Cognitive, behavioral, and social functioning in children and adults with Dravet syndrome.

AIM: The objective of the study was to delineate the cognitive, behavioral, psychological, and social functioning of individuals with Dravet syndrome. METHOD: Cognitive, behavioral, and social functioning were assessed in patients with Dravet syndrome by comprehensive, age-appropriate standardized neuropsychological testing. Primary caregivers completed standardized measures regarding participants' behavior, psychological status, adaptive functioning, and social skills, including their involvement with intervention services. RESULTS: The cohort comprised 45 patients, aged 2-30 years. Intellectual functioning ranged from average intellect to profound intellectual disability, with a decrease in cognitive and adaptive functioning with age. Only 6 children were able to complete the entire neuropsychological battery and showed a range of cognitive profiles. Five of 6 participants scored within the average range on Affect Recognition and 5/6 on Motor Free Visual Perception tests. Twenty-one (58%) participants had deficits in social skills and 18/27 (67%) in social communication, with 10 participants, who did not yet have a diagnosis of autism spectrum disorder (ASD), screening positive for social communication deficits. Behavioral problems were frequently reported, with attention problems in 24 (65%) and atypicality in 25 (70%). Despite this, parents reported that psychological services were the least utilized health interventions. CONCLUSIONS: Cognitive functioning varies markedly in individuals with Dravet syndrome, with some patients demonstrating global impairment while others have a discordant neuropsychological profile. Behavioral, psychological, social problems, and ASD are common. Social deficits should be reviewed to identify those who warrant ASD assessment. Early identification of behavioral and psychological disorders and targeted use of psychological intervention are essential components of holistic care in Dravet syndrome.

Pediatric epilepsy surgery patients show normal psychosocial development at long-term follow-up despite dissatisfying family dynamics.

Drug-resistant pediatric epilepsy involves unpredictable seizures and long-term medical management. Both factors can alter a child's psychosocial development and the dynamics of the family, to the detriment of patient and family wellbeing. While drug-resistant pediatric epilepsy can be successfully treated by neurosurgery in some cases, the outlook for psychosocial and family functioning after surgery remains unclear. A total of 163 participants across four groups took part in the current study: these were (i) individuals who had undergone surgical treatment of drug-resistant focal seizures approximately five years prior as children, and were now largely adolescents or young adults ('Patients'; n = 23), (ii) their caregivers ('Patient Caregivers'; n = 27), (iii) healthy individuals of similar age and gender to the Patients ('Controls'; n = 53), and (iv) their caregivers ('Control Caregivers'; n = 60). Based on similar software validated in adults, we built an interactive computer program, 'Living with Epilepsy', to evaluate the achievement of age-specific developmental tasks in Patients relative to their peers. The Family Adaptability and Cohesion Scale measured family dynamics. The findings showed that in the context of seizure freedom, after pediatric epilepsy surgery, Patients are similar to their healthy peers in terms of attaining developmental tasks, with no differences between the Patient and Control groups (P > .05). Family dynamics, however, seemed resistant to postsurgical adaptation, with Patients reporting lower levels of balanced family dynamics (cohesion, flexibility) and higher rates of unbalanced family dynamics (disengagement, chaos, rigidity, enmeshment) relative to Patient Caregivers (P < .001-0.041), and the Controls (P = .011-0.034). Patients also reported reduced family satisfaction compared with that of Patient Caregivers (P = .002), which was associated with polytherapy prior to surgery; that is, more drug-resistant seizures. These findings suggested that childhood-onset epilepsy has a lasting effect on family functioning, even when the child has an optimal medical and psychosocial outcome. These initial findings have significant implications for the provision of pre- to postoperative family support in pediatric epilepsy cases.

Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy.

