Astrocytes Might Be a Potential New Target to Better Treat Epilepsy

Summary, originally published in News Medical

A significant number of epilepsy patients does not respond to currently available drugs. A collaboration between researchers in Japan and at the Heinrich Heine University Düsseldorf (HHU) now addressed a cell type in the brain that has so far not received much attention in epilepsy therapy. In the current edition of the Journal of Neuroscience, they describe that astrocytes might be a potential new target to better treat this disease.

Together with colleagues in Japan, Prof. Dr. Christine Rose and her doctoral student Jan Meyer from the Institute of Neurobiology at HHU have performed a study to address the cellular mechanisms that promote the development of epilepsy. While up to now, most studies and anti-epileptic drugs targeted nerve cells (neurons), this research team focused on a class of glial cells known as astrocytes.

In their recent paper, the researchers show that epileptic discharges lead to a rise in the pH of astrocytes, that is in their intracellular ‘alkalization’. The change in pH disrupts the communication within the intercellular astrocyte networks. This reduced communication between astrocytes appears to exacerbate epileptic activity of neurons.

This finding points towards a potential new target for suppressing epileptogenesis at a very early stage, namely by using drugs to suppress changes in astrocytic pH accompanying neuronal activity.

Seizure Detection Devices: Exploring Caregivers’ Needs and Wishes

Abstract, originally published in Epilepsy & Behavior

Introduction: User preferences for seizure detection devices (SDDs) have been previously assessed using surveys and interviews, but these have not addressed the latent needs and wishes. Context mapping is an approach in which designers explore users’ dreams and fears to anticipate potential future experiences and optimize the product design.

Methods: A generative group session was held using the context mapping approach. Two types of nocturnal SDD users were included: three professional caregivers at a residential care facility and two informal caregivers of children with refractory epilepsy and learning disabilities. Participants were invited to share their personal SDD experiences and briefed to make their needs and wishes explicit. The audiotaped session was transcribed and analyzed together with the collected material using inductive content analysis. The qualitative data was classified by coding the content, grouping codes into categories and themes, and combining those into general statements (abstraction).

Results: “Trust” emerged as the most important theme, entangling various emotional and practical factors that influence caregiver’s trust in a device. Caregivers expressed several factors that could help to gain their trust in an SDD, including integration of different modalities, insight on all parameters overnight, personal adjustment of the algorithm, recommendation by a neurologist, and a set-up period. Needs regarding alerting seemed to differ between the two types of caregivers in our study: professional caregivers preferred to be alerted only for potentially dangerous seizures, whereas informal caregivers emphasized the urge to be alerted for every event, thus indicating the need for personal adjustment of SDD settings.

Conclusion: In this explorative study, we identified several key elements for nocturnal seizure detection devices implementation including the importance of gaining trust and the possibility to adjust seizure detection devices settings for different types of caregivers.

Epilepsy Research News: January 2021

This month’s research news includes announcements about CURE Epilepsy’s Frontiers in Research seminar series, and an announcement from the CDC about an incidence and etiology funding opportunity.

We also share that the NINDS Clinical Trials Methodology Course is accepting applications, and that the deadline to apply to the National Science Foundation Enabling Discovery Through Genomics (EDGE) Program is March 16.

These news items are summarized below.

Research Highlights

CURE Epilepsy’s Frontiers in Research Seminar Series has gone virtual!

As part of our on-going commitment to supporting the research community through these difficult times, we are conducting our research seminar series virtually with the topics below. Mark your calendars!

The virtual Frontiers in Research Seminar Series is sponsored by the Nussenbaum-Vogelstein Family.

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CDC Epilepsy Incidence and Etiology Funding Opportunity Announcement
Projects are intended to inform incidence and social determinants of epilepsy including risk factors and protective factors that affect epilepsy incidence. Information about epilepsy incidence will provide invaluable information to help better guide interventions or services for preventing epilepsy, treating and rehabilitating people with epilepsy, and minimizing their health disparities and adverse outcomes.

Click here for details. Search opportunity number by RFA-DP-21-004 and SIP 21-007.

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NINDS Clinical Trials Methodology Course-Application Deadline February 28
The NINDS Clinical Trials Methodology Course (CTMC) is accepting applications for the 2021 cohort. The overarching goal of the CTMC is to help investigators develop scientifically rigorous, yet practical clinical trial protocols. The focus is on investigators who have not previously designed their own prospective, interventional clinical trials.

