-third of newly diagnosed adult epilepsy patients remain untreated 3?years after diagnosis. We aimed to quantify and characterize this treatment gap within a large U.S. academic health system leveraging the electronic health record (EHR) for enriched clinical detail.

Methods: This retrospective cohort study evaluated the proportion of adult patients in the health system from 2012-2020 who remained untreated 3?years after initial epilepsy diagnosis. To identify incident epilepsy, we applied validated administrative health data criteria of two encounters for epilepsy/seizures and/or convulsions, and we required no ASM prescription preceding the first encounter. Engagement with the health system at least 2?years before and at least 3?years after diagnosis was required. Among subjects who met administrative data diagnosis criteria, we manually reviewed medical records for a subset of 240 subjects to verify epilepsy diagnosis, confirm treatment status, and elucidate reason for nontreatment. These results were applied to estimate the proportion of the full cohort with untreated epilepsy.

Results: Of 831 patients who were automatically classified as having incident epilepsy by inclusion criteria, 80/831(10%) remained untreated 3?years after incident epilepsy diagnosis. Manual chart review of incident epilepsy classification revealed only 33% (78/240) had true incident epilepsy. We found untreated patients were more frequently misclassified (p<0.001). Using corrected counts, we extrapolated to the full cohort (831) and estimated <1% to 3% had true untreated epilepsy.

Significance: We found a substantially lower proportion of patients with newly diagnosed epilepsy remained untreated compared to previous estimates from administrative data analysis. Manual chart review revealed patients were frequently misclassified as having incident epilepsy, particularly patients who were not treated with an ASM. Administrative data analyses utilizing only diagnosis codes may misclassify patients as having incident epilepsy.

Paradoxical Effects of Levetiracetam in People with Epilepsy with Rhythmic Epileptiform Discharges

Abstract found on PubMed

Objective: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects.

Methods: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors.

Results: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects.

Conclusions: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

A Unified Hypothesis of SUDEP: Seizure-Induced Respiratory Depression Induced by Adenosine May Lead to SUDEP But Can be Prevented by Autoresuscitation and Other Restorative Respiratory Response Mechanisms Mediated by the Action of Serotonin on the Periaqueductal Gray

Featuring the work of former CURE grantee Dr. Carl Faingold

Abstract found on PubMed

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine-mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure-induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention.