The Difficult Journey of a Child with Dravet Syndrome: Perspectives from a Parent and the Neuropaediatrician
Patient/Guardian Author, Rennes, France
https://ror.org/05qec5a53grid.411154.40000 0001 2175 0984Department of Emergency and Specialist Paediatrics, Rennes University Hospital, Rennes, France
https://ror.org/05qec5a53grid.411154.40000 0001 2175 0984Service de Pédiatrie d’Urgences et de Spécialités, Centre Hospitalier Universitaire de Rennes, Hôpital Sud, 16, Boulevard de Bulgarie, 35203 Rennes Cedex 2, France
Abstract
Dravet syndrome (DS) is a rare and severe form of epilepsy, characterised by recurrent seizures that begin during the first year of life, leading to motor, cognitive and behavioural impairments. This article provides the perspectives of a parent of a child with DS (‘Ethan’) and the treating neuropaediatrician. Ethan’s seizures began when he was 9 months old, and were a mixture of focal seizures and status epilepticus. Numerous treatments were tried, including standard anti-seizure medications (such as levetiracetam, clobazam and fenfluramine), other medications (cannabidiol) and nonpharmacological approaches (ketogenic diet), with little success. When Ethan was 3 years old, a prolonged episode of status epilepticus precipitated by coronavirus disease 2019 (COVID-19) led to brain damage. Rehabilitation allowed Ethan to regain some of his previous functioning and, at the age of 38 months, combination therapy with clobazam, sodium valproate and stiripentol was begun and has successfully controlled Ethan’s seizures. Ethan’s father describes the stress that the diagnosis of DS, interactions with the healthcare system, and the search for effective treatment imposed on the family. Since Ethan’s seizures have been better controlled, the family has been able to lead a more normal life, and is now focused on supporting Ethan and looking to the future. Ethan’s neuropaediatrician outlines the approach she takes to the diagnosis and management of DS, including the importance of the clinician–parent relationship in imparting the diagnosis and making initial and ongoing treatment decisions. The preferred first-line treatment is sodium valproate, which is followed by sodium valproate–clobazam–stiripentol combination therapy, topiramate or a ketogenic diet as second-line options. In children > 2 years, cannabidiol and fenfluramine can also be considered. The aim of maintenance treatment (which will invariably be polytherapy) is to reduce the number of seizures, particularly status epilepticus, given the significant impact of this seizure type on patients and caregivers.
Key Summary Points
| Dravet syndrome (DS) is a rare and severe form of epilepsy that begins in the first year of life, and is associated with motor, cognitive and behavioural impairments. |
| This article provides the perspectives of the father of a child with DS (‘Ethan’) and the treating neuropaediatrician. |
| Ethan’s father describes the stress associated with parenting a child with DS, including the shock of the diagnosis and the numerous treatment changes, but also the significant positive impact that finding an effective treatment (combination therapy with clobazam, sodium valproate and stiripentol) has had on the family. |
| Ethan’s neuropaediatrician describes her approach to the diagnosis and treatment of DS, including the stepwise use of anti-seizure medications, from first-line sodium valproate to second-line therapies such as a sodium valproate–clobazam–stiripentol combination, topiramate, cannabidiol, fenfluramine and a ketogenic diet. |
| The neuropaediatrician emphasises the importance of a strong clinician–parent relationship for easing the difficulties that parents face in navigating the diagnosis and treatment of their child’s DS, and allowing the child to fulfil their potential. |
Parent’s Perspective
Beginnings and Diagnosis
Ethan (not his real name) is the second of our three children. He’ll turn 6 years old in 2025. He has an older brother aged 7 and a younger sister aged 3. The story of his Dravet syndrome began in February 2020 when we were living as French expatriates in Houston, Texas, United States of America (USA). Ethan was 9 months old at the time. We had taken Ethan and his brother on holiday back to France, and we were staying with my parents near Rennes in Brittany. Ethan had his first epileptic seizure during that trip. It lasted a long time, about an hour. My parents’ house is a long way from the hospital in Rennes, and so the transport time was interminable; it was horrible. At the time, we did not really understand what was happening, probably like all parents of children with epilepsy. There was no diagnosis following this first seizure.