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National Science Foundation Enabling Discovery Through Genomics (EDGE) Program-Application Deadline March 16
The goal of the EDGE program is to provide support for genomic research and associated theory, approaches, tools, and infrastructure development to address the mechanistic basis of complex traits in diverse organisms within the context (environmental, developmental, social, and/or genomic) in which they function.

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First-Ever Attempt to Treat Naturally Occurring Epilepsy in an Animal Using Transplanted Cells

Abstract, originally published by University of California San Francisco

A cellular therapy for epilepsy developed at UC San Francisco has been employed for the first time in a sea lion with intractable seizures caused by ingesting toxins from algal blooms. The procedure is the first-ever attempt to treat naturally occurring epilepsy in any animal using transplanted cells.

Since 2009, the lab of former CURE Epilepsy Grantee Dr. Scott Baraban has been developing a way to replace these damaged interneurons by transplanting embryonic MGE (medial ganglionic eminence) progenitor cells into the hippocampus. As discovered two decades ago by Baraban’s UCSF colleagues Arturo Álvarez-Buylla, PhD, and John Rubenstein, PhD, MGE cells normally migrate into hippocampus during brain development and integrate themselves into the local circuitry as inhibitory neurons.

Baraban’s group has shown that it’s possible to transplant embryonic MGE cells into the brains of adult rodents with temporal lobe epilepsy, where they quickly spread through the hippocampus and repair its damaged circuitry. The procedure reliably reduces seizures in these animals by 90 percent, along with other side effects of epilepsy, such as anxiety and memory problems.

Epilepsy Research News: December 2020

This month’s research news includes announcements about the Curing the Epilepsies 2021 Conference, and a reminder about the Cure Epilepsy and Taking Flight grant letters of intent (LOIs).

We also share that the Health Disparities Research Institute will be accepting applications, and that the TESS Research Foundation is hiring.

These news items are summarized below.

Research Highlights

Curing the Epilepsies 2021 Conference–January 4-6, 2021

Please join the epilepsy community from around the world to discuss the progress made in understanding the biological mechanisms underlying the epilepsies, and the inroads being made towards potential cures.

The main outcome and priority of the meeting will be to identify transformative research priorities that will accelerate development of cures and improve outcomes for people with epilepsy. The meeting takes place from January 4-6, 2021. It will be open to the public and freely available via livestream.

Learn more

Understanding & Treating Temporal Lobe Epilepsy
A team of researchers has found that an amino acid produced by the brain could play a crucial role in preventing cell loss and seizures associated with temporal lobe epilepsy. Utilizing an animal model of temporal lobe epilepsy, the research team found that administration of the amino acid D-serine prevented cell loss characteristic of temporal lobe epilepsy and reduced the number and severity of seizures.

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CURE Epilepsy and Taking Flight Grant Timeline–Letter of Intent (LOI) due January 11, 2021 9 PM EST
Reminder, CURE Epilepsy is accepting LOIs for both the CURE Epilepsy and Taking Flight grant awards now through Monday, January 11, 2021 at 9 PM ET. Don’t miss your opportunity to be considered!

  • CURE Epilepsy Award, $250,000 over two years: This award reflects CURE Epilepsy’s continued focus on scientific advances that have potential to truly transform the lives of those affected by epilepsy.
  • Taking Flight Award, $100,000 for one year: This award seeks to promote the careers of young epilepsy investigators, allowing them to develop a research focus independent of their mentors.
  • Research areas: Sudden unexpected death in epilepsy (SUDEP), acquired epilepsy, treatment-resistant epilepsy, pediatric epilepsy, and sleep and epilepsy

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2021 Health Disparities Research Institute–Accepting Applications February 1-March 8, 2021The next Health Disparities Research Institute–featuring lectures on minority health and health disparities research, mock grant review, seminars and more–will be held virtually August 9-13, 2021.

The program’s intent is to support early-career minority health/health disparities research scientists and stimulate research in the disciplines supported by health disparities science. Admission to this program is by application only. The application cycle is open February 1-March 8, 2021.

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Job Opportunity: Research Program Manager Position with TESS Research Foundation
Looking for an opportunity to make a difference in the area of rare epilepsies? The TESS Research Foundation is seeking a Research Program Manager to oversee all scientific research focused on SLC13A5 Epilepsy, including research coordination, grant program oversight, community outreach, and scientific communication and cultivation.

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Epilepsy Research News: December 2020

In this month’s news, we spotlight a publication describing CURE Epilepsy’s Infantile Spasms (IS) Initiativea collaborative research program that brought a team science approach to understanding the causes and potential treatments for IS. Running from 2013-2016, this program led to numerous advances in understanding the pathways in the brain involved in IS. 

