Focal to Bilateral Tonic-Clonic Seizures Predict Pharmacoresistance in Focal Cortical Dysplasia-Related Epilepsy

Abstract found on Wiley Online Library

Objective: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. 87% of FCD patients develop epilepsy (75% is pharmacoresistant (PRE)). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks.

Methods: Patients were selected retrospectively from radiology and surgical databases from Children’s National Hospital. Inclusion criteria: 3T MRI-confirmed FCD from 1/2011-1/2020; ages 0-days to 22-years at MRI; 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age of seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age of seizure onset, pathology, lobe, percentage default mode network (DMN) overlap) of FTBTC seizures.

Results: 117 patients had median age of seizure onset 3.00y (IQR 0.42 – 5.59y). 83 patients had PRE (71%); 34 had PSE (29%). Twenty (17%) patients had FTBTC seizures. 73 patients underwent epilepsy surgery. Multivariate regression showed FTBTC seizures are associated with increased risk of PRE (OR 6.41 95%CI 1.21 – 33.98, p=0.02). FCD hemisphere/lobe were not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. 72% (n=52) overall and 53% (n=9) of those with FTBTC seizures achieved Engel I outcome.

Significance: In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE, and can flag patients for earlier consideration of potentially curative surgery. FCD dominant network also contributes to FTBTC seizure clinical expression.

Differentiation of Epilepsy and Psychogenic Nonepileptic Events Based on Body Fluid Characteristic

Abstract found on Wiley Online Library

Objective: Differential diagnosis between epileptic seizures and psychogenic nonepileptic events (PNEEs) is a worldwide problem for neurologists. The present study aims to identify important characteristics from body fluid tests and develop diagnostic models based on them.

Methods: This is a register-based observational study in patients with a diagnosis of epilepsy or PNEEs at West China Hospital of Sichuan University. Data from body fluid tests between 2009 and 2019 were used as a training set. We constructed models with a random forest approach in eight training subsets divided by sex and categories of tests, including electrolyte, blood cell, metabolism, and urine tests. Then, we collected data prospectively from patients between 2020 and 2022 to validate our models and calculated the relative importance of characteristics in robust models. Selected characteristics were finally analyzed with multiple logistic regression to establish nomograms.

Results: A total of 388 patients, including 218 with epilepsy and 170 with PNEEs, were studied. The AUROCs of random forest models of electrolyte and urine tests in the validation phase achieved 80.0% and 79.0%, respectively. Carbon dioxide combining power, anion gap, potassium, calcium, and chlorine in electrolyte tests and specific gravity, pH, and conductivity in urine tests were selected for the logistic regression analysis. C (ROC) of the electrolyte and urine diagnostic nomograms achieved 0.79 and 0.85, respectively.

Significance: The application of routine indicators of serum and urine may help in the more accurate identification of epileptic and PNEEs.

Surgical Outcomes of Open and Laser Interstitial Thermal Therapy (LITT) Approaches for Corpus Callosotomy in Pediatric Epilepsy

Abstract found on Wiley Online Library

Objective: Corpus callosotomy (CC) is a palliative surgical intervention for patients with medically refractory epilepsy that has evolved in recent years to include a less invasive alternative with the use of laser interstitial thermal therapy (LITT). LITT works by heating a stereotactically placed laser fiber to ablative temperatures under real-time MRI thermometry. This study aims to 1) describe the surgical outcomes of CC in a large cohort of children with medically refractory epilepsy, 2) compare anterior and complete CC, and 3) review LITT as a surgical alternative to open craniotomy for corpus callosotomy.

Methods: This retrospective cohortcohort study included 103 patients <21 years old with at least 1 year follow-up at a single institution between 2003 and 2021. Surgical outcomes and the comparative effectiveness of anterior versus complete and open versus LITT surgical approaches were assessed.

Results: Complete callosotomy was the most common surgical disconnection (65%, n=67) followed by anterior two-thirds (35%, n=36), with a portion proceeding to posterior completion (28%, n=10). The overall surgical complication rate was 6% (n=6/103). Open craniotomy was the most common approach (87%, n=90), with LITT used increasingly in recent years (13%, n=13). Compared to open, LITT had shorter hospital stay (3  days [IQR 2-5] vs. 5 days [IQR 3-7]; p<0.05). Modified Engel I, II, III, and IV outcomes at last follow-up were 19.8% (n=17/86), 19.8% (n=17/86), 40.2% (n=35/86), and 19.8% (n=17/86). Of the 70 patients with preoperative drop seizures, 75% resolved postoperatively (n=52/69).