About 2 months later, when we were back in the USA, Ethan had more seizures, and Dravet syndrome was diagnosed. It was right in the middle of the coronavirus disease 2019 (COVID-19) pandemic and lock-down, and so we were unable to see Ethan’s epileptologist at the Texas Children’s Hospital face-to-face. It was rather a shock and very difficult to receive news like that over the telephone and in a foreign language. In the following weeks, we were lucky enough to be able to consult French experts on rare epilepsies by telephone, who gave us a better understanding of what we were facing.
We discovered that Ethan’s Dravet syndrome manifested itself as a mixture of short seizures (known as “focal”, which subside rapidly) and prolonged seizures (known as “status epilepticus”, which persist and lead to a trip to the emergency room and intensive care). Ethan did not have that many seizures at the beginning. Later, the disease intensified, and the worst time was between the ages of 18 and 30 months, when Ethan's seizures were the most frequent and severe. During this time, Ethan had almost exclusively episodes of status epilepticus: he had violent tremors and convulsions, with the start and the finish of the episode being very clear. It was more complicated when Ethan had a focal seizure that drifted into status epilepticus: we would give him rescue medication, but we did not know whether the seizure had become focal again or if it was still a status epilepticus. Another difficult aspect of his condition was that sometimes, after one status epilepticus had ended, another would start 30 to 40 minutes later. The uncertainty and the unpredictable nature of Ethan’s seizures made the whole situation very difficult; we were in a constant state of anxiety.
Treatments
Ethan has had so many treatments (Fig. 1), and we have followed them all so closely that sometimes we feel like experts. After his first status epilepticus in France in February 2020, Ethan was given levetiracetam (30 mg/kg/day in two doses). When we got back to the USA, as he continued to suffer from status epilepticus, the American team added clobazam at a dose of 0.6 mg/kg.
In addition to the pharmacological treatment, we also tried a ketogenic diet for 3 months when Ethan was about 18 months old. The logistics of that were very complicated (such as ensuring the correct dosage and transporting the food when travelling), and it had no tangible impact on the frequency of Ethan’s status epilepticus. Next, we tried cannabidiol for 3 months, but with no success.
The French doctors, who were advising us from a distance, recommended trying treatment with stiripentol. However, prescribing stiripentol as a first line of treatment for status epilepticus was not a common strategy in the USA and the American team recommended replacing it with fenfluramine, which we were hearing a lot about at the time. We felt lucky to have access to fenfluramine, the newest drug to arrive on the American market. We really wanted to stay on top of the most advanced therapeutic approaches! For 1 year, Ethan received a combination of clobazam (0.5 mg/kg/day) and fenfluramine (0.6 mg/kg/day), which he tolerated quite well. As Ethan still had many episodes of status epilepticus, we did try stiripentol (34 mg/kg/day) in addition to the clobazam/fenfluramine combination in May 2021. Ethan did not take stiripentol for very long because we did not notice any immediate beneficial effects on his status epilepticus, and we were concerned that the drug might be affecting his behaviour.
In total, we tried five combinations of drugs over a period of 2 years, with some form of change in treatment about every 3 months. We knew that the potential outcome of each status epilepticus could be fatal, which is why we wanted more than anything to find the right combination of drugs. We were under a lot of stress, but we simply could not accept waiting 6 months on a treatment that was not working! Each change of medication was hard to manage. First, we would see the adverse effects, especially during the first 3 weeks of treatment. Then, we would wait to see a change, which often did not come. And then the adverse effects would carry on, sometimes even persisting during the weeks when Ethan gradually stopped taking the treatment. These adverse effects could be mood swings or sleep problems, although they did eventually disappear. Starting or stopping medication sometimes also led to seizures.
