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Dravet syndrome, a developmental and epileptic encephalopathy, manifests with varying degrees of cognitive and communication impairment, postural and movement disorders (such as ataxia, coordination issues, and crouch gait) and behavioural challenges (including attention deficit/hyperactivity, oppositional/defiant behaviour, and autistic traits). Rehabilitation is a valuable tool for most patients, typically prescribed to address the most pressing issues. However, current practices often fall short in proactively preventing and treating known challenges associated with the syndrome, as indicated by the latest literature, at different life stages. Furthermore, there is a notable lack of evidence regarding treatment types and efficacy specific to people with Dravet Syndrome. Conducted in collaboration with one of the Italian Patient associations, this national survey provides a comprehensive view of the rehabilitation landscape in Dravet Syndrome, as perceived by caregivers. It outlines the types of treatments for 51 patients, based on age and relevant clinical features. The findings reveal a heterogenous rehabilitation approach, only partly tailored to the presence of specific comorbidities, and underline numerous unmet needs. Compared to the past there is indirect evidence that more patients are offered early rehabilitation. Nonetheless, while nowadays speech therapy and neuropsychomotor therapy are nearly universal for children up to the age of 10, some begin physiotherapy and psychotherapy thereafter, with a majority discontinuing treatments. Therefore, families of adolescent and adult patients often face a lack of comprehensive support, predominantly offered when epilepsy is more challenging to control affecting rehabilitation adherence and effectiveness. Finally, a negligible minority is offered treatments such as neurovisual training, augmentative and alternative communication, and occupational therapy. Many of these considerations could apply to other developmental and epileptic encephalopathy with lifelong disability. This survey calls for more data collection on this important topic for more efficient allocation of rehabilitation resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate costs associated with the current management of Dravet syndrome (DS), explore psychosocial aspects of the disease in caregivers and siblings, and identify patient characteristics associated with higher costs in a large, predominantly European survey cohort of patients and their caregivers conducted in 2016., Methods: Health and social care resource use, productivity and quality of life (QoL) data were summarised. Costs for European five (EU5) countries (France, Germany, Italy, Spain and UK) were calculated and patients with high and low current seizure burden compared. Direct healthcare costs and out-of-pocket costs were calculated using literature reported health service costs and participant reported costs, respectively., Results: Direct annual costs of management of non-seizure-related symptoms ($7929) contributed to approximately 50% of all costs (including medication). Excluding medication, non-seizure-related costs dominated costs of care. Cost for patients with high seizure burden were higher for seizure-related healthcare use and physiotherapy, but lower for other therapies. Most (80%) caregivers reported an influence on their career choices and 28% of those in work had missed over three working days in the past four weeks for emergency or routine needs of their child. Caregivers had little free time, relied on family members for support and respite, and experienced emotional stress and uncertainty about their child's future healthcare needs., Conclusion: Families caring for a DS patient manage considerable social and financial impacts. Total direct costs of DS patients (excluding drugs) are driven by non-seizure-related healthcare use and high seizure burden is associated with higher healthcare costs., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Loss-of-function mutations in SCN1A cause Dravet syndrome (DS), a catastrophic childhood epilepsy in which patients experience comorbid behavioral conditions, including movement disorders, sleep abnormalities, anxiety, and intellectual disability. To study the functional consequences of voltage-gated sodium channel mutations, we use zebrafish with a loss-of-function mutation in scn1lab , a zebrafish homolog of human SCN1A . Homozygous scn1lab s552/s552 mutants exhibit early-life seizures, metabolic deficits, and early death. Here, we developed in vivo assays using scn1lab s552 mutants between 3 and 6 d postfertilization (dpf). To evaluate sleep disturbances, we monitored larvae for 24 h with locomotion tracking software. Locomotor activity during dark (night phase) was significantly higher in mutants than in controls. Among anticonvulsant drugs, clemizole and diazepam, but not trazodone or valproic acid, decreased distance moved at night for scn1lab s552 mutant larvae. To monitor exploratory behavior in an open field, we tracked larvae in a novel arena. Mutant larvae exhibited impaired exploratory behavior, with increased time spent near the edge of the arena and decreased mobility, suggesting greater anxiety. Both clemizole and diazepam, but not trazodone or valproic acid, decreased distance moved and increased time spent in the center of the arena. Counting inhibitory neurons in vivo revealed no differences between scn1lab s552 mutants and siblings. Taken together, our results demonstrate conserved features of sleep, anxiety, and movement disorders in scn1lab mutant zebrafish, and provide evidence that a zebrafish model allows effective tests of treatments for behavioral comorbidities associated with DS.

Improved control of epilepsy has permitted an increasing number of young persons with epilepsy to attend university. This study was designed to assess the impact of epilepsy on their education, employment, family and social life. We studied fifteen randomly selected full time university students, aged 20-28 years, who had a well documented history of partial or generalized epilepsy. One third still had seizures, over 90% were taking antiepileptic medication and all were followed by a neurologist. Interviews were conducted according to a standard open-ended questionnaire lasting 1.5 hours. After an initial adjustment period, most did not feel that epilepsy constituted a handicap to their education. They learned about epilepsy, did independent research and one quarter chose careers in the health sciences. Most reported occasional negative experiences, but were reluctant to interpret this as evidence of discrimination. All felt that they had had equal opportunities at school and at work. They were selective about imparting knowledge about their seizures to students, staff and employers, but did not hide their epilepsy. Subjects had high vocational aspirations and academic motivation reflecting good intelligence and previous educational achievements. Their positive attitude, enthusiasm and denial of difficulties were striking. This reflects improved seizure control as well as family and social support in this group of young people.

Myoclonic dystonia is a rare disorder that occurs in an hereditary and a sporadic form. The autosomal-dominantly inherited form is responsive to alcohol but not to other drugs. The sporadic form has been relatively resistant to drug treatment. We report a young man with myoclonic dystonia who displayed only little response to alcohol but improved significantly with a combination of sodium valproate for myoclonus and trihexiphenidyl hydrochloride for dystonia. His rehabilitation, however, was confounded by public authorities who thought the patient's appearance was indicative of drug use.