Also, this month we feature news from the EPISTOP study showing that preventative treatment with the drug vigabatrin decreased the number of days with seizures as well as the severity of epilepsy in infants with tuberous sclerosis complexWe also highlight recent work from CURE Epilepsy Grantee Dr. Jeffrey Loeb, whose team identified a protein found in healthy brain tissue that may work to prevent the spread of seizures. 

These studies and more are summarized below. 

Research Highlights

Infantile Spasms
This recent publication highlights CURE Epilepsy’s Infantile Spasms (IS) Initiative, established in 2013 to support collaborative, team science-based and milestone-driven effort to advance the understanding of causes of and potential treatments for IS. The combined efforts of the research team led to numerous advances in understanding the causes of IS. It also brought together a diverse group of investigators–who otherwise would not have collaborated–to study therapies for IS.

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Preventing the Spread of Seizures
New research may explain what prevents seizures in certain areas of the brain from spreading to other areas of the brain. In a study funded by the National Institutes of Health/American Epilepsy Society, CURE Epilepsy Grantee Dr. Jeffrey Loeb and his colleagues found that a protein called DUSP4 was increased in healthy brain tissue directly next to epileptic brain tissue. The research suggests that DUSP4 may work to prevent the spread of epilepsy in the brain and that boosting levels of DUSP4 could be a novel way of preventing or treating epilepsy.

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Tuberous Sclerosis Complex Treatment
Preventive treatment with vigabatrin effectively decreased the risk and severity of epilepsy in infants with tuberous sclerosis complex who were enrolled in the EPISTOP multi-center study. Vigabatrin resulted in a significantly longer time to first clinical seizure compared with conventional treatment as well as a lower proportion of days with seizures until age 2, according to the study findings. The EPISTOP study has shown that it may be possible to change the natural history of severe infantile epilepsy through early intervention with antiepileptic therapy,” the researchers wrote.

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Epilepsy and Dementia
Late-onset epilepsy has been linked to a substantially increased risk of subsequent dementia. Results of a retrospective analysis show that patients who develop epilepsy at age 67 or older have a threefold increased risk of subsequent dementia versus their counterparts without epilepsy. “We are finding that just as the risk of seizures is increased in neurodegenerative diseases, the risk of dementia is increased after late-onset epilepsy and seizures,” study investigator Emily L. Johnson, MD, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview. “Several other on-going studies are finding similar results,” she added.

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Epilepsy Treatment Expansion Approval
The FDA expanded its approval of lacosamide, marketed as Vimpat, to include add-on therapy for primary generalized tonic-clonic seizures as well as an IV formulation for patients aged 4 years and older.

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Free App Helps With Optimal Choice of Antiseizure Medication

Abstract, originally published in Epilepsia

Objective: Optimal choice of antiseizure medication (ASM) depends on seizure type, syndrome, age, gender, comorbidities and co-medications. There are no fixed rules on how to weigh these factors; choices are subjective and experience-driven. We investigated agreement among experts in selecting ASM as monotherapy and used their prevailing choices to validate a web-based decision-support application.

Methods: Twenty-four international experts, blinded to the app, selected the optimal ASM for 25 individual patient?cases covering a wide variation of seizure types and other factors influencing ASM selection. The app ranked ASMs in order of likely appropriateness for each case. In a second step, experts rated anonymously the choices of the app.

Results: Of the 25 patient-cases (age 13-74 years), 13 were female, 18 (72%) had comorbidities, six (24%) were on contraceptives, and 13 (52%) had other co-medications. The median number of experts who selected the same ASM for a given case was 15 (62.5%) and interquartile range (IQR) 13-18 (54%-75%). Gwet’s agreement coefficient among experts was 0.38 (95% confidence interval [CI] 0.32-0.44), corresponding to a “fair” agreement. Agreement between the app and the prevailing expert choice for each case was 0.48 (95% CI 0.29?0.67), corresponding to a “moderate” beyond chance agreement. The percent agreement between the highest ranked selections of the app and the expert selections was 73% (95% CI 64%-82%). Ninety-five percent of the experts considered that no incorrect or potentially harmful ASMs were ranked highest by the app, and most experts strongly agreed with the app’s selections.

Significance: This app, now validated by experts, provides an objective, reproducible method for selecting antiseizure medication that accounts for relevant clinical features. It is freely available at:

Would people living with epilepsy benefit from palliative care?