Living with the Seizures
Between the ages of 18 and 30 months, Ethan had two or three episodes of status epilepticus a month, usually lasting between 30 minutes and 1 hour. We put in place an emergency protocol to manage his status epilepticus at home and in hospital. When Ethan had a status epilepticus, first we would administer the rescue medications ourselves [intranasal midazolam (2 × 5 mL) and/or rectal diazepam (10 mL)]. Then, if the seizure continued, we would take him to the emergency room.
At that time, Ethan spent the weekdays in a daycare centre for children with disabilities. When Ethan had an episode of status epilepticus there, the nurses would take him straight to the hospital, because it was much closer than our home. The daycare staff would inform us immediately, and we would join Ethan at the hospital where we would find him in a very “foggy” state. In hospital, if Ethan's status epilepticus was resistant and the medical team had to administer stronger medications, he would end up in intensive care. Throughout this period, the American medical teams worked miracles and saved my son every time. I recall being in the emergency room and seeing 20 or 30 healthcare staff surrounding my tiny child, trying to save him. It was a very stressful time.
Living as a Parent of a Child with Epilepsy
As the parent of a child with epilepsy, you are faced with a dilemma. On the one hand, you want to protect your child against seizures. The only way to do this is medical treatment, which may have adverse effects, and you have to live with those. On the other hand, you want to protect your child from those same adverse effects and take the risk of the child having seizures that you think you can manage. Naively, we wanted the latter.
I regret that nobody explained to us that Ethan had very severe seizures and that we had no choice: intensive treatment was necessary in his case. We did not understand that status epilepticus should not be happening every 2 weeks, which was the case for Ethan. Indeed, we learnt later that the period from age 1 to 4 years is critical, and that it is essential to protect the child's brain during this period with effective drug treatment. We did not understand that we did not need to worry about the adverse effects of a drug, because any drug can be withdrawn later once this critical period is past. I placed a lot of hope in the rescue medication to stop the status epilepticus, and only later realised that it was the maintenance treatment that allowed rescue medication to be more effective during an episode.
Ethan's disease meant that we could never stay far from a hospital. Even when we went somewhere, we always looked to see where the nearest hospital was. For the first 3 years of Ethan's life, we were hypervigilant to anything that might trigger a seizure. For example, we did not go to the beach. With some children, a seizure can be triggered by a gust of wind, a bright light or a hot spell. In Houston, we had a swimming pool, and Ethan had several seizures because of the reflection of the light on the water. Without an effective medication regimen, we felt at the mercy of everything. We got used to being on permanent alert. I was constantly fretting about where my phone was, and where the rescue medications and emergency protocol were.
Between the ages of 18 and 30 months, when Ethan was having weekly episodes, my stress level never fully dropped. Managing the moments when Ethan ended up in intensive care and we were interacting with medical staff in a foreign language was very complex. It slowed down my communication with the medical team and increased my anxiety. For the sake of our mental health, we decided to return to France. Throughout our time in the USA, we were never able to return to France together as a family, as one of us always had to stay with Ethan. The epileptologist had strongly advised us against air travel because of Ethan’s unstable condition and the risk of a seizure mid-flight.
In December 2021, we moved back to France, to Rennes, where I am originally from. Ethan and I flew directly from Houston to Rennes in a medical plane with two nurses on board and resuscitation equipment. Thankfully, the trip passed without incident. In France, Ethan's follow-up was taken care of by Dr Napuri, at the Rennes University Hospital. Our return enabled us to review the basics of Ethan's treatment, and look at what was and what was not working. A week after our return to France, on Christmas Day, Ethan suffered a severe status epilepticus. Dr Napuri suggested trying sodium valproate, which we had never tried before. After sodium valproate initiation (250 mg twice daily), we observed a clear reduction in the frequency of Ethan’s status epilepticus episodes, with a period of 3 months without an episode. After the next episode, Dr Napuri recommended that we add stiripentol to act on the intensity of the seizures. When we had used stiripentol previously (in the USA), the side effects were difficult to manage, and I have to admit that we did not start stiripentol again as soon as we got the prescription.