Significance: No significant differences in seizure outcome between patients who underwent only anterior corpus callosotomy and complete corpus callosotomy were observed. LITT is a less invasive surgical alternative to open craniotomy for corpus callosotomy, associated with similar seizure outcomes, lower blood loss, shorter hospital stays, and lower complication rates, but with longer operative times, when compared with the open craniotomy approach.

Ictal Blinking Triggered by Isolated Spikes as the Only Manifestation of Seizures

Abstract found on Wiley Online Library

Objective: To describe blinking as the only manifestation of seizures from isolated focal and generalized cortical spikes and investigate the relationship between blinks and epileptic discharges.

Methods: We measured the latency from the onset of spikes to the onset of blinks in two patients using electroencephalogram (EEG) and an electrooculogram (EOG), and calculated the median latency in both cases. We analyzed the latency from spike onset to the onset of additional specific eye movements, seen only in the second case. To determine the frequency of spontaneous blinks (not triggered by spikes), we defined a “control point” at 45?s following a random spike for the first case. We tested for statistically significant associations between latencies of blinks (Case 1) as well as between latencies of blinks and specific eye movements (Case 2).

Results: A total of 174 generalized spike-waves followed by a blink were analyzed in the first patient. Approximately 61% of the blinks occurred within 150–450?ms after the onset of the spike. Median latency for blinks following a spike was 294?ms compared to 541?ms for control blinks (p = .02). For the second patient, a total of 160 eye movements following a right occipito-parietal spike were analyzed. The median spike-blink latency in the second case was 497 milliseconds. Median latencies of spike onset to contralateral oblique eye movements with blink and left lateral eye movements were 648 and 655 milliseconds, respectively.

Conclusions: Our study shows that isolated cortical spikes can induce epileptic seizures consisting exclusively of blinks. These findings emphasize the importance of careful EEG and EOG analysis to determine blinking as the only ictal phenomenon. We additionally describe a new technique to prove the temporal relationship between cortical discharges and a specific movement when, in addition to the movements triggered by a spike, the same movement is also spontaneously performed by the patient (in this case, blinking).

Perceived Seizure Risk in Epilepsy – Chronic Electronic Surveys With and Without Concurrent EEG

Abstract found on PubMed

Objective: Previous studies suggested that patients with epilepsy might be able to forecast their own seizures. This study aimed to assess the relationships between premonitory symptoms, perceived seizure risk, and future and recent self-reported and EEG-confirmed seizures in ambulatory patients with epilepsy in their natural home environments.

Methods: Long-term e-surveys were collected from patients with and without concurrent EEG recordings. Information obtained from the e-surveys included medication adherence, sleep quality, mood, stress, perceived seizure risk and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed-effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with the seizure forecasting classifiers and device forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC).

Results: Fifty-four subjects returned 10,269 e-survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed that increased stress (OR = 2.01, 95% CI = [1.12, 3.61], AUC = 0.61, p = 0.02) was associated with increased relative odds of future self-reported seizures. Multivariate analysis showed that previous self-reported seizures (5.37, [3.53, 8.16], 0.76, < 0.001) were most strongly associated with future self-reported seizures and high perceived seizure risk (3.34, [1.87, 5.95], 0.69, < 0.001) remained significant when prior self-reported seizures were added to the model. No correlation with medical adherence was found. No significant association was found between e-survey responses and subsequent EEG seizures.

Significance: Our results suggest that patients may tend to self-forecast seizures that occur in sequential groupings and that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self-predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting.

