Understanding neurodevelopmental trajectories and behavioral profiles in SCN1A-related epilepsy syndromes.

BACKGROUND: A pathogenic variant in SCN1A can result in a spectrum of phenotypes, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS + ) syndrome. Dravet syndrome (DS) is associated with refractory seizures, developmental delay, intellectual disability (ID), motor impairment, and challenging behavior(1,2). GEFS + is a less severe phenotype in which cognition is often normal and seizures are less severe. Challenging behavior largely affects quality of life of patients and their families. This study describes the profile and course of the behavioral phenotype in patients with SCN1A-related epilepsy syndromes, explores correlations between behavioral difficulties and potential risk factors. METHODS: Data were collected from questionnaires, medical records, and semi-structured interviews. Behavior difficulties were measured using the Adult/Child Behavior Checklist (C/ABCL) and Adult self-report (ASR). Other questionnaires included the Pediatric Quality of Life Inventory (PedsQL), the Functional Mobility Scale (FMS) and the Sleep Behavior Questionnaire by Simonds & Parraga (SQ-SP). To determine differences in behavioral difficulties longitudinally, paired T-tests were used. Pearson correlation and Spearman rank test were used in correlation analyses and multivariable regression analyses were employed to identify potential risk factors. RESULTS: A cohort of 147 participants, including 107 participants with DS and 40 with genetic epilepsy with febrile seizures plus (GEFS + ), was evaluated. Forty-six DS participants (43.0 %) and three GEFS + participants (7.5 %) showed behavioral problems in the clinical range on the A/CBCL total problems scale. The behavioral profile in DS exists out of withdrawn behavior, aggressive behavior, and attention problems. In DS patients, sleep disturbances (ß = 1.15, p < 0.001) and a lower age (ß = -0.21, p = 0.001) were significantly associated with behavioral difficulties. Between 2015 and 2022, behavioral difficulties significantly decreased with age (t = -2.24, CI = -6.10 - -0.15, p = 0.04) in DS participants aging from adolescence into adulthood. A decrease in intellectual functioning (ß = 3.37, p = 0.02) and using less antiseizure medications in 2022 than in 2015, (ß = -1.96, p = 0.04), were identified as possible risk factors for developing (more) behavioral difficulties. CONCLUSIONS: These findings suggest that, in addition to epilepsy, behavioral difficulties are a core feature of the DS phenotype. Behavioral problems require personalized management and treatment strategies. Further research is needed to identify effective interventions.

Exploring individual parent-to-parent support interventions for parents caring for children with brain-based developmental disabilities: A scoping review.

BACKGROUND: Brain-based developmental disabilities (BBDDs) comprise a large and heterogeneous group of disorders including autism, intellectual disability, cerebral palsy or genetic and neurodevelopmental disorders. Parents caring for a child with BBDD face multiple challenges that cause increased stress and high risk of mental health problems. Peer-based support by fellow parents for a various range of patient groups has shown potential to provide emotional, psychological and practical support. Here, we aim to explore existing literature on individual peer-to-peer support (iP2PS) interventions for parents caring for children with BBDD with a view to (1) explore the impact of iP2PS interventions on parents and (2) identify challenges and facilitators of iP2PS. METHOD: An extensive literature search (January 2023) was performed, and a thematic analysis was conducted to synthesize findings. RESULTS: Fourteen relevant articles revealed three major themes regarding the impact of iP2PS on parents: (1) emotional and psychological well-being, (2) quality of life and (3) practical issues. Four themes were identified describing challenges and facilitators of iP2PS: (1) benefits and burden of giving support, (2) matching parent-pairs, (3) logistic challenges and solutions and (4) training and supervision of parents providing peer support. CONCLUSIONS: This review revealed that iP2PS has a positive impact on the emotional and psychological well-being of parents, as well as the overall quality of life for families caring for a child with a BBDD. Individual P2PS offers peer-parents an opportunity to support others who are facing challenges similar to those they have experienced themselves. However, many questions still need to be addressed regarding benefits of different iP2PS styles, methods of tailoring support to individual needs and necessity of training and supervision for peer support providers. Future research should focus on defining these components and evaluating benefits to establish effective iP2PS that can be provided as standard care practice for parents.

Challenging behavior in children and adolescents with Dravet syndrome: Exploring the lived experiences of parents.

BACKGROUND: Dravet syndrome (DS) is a monogenic syndrome associated with SCN1A mutations in the majority of patients and characterized by devastating epilepsy, that may be life-threatening. Aside from refractory seizures, core symptoms of DS include behavioral difficulties, developmental delay, cognitive impairment, and motor dysfunction. Previous DS research has mainly focused on epileptic seizures and pharmacological management and less on behavioral difficulties. This study aims to explore the lived experience of parents supporting a child with DS, with a focus on behavioral aspects. METHODS: We performed a qualitative study using focus groups and following the consolidated criteria for reporting qualitative research (COREQ) guidelines. We organized three focus groups with parents of children and adults with DS and used a pre-defined topic list of open questions, similar for each focus group to ensure comparability. The focus groups were video recorded, transcribed, and anonymized. Data were analyzed using an iterative coding process where codes were sorted into themes. Differences in coding among the researchers were discussed until a consensus was reached. RESULTS: In total, twenty parents (mothers only) participated in the study. The age of children with DS ranged between 3 to 22 years with a mean age of 11.8 years. A range of behavioral difficulties emerged from the thematic analysis. Overall, the most commonly mentioned behavioral difficulties were aggression, dangerous behavior, impulsivity, hyperactivity, routinized and compulsive habits. Our results showed different behavior per age group, with more externalizing behaviors such as aggression and impulsivity in children aged 3-13 years; and more internalizing behavior such as routinized and compulsive habits in adolescents and young adults (14-22 years). This results in a different kind of support these families need and should be acknowledged when in consult with a healthcare professional. Parents reported that challenging behavior was a source of stress and impacted negatively on their family's quality of life. Parents reported feeling alone in their search for solutions, and many explored options outside the traditional medical context. CONCLUSION: Our results suggest that the challenging behavior associated with DS leads to a huge burden of care. Healthcare professionals working with DS patients may need to develop shared decision-making strategies that take into account challenging behavior.

Trashing Property: Characteristics of Psychiatric Patients Who Engage in Domestic Property Damaging.

This descriptive record-based study included 75 patients who had engaged in domestic property damaging (DPD) and needed assessment by an urban emergency psychiatric service team in The Netherlands. The DPD patients were compared to 1145 other patients referred because of aggression, suicidality or other reasons. DPD patients were more often diagnosed with a psychotic disorder or a manic episode, had more often a migration background, were less often diagnosed with depression, and had lower GAF scores. There were no differences with respect to personality disorders or substance use. DPD patients were two to six times more likely to be (mostly involuntarily) admitted to a psychiatric department (64%), than the other patient groups (aggression 45%, suicidality 21%, other referral reasons 37%). The findings indicate that DPD patients represent an exclusive group who possibly have more intercultural and communication disadvantages due to less cultural acceptance or lack of knowledge about mental healthcare in the Netherlands.

Quality of life in SCN1A-related seizure disorders across the lifespan.

This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other SCN1A-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a SCN1A-related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [ß = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (ß = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (ß = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, P < 0.05), mediated by a lower prevalence of behavioural problems (ß = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (ß = -0.1, 95%CI (-0.2 to -0.0)) and older age (ß = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.

The Impact of Cannabidiol on Human Brain Function: A Systematic Review.

Background: Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Methods: Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis. Results: One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Conclusion: Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD's therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.