In July 2022, at the age of 3 years, Ethan contracted COVID-19. The fever triggered an episode of status epilepticus. As usual, we gave his emergency medication at home, but it did not help. The ambulance was late, and so we had to take him to hospital ourselves. In the management of Dravet syndrome, it is essential to act as quickly as possible, as this increases the chances of stopping the seizure. After Ethan was admitted, I had to leave the hospital to take my daughter to nursery. Ethan went into intensive care. When I returned to the hospital, he was still in status epilepticus; the episode had lasted 2 h. Getting Ethan's first intravenous drug into him had taken 35 to 40 minutes, because he does not have very visible veins, and it took the medical team a long time to access the vein. The episode was resistant to other drugs, and so, as a last resort, he was given thiopental, which eventually stopped the seizure. Ethan fell into a coma for 10 days. We had already had episodes where it took Ethan a few days to wake up, but we soon realised that this time was different. After a few days, the doctors told us that he had probably suffered some form of brain damage.
This was the turning point in his life—and in ours. After he woke up from the coma, Ethan could no longer walk or talk. Until then, despite everything that had happened to us, we had been doing well. We had always been reunited with our son 2 or 3 days after the previous episodes, even very severe ones. For the first 3 years of his life, we focused on education to counter the effects of the disease. Ethan had only slight delays in learning, but overall, he was ahead of schedule. After this last serious episode, we felt that everything we had worked for had been swept away.
Ethan spent 3 months in rehabilitation and slowly learned to walk and talk again, but did not regain his previous abilities, especially in terms of language. Fenfluramine was progressively stopped [reduced every 15 days by 0.2-mL increments, starting from 1 mL (2.5 mg) each morning and evening] and stiripentol was slowly initiated (50 mg morning and night during the first week, 150 mg morning and night over the next 15 days, then 200 mg morning and night). The adverse effects of stiripentol on Ethan’s behaviour were still present, but milder. At this time, we finally arrived at the optimal combination for Ethan: clobazam solution [4 mL (4 mg) morning and evening], sodium valproate solution (175 mg morning and evening) and stiripentol (250 mg morning and evening). We have since lowered clobazam to 0.9 mL twice a day and sodium valproate to 50 mg twice a day. We use the same dose, however, for stiripentol. I remembered the very good advice of a parent who told me ‘When a drug works, you will see it’. This is exactly what we observed with this combination. It worked 100%. Not 50%, 100%! Ethan no longer had any episodes of status epilepticus. Despite the relief of having finally found an effective treatment, I was also deeply frustrated that we had only managed to find the right combination after the most serious episode he had ever had.
Living as a Family with Dravet Syndrome
We are lucky because Ethan is a very happy child, and he lives well with his disability. He sometimes displays aggression, probably linked to his treatment, his cognitive delay and his autistic traits, but he is generally cheerful. In our family life, we have always tried to make Ethan's disease a joyful experience for our children. We talk freely with them about the disease. His older brother asks us lots of questions about Ethan’s disability. His little sister is conscious that Ethan is different but cannot put it into words yet. When we were in the USA, it was terrible for my oldest son, because he saw everything: Ethan's seizures, our panic and our tears. Incredibly, he acquired an astonishing serenity in the face of his brother's condition. When a seizure occurred, he would go off on his own while we looked after Ethan, and he would not panic. On the other hand, we do have to take more care of Ethan, and this is sometimes a source of frustration for his brother and sister.
