Highly Purified Cannabidiol Improves Stability and Postural Tone in Adult Patients with Lennox-Gastaut Syndrome: a Case Series

Abstract found on PubMed

Lennox-Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy associated with numerous neurological signs and symptoms. Altered postural tone and the need for a caregiver-assisted wheelchair are features characterizing patients with LGS. Highly purified cannabidiol (CBD) is a novel antiseizure medication recommended for seizure treatment, in combination with clobazam, in patients with LGS. Adding CBD to the previous antiseizure medication treatment helps reduce seizure frequency, specifically drop seizures, in patients with LGS in both clinical trials and real-world studies. However, no data about drug effects on postural tone, motor activity, gait and stability are available. In this case series, three adult patients diagnosed with LGS were treated with CBD as an add-on. During the follow-up, a slight improvement in seizure frequency was observed. Unexpectedly, an amelioration in postural tone and stability, measured using the validated Gross Motor Function Classification System, was also detected. Our case series suggests that CBD may help manage patients with LGS regarding seizure control and improve other aspects of the clinical spectrum of the disease, such as postural tone and stability. The mechanisms at the basis of this improvement may be related, other than seizure reduction, to the drug’s effect on the brain locomotor centers, as demonstrated in animal model studies.

Health-Related Quality of Life in Adults with Drug-Resistant Focal Epilepsy Treated with Modified Atkins Diet in a Randomized Clinical Trial

Abstract found on PubMed

Ketogenic diet, a high-fat, low-carbohydrate diet, is an established treatment for patients with severe epilepsy. We have previously reported a moderate reduction in seizure frequency after treatment with a modified Atkins diet. This study aimed to see whether dietary therapy impacts the patients’ health-related quality of life (HRQOL). In a randomized controlled design, we compared the change in self-reported HRQOL among adults with difficult-to-treat epilepsy after a 12-week diet intervention. Thirty-nine patients with drug-resistant focal epilepsy (age 16 – 65 years) were randomized to eat a modified Atkins diet with maximum 16 grams of carbohydrate per day (diet group, n=19) or to continue eating habitual diet (control group, n=20). No changes to the other epilepsy treatments were allowed. Patient reported HRQOL was assessed with the Quality of Life in Epilepsy Inventory-89 (QOLIE-89). The diet group experienced a statistically significant improvement in mean total score of QOLIE-89 of 10 points compared to controls (p=0.002). Moreover, although not statistically significant when using a cut-off of 50% seizure reduction, our data suggest an association between diet-induced reduction in seizure frequency and improvement of HRQOL. The improvement in HRQOL was not associated with diet-induced weight reduction.

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy

Abstract found on Jama Network

Importance: Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.

Objective: To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.

Data Sources: Systematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.

Study Selection: Randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.

Conclusions and Relevance: This study found that all dietary therapies are effective in the short term. However, the modified Atkins diet had better tolerability, a higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than the ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

Caregiver Burden and COVID-19: How Epilepsy Caregivers Experienced the Pandemic

Abstract found on PubMed

Introduction: Caregivers of adults with epilepsy face unique challenges, yet most studies focus on the impact of epilepsy on those living with the condition, rather than the impact on caregivers. Our objective was to evaluate whether caregivers’ pandemic-related changes and experiences – namely those related to their health, healthcare access, and well-being – were associated with their caregiving burden.

Methods: Caregivers of adults with epilepsy (n = 261) were recruited through Qualtrics Panels to participate in an online survey examining health, well-being, COVID-19 experiences, and caregiver burden from October-December, 2020. The burden was measured using the Zarit 12-item measure; the clinically significant burden was defined as a score greater than 16. Adjustments were made to account for burden scores related to exposures of interest. Chi-square tests, t-tests, and generalized linear regression models were used to compare cross-sectional associations between COVID-19 experiences and burden.

Results: Over half (57.9%) of caregivers had clinically significant caregiver burden. Most reported increased anxiety (65%), stress (64%), and sense of social isolation (58%) during the pandemic. Many caregivers reported that their sense of control over their life (44%) and their use of healthcare changed (88%) due to COVID-19. In adjusted models, caregivers who reported increased anger, increased anxiety, decreased sense of control, or changes in healthcare utilization during COVID-19 had about twice the odds of having clinically significant caregiver burden compared to caregivers who did not report changes.

