Tanja S. Kellermann

Mapping the landscape of cognitive development in children with epilepsy

OBJECTIVE Normal childhood development is defined by age-dependent improvement across cognitive abilities, including language, memory, psychomotor speed and executive function. Epilepsy is often associated with a global disruption in cognitive development, however, it is still largely unknown how epilepsy affects the overall organization of overlapping cognitive domains. The aim of the study was to evaluate how childhood epilepsy affects the developmental interrelationships between cognitive domains. METHODS We performed a comprehensive assessment of neuropsychological function in 127 children with new onset epilepsy and 80 typically developing children matched for age, gender, and socio-demographic status. A cross-correlation matrix between the performances across multiple cognitive tests was used to assess the interrelationship between cognitive modalities for each group (patients and controls). A weighted network composed by the cognitive domains as nodes, and pair-wise domain correlation as links, was assessed using graph theory analyses, with focus on global network structure, network hubs and community structure. RESULTS Normally developing children exhibited a cognitive network with well-defined modules, with verbal intelligence, reading and spelling skills occupying a central position in the developing network. Conversely, children with epilepsy demonstrated a less well-organized network with less clear separation between modules, and relative isolation of measures of attention and executive function. CONCLUSION Our findings demonstrate that childhood-onset epilepsy, even within its early course, is associated with an extensive disruption of cognitive neurodevelopmental organization. The approach used in this study may be useful to assess the effectiveness of future interventions aimed at mitigating the cognitive consequences of epilepsy.

Development and validation of the NDDI-E-Y: a screening tool for depressive symptoms in pediatric epilepsy

To validate the revised 12‐item revised Neurological Disorders Depression Inventory‐Epilepsy for Youth (NDDI‐E‐Y), a self‐report screening tool for depressive symptoms tailored to youth ages 12–17 with epilepsy.

Determining patient needs: A partnership with South Carolina Advocates for Epilepsy (SAFE)

PURPOSE The purpose of this study was to collaborate with a community partner to administer a current needs assessment of persons with epilepsy (PWE) and determine the types of resources that PWE would like to access through the community partner. METHODS A self-report needs assessment survey was administered to caregivers and PWE across the state of South Carolina during a community partner educational workshop (n=20) and via secure software distributed through an email link (n=54). KEY FINDINGS The most frequently reported challenges (>50%) were concerns about finding time to participate in epilepsy community activities, the personal safety of the PWE, finding social connections or social support, finding mental or behavioral health services, and work concerns. However, top ranked concerns centered on personal safety (27.8%), lack of insurance/not enough money to pay for epilepsy treatment (15.3%), and difficulty with daily management of epilepsy (13.9%). Participants reported likely engagement with the epilepsy community partner via in-person meetings, over the phone, and through social media contacts; however, there were differences between PWE and caregivers regarding preferences for communication. Almost 60% endorsed that they would likely participate in a brief program to learn skills to manage their epilepsy daily. SIGNIFICANCE Persons with epilepsy in South Carolina continue to have many unmet needs and would access resources, if available, from a state-wide epilepsy community partner via various modes of communication.

Validation of the PedsQL Epilepsy Module: A pediatric epilepsy‐specific health‐related quality of life measure

To validate a brief and reliable epilepsy‐specific, health‐related quality of life (HRQOL) measure in children with various seizure types, treatments, and demographic characteristics.

Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF

Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory‐Epilepsy for Youth (NDDI‐E‐Y) and the Neuro‐QOL Depression Short Form (Neuro‐QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Childrens Depression Inventory‐2 (CDI‐2).