Regarding my wife's and my acceptance of Ethan's disease, there was a kind of scissor effect. My wife had a very hard time with the diagnosis, whereas somehow it was not so difficult for me. Over time, I had a harder time with the disease, whereas she managed it better. Even today, I find it hard to accept. We have talked about it with Dr Napuri on many occasions—she is a great support when it comes to psychology—and I am also being followed by a therapist. Coming back to France allowed us to verbalise our emotions and receive more support from our family. I had to change jobs because my employer did not understand what we were going through. Our mental health is a priority for my wife and I, so that we can take care of our family and each other.
My relations with the medical profession have sometimes been tense, often because of the urgency I felt was needed to save my son. We have been through dozens and dozens of seizures, and we know Ethan’s emergency protocol inside out. As very involved parents, we need the medical profession to treat us as equals and it is very frustrating when our role as a parent is not recognised for its true value. We appreciate the empathy, listening skills and understanding of Dr Napuri, who knows how to give us recommendations without imposing them, and explain why they makes sense.
In the USA and France, we have been able to count on patient associations dedicated to Dravet syndrome. Generally, American patient associations are large structures, with salaried employees. They raise a lot of money and even finance studies. There are Facebook chats where sometimes I get the answers to my questions before the doctor at the hospital responds! In France, the associations are smaller, but still present. For information on administrative procedures, a specialist lawyer can be consulted at the French patient association, Alliance Syndrome de Dravet. Since Ethan's major episode and coma, I have left all these networks, because it has become too painful.
At present, Ethan attends nursery school with the help of a full-time schooling life auxiliary. He has spent an extra year in nursery school. Our hope is that he will then enter a medical–educational institute (MEI) for his first year of primary school, because of his difficulty interacting with others.
Now that Ethan's treatment is working better, we are much less anxious about going out with him, even though we still have our charged phones and rescue medication with us. We can finally go to the beach, where we spend the summer. In our daily lives, there remain two difficult aspects to manage. Firstly, Ethan's behavioural problems: his lack of concentration, his stubbornness, his fixation on certain actions (such as throwing objects), and the complicated transitions between daily activities. Secondly, we are experiencing difficulties with the effect of Ethan's treatment: the school reports that Ethan is foggy in the morning, which corresponds to the learning part of his day. He is at his best at the end of the day, after his nap. On Dr Napuri's advice, we tried splitting the doses of medication in half and spacing them out, but it did not work very well. I would really like us to make progress on this point.
As do all parents, we are still hoping for the miracle drug for our child. As we were preparing to leave the USA, there was a phase 1/2 study about to be launched for an innovative drug from Stoke Therapeutics [1]; it was difficult for us to leave knowing this. Ethan was also eligible for an Encoded Therapeutics phase 1/2 gene therapy study [2], but then he had a rhinovirus infection and could not participate. However, the further along we are in our child's disease, the less we are looking for the miracle drug, unlike in the early years. Parents' considerations evolve as Dravet syndrome progresses, and, today, our concern is to support our child and ensure his future.
Compliance with Ethics Guidelines
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Written informed consent to publish this report was obtained from the patient’s legal guardian.
Neuropaediatrician’s Perspective
I am a neuropaediatrician at the University Hospital in Rennes. I am a co-ordinator for the Centre de Référence Epilepsies Rares in Rennes and I visit an MEI, a special school for children with epilepsy, once a week. I have been following Ethan since 2022, shortly after his return to France.
Dravet syndrome is a rare and severe form of epilepsy characterised by the occurrence of generalised and unilateral, clonic or tonic–clonic seizures within the first year of life [3]. Its incidence is estimated to be between 1 in 20,000 and 1 in 45,000 live births [3, 4]. Other features of Dravet syndrome include motor, cognitive and behavioural impairments, which become evident throughout childhood [3]. The frequency of seizures is high in the first 5 years of life and tends to decrease with age, but epilepsy persists throughout life and few children are seizure-free even into adulthood [5]. First seizures are classically triggered by fever, infection or vaccination [3]. Status epilepticus, a prolonged seizure lasting at least 30 min, occurs commonly in patients with Dravet syndrome and can lead to hospitalisation or even be fatal [3, 6]. The mortality rate for patients with Dravet syndrome is high, up to 15%, with the most common causes of death being sudden unexpected death in epilepsy (SUDEP) and status epilepticus [6–8].