Discussion: Changes experienced by caregivers of adults with epilepsy during the pandemic were strongly associated with clinically significant levels of caregiver burden. These findings demonstrate the link between mass-level events, such as a pandemic, the burden caregivers of adults with epilepsy may carry, and subsequent psychological outcomes.

Conclusion: Caregivers of adults with epilepsy may need support to reduce the negative impact of COVID-19-related experiences and should be connected to healthcare and resources that can help alleviate their burden.

CURE Epilepsy Update March 2023

Greetings Epilepsy Community,

As CURE Epilepsy continues to celebrate our 25^th anniversary, I’m reminded again of how far we have come as a community, how we have advanced our understanding of the brain, and how much closer we are to cures. This anniversary has given us a wonderful opportunity to look back on our accomplishments over the years and share with you the impact that your support and donations have made. We will continue to share stories of impact with you in our monthly Discovery emails, in our webinars, and on social media.

If you will indulge me for a moment, I would like to call out the amazing team at CURE Epilepsy that drives this impact on behalf of our community to get us to a world without seizures. By the time you read this, Employee Appreciation Day on March 3^rd will have passed, but I have the privilege of working with the most amazing, dedicated team of scientists, fundraisers, communications professionals, and support staff that any leader could ask for. The CURE Epilepsy staff is deeply committed to driving our mission, ensuring that we steward every dollar donated by the community. For those of you who have had the opportunity to interact with these wonderful people, I hope that you share my sentiment.

And if you haven’t had a chance to meet the team, we hope to see you at CURE Epilepsy or community events throughout the year, whether that be at our 25^th Anniversary Gala in Chicago this May, at the Purple Day® Expo in Florida later this month, or at one of the many CURE Epilepsy champion events held in your communities

With a commitment to inspire hope and deliver impact.

In this CURE Epilepsy Update, please find information on:

Tickets Now Available for our 25th Anniversary Gala in Chicago

Get your tickets today for our 25th Anniversary Gala in Chicago to be held on Saturday, May 6 at the Sheraton Grand Chicago Riverwalk. Join us in celebrating 25 years of inspiring hope and delivering impact and help us raise money to continue funding innovative epilepsy research.

Get Tickets

Take Our Important Community Survey Before it Closes

As we celebrate our 25th anniversary this year, we are looking ahead to continued progress in finding cures for epilepsy. To make sure we are meeting your needs at this organizational milestone, we are conducting a community survey to inform our 5-year strategic planning process. We want to better understand your interests and needs, our organizational strengths and weaknesses, and how we can better serve and communicate with the broader epilepsy community.

The deadline to submit your feedback is today at 11:59pm CST. We appreciate you sharing your thoughts and helping ensure that CURE Epilepsy incorporates feedback from individuals living with epilepsy, their loved ones, caregivers, epilepsy researchers, and clinicians in the community. If you have any difficulties accessing or completing the survey, please email dana.vielmetti@cureepilepsy.org.

Take Survey Now

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

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. In this latest CURE Epilepsy Discovery, we highlight Brian Litt at the University of Pennsylvania who was funded by CURE Epilepsy in 2011, and whose work has led to the development of electrodes and technology that offer incredible precision in recording from and stimulating neurons.

Read Discovery

Paws for a Cause Awareness Event

Join Miami University’s PAWS for a Cause student organization for a hybrid (live + virtual), educational event featuring people living with epilepsy and family members sharing their experiences with service dogs. CURE Epilepsy’s CEO, Beth Lewin Dean, will also speak briefly about epilepsy and our organization.

Learn More

Watch Our Webinar: Cutting-Edge Technologies for Treating Nano-Rare Epilepsies

Did you miss our January webinar? Don’t worry, you can now watch the recording or read the transcript on our website! This webinar discusses the use of individualized antisense oligonucleotide (ASO) treatments for patients with nano-rare epilepsies. ASOs are short strands of modified deoxyribonucleic acids (DNA) that can be developed rapidly and inexpensively and can specifically target and potentially halt the development of disease-causing proteins, thus attempting to change the course of the disease.

