Self-esteem Mediates Mental Health Outcomes in Young People with Epilepsy

Summary, published in Epilepsia

Objective: To evaluate the extent to which self-esteem mediates the impacts of epilepsy-specific and environmental factors on mental health outcomes in young people with epilepsy.

Methods: A prospective cohort of 480 young people with epilepsy and their families participated in five visits over 28 months. We collected data on clinical seizure burden, cognitive comorbidity, peer and parental support, self-esteem, and self-reported mental health symptoms. We used structural equation modeling to specify and test relationships among these constructs simultaneously. Direct, indirect, and total effects were estimated with confidence intervals constructed through bias-corrected bootstrapping.

Results: Self-esteem mediated the effects of clinical seizure burden ( ?? = 0.23, 95% confidence interval [0.05, 0.42]) and peer support ( ?? = ?0.15, 95% CI [?0.28, ?0.03]) on mental health. There were no mediating effects of parental support ( ?? = ?0.07, 95% CI [?0.14, 0.00]) or cognitive comorbidity ( ?? = ?0.01, 95% CI [?0.02, 0.01]) on mental health.

Significance: We found evidence that self-esteem mediates the impact that both clinical seizure burden and peer support have on mental health outcomes, indicating that assessment of and interventions targeting self-esteem may be appropriate for young people with epilepsy. Supporting self-esteem could mitigate negative influences on mental health, whether from resistant epilepsy or low peer support.

Intellectual Outcome from 1 to 5 years After Epilepsy Surgery in 81 Children and Adolescents: A Longitudinal Study

Abstract, published in Seizure

Objective: This longitudinal study aimed to measure the time course of intellectual changes after pediatric focal resective epilepsy surgery and to identify their predictors.

Methods: We analyzed a cohort of 81 school-aged children with focal epilepsy and intractable seizures who underwent neurosurgery (focal resection) from 2000 to 2018 in La Timone Hospital (Marseille). Neuropsychological assessments were carried out before and then 1, 2, 3, and 5 years after epilepsy surgery.

Results: Eighty-one patients with a median age at surgery of 13.74 years [4.25] were enrolled. Overall, 45 of the 81 (55%) recruited patients were improved after the surgery on at least one of the five domains of the Wechsler Intelligence Scale. Temporal lobe localization and postoperative seizure freedom were the main prognostic factors impacting intellectual outcome (improvement and decline) after epilepsy surgery. Younger patients at surgery were less likely to have a postoperative IQ decline. Intellectual improvement after epilepsy surgery could be delayed for up to 5 years after surgery and concerned all intellectual domains except the Verbal Comprehension Index (VCI). Intellectual decline after epilepsy surgery occurred mainly during the first two years after the surgery and was reflected in full-scale intelligence quotient (FSIQ) and Working Memory Index (WMI).

Conclusions: Our study points out that children and adolescents with temporal lobe epilepsy who achieved freedom from seizure after epilepsy surgery are the leading candidates for achieving postoperative intellectual improvement. This enhancement in intellectual function shows a long time course, whereas intellectual decline is evidenced earlier.

Impaired Social Attention Detected Through Eye Movements in Children with Early-onset Epilepsy

Abstract, posted in Epilepsia

Objectives: Children with early-onset epilepsy (CWEOE; epilepsy onset before 5 years) exhibit impaired social functioning, but social attention has not yet been examined. In this study we sought to explore visual attention via eye tracking as a component of social attention and examine its relationship with social functioning and Autism Spectrum Disorder (ASD) risk scores.

Methods: Forty-seven CWEOE (3-63 months) and 41 controls (3-61 months) completed two eye-tracking tasks: (1) preference for social versus nonsocial naturalistic scenes, and (2) face region preference task. ASD risk was measured via the Modified Checklist for Autism in Toddlers or Conners Early Childhood Total Score. Social functioning was assessed via the Greenspan Social-Emotional Growth Chart, or Infant-Toddler Social & Emotional Assessment Competence Scale, or Conners Early Childhood Social Functioning Scale, depending on age. Fixation preferences for social scenes and eyes were compared between groups and evaluated by age and social functioning scores.

Results: Regression analysis revealed that CWEOE viewed the social scene to a significantly less degree than controls. The greatest difference was found between the youngest CWEOE and controls. Fixation duration was independently and significantly related to social functioning scores. There were no significant differences between CWEOE and controls in the face scanning task, and there was no significant relationship between either task and ASD risk scores.