The classic care pathway begins with a baby aged between 4 and 6 months arriving at the emergency department with a prolonged seizure (between 5 and 29 minutes), or even a status epilepticus, which may be unilateral, or generalised and febrile. This clinical presentation alerts the paediatricians, who inform the neuropaediatrician. For this first episode, the baby is hospitalised and we meet the parents, because a seizure is always panic-inducing. We take the time to explain clearly to the family what has happened. In the case of a prolonged seizure or status epilepticus, the child will be prescribed a treatment, usually sodium valproate. An magnetic resonance imaging (MRI) scan and an electroencephalogram (EEG) will be performed, particularly if a deficit results from this seizure. In the case of Dravet syndrome, the MRI and EEG are usually normal, which is a second warning sign for us [7, 9].
When the febrile seizure occurs before 6 months of age, we systematically give the parents a consultation appointment for follow-up in the neuropaediatric department in the subsequent month or two. In cases where the baby has had other febrile seizures requiring a visit to the emergency department before consultation, we discuss epileptic diseases with the parents. At this stage, we remain broad and do not yet specifically mention Dravet syndrome. Other causes cannot be formally ruled out, although they are less likely. To refine the diagnosis, we prescribe investigations to look for a structural cause (an MRI scan) or a genetic cause (genetic testing on blood samples). Pathogenic variants in SCN1A—the gene encoding the α1 subunit of the voltage-gated sodium channel—are present in the majority (70–80%) of patients with Dravet syndrome [9, 10]. The typology of the seizures and the normality of the EEG tracings can be helpful in establishing a differential diagnosis [3]. However, the diagnosis is above all clinical, with the age of onset of seizure and the evolution of the child's condition in the 2 to 3 months following the first seizure providing particular guidance. For example, a hemi-corporeal status epilepticus with fever, followed rapidly by a second status epilepticus, in a 4-month-old baby is suggestive of Dravet syndrome. A positive genetic test for a pathogenic variant of the SCN1A gene helps to confirm the diagnosis. In March 2020, a pathogenic variant of the SCN1A gene was identified in Ethan.
The announcement of the diagnosis must be made during consultations with the parents (both, if possible) that last for enough time to allow the parents’ questions to be answered and for everything that is going to happen for the child and the family to be explained. In practice, this is done in several stages: there is the day of the announcement and then we see the parents again shortly afterwards, in the weeks that follow, to answer any questions they may have and to go over specific points. Numerous topics need to be discussed with the family, including practical advice on recognising and managing seizures, rescue medications in the event of prolonged seizures, maintenance therapies, and follow-up of the child. A number of initiatives are now being undertaken to communicate diagnosis [11–18].
After diagnosis, there are regular scheduled follow-up visits for a child with Dravet syndrome. In the first 2 to 3 months, a consultation occurs frequently because of questions from the family and a possible change in treatment. The impact of Dravet syndrome on family life, childcare arrangements and daily life requires us to meet with the family regularly. When we intend to change the treatment, we explain the reasons to the parents, the pros (the benefits of treatment) and the cons (the adverse effects of treatment). We doctors are the experts on the disease and its treatment, while the parents are the experts on their child. Together, each with our own expertise, we will work to find what is best for the child. I am convinced that dialogue and sharing our reasoning to explain the meaning of our treatment decisions increase the chances of adherence to treatment by parents.
