Interviews with Pediatric Neurologists and Epileptologists Uncover Need for Standardized Sexual and Reproductive Healthcare for Adolescent and Young Adult With Epilepsy

OBJECTIVE: The objective of this study was to explore the attitudes and practices of pediatric neurologists and epileptologists regarding sexual and reproductive healthcare for adolescent and young adult women with epilepsy (WWE).

BACKGROUND: Adolescent and young adult WWE have unique sexual and reproductive healthcare needs, including counseling on teratogenesis, folic acid, and interactions between contraception and antiseizure medications. There are no prior studies regarding sexual and reproductive healthcare practices of pediatric neurologists or epileptologists.

DESIGN/METHODS: Individual semi-structured interviews were conducted with pediatric neurologists and epileptologists regarding their attitudes, practices, and experiences with sexual and reproductive healthcare for adolescent and young adult WWE. Interviews were audio-recorded and transcribed verbatim. Qualitative analysis was conducted using a thematic analysis approach.

RESULTS: Six child neurologists and 10 epileptologists (44% male) participated. Major themes included the following: (1) Sexual and reproductive healthcare is important for adolescent WWE, and neurologists have a key role in providing this care. (2) Sexual and reproductive healthcare should be comanaged with a primary care provider or women’s health provider although neurologists have significant concerns regarding comanagement. (3) There is wide variability in sexual and reproductive healthcare practice among pediatric neurologists and epileptologists. Important subthemes included parent education and differences in sexual and reproductive healthcare practices for women with intellectual disabilities. (4) Many systemic and interpersonal barriers exist to delivering sexual and reproductive healthcare to adolescent and young adult WWE. Important barriers included limited time; provider, patient, or family discomfort; and lack of necessary knowledge or expertise. (5) Providers desire standardization of sexual and reproductive healthcare for adolescent WWE along with patient and provider education.

CONCLUSION: This is the first study to assess attitudes and practices of pediatric neurologists and epileptologists regarding sexual and reproductive healthcare for adolescent and young adult WWE. Our findings suggest that there is a need for development of improved systems for sexual and reproductive healthcare delivery and comanagement for adolescent and young adult WWE. Providers identified many barriers and facilitators that might serve as the basis for interventions to improve care.

Pilot Study Suggests Sleep Monitoring Alone, With or Without Cognitive Behavioral Therapy, May Improve Sleep Quality and Quality of Life for People with Epilepsy

Sleep difficulties are commonly reported by patients with epilepsy and can have a detrimental impact on overall quality of life. The purpose of this pilot study was to assess the efficacy of a psychotherapeutic approach, namely Cognitive Behavioral Therapy for Insomnia (CBT-I), in improving sleep quality in patients with epilepsy.

Twenty outpatients with epilepsy who reported poor sleep quality were randomized to either a control or CBT-I treatment group, which involved four group-based CBT-I sessions, delivered on a weekly basis. In addition to completing a range of standardized measures related to sleep quality and quality of life, participants also monitored their sleep with a self-completed sleep diary over a two-week period, on two separate occasions.

Following CBT-I treatment, no between-group difference was found on any sleep or quality of life measure. However, both the treatment and control groups improved on measures of sleep quality, quality of life, sleep hygiene behaviors, and dysfunctional beliefs about sleep. These findings suggest that sleep monitoring alone may have the potential for prompting healthy behavior change in this clinical population.

Smartphone Videos Help Diagnose Epileptic Seizures

Smartphone videos taken by witnesses could help physicians diagnose epileptic seizures, according to a study published in JAMA Neurology.

“The findings from our study demonstrate ability of patient-generated smartphone videos to predict an inpatient video-[electroencephalogram] diagnosis of epilepsy as well as nonepileptic events in expert hands,” William O. Tatum, DO, neurologist at the Mayo Clinic, told Healio Primary Care. “Furthermore, the use of smartphone videos showed added value to a history and physical examination, especially when motor signs were present.”

Researchers conducted a prospective, masked diagnostic accuracy study at eight academic epilepsy centers in the United States between Aug. 31, 2015, and Aug. 31, 2018. The analysis included 44 patients who volunteered witness-recorded smartphone videos.

The diagnostic performance of smartphone videos was compared with the diagnostic performances of history and physical examinations and video electroencephalogram monitoring (VEM). Ten epilepsy experts and nine senior neurology residents reviewed the smartphone videos.