Watch

Our next webinar will take place on Wednesday, March 29 at 2 pm ET and will review the basics of cannabis biology and the differences between cannabis strains, as well as explain the medical uses of medical marijuana and the recent approval of CBD to treat specific types of epilepsy. Thank you to Jazz Pharmaceuticals for their generous support of this webinar. Stay tuned for more information.

Register

Fox 11 Los Angeles Speaks with CURE Epilepsy’s Chief Scientific Officer, Dr. Laura Lubbers

CURE Epilepsy’s Chief Scientific Officer, Dr. Laura Lubbers, spoke with Fox 11 Los Angeles last week on their segment aimed at raising awareness of epilepsy, Sudden Unexpected Death in Epilepsy (SUDEP), and infantile spasms. Additional guests on the segment include CURE Epilepsy community member Francesca Calloway, mother of a child with epilepsy, and an Associate Clinical Professor of Pediatrics at UCLA, Dr. Shaun Hussain.

Watch

Visit CURE Epilepsy at the 4th Annual Purple Day® for Epilepsy Awareness Around the World Expo

The Purple Day® for Epilepsy Awareness Around the World Expo is taking place Saturday, March 25, 2023, from 8:15 am-5 pm ET at Disney’s Contemporary Resort in Florida. Programming is specifically designed for patients and caregivers living with epilepsy as a shared opportunity to meet, engage, and be inspired to increase epilepsy awareness in their own community. In addition, patients and caregivers can explore the expo and learn more about the services and support available to them. CURE Epilepsy will present the Purple Day® Talk session “CURE Epilepsy’s Research & Response to the Rare Epilepsy Community” during the expo. Be sure to stop by our booth and say hi!

Learn More

Mind Your Brain Conference at Penn Medicine

Register today for The Mind Your Brain conference (which can be attended in person or virtually). This conference is focused on Traumatic Brain Injury (TBI) survivors, families and friends and is designed to share research, insights, therapies and other useful information with attendees, and also provide a forum for attendees to interact and connect with others affected by a brain injury.

Register

What’s New from the Seizing Life® Podcast

After Decades of Seizures, an Epilepsy Diagnosis Begins to Provide Answers

Carmen Zannier shares her 35-year epilepsy journey, discusses her recent decision to go public with her diagnosis, and explains how her passion for mountain climbing has led her to raising funds for epilepsy research.

Watch or Listen

Epilepsy Can’t Stop Young Girl’s Competitive Spirit

When it became clear that Christiane needed special attention and considerations in her training program, her father decided to become her coach. Despite experiencing seizures before races, Christiane has continued to compete at the highest level, making it to the final round of the 2021 Junior Olympics in the 100-meter dash. Even as they struggle to control Christiane’s seizures, her parents continue to support and encourage Christiane’s passion for running, and Christiane’s competitive spirit remains intact as she looks forward to the next Junior Olympic trials.

Watch or Listen

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

The CURE Epilepsy Store

Need apparel or accessories to raise epilepsy awareness? Check out the CURE Epilepsy Store!

Shop

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

January 1 – December 31, 2023 – CURE Epilepsy’s 25^th Anniversary
March 25 – Purple Day® Expo at Disney World
March 26 – Purple Day®
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 Michael’s Story

Life After SUDEP: Experiences of Traumatic Loss and Growth

Abstract found on PubMed

Purpose: To understand the experiences of bereaved relatives of individuals who passed due to sudden unexpected death in epilepsy (SUDEP) and to explore the impacts of death in their lives.

Methods: The principles of fundamental qualitative description informed all design decisions. Stratified purposeful sampling included 21 bereaved relatives (parent, sibling, or spouse/partner), aged at least 18 years, of persons who passed away because of SUDEP. In-depth one-to-one interviews were conducted. Directed content analysis was used to code, categorize, and synthesize the interview data.

Results: There was some criticism of emergency response and medical professionals involved in providing insensitive or poor care immediately after SUDEP occurred. Personal hardships described by participants following SUDEP included loss of personal identity, feeling depressed, experiencing guilt, having panic attacks, requiring therapy, as well as having difficulty with anniversaries, dates, and cleaning up a child’s room. Bereaved spouses and parents in particular spoke of experiencing challenges in maintaining other relationships following the death. Some participants spoke of experiencing increased financial hardships. Ways of coping included keeping oneself busy, honoring the memory of the loved one, relying on friends and families, and engaging in advocacy/community work, including raising awareness on epilepsy and SUDEP.