Sodium valproate is the drug of choice in France as first-line maintenance therapy for seizures due to Dravet syndrome [7, 19]. As second line, a combination of sodium valproate–clobazam–stiripentol, or topiramate or a ketogenic diet should be considered [7, 19]. In children aged 2 years and over, cannabidiol and fenfluramine can be proposed [7]. The second line of treatment should be adapted to the child’s developmental profile, the frequency of status epilepticus and the different types of seizures. Anti-seizure drugs need to be combined and polytherapy is inevitable. In practice, I prescribe sodium valproate as first-line treatment and if, within 2 months, the child presents with a recurrence of seizures, I add clobazam. In the following 2 months, if the child's condition does not improve, stiripentol is added (according to French National Diagnostic and Care Protocol [20]). With this combination of drugs (sodium valproate–clobazam–stiripentol), I allow 4 to 6 months to assess effectiveness. Initially, the target is the frequency of status epilepticus. The improvement must be visible, and the combination must be well tolerated. A new drug is introduced over a period of 1 month, in several stages and in gradually increasing doses. During this month, we cannot assess the effectiveness of the treatment. It is very important to take the time to balance the combination of the different drugs, to ensure that they are well tolerated; their effectiveness will be assessed afterwards. When a drug is started too quickly, adverse effects are likely to be greater, prompting parents to wish to stop treatment.
Appropriate maintenance treatment helps to reduce the number of seizures, particularly the status epilepticus, while being well tolerated. I agree with Ethan's father that, when the right combination is used, the patient can improve and in some cases become status epilepticus-free. Having effective treatment makes a huge difference to parents’ lives. The daily lives of parents of a child suffering from epilepsy with frequent status epilepticus are complicated and highly stressful, due to the unpredictability of seizures, administering rescue medication, calling an ambulance and travelling to the emergency department. Caring for a child with status epilepticus affects daily activities, family relationships and the social life of caregivers [21].
My first consultation with Ethan took place in January 2022, shortly after his return to France and the status epilepticus on Christmas Day. Between January and July, we saw each other in consultation three or four times and almost every 2 weeks for status epilepticus in the emergency department. I gradually built up a relationship of trust with Mr Reboux and his wife, creating what I feel is a strong therapeutic alliance. As paediatric neurologists, our medical approach is holistic and not only focused on care, but also on development, rehabilitation and organisation within the family. Mr Reboux and his wife, like many parents whose children suffer from Dravet syndrome, are very well informed, and were in close contact with patient associations. They were very up to date with the latest drugs! I attach great importance to listening to parents and taking their priorities into account; we define the objectives together. Progressively, the therapeutic objectives have focused on optimising the maintenance treatment while updating the emergency protocol, and Mr Reboux and his wife agreed to the proposed changes in Ethan’s treatment.
Ethan has a very severe form of epilepsy, with each seizure evolving into status epilepticus and at least one status epilepticus a month. In patients with Dravet syndrome, a personalised protocol for the management of seizures emergencies, such as status epilepticus, is an important part of the care pathway [7, 9]. Ethan’s emergency protocol included initial rescue medication at home (buccal midazolam or rectal diazepam), then, if the seizure persisted, a call to the ambulance and, on arrival at hospital, intravenous levetiracetam (40 mg/kg) and phenytoin (15 mg/kg). If the seizure stopped, he was monitored in the emergency department for 4 to 5 hours and then allowed to go home. If the seizure continued, midazolam (100 to 200 µg/kg/h) and phenobarbital were administered in stages, and he remained in hospital at least until the day after the seizure. If midazolam and/or phenobarbital were administered, he had to be monitored and receive respiratory assistance in the intensive care unit and was not discharged until the following day. Since coming to Rennes, Ethan has had to go into intensive care twice.
After the introduction of sodium valproate in January 2022, we saw a 12-week seizure-free period. At the time, Ethan was also taking fenfluramine. I advised his parents to start stiripentol and, in June, I wrote a prescription for it. In July, Ethan had status epilepticus with onset during a COVID-19 infection. This episode had a massive impact on him, requiring a longer hospital stay and a lot of rehabilitation work. At the same time, while he was hospitalised, we implemented the change in treatment that we had planned with Ethan’s parents—stopping fenfluramine and adding stiripentol to sodium valproate and clobazam—and the effect on his epilepsy was rapid and very significant. The effectiveness of treatment with stiripentol in addition to clobazam or sodium valproate in reducing the incidence of status epilepticus in patients with Dravet syndrome has been demonstrated in several retrospective and prospective observational studies [22].
