June 2026 Research Update

Across these papers, the main pattern was that add-on antiseizure medicines were studied in everyday care settings (not randomized trials), so results show what happened for selected patients but cannot prove cause and effect. Fenfluramine had the largest real-world datasets and was linked with seizure reductions over time and fewer seizure-related healthcare visits, with many people staying on treatment. Cenobamate and perampanel data were more limited for Dravet syndrome specifically, with responses varying between individuals and side effects still important to track. [1] [2] [3] [4]

In a multicenter retrospective study of 166 children and adults with developmental and epileptic encephalopathies (including Dravet syndrome), fenfluramine use was followed by a median 68.8% seizure reduction at 12 months, and 61% had at least a 50% reduction. Many people stayed on fenfluramine at 12 months (77.1%), while side effects were reported in 68.1% and led to stopping fenfluramine in 12%. The study also reported improvements in daily-life areas such as cognition, behavior, sleep, and caregiver-rated overall status for some participants. [1]

A separate US health insurance claims study focused specifically on Dravet syndrome and looked at whether people stayed on fenfluramine and how often they used rescue medicines and seizure-related healthcare. Persistence at 6 months was 84%, and among those who remained on fenfluramine, rescue medicine fills and seizure-related visits (including emergency room and inpatient visits) decreased over the same period. These results suggest reduced healthcare use among persistent users, but claims data do not directly measure seizure counts or capture all reasons for changes in care. [2]

Evidence for cenobamate in Dravet syndrome in this set came from a two-patient pediatric case series with SCN1A-related Dravet syndrome, where one child had about an 80% reduction in total seizures and generalized tonic-clonic seizures during treatment and a rebound during tapering, and another had suppression of generalized tonic-clonic seizures over 12 months at a low maintenance dose. Because this describes only two individuals, it cannot show how often this response happens or how safe it is across broader groups, and the authors noted that seizures could worsen in some cases. [3]

Perampanel was studied as add-on treatment in a real-world open-label group of 87 infants and toddlers with drug-resistant epilepsy (not mainly Dravet syndrome), with about 44.4% having at least a 50% seizure reduction at 12 months and 23.5% reported seizure freedom. Side effects occurred in 23.0%, most often sleepiness (11.5%) and irritability or aggressive behavior (9.2%), and 55.2% remained on treatment at 12 months. Because only a few participants had Dravet syndrome, these numbers may not reflect outcomes for Dravet syndrome specifically. [4]

A five-patient case series from Pakistan highlighted that Dravet syndrome can involve multiple seizure types, fever-triggered seizures, and universal developmental delays, and that seizure control may remain difficult even with combinations of commonly used antiseizure medicines (including cannabidiol in some cases). This report mainly describes local experience and care challenges rather than testing one medicine in a way that can be compared across patients. [5]

For patients and caregivers, this group of studies adds real-world information about how seizure medicines are being used over months to a year, including how often people continue them and what kinds of side effects are reported. The fenfluramine studies are most directly relevant to Dravet syndrome and suggest that, in everyday care, many patients stay on treatment and may have fewer seizures and fewer seizure-related urgent visits, though these designs cannot prove fenfluramine caused the changes. Cenobamate and perampanel results in this set are early or not Dravet-focused, so it remains uncertain which Dravet syndrome subgroups might benefit most and how risks compare across larger numbers of patients.

Across these papers, genetic testing most often pointed to changes in SCN1A and other seizure-related genes, helping explain why some children with early fever-related seizures later develop Dravet syndrome. Evidence also showed that broader gene testing can uncover other causes of developmental and epilepsy syndromes, while real-world factors like test cost can limit who gets tested and how families are evaluated. [6] [7] [8]

In a single-center study of 233 Chinese children with high-risk febrile seizures, about 3 in 10 had a clear genetic answer on a targeted epilepsy gene panel, and many of the positive results involved voltage-gated sodium channel genes. SCN1A was the most common gene found, and among children with an SCN1A change, most later progressed to Dravet syndrome. [6]

