Understanding lived experiences with KCNQ2 developmental and epileptic encephalopathy.

Background: KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) is a rare pediatric disorder characterized by seizures and neurodevelopmental impairments. Parent- and healthcare professional (HCP)-reported outcomes regarding the impacts of seizures and neurodevelopmental impairments may guide the design of clinically meaningful KCNQ2-DEE outcome measures.

Methods: Parents of children with KCNQ2-DEE (N = 53) and HCPs with KCNQ2-DEE expertise (N = 2) participated in qualitative interviews exploring signs, symptoms, and impacts of KCNQ2-DEE, and how varying KCNQ2-DEE phenotypes affect child development.

Comparative effectiveness of second-line treatments for epileptic spasms.

Objective: This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS).

Methods: Infants aged 2-24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high-dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment.

Caregiver-reported meaningful change in functional domains for individuals with developmental and epileptic encephalopathy: A convergent mixed-methods design.

Aim: To investigate how caregivers of children with developmental and epileptic encephalopathy and severe developmental impairments describe meaningful change for functional domains and why it is important.

Method: This was a convergent mixed-methods design study. A survey was completed by 267 parents of children aged 12 months or older.

Caregiver-reported non-seizure and seizure outcomes with cannabidiol and clobazam in patients aged ≥2 years with Lennox-Gastaut syndrome or Dravet syndrome: A subgroup analysis of the BECOME survey.

Purpose: This subgroup analysis of the BECOME (BEhavior, COgnition, and More with Epidiolex®) survey analyzed caregiver-reported seizure and non-seizure outcomes, including changes in caregiver burden, following cannabidiol (CBD) treatment in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) aged ≥2 years taking concomitant clobazam, aligned with the European Medicines Agency indication.

Methods: US-based caregivers of patients with LGS/DS receiving CBD (Epidiolex®, 100 mg/mL oral solution) for ≥3 months rated patient outcome changes, comparing the previous month with pre-CBD initiation. Multiple-choice and rank-order questions with symmetrical 3-, 5-, or 7-point scales ranging from worsening to improvement were used.

Gross Motor Function in Individuals With SCN2A-Related Disorders: The Clinical Trial Readiness Study.

Background And Objectives: SCN2A-related disorders (RDs) are genetic conditions characterized by severe to profound impairments in multiple domains including gross motor function, which could serve as a nonseizure outcome in precision medicine therapy trials. This study evaluated specific properties of the Vineland Adaptive Behavior Scales-3 (VABS3) and other motor assessments for their fitness for use in trials of SCN2A-RDs.

Methods: Sixty-five families recruited through the FamileSCN2A foundation enrolled their affected children ("participants," 28 female, median age 6.

Dravet syndrome: From neurodevelopmental to neurodegenerative disease?

Objective: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency in the majority of cases. Caregivers of adults with DS often complain about the loss of previously acquired skills. We set out to explore these perceptions and determine whether abnormalities reported were detectable in validated tests.

Vineland-3 Growth Scale Values: Psychometric Properties for Clinical Trial Readiness in SCN2A.

The Vineland Adaptive Behavior Scales-3rd Edition (Vineland-3) is one of the most used measures of adaptive behavior among those with sodium channel protein type 2 subunit alpha related disorders (SCN2A-RDs). Several disease-modifying treatments are in early trials for SCN2A-RDs, and as such, clinical outcome assessments (COAs) are necessary. The Vineland-3 introduced growth scale values (GSVs), which are useful for measuring within-person change and thus may be useful in future clinical trials.

The Feasibility of Personalized Endpoints in Assessing Treatment Outcomes for Rare Diseases: A Pilot Study of Goal Attainment Scaling in SCN2A-Associated Developmental Epileptic Encephalopathy.

Objectives: For individuals living with rare neurodevelopmental disorders, particularly those who are at the most severe end of the spectrum, standardized outcome measures may lack the sensitivity to capture small but meaningful changes. Personalized endpoints such as goal attainment scaling (GAS) allow the assessment of treatment response across variable baseline states and disease manifestations and, thus, provide a highly sensitive measure of efficacy. The current study tested the feasibility of using GAS in rare SCN2A-associated developmental and epileptic encephalopathy (SCN2A-DEE).