OBJECTIVE: To identify the genetic basis of a family segregating episodic ataxia, infantile seizures, and heterogeneous epilepsies and to study the phenotypic spectrum of KCNA2 mutations. METHODS: A family with 7 affected individuals over 3 generations underwent detailed phenotyping. Whole genome sequencing was performed on a mildly affected grandmother and her grandson with epileptic encephalopathy (EE). Segregating variants were filtered and prioritized based on functional annotations. The effects of the mutation on channel function were analyzed in vitro by voltage clamp assay and in silico by molecular modeling. KCNA2 was sequenced in 35 probands with heterogeneous phenotypes. RESULTS: The 7 family members had episodic ataxia (5), self-limited infantile seizures (5), evolving to genetic generalized epilepsy (4), focal seizures (2), and EE (1). They had a segregating novel mutation in the shaker type voltage-gated potassium channel KCNA2 (CCDS_827.1: c.765_773del; p.255_257del). A rare missense SCN2A (rs200884216) variant was also found in 2 affected siblings and their unaffected mother. The p.255_257del mutation caused dominant negative loss of channel function. Molecular modeling predicted repositioning of critical arginine residues in the voltage-sensing domain. KCNA2 sequencing revealed 1 de novo mutation (CCDS_827.1: c.890G>A; p.Arg297Gln) in a girl with EE, ataxia, and tremor. CONCLUSIONS: A KCNA2 mutation caused dominantly inherited episodic ataxia, mild infantile-onset seizures, and later generalized and focal epilepsies in the setting of normal intellect. This observation expands the KCNA2 phenotypic spectrum from EE often associated with chronic ataxia, reflecting the marked variation in severity observed in many ion channel disorders.

Developmental outcomes of childhood-onset temporal lobe epilepsy: a community-based study.

PURPOSE: To assess the impact of childhood-onset temporal lobe epilepsy (TLE) on the attainment of normative developmental tasks and identify predictors of long-term developmental outcomes. METHODS: In 1992-1993, a prospective longitudinal cohort study of childhood-onset TLE was commenced in the State of Victoria, Australia. At review in 2004-2006, we assessed developmental tasks, which are age-specific individual psychosocial achievements tied to particular phases of the lifespan. The cohort comprised 54 individuals (33 female) with a mean age of 20 years (range 12-29), and mean age at TLE onset of 6 years (range 0.2-15). KEY FINDINGS: Individuals were clustered into three groups representing distinct developmental trajectories: (1) a Normal group (52%) who achieved most of their developmental tasks, (2) an Altered group (37%) who achieved some, and (3) a Delayed group (11%) who achieved few. The groups showed significant cognitive differences, with the Normal group outperforming the Altered and Delayed groups on a range of measures (p < 0.05). Multiple discriminant function analysis indicated that membership of the groups was independently predicted by the chronicity of seizures, cognitive functioning, having surgically remediable epilepsy, and gender (p < 0.001). Seizure chronicity and cognition discriminated between all three trajectories, while surgical intervention and gender primarily discriminated between the Altered and Delayed trajectories. SIGNIFICANCE: Childhood-onset TLE can disrupt achievement of normative developmental tasks that is independently predicted by medical, biologic, and cognitive factors. Assessment of developmental tasks across the lifespan provides a practical framework for guiding prognostic counseling of patients and families.

Psychological outcome profiles in childhood-onset temporal lobe epilepsy.

PURPOSE: To examine the effect of childhood-onset temporal lobe epilepsy (TLE) on long-term psychological function and to identify outcome profiles related to the natural course and treatment of TLE. METHODS: Psychological function was studied in a prospective, community-based cohort of childhood-onset TLE, approximately 13 years following seizure onset. Fifty-three patients were assessed using a semi-structured psychosocial interview, supplemented by self-report questionnaires measuring quality-of-life, depression, self-esteem, and anxiety. RESULTS: Common patterns were observed, giving rise to four distinct patient groups and psychological outcomes: (1) patients who experienced spontaneous remission of their seizures fared best; their psychological profile was characterized by heightened worry about the possibility of seizure recurrence; (2) patients who progressed to surgery and were seizure free reported adjustment difficulties associated with learning to become "well"; (3) patients who progressed to surgery and were not seizure free had the poorest psychological outcomes, with depression featuring prominently; and (4) patients with ongoing intractable epilepsy reported psychological and social features consistent with the effects of their chronic illness. DISCUSSION: Patients with childhood-onset TLE face distinctive long-term psychological challenges. The specific nature of these challenges can be understood in terms of the natural evolution and treatment of their epilepsy.