That same study reported that children with a confirmed disease-causing genetic change had higher rates of severe seizure events and developmental delay than children without a clear genetic result. The authors also described that genetic results often led clinicians to change anti-seizure medicines, and they noted seizure worsening in several children who were taking sodium channel-blocking medicines before the genetic result was known. [6]

A case report of two Palestinian siblings illustrated how one child with a confirmed SCN1A change fit Dravet syndrome while a younger sibling did not yet meet Dravet criteria and had a milder picture on the same SCN1A-related spectrum (called GEFS+), with close follow-up advised; genetic testing for other family members was limited by cost. The report also described seizure worsening with carbamazepine in the child with Dravet syndrome, emphasizing the practical challenges of diagnosis and medicine access in resource-limited settings. [7]

A small case series reported novel genetic changes in PLPBP, SCN1A, and SLC6A1 in three people with developmental and epileptic encephalopathy. This highlights that severe early-onset epilepsy can have different genetic causes and that broader testing can identify different genetic explanations. [8]

A separate population exome study in 6,739 Russians looked for rare genetic changes that could increase the chance of serious medication side effects across several conditions, including Dravet syndrome. The study identified a small group of people carrying clinically significant variants in multiple genes, including SCN1A, but it did not include information on symptoms or actual drug exposures, so it mainly serves as background on how often such variants may appear in a population. [9]

For families affected by Dravet syndrome or early severe febrile seizures, these studies reinforce that a genetic result, especially involving SCN1A, can help clarify the likely diagnosis pathway and may help explain why seizures and development change over time. They also show important uncertainties and limits: not everyone gets a clear result from a panel, different genes can lead to similar symptoms, and access to testing (and to recommended therapies) can be uneven depending on cost and local resources. The population-level screening study is not a guide to individual risk, but it reflects growing interest in using genetic information to anticipate medication safety issues in some inherited conditions. [6] [7] [8] [9]

Across these studies, long-term outcomes in childhood-onset developmental and epileptic encephalopathies (including Dravet syndrome) were mixed: some children became seizure-free over time, while others continued to have hard-to-control seizures and ongoing developmental challenges. Mortality, including sudden unexpected death in epilepsy (SUDEP), was measurable in research datasets, with rates differing by syndrome and with uncertainty about how well trial-based numbers reflect everyday life. [10] [11]

In a longitudinal cohort of 255 children followed for a median of 5 years, 40.4% achieved seizure freedom by last follow-up, and having a positive genetic test did not independently predict seizure freedom or developmental outcome. Instead, earlier developmental concerns (such as delay before seizures or loss of milestones) were linked to worse developmental outcomes later on. In syndrome-specific analysis, genetically confirmed Dravet syndrome showed a higher likelihood of drug-resistant epilepsy (seizures that remain difficult to control). [10]

A Bayesian meta-analysis combining randomized trials and long-term extension studies (3757 patients across several developmental and epileptic encephalopathies) estimated overall mortality at 8.76 per 1000 person-years and SUDEP at 4.32 per 1000 person-years. For Dravet syndrome specifically, the estimate was 8.0 per 1000 person-years for mortality and 7.59 per 1000 person-years for SUDEP, based on deaths observed in the included trial datasets. The authors noted that trial-based data may underestimate mortality and SUDEP and called for prospective, population-based studies to better define real-world rates. [11]

For families living with Dravet syndrome, these studies add context about what has been observed over years of follow-up: seizure and developmental paths can differ greatly between children, and a confirmed genetic result by itself did not explain who became seizure-free in one cohort, even though genetically confirmed Dravet syndrome was linked to a higher chance of ongoing difficult-to-control seizures. The mortality and SUDEP estimates provide a way to understand risk at a population level, but the numbers here mainly reflect clinical trial participants and may not match real-world experience, so uncertainty remains about the true day-to-day risk outside research studies. [10] [11]

Across these papers, the overall pattern is that Dravet syndrome is not only about seizures: changes in stress biology, sleep regulation, and the balance of brain signaling in specific circuits may also matter. Most evidence here comes from mouse models, so it helps explain possible mechanisms rather than proving what happens in people. Together, the studies point to stress and sleep-related brain regions as places where the SCN1A-related condition can reshape how circuits work, sometimes in a way that could worsen outcomes. [12] [13] [14] [15]