Abstract, originally published in Epilepsy & Behavior

Palliative care (PC) is an approach to the care of persons living with serious illness and their families that focuses on improving quality of life and reducing suffering by addressing complex medical symptoms, psychosocial needs, spiritual well-being, and advance care planning. While PC has traditionally been associated with hospice care for persons with cancer, there is now recognition that PC is relevant to many noncancer diagnoses, including neurologic illness, and at multiple points along the illness journey, not just end of life.

Despite the recent growth of the field of neuropalliative care there has been scant attention paid to the relevance of PC principles in epilepsy or the potential for PC approaches to improve outcomes for persons living with epilepsy and their families. We believe this has been a significant oversight and that PC may provide a useful framework for addressing the many sources of suffering facing persons living with epilepsy, for engaging patients and families in challenging conversations, and to focus efforts to improve models of care for this population.

In this manuscript we review areas of significant unmet needs where a PC approach may improve patient and family-centered outcomes, including complex symptom management, goals of care, advance care planning, psychosocial support for patient and family and spiritual well-being. When relevant we highlight areas where epilepsy patients may have unique PC needs compared to other patient populations and conclude with suggestions for future research, clinical, and educational efforts.

Affordability, availability and tolerability of anti-seizure medications are better predictors of adherence than beliefs: Changing paradigms from a low resource setting

Abstract, originally published in Seizure

Objectives: Anti-seizure medication (ASM) non-adherence contributes to treatment gap and increases mortality and morbidity associated with epilepsy. Beliefs about medications are considered better predictors of ASM non-adherence than clinico-demographic factors. We aimed to look into ASM non-adherence rates among adults with epilepsy (AWE), identify the contributing barriers and determine whether medication beliefs were more powerful predictors than clinico-demographic factors.

Methods: This was a cross-sectional study of AWE receiving ASMs. Participants (n = 304) were assessed by validated questionnaires, for non-adherence (8-item Morisky Medication Adherence Scale) and perceptions of ASMs (Beliefs about Medicines Questionnaire) along with clinico-demographic details.

Results: Our group with high literacy and low-income had a high non-adherence rate (55 %) despite having positive beliefs (Mean necessity-concern differential [NCD] = 2.86). Among the beliefs, ASM non-adherence was significantly associated with ASM-concern (t = 4.23, p < 0.001) and NCD (t = -4.11, p < 0.001). Stepwise multiple linear regression analysis showed that non-adherence was significantly associated with per-capita income (? -0.215, p < 0.001), ASM side effects (? 0.177, p = 0.001), high seizure frequency (? 0.167, p = 0.002), ASM availability (? -0.151, p = 0.004), ASM costs (? -0.134, p = 0.013 and NCD (? -0.184, p = 0.001). NCD accounted for 2.9 % of the variance in non-adherence whereas the other clinico-demographic variables together accounted for 14.6 %.

Conclusion: We describe a paradigm shift in adults with epilepsy with high non-adherence to anti-seizure medications, wherein clinico-demographic variables emerge as better predictors of non-adherence than beliefs. High literacy facilitates the perception of need for anti-seizure medications whereas costs and side effects hamper adherence.

Effects of valproate (Depakote), lamotrigine (Lamictal), and levetiracetam (Keppra) monotherapy on bone health in newly diagnosed adult patients with epilepsy

Abstract, originally published in Epilepsy & Behavior

Purpose: The aim of this study was to evaluate the effects of valproate (VPA), lamotrigine (LTG), and levetiracetam (LEV) on bone turnover and bone mineral density (BMD) in newly diagnosed adult patients with epilepsy.

Methods: Eligible adult patients who were newly diagnosed with epilepsy were treated with VPA, LTG, and LEV. The chemical indicators of bone metabolism and BMD were measured before treatment and 2 years after treatment with different antiseizure medication (ASM) monotherapies. Then, the differences in these parameters before and after treatment were analyzed.

Results: One hundred twenty-four patients completed the 2 years follow-up; 43 received monotherapy with VPA, 32 received LTG, and 49 received LEV. Serum parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), and ?-cross-linked C-telopeptide of type I collagen (?-CTX) levels were elevated in adult patients after 2 years of VPA administration; the serum procollagen I intact N-terminal peptide (PINP) level was noticeably higher in patients after LEV treatment than before treatment. Meanwhile, the BMD of the lumbar spine and femoral neck did not change in patients treated with VPA, LTG, and LEV.

Conclusions: Valproate altered bone turnover in adult patients with epilepsy, while lamotrigine and levetiracetam did not exert harmful effects on bone health in adult patients.