Conclusions: Sudden unexpected death in epilepsy affected several aspects of the day-to-day lives of bereaved relatives. Though methods of coping were similar to the usual strategies adopted by all bereaved relatives, advocacy work related to raising awareness about epilepsy and SUDEP was unique to this group. Guidelines on SUDEP should ideally include recommendations for trauma-informed support and assessment for depression and anxiety to the bereaved relatives as well.

Epilepsy Diagnosis Using a Clinical Decision Tool and Artificially Intelligent Electroencephalography

Abstract found on PubMed

Objective: To construct a tool for non-experts to calculate the probability of epilepsy based on easily obtained clinical information combined with an artificial intelligence readout of the electroencephalogram (AI-EEG).

Materials and methods: We performed a chart review of 205 consecutive patients aged 18 years or older who underwent routine EEG. We created a point system to calculate the pre-EEG probability of epilepsy in a pilot study cohort. We also computed a post-test probability based on AI-EEG results.

Results: One hundred and four (50.7%) patients were female, the mean age was 46 years, and 110 (53.7%) were diagnosed with epilepsy. Findings favoring epilepsy included developmental delay (12.6% vs 1.1%), prior neurological injury (51.4% vs 30.9%), childhood febrile seizures (4.6% vs 0.0%), postictal confusion (43.6% vs 20.0%), and witnessed convulsions (63.6% vs 21.1%); findings favoring alternative diagnoses were lightheadedness (3.6% vs 15.8%) or onset after prolonged sitting or standing (0.9% vs 7.4%). The final point system included 6 predictors: Presyncope (-3 points), cardiac history (-1), convulsion or forced head turn (+3), neurological disease history (+2), multiple prior spells (+1), postictal confusion (+2). Total scores of ?1 point predicted <5% probability of epilepsy, while cumulative scores ?7 predicted >95%. The model showed excellent discrimination (AUROC: 0.86). A positive AI-EEG substantially increases the probability of epilepsy. The impact is greatest when the pre-EEG probability is near 30%.

Significance: A decision tool using a small number of historical clinical features accurately predicts the probability of epilepsy. In indeterminate cases, AI-assisted EEG helps resolve uncertainty. This tool holds promise for use by healthcare workers without specialty epilepsy training if validated in an independent cohort.

Sense of Control, Selective Attention, Cognitive Inhibition, and Psychosocial Outcomes after Retraining and Control Therapy (ReACT) in Pediatric Functional Seizures

Abstract found on PubMed

Background: Differences in sense of control, cognitive inhibition, and selective attention in pediatric functional seizures (FS) versus matched controls implicate these as potential novel treatment targets. Retraining and Control Therapy (ReACT), which targets these factors, has been shown in a randomized controlled trial to be effective in improving pediatric FS with 82% of patients having complete symptom remission at 60 days following treatment. However, post-intervention data on sense of control, cognitive inhibition, and selective attention are not yet available. In this study, we assess changes in these and other psychosocial factors after ReACT.

Methods: Children with FS (N = 14, M_age = 15.00, 64.3% female, 64.3% White) completed 8 weeks of ReACT and reported FS frequency at pre and post-1 (7 days before and after ReACT). At pre, post-1, and post-2 (60 days after ReACT), all 14 children completed the Pediatric Quality of Life Inventory Generic Core Scales, Behavior Assessment System (BASC2), and Children’s Somatic Symptoms Inventory-24 (CSSI-24), and 8 children completed a modified Stroop task with seizure symptoms condition in which participants are presented with a word and respond to the ink color (e.g., “unconscious” in red) to assess selective attention and cognitive inhibition.