New Tool for Investigating Brain Cells, Epilepsy, Parkinson’s, & More

NMDARs (N-methyl-D-aspartate receptors) serve as valves on nerve cells, controlling the flow of electrical signals in the brain. This special group of receptors is suspect in many neurological diseases, including Alzheimer’s, epilepsy, stroke, and Parkinson’s. Biologists from Cold Spring Harbor Laboratory (CSHL) and chemists from the University of Bristol have joined forces, creating a chemical compound to enable more precise investigation of NMDAR activity.

In the latest issue of Nature Communications, CSHL Professor Hiro Furukawa and colleagues detailed how they identified and perfected a chemical compound that inhibits, or stops the activity of certain NMDARs. By inhibiting some NMDARs while letting others function, researchers can now identify the roles different types of NMDA receptors play in both healthy and diseased brains.

Jue Xiang Wang, a graduate of CSHL’s Ph.D. program who helped lead the research, explained that the CSHL-Bristol team investigated how the novel compound UBP791 targets a pair of NMDAR subunits called GluN2C and GluN2D.

Furukawa’s lab worked with Professor David Jane’s chemistry lab at the University of Bristol to improve the NMDAR-targeting compound. The CSHL lab specializes in visualizing the physical structure of NMDARs using a technique called X-ray crystallography. Knowing the structure of the receptor was critical for the chemists, who were then able to design UBP791 to connect specifically with the GluN2C and GluN2D receptors much like how a key is made to fit into specific locks. Studying what makes UBP791 fit particularly well further allowed the scientists to improve the compound, creating its latest version, UBP1700.

The UBP1700 compound is more precise than any of its predecessors and ”it’s also more potent,” said Wang. “That’s important because researchers will only need small amounts of the compound to shut down the targeted receptors. This limits the potential for side-effects that the compound might produce.”

Moving forward, Furukawa’s lab and their Bristol collaborators will be working on further refining the new compound for use in research.

Novel Model Predicts Drug-Resistant Epilepsy in Children With Cerebral Palsy

A low Apgar score at 5 minutes, neonatal seizures, focal-onset epilepsy, and focal slowing on electroencephalogram (EEG) are risk factor variables that cumulatively form an accurate model for predicting the risk for drug-resistant epilepsy in children with cerebral palsy. This is according to results of a study in the Journal of Child Neurology.

The study was a single-center, observational, retrospective chart review of 118 children with cerebral palsy and either drug-resistant epilepsy (n = 52) or controlled epilepsy (n = 66). Several clinical variables and patient characteristics were analyzed regarding their association and the incidence of drug-resistant epilepsy.

According to the investigators, this study may assist healthcare practitioners to “complete a clinical picture of ‘high-risk epilepsy’ and thereby further assist in the consideration of alternative therapeutic avenues in reaching the goal of reducing the burden of poor seizure control in children with cerebral palsy.”

Ways to Give

Physically Active Children with Epilepsy Have Good Objective Sleep Duration and Efficiency Despite Subjective Reports of Fatigue and Sleep Problems

OBJECTIVE: The aim of this study was to longitudinally characterize in children with epilepsy the objective and subjective sleep quality and the relationship between increased physical activity and sleep as well as measures of psychosocial well-being.

METHODS: Baseline physical activity and sleep were established in children with epilepsy over four weeks, prior to a 12-week exercise intervention (weekly meeting with exercise counselor). Participants continuously wore a wrist pedometer (Fitbit Flex®) to capture daily number of steps, sleep efficiency, and total sleep time. The Early Childhood Epilepsy Severity Scale (E-Chess) assessed baseline epilepsy severity. Subjective sleep quality (Children’s Sleep Habits Questionnaire, CSHQ), quality of life (KIDSCREEN-27; Pediatric Quality of Life Inventory, PedsQL™, 4.0 Core), fatigue (PedsQL™ Multidimensional Fatigue Scale), depression (Children’s Depression Inventory-Short), and anxiety (Multidimensional Anxiety Scale for Children) were assessed pre- and post-interventions.

RESULTS: Our cohort of 22 children with epilepsy aged 8-14 years was similarly active to peers (11,271 ± 3189 mean steps per day) and displayed normal sleeping patterns (mean sleep efficiency: 87.4% ± 3.08 and mean total sleep time: 521 ± 30.4). Epilepsy severity assessed by E-Chess was low to moderate (median baseline E-Chess score of 6, interquartile range: 5-7). Study outcomes did not change with the intervention. Older children and those with lower baseline activity were more likely to increase their activity during the intervention. Changes in physical activity were not associated with changes in sleep outcomes when accounting for age, sex, and baseline E-Chess score. Subjective sleep quality marginally improved with the intervention (CSHQ total score: 44.5 ± 5.8 at baseline and 41.6 ± 7.2 at the end of study, p = 0.05). Quality of life, fatigue, depression, and anxiety did not change with the intervention (p = 0.55, 0.60, 0.12, and 0.69, respectively).

