Dravet syndrome management

Management of Dravet syndrome is not limited to antiepileptic treatments. Indeed there is currently no cure for this syndrome. The only possible currently available treatment is a symptomatic treatment of the seizures. Comprehensive care of the patient aims to also consider and treat all other disorders.



All treatments should be taken under the supervision of a doctor licensed to treat this type of epilepsy in your country. Many antiepileptic treatments are available worldwide, but they may not all have marketing authorisation in your country.

Several pharmacological and non-pharmacological treatments can be used for Dravet syndrome patients. You should keep in mind that seizures are highly pharmacoresistant and their complete control cannot generally be achieved. So, persistence of some seizures is preferable to heavy and deleterious polytherapy.

  • The biggest question is: “When to start continuous treatment and how to conduct it?”
  • In an infant aged less than one, after the first isolated
    febrileWith fever
    afebrileWithout fever
    seizure, both the “Epileptic syndromes in infancy, childhood and adolescence” and “Topics in Epilepsy” books on Dravet syndrome recommend, if a second seizure happens, starting by using rectal diazepam or buccal/nasal midazolam, when available, in order to stop a possible prolonged seizure.

It is reasonable to start continuous treatment as soon as the diagnosis of Dravet syndrome is strongly suspected. If you should need more clinical information on diagnosis, please refer to its dedicated section.

In addition or in substitution to pharmacological treatments, non-pharmacological treatments may be part of the therapeutic arsenal.

The following treatment algorithm published by Ch. Dravet and R. Guerrini can be helpful.

A/ Pharmacological

  • Satisfactory management of Dravet syndrome is hard to achieve as the intractability of seizures is the hallmark of the disease. Pharmacological treatment is nevertheless the mainstay of disease management, and several antiepileptic drugs are available. In the chapter about Dravet syndrome in “Epileptic syndromes in infancy childhood and adolescence - Fifth Edition”, the authors listed “useful”
    AEDsAntiEpileptic Drugs
    as follows.

Valproate is usually the first-line treatment, notably for preventing the recurrence of febrile seizures. Even though well-controlled and long-term efficacy studies are lacking, valproate is widely used in Dravet patients.

Benzodiazepines prevent or stop long-lasting seizures, in particular status epilepticus. Clonazepam and clobazam are the most frequently prescribed benzodiazepines in Dravet patients. Clobazam is usually combined with valproate for the long-term treatment of the disease, while clonazepam, available as a solution for injection, is often used as a rescue medication in the hospital setting in order to end long-lasting seizures.

  • Stiripentol is the only treatment that has demonstrated its efficacy in Dravet syndrome patients in randomized, double-blind, placebo-controlled trials. Its efficacy was assessed as an add-on therapy to valproate and clobazam in two studies, STICLO France (Chiron et al., 2000) and STICLO Italy (Guerrini et al., 2002). In STICLO France, 41 Dravet patients were evaluated, of whom 21 received stiripentol and 20 placebo. In STICLO Italy, 23 patients were evaluated, 12 received stiripentol and 11 placebo. In STICLO France, 71% of the stiripentol patients were
    responders Patients with a reduction of at least 50% seizures compared to the base line.
    versus 5% in the placebo group. Results were comparable in STICLO Italy with 67% responders in the stiripentol group versus 9 % in the placebo group.
  • In STICLO France, 100% of patients receiving stiripentol experienced an adverse event compared to 45% in the placebo group. The most frequently reported events were drowsiness, gastro-intestinal disorders (anorexia, abdominal pains, nausea, vomiting), and neurological disorders (ataxia, tremors, hypotonia). These adverse events were reduced or disappeared after reduction of the doses of clobazam and/or valproate.
  • In STICLO Italy, 83% of the patients under stiripentol experienced an adverse event compared to 27% in the placebo group.
  • Interestingly, similar results were observed in non-caucasian Japanese patients (Inoue et al., 2009;).
  • Regarding the long-term efficacy and safety of stiripentol, a study performed by Than et al. (2002) showed that the reduction in frequency and duration of seizures, notably
    status epilepticusSeizures lasting for more than 30 minutes
    , was maintained over time.

Topiramate has been studied in open-label trials only (Nieto-Barrera et al., 2000; Coppola et al., 2002; Villeneuve et al., 2002; Grosso et al., 2005; Kröll Seger et al., 2006). Results showed that a ≥50% reduction of seizures occurred in 50 to 85% of patients, of whom 16 to 18% were seizure free for a period of 11 to 13 months. Fifteen percent of patients experienced side effects, mainly anorexia and weight loss but also behavioural disturbances, emotional and language regression. A slow titration facilitated a better tolerance.