Assessing Communication Impairments in a Rare Neurodevelopmental Disorder: The Clinical Trials Readiness Study.

Background And Objectives: -related disorders (-RDs) entail severe impairments in multiple domains that could serve as nonseizure outcomes in clinical trials. This study evaluated the fitness for purpose of several clinical instruments with both standardized and alternative scoring and with some measures used out of their intended age range for assessing communication in -affected participants.

Methods: Parents of -affected children were recruited through FamilieSCN2A Foundation outreach for a combined cross-sectional and longitudinal study.

Novel approaches to measuring cognition in individuals with severe to profound functional impairment: A pilot study in SCN2A-related disorder.

Valid clinical outcome assessments with the ability to capture meaningful aspects of neurodevelopment for individuals with neurogenetic conditions associated with profound functional impairments are lacking, yet critical for clinical care and clinical trial readiness. The purpose of this pilot study was to examine and compare the initial psychometric properties of a series of commonly used standardized and norm-referenced measures of cognition and adaptive functioning as well as alternative measures of neurobehavioral functioning designed to capture responsivity (i.e.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.

Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Infants, Children, and Adolescents with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes.

Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders.

SCN2A-related disorders secondary to altered function in the voltage-gated sodium channel Nav1.2 are rare, with clinically heterogeneous expressions that include epilepsy, autism and multiple severe to profound impairments and other conditions. To advance understanding of the clinical phenotypes and their relationship to channel function, 81 patients (36 female, 44%, median age 5.

Caregiver-reported outcomes with real-world use of cannabidiol in Lennox-Gastaut syndrome and Dravet syndrome from the BECOME survey.

Purpose: Plant-derived highly purified cannabidiol (CBD) reduced the frequency of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) and improved the overall condition of patients in placebo-controlled phase 3 clinical trials. Anecdotal reports also suggest a positive effect on nonseizure outcomes. In this study, we aimed to identify, through a caregiver survey which nonseizure outcomes were most likely to change in these patients.

FDA Patient-Focused Drug Development Guidances: Considerations for Trial Readiness in Rare Developmental and Epileptic Encephalopathies.

Developmental and epileptic encephalopathies (DEE) are rare, often monogenic neurodevelopmental conditions. Most affected individuals have refractory seizures. All have multiple severe impairments which can be as life-limiting as or more limiting than the seizures themselves.

Epilepsy in childhood and school performance: a nation-wide cohort study.

Childhood epilepsy has been linked to poor academic performance, but large-scale studies are lacking. In this nation-wide study of school-aged children, we examined the association between childhood epilepsy and school performance in standardized tests according to phenotypic and treatment-related characteristics. We performed a matched register-based cohort study of children born in Denmark (1997-2009) who participated in the Danish National School Test Programme between 2010 and 2019.

Epilepsy and COVID 2021.

Coronavirus 19 (COVID-19) has infected over 400 million people worldwide. Although COVID-19 causes predominantly respiratory symptoms, it can affect other organs including the brain, producing neurological symptoms. People with epilepsy (PWE) have been particularly impacted during the pandemic with decreased access to care, increased stress, and worsening seizures in up to 22% of them probably due to multiple factors.

Measuring the inch stones for progress: Gross motor function in the developmental and epileptic encephalopathies.

Objective: Developmental and epileptic encephalopathies (DEE) entail moderate to profound impairments in gross motor skills and mobility, which are poorly quantified with clinical outcomes assessments (COA) used in neuro-typical populations. We studied the motor domain of the Adaptive Behavior Assessment System-3 for ages 0-5 years (ABAS) used outside of its intended age range with a focus on raw scores.

Methods: In a cross-sectional survey, 117 parents of children with a variety of DEEs (ages 1-35 years, median = 9) completed the motor domain section of the ABAS.

Staring Spells: How to Distinguish Epileptic Seizures from Nonepileptic Staring.

Objective: To determine the nature of staring spells and factors distinguishing epileptic from nonepileptic staring spells, we studied the clinical and demographic features of children with staring spells referred to a regional new-onset seizure clinic.

Study Design: Our retrospective chart review encompassed 2818 consecutive patients evaluated in the new-onset seizure clinic between September 22, 2015, and March 19, 2018. We identified 121 patients with newly presenting staring spells.