Results: Awareness that control was manipulated in the turbulence condition of the MAT increased at post-1 vs. pre- (p = 0.02, ?² = 0.57). This change correlated with a reduction in FS frequency after ReACT (r = 0.84, p < 0.01). Reaction time significantly improved for the seizure symptoms Stroop condition at post-2 compared to pre- (p = 0.02, ?² = 0.50), while the congruent and incongruent conditions were not different across time points. Quality of life was significantly improved at post-2, but the improvement was not significant when controlling for change in FS. Somatic symptom measures were significantly lower at post-2 vs. pre (BASC2: t(12) = 2.25, p = 0.04; CSSI-24: t(11) = 4.17, p < 0.01). No differences were observed regarding mood.

Conclusion: Sense of control improved after retraining and control therapy (ReACT), and this improvement was proportional to a decrease in functional seizures (FS), suggesting this as a possible mechanism by which ReACT treats pediatric FS. Selective attention and cognitive inhibition were significantly increased 60 days after ReACT. The lack of improvement in QOL after controlling for change in FS suggests QOL changes may be mediated by decreases in FS. ReACT also improved general somatic symptoms independent of FS changes.

Peri-Ictal Headache: An Underestimated Prognostic Finding Associated with Idiopathic Epilepsies

Abstract found on PubMed

Objective: There are a handful of studies investigating peri-ictal headache (PIH) and its clinical associations in patients with idiopathic/genetic epilepsies (I/GE). This multi-center study aimed to investigate PIH, which is an ignored comorbid condition in patients with I/GE, by headache experts and epileptologists working together.

Methods: The data were collected from a cross-sectional large study, using two structured questionnaires for headache and epilepsy features, fulfilled by neurologists. Headaches were classified according to the International Classification of Headache Disorders, third edition, whereas seizure and syndrome types were diagnosed according to International League Against Epilepsy criteria. The patients with a headache starting 24 hours before the onset of the seizure (preictal) or within 3 hours after the seizure (postictal) were defined as patients with PIH. We compared demographic and clinical differences between two groups of patients with and without PIH statistically and used ROC curves to determine a threshold of the total number of seizure triggers associated with the occurrence of PIH.

Results: Among 809 (531 females, 65.6%) consecutive patients with I/GE, 105 (13%) patients reported PIH (22 preictal, 82 postictal headaches, and one with both types). Peri-ictal headache was more frequently reported by females and those having a family history of migraine or epilepsy, and it was significantly associated with lower rates of seizure freedom for more than five years, drug resistance, and use of polytherapy, remarkably. Moreover, ROC curves showed that having more than 3 seizure triggers was associated with the presence of PIH.

Conclusion: Our findings revealed that PIH may be linked to poor outcomes in I/GEs and seems to be related to a lower ictal threshold precipitated by multiple triggers. Future prospective studies will illuminate the unknown underlying mechanisms and appropriate management strategies for PIH to improve the prognosis.

A Pharmacokinetic Model of Anti-Seizure Medication Load to Guide Care in the Epilepsy Monitoring Unit

Abstract found on PubMed

Objective: Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering anti-seizure medications (ASMs) in the Epilepsy Monitoring Unit (EMU). The relationship between ASM taper strategy, seizure timing and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU.

Methods: We studied 80 patients who underwent intracranial EEG recording for epilepsy surgery planning. We developed a first-order pharmacokinetic model of the ASMs administered in the EMU to generate a continuous metric of overall ASM load. We then related modeled ASM load to seizure likelihood and severity. We determined the association between the rate of ASM load reduction, the length of hospital stay and the probability of having a severe seizure. Finally, we used modeled ASM load to predict oncoming seizures.

Results: Seizures occurred in the bottom 50^th -percentile of sampled ASM loads across the cohort (p < 0.0001, Wilcoxon sign-rank test), and seizures requiring rescue therapy occurred at lower ASM loads than seizures that did not require rescue therapy (logistic regression mixed effects model, odds ratio = 0.27, p = 0.01). Greater ASM decrease early in the EMU was not associated with an increased likelihood of having a severe seizure, nor with a shorter length of stay.

Significance: A pharmacokinetic model can accurately estimate anti-seizure medication (ASM) levels for patients in the EMU. Lower modeled ASM levels are associated with increased seizure likelihood and seizure severity. We show that ASM load, rather than ASM taper speed, is associated with severe seizures. ASM modeling has the potential to help optimize taper strategy to minimize severe seizures while maximizing diagnostic yield.