Integrated Psychological Care services within Seizure Settings: Key Components and Implementation Factors Among Example Services in Four ILAE Regions: A Report by the ILAE Psychiatry Commission

Abstract found on Wiley Online Library

Mental health comorbidities are prevalent and problematic in patients with seizures but often suboptimally managed. To address common gaps in care, the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy (ILAE) Psychiatry Commission was tasked with providing education and guidance on the integration of mental health management (e.g., screening, referral, treatment) into routine seizure care. This report aims to describe a variety of established services in this area, with a specific focus on psychological care models. Services were identified by members of the ILAE Psychiatry Commission and authors of psychological intervention trials in epilepsy. A total of eight services met inclusion criteria and agreed to be showcased. They include three pediatric and five adult services located across four distinct ILAE regions (Europe, North America, Africa, Asia Oceania). The report describes the core operations, known outcomes, and implementation factors (i.e., barriers and facilitators) of these services. The report concludes with a set of practical tips for building successful psychological care services within seizure settings, including the importance of having local champions, clearly defining the scope of the service, and establishing sustainable funding models. The breadth of exemplars demonstrates how models tailored to the local environment and resources can be implemented. This report is an initial step to disseminate information regarding integrated mental health care within seizure care settings. Future work is needed to systematically examine both psychological and pharmacological care models and to further establish the evidence base in this area, especially around clinical impact, and cost-effectiveness.

Twenty-Five Years of Epilepsy Surgery at a Central European Comprehensive Epilepsy Center – Trends in Intervention Delay and Outcomes

Abstract found on Wiley Online Library

Objective: We analyzed trends in patients’ characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy.

Methods: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n=95), 2001-2010 (n=295) and 2011-2022 (n=314) based on first evaluation at the center.

Results: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996-2000, 21.3 from 2001-2010, and 21.3 from 2011-2020, p=0. 718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67% – 70% – 52%, p <0.001). Correspondingly, extratemporal resections have become more frequent with significant increase in surgeries for focal cortical dysplasias (2% – 8% – 19%, p <0.001). For resections, better outcomes (ILAE scores 1a-2) have been achieved in extratemporal lesional (0% – 21% – 61%, p=0.01, at least two years follow-up) patients. In temporal lesional patients, outcomes remained unchanged (at least 77% success rate). A longer duration of epilepsy predicted a less favorable outcome for resective procedures (p=0.024) in patients with disease duration of less than 25 years.

Significance: The spectrum of epilepsy surgery is shifting towards non-lesional and extratemporal cases. While success rates of extratemporal resections at our center are getting better, the average duration of epilepsy before surgical intervention is still very long and is not improving. This underscores the need for stronger collaboration between epileptologists and outpatient neurologists to ensure prompt and effective treatment for patients with drug-resistant epilepsy.

Seizure Features and Outcomes in 50 Children with GATOR1 Variants: A Retrospective Study, More Favorable for Epilepsy Surgery

Abstract found on Wiley Online Library

Objectives: To summarize the clinical features of epilepsy related to DEPDC5, NPRL2, and NPRL3 genes encoding the GATOR1 complex in children, and to evaluate the factors affecting the prognosis of these epilepsies.

Methods: In this retrospective study, we reviewed the clinical and genetic characteristics of children with epilepsy related to GATOR1 variants who were admitted to the Peking University First Hospital between January 2016 and December 2021. Potential prognostic factors were assessed by comparing children with and without ongoing seizures.

Results: Fifty probands, including 31 boys and 19 girls were recruited. The median age at onset of epilepsy was 4 months, and 64% of patients had early-onset epilepsy (?1 year). The most frequent epileptic seizure type was focal seizure (86%). Among the 50 patients, only 6 were with de novo variants. According to the novel classification framework for GATOR1 variants, 36 patients were with pathogenic variants and 14 with likely pathogenic variants. DEPDC5 variants were found in 37 patients, NPRL3 in 9, and NPRL2 in 4. The phenotype was similar among the probands, with variants in DEPDC5, NRPL2, or NPRL3 respectively. 76% (38/50) epilepsy related to GATOR1 complex gene variants were neuroimaging positive, including Brain MRI positive in 31 patients, and MRI combined FDG-PET positive in the other 7 patients. Twenty-seven patients underwent epilepsy surgery. In total, after initial anti-seizure medications alone, 92% (46/50) patients were drug-resistant epilepsies, only 8% (4/50) of the probands became seizure-free but seizure-free (?6m) occurred in 92.6% (25/27) of patients with drug-resistant epilepsy after epilepsy surgery at the last follow-up. Patients undergoing epilepsy surgery had better epilepsy prognosis.

Significance: Epilepsy related to GATOR1 complex gene variant had high possibility to be drug-resistant epilepsy and to have positive neuroimaging finding. Epilepsy surgery is the only favorable factor for better seizure prognosis in this kind epilepsy.

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.

