Paired blood and brain tissue methylation biomarkers in focal cortical dysplasia.

Focal Cortical Dysplasia (FCD) is a common cause of drug-resistant epilepsy. These abnormalities arise during embryonic development and are challenging to classify due to their complex nature. The most recent classification update of FCD incorporates genetic and epigenetic results with other clinical data for the management of epilepsy associated with these lesions.

Characterizing Developmental and Behavioral Profiles in Developmental Synaptopathies to Inform Clinical Trial Endpoints.

The Developmental Synaptopathies Consortium is a multisite natural history network studying rare, neurogenetic syndromes associated with synaptic dysfunction and developmental delays. One aim of the Consortium is clinical trial readiness, including identifying clinical concepts and validating their measurement. We evaluated the scope and limitations of conventional cognitive and behavioral measurement strategies in 2-21-year-olds with Phelan-McDermid syndrome (PMS; N = 98), Tuberous Sclerosis Complex (TSC; N = 98), and PTEN Hamartoma Tumor syndrome (PHTS; N = 69).

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to youths with drug-resistant epilepsy.

Rationale: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) is a consensus-based, empirically driven taxonomy of cognitive disorders validated in adults with epilepsy. This study explores the applicability of the IC-CoDE to a pediatric cohort with drug resistant focal epilepsy (DRE).

Methods: One hundred sixty youths (ages 5-18) with DRE received comprehensive neuropsychological evaluations assessing the five cognitive domains defined by the IC-CoDE taxonomy.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to youths with new and recent onset epilepsies.

Rationale: The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is an algorithmic approach to identifying cognitive phenotypes in epilepsy that to date has been investigated only in adults with temporal and frontal lobe epilepsy. The purpose of this investigation is to explore the applicability of IC-CoDE to youths with new and recent onset focal and generalized idiopathic epilepsies as well as the impact of modifications of cognitive domain construction on IC-CoDE outcomes.

Method: 222 youths (ages 8-18), including 134 with new/recent onset idiopathic epilepsies and 88 typically developing controls, were administered a comprehensive neuropsychological battery assessing 5 cognitive domains (language, visuospatial, memory, attention/processing speed, executive function).

Clinical and Cognitive Profiles of Individuals with Alzheimer's Disease and Comorbid Seizures.

Objective: Seizures are a highly prevalent comorbidity in Alzheimer's disease (AD), with a 2- to 6-fold increased risk, and are associated with accelerated cognitive decline. Despite growing research on seizure detection and treatment in AD, the cognitive profiles of individuals with both AD and seizures remain poorly characterized using comprehensive neuropsychological methods.

Methods: Clinical and cognitive data from individuals age 65+ with AD were analyzed from the National Alzheimer's Coordinating Center (NACC) dataset.

Automated identification of older adults at risk for cognitive decline.

Introduction: Automated models that predict cognitive risk in older adults can aid decisions about which patients to screen in busy primary care settings.

Methods: In this retrospective prediction model development study, we conducted formal cognitive testing on 337 older primary care patients to establish cognitive status. We used up to 5 years of prior discrete-field electronic health record (EHR) data to develop a multivariable prediction model that differentiates patients with impaired versus intact cognition.

Predicting memory decline from left temporal lobe epilepsy surgery using preoperative fMRI: a multicenter study.

Objective: While fMRI language laterality has been used to predict verbal memory after epilepsy surgery, supporting evidence is not yet definitive. The FMRI in Anterior Temporal Epilepsy Surgery (FATES) project was a prospective observational cohort study at 10 US epilepsy centers, performed to determine whether a multivariable model including fMRI language laterality can predict verbal memory outcome 6 months after left temporal lobe epilepsy surgery.

Methods: This analysis includes 70 adults who underwent left temporal lobe epilepsy surgeries including hippocampal resection for treatment of epilepsy.

Feasibility of and patient satisfaction with Readiness Brain Operation Optimization Training, a manualized cognitive prehabilitation program for epilepsy surgery.

Objective: Readiness Brain Operation Optimization Training (ReBOOT) is a manualized cognitive prehabilitation program for patients considering epilepsy surgery designed to improve presurgical preparedness through education and reduce the impact of postsurgical cognitive changes with preemptive cognitive compensatory training. The purpose of this study was to understand the feasibility of cognitive prehabilitation, examine patient satisfaction with ReBOOT, and assess changes in compensatory strategy use following ReBOOT.