  • Bromide is the oldest antiepileptic drug and is still widely used in Germany and Japan. Studies have shown significant results regarding
    convulsive seizures Seizures including more or less violent motor phenomena (hypertonia, convulsions…).
    and status epilepticus.(Oguni et al. 1994; Tanabe et al. 2008; Inoue et al. 2009). A recent retrospective analysis of 32 Dravet patients with a SCN1A mutation confirmed the interest of bromide therapy.
  • Levetiracetam was evaluated as add-on therapy in a multicentre, open-label trial in 28 patients over a 6 to 36 month-period (Striano et al., 2007). In the 23 patients who completed the trial, responders were 64.2%, 60%, 60% and 44.4% for tonic-clonic, myoclonic, focal and absence seizures, respectively. Eighteen percent of patients withdrew from the study for side effects such as irritability, cutaneous rash, worsening of myoclonic seizures and thrombocytopenia.
  • Zonizamide was described throughout Japanese studies (Kanazawa & Shirane, 1999) to be effective in borderline forms of Dravet syndrome but no data are available in Europe. In addition, retrospective surveys in Japanese patients reported the interest of zonizamide for the management of convulsive seizures (Tanabe et al. 2008; Inoue et al. 2009) in Dravet patients.
  • Ethosuximide was used in patients suffering from countless myoclonic seizures. However ethosuximide is not active on convulsive and focal seizures, and it can trigger deleterious side-effects (loss of appetite, withdrawn behaviour).
  • Piracetam was used, as ethosuximide, in patients with frequent myoclonic seizures, but high doses are required that are often not well tolerated.
  • Barbiturates have been widely prescribed despite their controversial use, but without clear improvement in reducing the number of seizures. They are now no longer prescribed in infants and young children. They can be useful in cases of convulsive seizures and status epilepticus resistant to valproate and benzodiazepines.
  • Corticosteroids, used in cycles of treatment, can be useful in cases of repeated status epilepticus but do not have long-term efficacy.
  • Verapamil, a voltage-gated calcium channel blocker, was successfully used as an add-on therapy in four patients (Ianetti et al.,2009; Nicita et al, 2013), resulting in seizure-free periods of six months to more than one year. An open trial is currently on-going in the USA.

1- Recommended treatments

The first classical chronic pharmacological treatment option after first seizures is valproate monotherapy. It is generally well tolerated but, in case of vomiting, close monitoring of valproate plasma concentration as well as biological constant should be performed to avoid risks of hepatic failure.

When seizures are no longer controlled by average valproate plasma concentration, three options are possible :

The first one is the polytherapy combination of valproate and clobazam. In case of failure, add stiripentol*. For Dravet syndrome patients with tonic-clonic seizure, the European Medecine Agency (EMA), the Canadian and Japanese Health Agencies recommend the combination of valproate, clobazam and stiripentol*.

The second is valproate and topiramate, as shown by Barrera et al. in 2003. In case of failure, clobazam can be added.

The third is to associate bromide to valproate.

As a remark, some authors like Ceulemans in 2004, propose limiting the chronic use of benzodiazepines because of their side-effects.

*Only available in EMA member states (full marketing authorisation 2014 following conditional marketing authorisation since 2007), Canada (2012) and Japan (2012). In some countries it has an orphan drug status.

2- Also used

Generally, even during therapy with recommended treatments, seizures are not totally controlled or, even if initially controlled, treatment loses efficacy over time. In this case a change of antiepileptic may be required. To avoid a too heavy and too complicated polytherapy approach, substitution of an antiepileptic rather than an addition should be considered. Clonazepam, zonisamide and levetiracetam in various combinations, with or without stiripentol, can be one of these alternative treatments.

3- Emergency

  • When a
    convulsive seizures Seizures including more or less violent motor phenomena (hypertonia, convulsions…).
    occurs, acute treatment should be considered if the seizure last more than 3 minutes because it will generally last more than 5 minutes and evolve into
    status epilepticusSeizures lasting for more than 30 minutes
  • Benzodiazepines are the drugs of choice and can be used according to different modalities.