CURE Epilepsy Update June 2023

Greetings Epilepsy Community,

Summer is here and brings many things to appreciate and enjoy. The weather is warmer, students are completing their school year, graduation ceremonies are taking place, and many CURE Epilepsy Champions hold their events. These Champions are working on events across the United States, rallying their professional networks, friends, family members, and local businesses to help increase epilepsy awareness and raise money for critical epilepsy research. In honor of CURE Epilepsy’s 25th anniversary, we have created the 2023 Champion Challenge, where we are challenging our existing and new Champions to raise a total of $425,000 this year. We are currently at just over $270,000 (well over halfway to our goal)!

I am honored to lead an organization that has so many dedicated community members who are focused on making our goal of a world without epilepsy a reality. We’ve already seen some creative CURE Epilepsy Champion events this year including a 40-mile bike tour, partnering with a local Massachusetts brewery for a month, the second annual Mansfield Walk to CURE Epilepsy (focused on SUDEP awareness), EpiPalooza (a multi-concert performance focused on epilepsy awareness), and the 10th annual 5K Strides for Epilepsy in Maryland (the longest running CURE Epilepsy Champion event)! Coming up this summer we still have plenty of Champion events including the annual Ella’s Race in Illinois, an EpiPalooza concert in North Carolina, and more. If you are interested in hosting a Champion event of your own, you can learn more about how to do so here.

With a commitment to inspire hope and deliver impact.


In this CURE Epilepsy Update, please find information on:


Watch the Recording of Our Webinar: Mental Health and Childhood Epilepsy

Watch the recording or access the transcript for our latest webinar, Mental Health and Childhood Epilepsy. Epilepsy is not a mental health disorder, but epilepsy or epilepsy medications can impact an individual’s mental health. It is important for medical professionals and caregivers to address these concerns quickly. This webinar with Dr. Clemente Vega covers the prevalence of mental health conditions in children with epilepsy, risk factors, resources, and more.

 

Watch

 


Epilepsy Awareness Night at Chicago White Sox Game

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

 

Tickets

 


New Epilepsy Surgery Resource

Surgery may help cure or significantly reduce the incidence of seizures. To help individuals learn about surgical options and what epilepsies they work for best, CURE Epilepsy has created the Epilepsy Surgery section of our Understanding Epilepsy resource.

 

Explore Resource

 

 


CURE Epilepsy CARES Comes to Seattle

CURE Epilepsy CARES (Conversations About Research in Epilepsy & Seizures) is a free, educational event for patients, families, medical professionals, researchers, and all those touched by or interested in learning more about epilepsy. Join us in Seattle on Saturday, June 10 as clinicians answer your questions about cutting-edge research and epilepsy treatments.

 

Register

 


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.

 

Register

 


CURE Epilepsy Discovery: Strides Made in the Understanding of Acquired Epilepsies by CURE Epilepsy Grantees

 

An acquired epilepsy can occur as a result of brain infection, tumor, or injury leading to spontaneous seizures. CURE Epilepsy grantees, Dr. Annamaria Vezzani and Dr. Teresa Ravizza, study neuroinflammation and the underlying mechanisms that may contribute to epileptogenesis. Their work is instrumental not only to understanding why and how the brain generates and sustains seizures, but also to discovering biomarkers that could predict if someone will have seizures. The ultimate hope is that the work of Drs. Vezzani and Ravizza will lead to the ability to prevent or cure acquired epilepsies.

Explore Discovery


 

What’s New from the Seizing Life® Podcast

A Daughter’s Diagnosis Inspires Concerts for Epilepsy

 

Matt Perrone shares his epilepsy onset and treatment journey, the impacts of seizures and medication on his mental health, and how his daughter’s diagnosis at the age of four spurred him to create EpiPalooza, a multi-band concert aimed at raising awareness and funds for epilepsy research.

Watch or Listen

 

 

Epilepsy Researcher Compounds Lab Work with Fundraising

 

Dr. Patrice Jackson-Ayotunde, an organic chemist and Associate Professor of Pharmaceutical Sciences at the University of Maryland Eastern Shore (UMES), explains why bringing new epilepsy drugs to market can take 15 to 20 years and tells us about the UMES 5K Strides for Epilepsy fundraiser that she and her students have been running for the past 10 years.

Watch or Listen

 

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


The CURE Epilepsy Store

 

Start summer off right with apparel or accessories to spread epilepsy awareness and help support funding research to find a cure!

 

Shop

 


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