SIGNIFICANCE: Children with epilepsy who are as active as peers without epilepsy have good objective measures of sleep despite self-reported fatigue and parent-reported sleep problems. The physical activity of initially less active and older children with epilepsy may benefit from an exercise counseling intervention.

CURE Discovery: Predicting Focal Epilepsy’s Path through the Brain

Key Takeaways

Dr. Jennifer Gelinas

  • In a study funded in part by CURE, Dr. Jennifer Gelinas aimed to understand how focal epilepsy resulting in partial seizures can progress to different parts of the brain over time.
  • She discovered that abnormal electrical activity between seizures can affect regions of the brain outside of a person’s epileptic network (regions of the brain involved in creating and spreading seizures).
  • Examining these interactions may provide opportunities to predict how focal epilepsy might progress in individuals.

Deep Dive

Focal epilepsy is often a progressive and unpredictable disease because focal seizures can evolve into new, individual-specific seizure types over time, making treatment challenging.

Interictal discharge

Some people with focal epilepsy experience seizures that get worse with time, while other individuals have a more stable course. CURE grantee, Dr. Jennifer Gelinas at Columbia University, hopes to understand how and why this variability happens. The aim of her CURE-funded work is to find ways to predict how focal epilepsy will progress to other regions of the brain so that doctors can treat patients more effectively.

Dr. Gelinas previously reported that, in a rat model of temporal lobe epilepsy, interictal epileptiform discharges (IEDs) can trigger neural activity in distant brain regions.1 IEDs are a type of abnormal electrical activity that occurs between seizures. Now in her recently published study,2 funded partly by CURE, Dr. Gelinas sought to understand how IEDs can affect the progression of focal epilepsy over time in people.

For this study, Dr. Gelinas and her team analyzed intracranial EEG (iEEG) recordings from 10 people with focal epilepsy who were undergoing clinical evaluation for epilepsy surgery. For each person, the team first identified brain regions where IEDs could be detected. They then located brain regions which had abnormal neural activity in response to IEDs. Although the patterns of neural activity coupled with IEDs were specific to each person, in each case they were located in distant brain regions outside the patient’s epileptic network. Moreover, distant brain regions where neural activity coupled with IEDs was detected had different characteristics compared to regions that were not affected by IEDs. The researchers also found that affected regions could be identified even in the absence of detectable IEDs.

This important study suggests that abnormal electrical activity (such as IEDs) in one part of the brain can disrupt normal neural activity in distant parts of the brain and may be an indicator of where the epileptic network will spread. Detection and manipulation of these patterns may present opportunities for diagnosis and therapies to prevent the spread of the network to other brain regions.

Dr. Gelinas was awarded a $100,000 Taking Flight grant by CURE in 2018. This grant seeks to promote the careers of young epilepsy investigators to allow them to develop a research focus independent of their mentor.

1 Gelinas J.N., Khodagholy D. et. al., Interictal epileptiform discharges induce hippocampal-cortical coupling in temporal lobe epilepsy. Nat Med. 2016 Jun;22(6):641-8. 2016;57:178–82
2 Dahal P., Ghani N., et. al. Interictal epileptiform discharges shape large-scale intercortical communication. Brain. 2019 Nov 1;142(11):3502-3513

Prevalence of Active Epilepsy, Lifetime Epilepsy Prevalence, and Burden of Epilepsy in Sub-Saharan Africa from Meta-Analysis of Door-to-Door Population-Based Surveys

BACKGROUND: There is marked variation in the prevalence of epilepsy across Sub-Saharan Africa (SSA). In order to accurately estimate the clinical and public health impacts of epilepsy in the region, robust and reliable epidemiological data are required for appropriate estimation of logistical, economical, and social impacts of epilepsy including policy formulation and intervention in the region.

OBJECTIVE: The team sought to evaluate the prevalence of active epilepsy (AE) and lifetime epilepsy prevalence in SSA using available data collected at community level.

METHODS: The team carefully searched online databases and identified the required articles using prespecified criteria. Random-effects model (REM) was used to estimate the active and lifetime prevalence from data generated from studies in SSA.. The burden of epilepsy, in terms of the number of people with the disease, was also obtained. Heterogeneity in the analysis was further explored using subgroup analysis and meta-regression techniques.