Methods: Seventeen participants (65% female, mean age = 41 years) considering epilepsy surgery were enrolled in ReBOOT, which includes two one-on-one psychoeducation sessions, four group sessions on cognitive compensatory strategies, and weekly goal setting to facilitate implementation of strategies.

Clinical implications of naming performance and seizure lateralization in bilingual children with epilepsy.

Objective: Naming difficulty is a common symptom of left (i.e., language dominant) hemisphere epilepsy.

Comparative Review of Seizure and Cognitive Outcomes in Resective, Ablative, and Neuromodulatory Temporal Lobe Epilepsy Surgery.

Resective surgery for drug-resistant temporal lobe epilepsy remains underutilized in the United States. While anteromesial temporal lobectomy consistently achieves the highest rates of long-term seizure freedom, it comes with greater risks for memory and language decline. Magnetic resonance imaging-guided laser interstitial thermal therapy and neuromodulation have gained popularity due to perceived lower surgical risk and faster recovery, although they yield lower rates of sustained seizure freedom.

Neuropsychological functioning in children and adolescents with pharmacoresistant epilepsy due to malformations of cortical development.

Purpose: Almost half of pharmacoresistant epilepsies in childhood and adolescence are caused by malformations of cortical development (MCDs), but little is known about the associated neuropsychological morbidities. This study comprehensively characterized presurgical neuropsychological functions in children and adolescents with pharmacoresistant epilepsy due to MCDs and examined their relationships to neuropathological substrate and other clinical variables.

Methods: Retrospective data were obtained from 137 children and adolescents (mean age = 13 years; 58 % male) who underwent resective surgery for treatment of epilepsy and had pathologically-confirmed MCDs.

Analysis of practical judgment in older adults with epilepsy: An exploratory, multicenter cohort study.

Despite the high prevalence of cognitive deficits in older people with epilepsy (PWE), their ability to judge and make decisions in daily life remains unexplored. In 61 older PWE (55-90 years) from the multicenter BRain Aging and Cognition in Epilepsy (BrACE) study, we examined everyday judgment, as measured by the Test of Practical Judgment (TOP-J: 9 questions, score range = 0-27; higher score = better judgment) and evaluated its association with clinical and demographic characteristics, global cognition, neuropsychological performance, subjective cognition, and quality of life (QOL). In our participants (mean age ± standard deviation [SD] = 66.

Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability.

Social attention is a key aspect of neurodevelopment and is significantly altered in neurodevelopmental genetic syndromes and many individuals with idiopathic autism spectrum disorder (ASD). The primary aim of the present study was to examine the psychometric properties of webcam-collected social attention measurements, including four new specific aspects of social attention, in three genetic syndromes (PTEN Hamartoma Tumor Syndrome-PHTS; Malan Syndrome-NFIX; and SYNGAP1-related disorder-SYNGAP1), a mixed group of other neurodevelopmental genetic syndromes (Other NDGS), and individuals with a range of idiopathic neurodevelopmental disorder (NDD). The secondary aim was to evaluate the construct validity of these social attention measurements, including evaluating known-groups validity across study groups and concurrent validity for separating ASD and non-ASD cases.

External validation of the Memory Assessment Clinics Scale for Epilepsy (MAC-E).

Objective: This study aimed to externally validate the Memory Assessment Clinics Scale for Epilepsy (MAC-E), a brief self-report measure of subjective memory complaints in adults with epilepsy.

Methods: A cross-sectional study was conducted including adults with focal pharmacoresistant epilepsy from three Level 4 epilepsy centers in the U.S.

Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR.

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.

Quantifying neurobehavioral profiles across neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders.

Aim: To examine neurobehavioral findings in three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome [mutations in the NFIX gene], and SYNGAP1-related disorder), a mixed group of other neurodevelopmental genetic syndromes (NDGS), idiopathic neurodevelopmental disorder, and neurotypical control participants.

Method: Using a longitudinal case-control design, caregivers reported neurobehavioral information for 498 participants (PTEN hamartoma tumor syndrome n = 112, Malan syndrome n = 24, SYNGAP1-related disorder n = 47, other NDGS n = 72, idiopathic neurodevelopmental disorder n = 54, neurotypical siblings n = 74, and unrelated neurotypical control participants n = 115) at three timepoints (baseline, and 1-month and 4-month follow-ups) using the online-administered Neurobehavioral Evaluation Tool (NET).