Significance: Children with early-onset epilepsy exhibit task-specific atypical social attention early in the course of the disease. This may be an early marker of impaired social development, and it suggests abnormal social brain development.

Epilepsy Surgery in Infants up to 3 months of Age: Safety, Feasibility, and Outcomes: A Multicenter, Multinational Study

Summary, published in Epilepsia

Objective: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on “ultra-early” epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study’s goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months.

Methods: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications.

Results: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19–104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1–3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections).

Significance: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Pediatric Epilepsy and Psychoeducational Interventions: A review of the Literature

Abstract, published in Epilepsy & Behavior

For many individuals, living with epilepsy is truly a family affair throughout the life span. When it comes to childhood epilepsy, the unpredictability of seizure patterns, comorbid conditions, the risk of sudden unexpected death in epilepsy (SUDEP), and societal stigma can be emotionally taxing on children and their primary caregivers. To this end, this article proposes to review psychoeducational interventions provided to primary caregivers of children with an epilepsy diagnosis and the impact of such interventions on general parental coping skills. There were three main themes identified (1) caregivers’ knowledge and self-efficacy about seizure management; (2) parental epilepsy-related fears, anxiety, and stress; (3) parental sleep quality and SUDEP psychoeducation. Overall, considering research limitations, providing epilepsy-related psychoeducational interventions to primary caregivers of children with epilepsy seems to have promising evidence in the literature. After receiving such interventions, the studies show that caregivers’ psychosocial outcomes improved; they become more empowered to manage their children’s seizures and advocate for their children’s psychosocial needs.

A children’s epilepsy diagnosis aid: Development and early validation using a Bayesian approach

Abstract, published in Epilepsy & Behavior

Introduction: The diagnosis of epilepsy in children is difficult and misdiagnosis rates can be as much as 36%. Diagnosis in all countries is essentially clinical, based on asking a series of questions and interpreting the answers. Doctors experienced enough to do this are either scarce or absent in very many parts of the world so there is a need to develop a diagnostic aid to help less-experienced doctors or non-physician health workers (NPHWs) do this. We used a Bayesian approach to determine the most useful questions to ask based on their likelihood ratios (LR), and incorporated these into a Children’s Epilepsy Diagnosis Aid (CEDA).

Methods: Ninety-six consecutive new referrals with possible epilepsy aged under 10 years attending a pediatric neurology clinic in Khartoum were included. Initially, their caregivers were asked 65 yes/no questions by a medical officer, then seen by pediatric neurologist and the diagnosis of epilepsy (E), not epilepsy (N), or uncertain (U) was made. The LR was calculated and then we selected the variables with the highest and lowest LRs which are the most informative at differentiating epilepsy from non-epilepsy. An algorithm, (CEDA), based on the most informative questions was constructed and tested on a new sample of 47 consecutive patients with a first attendance of possible epilepsy. We calculated the sensitivity and specificity for CEDA in the diagnosis of epilepsy.

Results: Sixty-nine (79%) had epilepsy and 18 (21%) non-epilepsy giving pre-test odds of having epilepsy of 3.83. Eleven variables with the most informative LRs formed the diagnostic aid (CEDA). The pre-test odds and algorithm were used to determine the probability of epilepsy diagnosis in a subsequent sample of 47 patients. There were 36 patients with epilepsy and 11 with nonepileptic conditions. The sensitivity of CEDA was 100% with specificity of 97% and misdiagnosis 8.3%.

Conclusion: Children’s Epilepsy Diagnosis Aid has the potential to improve pediatric epilepsy diagnosis and therefore management and is particularly likely to be useful in the many situations where access to epilepsy specialists is limited. The algorithm can be presented as a smartphone application or used as a spreadsheet on a computer.

Phenotypic Analysis of Catastrophic Childhood Epilepsy Genes

Abstract, published in Communications Biology

Genetic engineering techniques have contributed to the now widespread use of zebrafish to investigate gene function, but zebrafish-based human disease studies, and particularly for neurological disorders, are limited. Here we used CRISPR-Cas9 to generate 40 single-gene mutant zebrafish lines representing catastrophic childhood epilepsies. We evaluated larval phenotypes using electrophysiological, behavioral, neuro-anatomical, survival and pharmacological assays. Local field potential recordings (LFP) were used to screen ?3300 larvae. Phenotypes with unprovoked electrographic seizure activity (i.e., epilepsy) were identified in zebrafish lines for 8 genes; ARX, EEF1A, GABRB3, GRIN1, PNPO, SCN1A, STRADA and STXBP1. We also created an open-source database containing sequencing information, survival curves, behavioral profiles and representative electrophysiology data. We offer all zebrafish lines as a resource to the neuroscience community and envision them as a starting point for further functional analysis and/or identification of new therapies.

