Prof. Hideo Yamanouchi discusses the lifelong impact of Dravet syndrome, the importance of adaptive functioning and genetic diagnosis, and how emerging targeted therapies could reshape treatment goals beyond seizure reduction.
Dravet syndrome is increasingly understood as a lifelong genetic neurodevelopmental disorder, with consequences extending far beyond seizures. Cognitive and behavioural difficulties, impaired communication and mobility, sleep disturbance and reduced independence can contribute substantially to disease burden for people living with Dravet syndrome and their families.
As genetically targeted therapies move through clinical development, the outcomes that define meaningful treatment benefit are also evolving. touchNEUROLOGY spoke with Professor Hideo Yamanouchi, Professor of Pediatrics and Director of the Comprehensive Epilepsy Center at Saitama Medical University Hospital, Japan, about the lifelong impact of Dravet syndrome, remaining unmet needs, the assessment of adaptive functioning and the potential for earlier genetic diagnosis and disease-modifying approaches to change care.
Looking beyond seizures in Dravet syndrome
What are the key cognitive, behavioural, developmental and functional consequences of Dravet syndrome that clinicians should consider alongside seizure control?
Dravet syndrome affects the whole person, not only seizure frequency. Development may be initially typical, but slowing or plateauing commonly becomes apparent during early childhood, with variable intellectual disability and prominent difficulties in language, attention, executive function and processing speed.
Behavioural and psychiatric features may include autistic traits, hyperactivity, irritability, anxiety and challenging behaviour. Motor problems, including ataxia, hypotonia and impaired coordination, can also occur and, in older patients, crouch gait or parkinsonian features may progressively restrict mobility.
Sleep disturbance, feeding and growth problems, dysautonomia and recurrent injuries can add substantially to disability.
The balance of these problems changes across the lifespan. Some seizure types may become less frequent in adulthood, whereas communication, mobility, self-care and social participation may remain severely limited. Clinicians should therefore follow development, adaptive functioning, behaviour, motor function, sleep, nutrition and mental health longitudinally.
Meaningful care also requires attention to safety, educational and social participation, and caregiver and sibling wellbeing, rather than using seizure counts as the sole indicator of disease burden.
Unmet needs across childhood and adulthood
Despite advances in antiseizure medications, what unmet needs remain for people living with Dravet syndrome and their families across childhood and adulthood, and how do these affect everyday functioning and quality of life?
Important unmet needs remain despite newer syndrome-specific antiseizure medicines. Many people continue to experience convulsive or prolonged seizures, status epilepticus, injuries and emergency admissions, and remain at elevated risk of premature death, including sudden unexpected death in epilepsy (SUDEP).
Complete seizure freedom is uncommon, while polytherapy may contribute to sedation, appetite or weight problems, behavioural effects and a substantial daily treatment burden. Current antiseizure treatments also do not reliably normalise the neurodevelopmental trajectory.
For families, unpredictability is itself disabling. Continuous supervision, disrupted sleep, avoidance of triggers, rescue-medication planning and restrictions on school, work and travel can affect the entire household.
Communication, learning, behaviour, mobility, feeding, sleep and autonomy may be at least as important as seizures, and the psychological and financial burden on caregivers can be profound.
These gaps often widen in adulthood, when access to syndrome-specific expertise, rehabilitation and coordinated social support becomes more limited. The principal unmet need is therefore a safer and more predictable life: fewer severe seizures, preservation or acquisition of useful skills, lower treatment toxicity, greater participation and independence, and coordinated multidisciplinary support throughout life.
Defining meaningful disease modification
As genetically targeted therapies emerge, what would meaningful disease modification in Dravet syndrome look like, and which outcomes beyond seizure reduction should be considered when assessing treatment benefit?
For SCN1A-related Dravet syndrome, meaningful disease modification would alter the trajectory associated with SCN1A haploinsufficiency, rather than simply suppressing seizures while treatment is present.
It should provide durable reductions in convulsive and prolonged seizures and status epilepticus, but also preserve or improve communication, learning, behaviour, mobility and self-care.
Other relevant outcomes include sleep, injuries, rescue-medication use, hospital admissions, quality of life, caregiver burden and, ultimately, mortality risk.
Age and timing are crucial. In a young child, benefit may mean preventing developmental slowing and enabling the acquisition of new skills; in an adolescent or adult, stabilisation or a modest gain in communication or independence may be highly meaningful.
Outcomes should therefore be age-appropriate, measured longitudinally and interpreted against natural-history data.
Phase 1/2a and open-label extension studies of zorevunersen have reported sustained reductions in seizures alongside improvements in adaptive behaviour, overall clinical status and quality of life.1
These findings are encouraging, but they do not yet establish disease modification because the studies lacked a randomised control group.
Confirmation will require results from the ongoing sham-controlled Phase 3 EMPEROR study, together with longer-term evidence of durability and safety.
