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.

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.

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: https://epipick.org.

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.

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.

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.