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory

OBJECTIVE Normal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC. METHODS Neuropsychological assessment was performed in 100 patients with TLE and 82 HC. For each group, an adjacency matrix was constructed representing pair-wise correlation coefficients between raw scores obtained in each possible test combination. For each cognitive network, each node corresponded to a cognitive test; each link corresponded to the correlation coefficient between tests. Global network structure, community structure, and node-wise graph theory properties were qualitatively assessed. RESULTS The community structure in patients with TLE was composed of fewer, larger, more mixed modules, characterizing three main modules representing close relationships between the following: 1) aspects of executive function (EF), verbal and visual memory, 2) speed and fluency, and 3) speed, EF, perception, language, intelligence, and nonverbal memory. Conversely, controls exhibited a relative division between cognitive functions, segregating into more numerous, smaller modules consisting of the following: 1) verbal memory, 2) language, perception, and intelligence, 3) speed and fluency, and 4) visual memory and EF. Overall node-wise clustering coefficient and efficiency were increased in TLE. SIGNIFICANCE Adults with TLE demonstrate a less clear and poorly structured segregation between multiple cognitive domains. This panorama suggests a higher degree of interdependency across multiple cognitive domains in TLE, possibly indicating compensatory mechanisms to overcome functional impairments.

Implementation of psychological clinical trials in epilepsy: Review and guide

The International League Against Epilepsy (ILAE) Neuropsychiatry commission and United States Institute of Medicine report both identified cognitive and psychological comorbidities as a significant issue for individuals with epilepsy, with rates as high as 60%. However, there is a paucity of evidence-based treatments for many psychological conditions (e.g., learning disorders, cognitive disorders, behavioral disorders). Because of inherent challenges in the implementation of psychological therapy trials and specific considerations for the population with epilepsy, the focus of the current review was to provide guidance and recommendations to conduct psychological trials for individuals with epilepsy. Several key areas will be discussed, including selection of patients, trial design, psychological intervention considerations, outcomes and evaluation of results, publication of trial results, and special issues related to pediatric clinical trials. Rigorously designed psychological therapy trials will set the stage for evidence-based practice in the care of individuals with epilepsy, with the goal of improving seizures, side effects, and HRQOL.

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy.

Behavioral health referrals in pediatric epilepsy

The purpose of this study was to examine the feasibility of a behavioral health referral protocol and barriers to behavioral health care in a pediatric epilepsy clinic. A sample of 93 youth with epilepsy ages 10-17 and caregivers completed behavioral health and seizure severity measures during a routine epilepsy clinic visit. Key findings are that 47 (50.5%) of the youth screened positive for a behavioral health referral, and 35 of these youth were referred for behavioral health services. However, only 20% made and presented for the behavioral health appointment. The most commonly cited barrier for accessing and utilizing behavioral health care was stigma related- a mental health label for the child. The significance of this study lies in the revelation that solely screening for and educating caregivers about behavioral health symptoms and providing behavioral health referral information is not an ideal model. Instead, stigma related barriers point to the necessity of continued integrated physical and behavioral health care within the pediatric epilepsy visit.

Behavioral health in young adults with epilepsy: Implications for transition of care

AIM Neurodevelopmental and behavioral health disorders commonly occur with epilepsy, yet risk for young adults is unknown. The aim of this study was to determine the distribution and risk characteristics of neurodevelopmental and behavior health comorbidities among young adults with epilepsy compared with those among young adults with migraine and healthy controls. METHOD A case-control study examining hospital admission, outpatient, and emergency department (ED) visits for young adults with an ICD-9-CM diagnosis of epilepsy, migraine, or lower extremity fracture (LEF) was conducted. The association of epilepsy, migraine, or LEF with comorbidities was evaluated with univariate and multivariate polytomous logistic regression. RESULTS From 2000 to 2013, 29,139 young adults ages 19 to 25years were seen in hospitals and EDs for epilepsy (5666), migraine (17,507), or LEF (5966). Young adults with epilepsy had higher proportions of behavioral health comorbidities (51.8%) compared with controls with migraine (37.6%) or LEF (21.6%). In young adults with epilepsy compared with migraine, the increased risk of having any behavioral health comorbidity was 76%, and neurodevelopmental comorbidity was 297%. After adjustment, young adults with epilepsy showed significantly higher odds of each behavioral health comorbidity compared with controls with migraine and LEF. INTERPRETATION Young adults with epilepsy are particularly susceptible to behavioral health and neurodevelopmental disorders. Results are discussed within the context of transition to adult care.