Measuring adaptive functioning in clinical trials
What current measures are used to assess adaptive functioning in Dravet syndrome trials, and how should clinicians interpret changes in these scores?
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), is an important measure of adaptive functioning used in Dravet syndrome natural-history studies and therapeutic trials.
Through a structured caregiver interview, it assesses communication, daily living skills and socialisation, with subdomains including receptive and expressive communication, personal skills, interpersonal relationships and coping.
Trials may complement it with clinician and caregiver global impressions, quality-of-life measures and age-appropriate developmental or cognitive assessments.
Interpretation requires care. Age-normed standard scores can decline even when a child is acquiring skills because the child may be progressing more slowly than typically developing peers.
Raw scores or growth scale values are therefore often more informative for assessing within-person change, particularly when standard scores are affected by floor effects.
A 2025 qualitative study found that gains of only 1–3 raw-score points, or approximately 2–3 growth scale values, in relevant Vineland-3 subdomains were considered meaningful by many caregivers and clinicians, especially when they translated into improved communication, safety or independence.2
No single threshold applies to every patient; changes should be interpreted according to age, baseline ability, the domain being assessed, informant consistency and natural-history expectations, and should be supported with observable real-world benefit.
Genetic diagnosis and lifelong management
How can earlier and more accurate genetic diagnosis, including testing or retesting in adults, support access to appropriate care and emerging clinical studies, and what is needed to ensure effective transition and lifelong management for people with Dravet syndrome?
Earlier genetic diagnosis can shorten the diagnostic odyssey, support appropriate syndrome-specific treatment and emergency planning, inform recurrence counselling, and facilitate access to specialist services and genotype-defined clinical studies.
In patients with Dravet syndrome caused by SCN1A loss-of-function variants, diagnosis can also help clinicians avoid inappropriate regular use of sodium-channel-blocking antiseizure medicines, while recognising that SCN1A variants can cause several phenotypes and must be interpreted in clinical context.
Testing should not stop in childhood. Adults with a history of infantile-onset prolonged febrile or hemiclonic seizures, recurrent status epilepticus, later drug-resistant epilepsy, intellectual disability or characteristic gait abnormalities may remain undiagnosed.
If earlier testing was negative or limited, clinicians should consider reanalysis and updated testing that includes sequencing and deletion/duplication analysis; broader epilepsy panels, exome or genome sequencing, or updated SCN1A analysis may be appropriate when the phenotype is atypical, or initial SCN1A testing remains negative.
Previously reported variants should also be periodically re-evaluated in light of evolving genetic knowledge and classification standards.
Diagnosis alone is insufficient. Begin transition planning well before transfer, include joint paediatric–adult review, and provide a portable medication and emergency plan.
Lifelong care should integrate neurology, rehabilitation, behavioural, nutritional, sleep and psychosocial services, while maintaining support for caregivers and facilitating participation in emerging trials.
References
- Laux L, Sullivan J, Perry MS, Brunklaus A, et al. Zorevunersen in Children and Adolescents with Dravet Syndrome. N Engl J Med. 2026 Mar 5;394(10):969-982. doi: 10.1056/NEJMoa2506295.
- Condon C, Parkerson KA, Dandurand A, et al. Qualitative evaluation of meaningful change in Dravet syndrome as measured by the Vineland-3: Caregiver and clinician perspectives. Epilepsy Behav. 2025;167:110381. doi:10.1016/j.yebeh.2025.110381.
About Prof. Hideo Yamanouchi
Hideo Yamanouchi, MD, is Professor of Pediatrics and Director of the Comprehensive Epilepsy Center at Saitama Medical University Hospital, Japan. After completing his training in paediatric neurology at the National Center of Neurology and Psychiatry (NCNP), he undertook a research fellowship at the Hospital for Sick Children in Toronto, Canada, where he conducted neuropathological research in epilepsy. He is a paediatric neurologist and epileptologist specialising in developmental and epileptic encephalopathies, epilepsy genetics, acute encephalopathy and status epilepticus. He has made extensive contributions to clinical care, research and medical education and has been actively involved in international child neurology initiatives. He has served as Secretary General of the Asian and Oceanian Child Neurology Association (AOCNA) since 2023. He previously served for six years as Chairperson of the Infantile Seizure Society (ISS) and currently serves as an Advisor to the Society. He has authored numerous scientific publications and continues to support education and capacity building in paediatric epilepsy worldwide.
Related content
Emerging advances in Dravet syndrome: Dravet Syndrome UK
More content in epilepsy
Cite: H Yamanouchi. Beyond seizure control in Dravet syndrome: Lifelong care and the promise of disease modification. touchNEUROLOGY. 28 September 2026.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: Hideo Yamanouchi has no actual or potential conflicts of interest in relation to this interview.
The content was developed and edited by human editors. No fees or funding were associated with its publication. touchNEUROLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
This content has been developed independently by Touch Medical Media for touchNEUROLOGY in collaboration with the author/speaker. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
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