In a mouse model, repeated restraint stress disrupted stress-hormone system regulation and changed behavior toward more anxiety-like activity, while also changing communication between neurons in a stress-related brain region called the bed nucleus of the stria terminalis (BNST). The same study reported increased mortality in stressed female Dravet syndrome mice, suggesting stress can have stronger effects in the Dravet model than in typical mice under the tested conditions. The circuit changes included shifts in both excitatory and inhibitory signaling onto BNST neurons that produce corticotropin-releasing factor (a stress-related signaling molecule), and stress blunted a form of synaptic plasticity in both Dravet and control mice. [12]

A separate report discussed work in another Dravet syndrome mouse model where sleep and body temperature regulation were linked: the mice had difficulty transitioning from wake to non-REM sleep, and warm environments did not trigger sleep in the usual way. Increasing Nav1.1 (the SCN1A-related sodium channel) expression in the anterior hypothalamus, or briefly activating hypothalamic neurons with a lab technique, restored warmth-related sleep onset and improved sleep-related brainwave measures, without changing interictal spikes in that report. This supports the idea that hypothalamus circuits involved in temperature and sleep timing can be part of the Dravet syndrome biology in mice. [13]

Two additional papers focused on how SCN1A-related changes may shape brain structure and inhibitory-cell function. One mouse study found that adult Dravet syndrome model mice showed increased Nav1.6 staining at the axon initial segment of parvalbumin interneurons, without similar increases in Nav1.2 or Nav1.3, suggesting a specific, later-developing compensatory change in a key inhibitory cell type. In a single-child case report, the hippocampus showed abnormal neuronal architecture, and the authors discussed prior literature suggesting SCN1A channels may play a role in brain formation. [14] [15]

For patients and caregivers, this group of studies mainly adds background about why stress, sleep disruption, and temperature-related sleep effects can be intertwined with brain circuit function in Dravet syndrome. The stress and sleep results come from mouse models and a commentary, and the brain-structure report is from one child, so it is not clear how broadly these findings apply across people with Dravet syndrome or how they relate to day-to-day symptoms in any individual. What remains uncertain is which exact cell types and circuits are most important in humans, how these circuit changes develop over time, and whether targeting these pathways would change clinical outcomes beyond what is already addressed by current care.

Across two case reports, the main pattern was that serious complications can arise either from epilepsy treatment safety monitoring or from unrelated medical conditions requiring surgery, and these situations may involve the heart and blood pressure. Because both reports describe single children with severe epilepsy syndromes, they show what can happen in individual situations but cannot tell how often these complications occur more broadly. [16] [17]

In one report, a 17-month-old child treated off-label with fenfluramine for SCN1B-related developmental and epileptic encephalopathy developed pulmonary arterial hypertension (high pressure in the blood vessels of the lungs) after about 11 months, detected on a heart ultrasound despite no symptoms. The pulmonary arterial hypertension improved after fenfluramine was stopped, but seizure control worsened after withdrawal, showing a difficult balance between seizure control and monitoring for rare safety problems. [16]

In another report, a 6-year-old child with Dravet syndrome had surgery to remove a catecholamine-secreting presacral neuroblastoma (a tumor that releases stress hormones that can raise blood pressure). The team described periods of high blood pressure during tumor handling and low blood pressure related to positioning and bleeding, followed by months of blood pressure medicine after surgery, with return to normal lifestyle by 18 months. This illustrates that major blood pressure instability can occur around surgery when hormone-releasing tumors are involved, even when care is carefully planned. [17]

For patients and caregivers, these papers mainly serve as background safety context: they describe rare, high-impact situations that may require extra monitoring and coordination between epilepsy care and other specialties. The fenfluramine report suggests that heart and lung-blood-pressure monitoring can matter, especially in very young children receiving off-label treatment, but it does not show how common this side effect is. The surgery report is relevant to families facing an additional diagnosis requiring an operation, showing that blood pressure changes can be a major focus of peri-operative care, but it is based on one patient and may not reflect typical surgical experiences. [16] [17]