Big Data Helps Assess Seizure Burden, Improve Outcomes in Pediatric Epilepsy Patients

Article, published in EurekAlert!

Researchers at Children’s Hospital of Philadelphia (CHOP) have demonstrated how to use standardized reporting of clinical data for seizures caused by a variety of neurological disorders, providing fundamental baseline information that can determine what methods work best for keeping seizures under control. The findings were published today in the journal Epilepsia.

In order to make improvements in epilepsy care, clinicians need a reliable and efficient method to measure outcomes. While Electronic Medical Records (EMR) are being used more frequently for research and quality improvement, important epilepsy outcome measures such as seizure frequency or quality of life are not documented in a standardized way that enables researchers to process large-scale data on the subject.

To help standardize how clinical data is recorded for epilepsy visits, the team at CHOP began using common data elements (CDEs) to ensure that relevant data is captured in a comparable way across studies and clinical visits. In this study, the researchers assessed the results from using CDEs in routine care for pediatric epilepsy over a 12-month period.

“For those of us who treat pediatric epilepsy patients, we are constantly trying to assess how we’re doing and how we can improve outcomes for our patients,” said Mark P. Fitzgerald, MD, PhD, a pediatric neurologist in the Division of Neurology at CHOP and first author of the study. “This study provides us with fundamental data that will serve as the foundation for how we treat our patients and inform how we achieve the best patient-centered outcomes possible.”

Febrile Seizure: What Information Can Caregivers Access Through YouTube?

Abstract, published in Seizure

Introduction: To analyze the content of Korean YouTube videos related to febrile seizures and examine the general characteristics, reliability, and quality of the videos.

Method: A search of YouTube was performed using three Korean keywords meaning “febrile seizure”, and a total of 1,641 videos were identified. Among them, 73 eligible videos were analyzed for their characteristics, quality, and reliability. The quality and reliability were rated using global quality (GQS) on a scale of 1-5 and the DISCERN instrument.

Results: The mean reliability and quality scores were 2.37±1.16 and 3.11±1.17 out of 5, respectively. Fifty-one of the 73 (69.8%) videos are related to febrile seizure management. Longer videos (13.94±20.06 vs 6.68±7.34) and videos with physicians (82.61% vs 32.00%) as the main speaker were higher quality.

Discussion: Both the quality and reliability of YouTube videos on febrile seizures were relatively low, and approximately only 30% of all videos were classified as high quality. Healthcare professionals should be aware that there is misinformation and low-quality information on social media and warn parents of this issue.

Differential Activation of Neuroinflammatory Pathways in Children with Seizures: A Cross-sectional Study

Abstract, published in Seizure

Purpose: Inflammation plays a crucial role in epileptogenesis. We analyzed inflammatory cytokines in plasma and saliva from children with seizures and healthy controls and measured their associations with HHV6 and EBV infection.

Methods: We analyzed plasma from 36 children within 24 h of seizures (cases) and 43 healthy controls and saliva from 44 cases and 44 controls with a multiplex immunoassay. Saliva from all controls and 65 cases and blood from 26 controls and 35 cases were also analyzed by PCR for viral DNA. Primary outcome was cytokine levels in cases vs. controls. Secondary outcomes included detection of HHV-6 and EBV viral DNA in cases vs. controls and viral loads in cases vs. controls. Statistical analysis included the Wilcoxon Rank Sum test, Fisher’s exact test, ANOVA, and Spearman correlation.

Results: Compared to controls, patients had higher levels of CCL11 (p = 0.0018), CCL26 (p<0.001), IL10 (p = 0.044), IL6 (p<0.001), IL8 (p = 0.018), and MIP1? (p = 0.0012). CCL11 was higher with 3 or more seizures (p = 0.01), seizures longer than 10 min (p = 0.001), and when EEG showed focal slowing (p = 0.02). In saliva, febrile seizures had higher levels of IL-1? (n = 7, p = 0.04) and new onset seizures had higher IL-6 (n = 15, p = 0.02). Plasma and saliva cytokine levels did not show a correlation. The frequency of HHV-6 and EBV detection was similar across groups and not different than controls. We found no correlation between viral load and cytokine levels.

Conclusions: We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to viral infection.