Rectal diazepam :

Rectal diazepam (using the same solution as for intramuscular/intravenous injections) is the most popular solution worldwide, since it can be easily administered by parents and caregivers in a daily life setting (or out of a medical setting). However, adolescents and adults might tend to refuse it, finding it discomfiting. In some countries, ready to use preparations are available. The dose must be indicated by the current doctor, taking the patient’s age and weight into account. The seizure usually stops in the minutes following administration.

Oral / Nasal midazolam :

Oral / Nasal midazolam solution has recently been demonstrated to provide the same results (Mc Mullan et al, 2010), but is not available in all countries. It can be also used by parents and caregivers. They need to be informed of the exact way of putting the solution inside the mouth, where it is absorbed by the sublingual and cheek mucosa, in order to avoid the patient swallowing it. The seizure stops in the minutes following administration.

Other benzodiazepines :

Other benzodiazepines, such as clonazepam and lorazepam, have not been studied but are likely to have the same effect as midazolam when used orally in the same way.

When a convulsive seizure does not stop after this treatment approach, medical intervention is needed, either a mobile medical emergency or in the emergency room at the hospital.

  • At this time, IV diazepam and/or midazolam are used in a setting with available respiratory and cardiac monitoring.
    IV phenytoin can be an option, whereas barbiturates should be used with caution because of toxic risk (Chipaux et al,2010).
  • In cases where seizures cannot be controlled and tend to turn into
    status epilepticusSeizures lasting for more than 30 minutes
    , other antiepileptic drugs and other procedures should be used as for other types of status epilepticus in children and in adults. It is beyond the scope of this document to detail them here.
  • When convulsive seizures are brief but repeated in clusters, the same treatment as for prolonged seizures should be applied when cluster lasts for several hours and when interictal intervals progressively shortens.
  • For other seizure types, the same approach is advised when they become frequent enough to impact the patient's activities and behaviour.

4- To avoid

  • The drugs discussed below have been clinically proved to worsen seizures of Dravet syndrome patients.
  • Carbamazepine, Phenytoin and Lamotrigine are three structurally different molecules, although have a common mechanism of action that could explain their ability to increase seizures in sodium channelopathy related epilepsies.
    Indeed, for all three of them the mechanism of action is involved in the use-dependent inhibition of the sodium channel necessary for the “firing” of action potentials, responsible for
    convulsive seizuresSeizures including more or less violent motor phenomena (hypertonia, convulsions…).
  • Horn et al. in 1986, Wakai et al. in 1996 and Wang et al. in 1996 reported an aggravation of seizures when Dravet syndrome patients are under Carbamazepine.
  • Regarding Phenytoin, as stated in the Dravet syndrome book of the "Topic on epilepsy series": “The aggravating effects of phenytoin (PHT) were reported anecdotally. Two authors reported paroxysmal movement disorders in patients with Dravet syndrome treated by polytherapy, including PHT (Saito et al., 2001; Ohtsuka et al., 2003). All patients presented with frequent seizures and the paroxysmal movements appeared after PHT dosage was increased, without additional signs of toxicity. This side effect of PHT is well known in patients with severe epilepsy and mental impairment (Dravet et al., 1980, 1983; Zaatreh et al., 2001). No clear information is available regarding possible worsening of seizures.”
  • Guerrini et al. in 1998, demonstrated the aggravating effect of lamotrigine on Dravet syndrome patients. This finding was later confirmed, in 1998, by Wallace. Guerrini’s study showed that in 17 out of 21 patients, lamotrigine has induced a worsening of seizures, mainly regarding convulsive (8 patients) and myoclonic (6 patients) ones. In most patients the worsening clearly appeared within three months after starting lamotrigine, but occasionally an insidious course was observed.
  • Vigabatrin increases myoclonic seizures in infants and children, and therefore should be avoided. An improvement of convulsive and focal seizures was observed in older patients.
  • Barbiturates have been largely used without clear improvement and their use is controversial. However, they can be useful in case of convulsive seizures and
    status epilepticusSeizures lasting for more than 30 minutes
    that are resistant to valproate and benzodiazepines.

B/ Non pharmacological

Often pharmacological treatments are not sufficient to control seizures. Some non-pharmacological treatments may be considered, such as ketogenic diet and vagus nerve stimulation, knowing that only the ketogenic diet has proven its efficacy in clinical studies. Since each child is unique, what might work for some may not work for others.