The serious episode of status epilepticus that Ethan experienced in July 2022 was triggered by a COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) probably caused a greater inflammatory response in Ethan’s body than other viruses would have done, leading to prolonged high fever. He developed a minor form of acute encephalopathy, a serious clinical condition induced by a refractory status epilepticus and characterised by impaired consciousness and multi-organ failure, which can lead to severe neurological sequelae and even death [23, 24]. When he woke up from his coma, Ethan's sequelae were loss of ability to walk and speak, and lack of eye contact. He was in constant motion and could not sit still. Ethan was transferred to a rehabilitation unit where he stayed for 3 months, until the end of September 2022. There, he was able to walk again. In 2023, a few months later, he began to speak again, although with a more limited vocabulary than before. Today, Ethan can move and run, and has enriched his language and developed relationships. There has been recovery, but he has not been able to reach his previous condition, and he has emotional and motor instability and has a developmental disorder. Ethan’s age—5 years—also corresponds to the age at which intellectual development disorders are most clearly observed in children with Dravet syndrome [3, 9]. His current deficits can probably be explained by a combination of the sequelae of his acute encephalopathy and the progression of his disease.
We have noted the comments from Ethan’s parents about his behaviour at school in the morning, that he has difficulty paying attention and can sometimes be less interactive and engaged at certain times of the day. We have tried a number of strategies to address this, including modifying the administration of stiripentol into three doses, and giving his dose of sodium valproate during the night and using a slow-release form and small doses spread throughout the day. However, Ethan's parents did not notice any improvement in his behaviour. I have tried to explain to them that it is difficult to differentiate between the effect of the treatment and the symptoms of the disease; indeed, the behaviours they are seeing could be symptoms of his condition. Today, we have decided to keep the dose of the three drugs he is taking as low as possible (sodium valproate: 17.5 mg/kg/day divided into two doses; clobazam: 0.5 mg/kg/day divided into two doses; stiripentol: 25 mg/kg/day divided into two doses).
The course of treatment for a child with Dravet syndrome depends on each individual case. If the child has achieved a prolonged period of seizure control and has episodes of fever without seizures, the treatment can be gradually simplified, by reducing to two drugs, for example. However, great prudence must be exercised, as there have been cases of recurrence after a reduction in treatment when everything has been going well for several years. When the disease progresses favourably, our aim is to give as few drugs as possible. With proper management and a strong therapeutic alliance between the medical team and the parents, our hope is to enable these children to lead the happiest lives possible.
Acknowledgements
Silvia Napuri would like to thank Romain Reboux for his open and important contribution to this article.
Medical Writing, Editorial and Other Assistance
We thank Anne-Coline Laurent, PharmD, PhD, and Sarah Dousset, PhD, for providing medical writing assistance on behalf of Springer Health + , France. Editorial assistance post submission was provided by Tracy Harrison, of Springer Health + . This medical writing support and editorial assistance was funded by Biocodex.
Funding
The journal’s Rapid Service Fee was funded by Biocodex. The authors were responsible for all content and editorial decisions. The authors received no payment for the development of this manuscript. Biocodex reviewed the manuscript for scientific accuracy only.
Data Availability
Data sharing is not applicable to this article as no data sets were generated or analysed during the current study.
Declarations
Conflict of Interest
Dr Napuri has been a speaker for UCB, and a member of an expert group for Biocodex and Jazz Pharma. Mr Reboux has no conflicts of interest to disclose.
Ethical Approval
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Written informed consent to publish this report was obtained from the patient’s legal guardian.