RESULT: A total of 39 and 12 community-based door-to-door surveys addressing AE and lifetime epilepsy, respectively, from different countries of SSA met the inclusion criteria for the study. Random-effects model estimates of overall prevalence of epilepsy were 9 per 1000 persons (95% confidence interval (CI): 8.0-9.9 per 1000 persons) for AE and 16 per 1000 persons (95% CI: 12.3-19.7 per 1000 persons) for lifetime epilepsy. The prevalence was highest in the Central Africa subregion with 30.2 per 1000 persons (95% CI: 6.2 to 66.7 per 1000 persons). The prevalence of AE in the rural settlement was twice that of the urban settlements. About 9,596,551 (95% CI: 8,530,267-10,556,206) people with AE and 17,060,535 (95% CI: 13,115,286-21,005,784) people with lifetime epilepsy live in SSA.

CONCLUSION: This study estimates the active (9/1000) and lifetime (16/1000) epilepsy with a remarkable burden of the disease in Sub-Saharan Africa. However, the prevalence, which is higher in the rural setting, varies within the subregion of Sub-Saharan Africa.

Latin American Summer School on Epilepsy Allows Scientists and Clinicians to Empathize With Their Patients Through Art

PURPOSE: The purpose of this study was to present and analyze the way epilepsy researchers and specialists present epilepsy through visual art forms.

METHODS: Students and epilepsy specialists, including clinicians and scientists, participating in the Latin American Summer School on Epilepsy (LASSE XIII) 2019 were asked to voluntarily portray epilepsy artistically by painting or drawing what they perceive that represents the feeling or challenges of persons with epilepsy. Resulting artwork was categorized according to several themes. The latter was analyzed in the clinical and social context of the disease.

RESULTS: Twenty-six paintings available for analysis have been reviewed. The three main interpretations of epilepsy were outlined as follows: epilepsy as an identity schism, epilepsy as a loss of control, and epilepsy as a complex condition. Five artworks best suited the first category as they presented people with faces split into healthy and diseased sides, representing the emotional and social burden of seizures. Three drawings defined epilepsy as a loss of control, visualizing that all the phases of seizure activity (ictal, postictal, and interictal) are able to imprison the patient by disrupting mental processes. The last theme included four artworks that defined epilepsy as being a multicomponent enigma: the intertwining of unresolved pathophysiologic processes and psychosocial burden accompanying the disease was emphasized. In addition, the challenges to care for the patients in order to improve not only seizures but also their quality of life were noticed as an idea complementing the visual definition of epilepsy.

CONCLUSION: Participants of LASSE XIII demonstrated an ability to empathize with their patients in retrospect by portraying the inner feelings of division and imprisonment of those having seizures. Epilepsy specialists visualize the disease as a composite phenomenon both in terms of its neural origin and of multidisciplinary requirements to implement its care.

Systematic Review Highlights That Clinicians Should Be Aware of Possible Skin-related Drug Reactions to Levetiracetam

PURPOSE: Recently, there have been an increased number of reports on levetiracetam (LEV) induced cutaneous adverse drug reactions (CADRs). This research team aimed to identify and critically evaluate all the descriptive studies on LEV induced-CADRs and to describe the possible clinical manifestations, management, and treatment outcomes of the condition.

METHODOLOGY: PubMed and grey literature databases were searched from inception to June 2019 without any restriction. The team also performed a bibliographic search for additional studies. Only descriptive studies on LEV-induced CADRs were included for our review. Study selection, data abstraction and quality assessment were performed by two contributors independently and disagreements were settled through consensus or through discussion with a third reviewer.

RESULTS: Data from 24 out of 88 studies, which included 25 patients (12 female and 13 male) aged from 40 weeks to 73 years, were reviewed. Patients received between 500 mg/day to 3000 mg/day of LEV. Drug reaction with eosinophilia and systemic symptoms syndrome, Steven-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, generalised hyperpigmentation and leucocytoclastic vasculitis were observed among the included patients. Immediate cessation of LEV, providing supportive care and use of topical antihistamines and anti-inflammatory drugs appeared to be the mainstay of management, and all patients were found to have recovered.

CONCLUSION: Clinicians should be aware of the possible cutaneous adverse drug reactions induced by levetiracetam to avoid the development of a potentially fatal condition. Immediate withdrawal of the drug and supporting care seem to be effective in the management of the cutaneous adverse drug reactions.