Results: NET scales had good scale and test-retest reliability.

A user's guide for the International Classification of Cognitive Disorders in Epilepsy.

To present the background, rationale, details pertaining to use and essential computational steps, synopsis of findings to date, and future directions for the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE)-an initiative of the ILAE Neuropsychology Task Force. Examined are: (a) the 6 steps leading to the derivation of a cognitive phenotype from neuropsychological test data with an accompanying case example, (b) concise review of all IC-CoDE research to date, (c) summary of identified correlates of IC-CoDE outcomes, and (d) future research and clinical directions for the initiative. The IC-CoDE is computationally uncomplicated with individual or group data and represents a novel approach leading to new insights in the neuropsychology of epilepsy, with applications to diverse datasets internationally informing the reliability and validity of the approach.

Multidisciplinary lifestyle interventions for neurological disorders during the Silent phase (MINDS) study: a multi-omics randomized controlled trial protocol.

Introduction: Given the prevalence and staggering cost of neurological disorders, there is dire need for effective early detection and intervention tools. Emerging evidence suggests that multidisciplinary lifestyle interventions (MLI) may mitigate the risk and progression of neurological disorders. The objectives of this protocol are (1) to test the impact of MLI on the progression of neurological disorders and (2) to identify multi-omic biomarkers for early stages of neurological disease and the impact of MLIs on these biomarkers.

Individual- and community-level social determinants of health are associated with cognition in older adults with focal epilepsy.

Objective: Epilepsy is associated with significant health disparities, including access to specialized care and adverse outcomes that have been associated with several social determinants of health (SDOH). We sought to examine the relationship between individual- and community-level SDOH and cognitive outcomes in older adults with epilepsy.

Materials And Methods: We collected clinical, SDOH, and neuropsychological data in 57 older adults with epilepsy.

Cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE): Cognitive phenotypes in people with temporal lobe epilepsy in India.

Objective: Efforts to understand the global variability in cognitive profiles in patients with epilepsy have been stymied by the lack of a standardized diagnostic system. This study examined the cross-cultural applicability of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) in a cohort of patients with temporal lobe epilepsy (TLE) in India that was diverse in language, education, and cultural background.

Methods: A cohort of 548 adults with TLE from Mumbai completed a presurgical comprehensive neuropsychological evaluation.

Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research?

Objective: This study evaluated the diagnostic performance of a widely available cognitive screener, the Montreal cognitive assessment (MoCA), to detect cognitive impairment in older patients (age ≥ 55) with epilepsy residing in the US, using the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) as the gold standard.

Methods: Fifty older adults with focal epilepsy completed the MoCA and neuropsychological measures of memory, language, executive function, and processing speed/attention. The IC-CoDE taxonomy divided participants into IC-CoDE Impaired and Intact groups.

Automated detection of cognitive impairment in clinical practice.

Objective: Cognitive impairment is now recognized as an impending public health crisis. About one-third of adults are concerned about their cognition, and the prevalence of objective cognitive impairment is much higher among those with neurological disorders. Existing screening tools are narrowly focused on detecting dementia in older adults and must be clinician-administered and scored, making them impractical for many neurology practices.

Utility of automated memory measures in identifying cognitive impairment in adults with epilepsy.

Objective: Cognitive impairment is prevalent in epilepsy and often presents at the time of initial diagnosis. This study sought to validate brief, self-administered, iPad-based recognition memory tasks in a sample of patients with epilepsy and to examine their screening utility in identifying patients with cognitive impairment.

Methods: The Words and Faces tests were administered to 145 adult patients with epilepsy along with a neuropsychological battery.

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.

Objective: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE.

Utility of the Brief Assessment of Cognitive Health (BACH) computerized screening tool in identifying MS-related cognitive impairment.

Background: Current guidelines recommend that individuals with MS are screened annually for processing speed deficits, often using the Symbol Digit Modalities Test (SDMT). However, given the heterogeneity of cognitive deficits in individuals with MS, other screening measures that assess a range of cognitive domains are necessary. The current cross-sectional study aimed to examine the ability of the computerized, self-administered Brief Assessment of Cognitive Health (BACH) screening measure to detect the presence of cognitive impairment in adults with MS as determined by performance on a standard neuropsychological test battery.