1- Ketogenic diet

The ketogenic diet is a high-fat, adequate-protein, low-sugar diet. The diet forces the body to burn fats rather than sugars. Normally, sugars contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain function. Generally, in the ketogenic diet the fat/carbohydrate and protein ratio is 4:1.

Several variants of this diet exist, such as the Atkins diet (fat/carbohydrate and protein ratio of 3:1), or the modified Atkins diet (fat/carbohydrate and protein ratio of 1:1). A ready-to-feed formula may be useful for maintaining this diet.

Because this diet must be strictly calculated and consumed, it requires clear understanding by the family, real compliance by the child, and permanent collaboration between the family and their doctor.

  • Several studies have demonstrated the efficacy of the ketogenic diet in patients with Dravet syndrome, resulting in a significant reduction (50%-100%) of the seizure frequency in 66% of children, accompanied by an improvement of behaviour, and allowing for a reduction in use of
    AEDsAntiEpileptic Drugs


These diets should only be initiated and undertaken under the supervision of a doctor knowledgeable about Dravet syndrome and the ketogenic diet, with the assistance of a dietician.

2- Vagus Nerve Simulation

Vagus Nerve Stimulation (VNS) consists of the surgical implantation along the vagus nerve, in the neck, of a device similar to a pace-maker. This procedure has been shown useful in various pharmacoresistant epilepsy types but does not seem as advantageous for patients with Dravet syndrome (Zamponi et al, 2010)

2/ Emergency protocol

  • Dravet syndrome can deeply affect family life, especially when the child presents long-lasting
    convulsive seizures Seizures including more or less violent motor phenomena (hypertonia, convulsions…).
    that can require hospitalisation.
  • If you are a physician regularly managing a Dravet child, the following approaches can be useful to help parents :
  • You can write an emergency protocol for parents to give to emergency medical health services, in which you detail the medications that the Dravet patient is currently receiving, the disease he/she is suffering from and what treatments to avoid.
  • You can also propose the “on watch parent” idea. This is where there is one “parent on call” who accompanies the Dravet child to the emergency room while the other parent, or another designated adult, stays with any other children so that they can continue their activities and avoid the trauma of hours in a hospital environment.
  • Furthermore you can advise parents to take the following items every time they leave the house: cell phone, status protocol, rescue benzodiazepines, diapers, cereal bars, oxygen bottle (optional), suction machine (optional).
  • To avoid long-lasting seizures or
    status epilepticusSeizures lasting for more than 30 minutes
    , you may want to provide guidance on the proper usage of emergency benzodiazepines, according to the available form in your country, using information provided in the Emergency seizure treatment section.

3/ Comprehensive care

Comprehensive care aims to prevent and/or treat problems other than seizures that come with Dravet syndrome (co-morbidities). Treatment may not eliminate these problems but may reduce their impact on patients and their families. This requires the collaboration between the physician and a multidisciplinary team who may give support to patients and their familes, allowing them the best quality of life possible. Providing this information in the Emergency parent’s protocol can be useful.

A/ Fever and vaccination

Fever is one of the most frequent triggering factors in Dravet syndrome, particularly in young children. It is noteworthy that often the temperature does not reach a level of true fever and may provoke seizures when it rises slightly (from 37 to 38 ° Celsius for example). This “fever” has a number of causes but is often related to infection.

1- Infections and fever

There is a general sense that Dravet syndrome patients are prone to infections although they do not have any known immunological deficiency. Common infections affect mainly upper respiratory tracts, lungs and urinary tracts. They should be appropriately treated, with or without antibiotics.

A correct dose of antipyretic medication (for example, acetaminophen or ibuprofen) is usually effective to decrease temperature. Be aware not to exceed reasonable doses because of the risk of hepatic toxicity due to interactions with the antiepileptic drugs.

Even if these patients are fever-sensitive, it is impossible to eliminate all infectious illnesses. They need to have a social life that is as normal as possible and should not be “isolated”.

2- Vaccination


All treatments should be taken under the supervision of a doctor licensed to treat this type of epilepsy in your country. Many antiepileptic treatments are available worldwide, but they may not all have marketing authorisation in your country.

Dravet syndrome has sometimes been mistakenly identified as a “vaccine encephalopathy” because the initial seizures appeared soon after a vaccination. But retrospective studies demonstrated that 92% of the studied Dravet syndrome patients who had their first seizure after a vaccination carried an SCN1A mutation. It is reasonable to think that vaccination may trigger an epileptic seizure episode in infants who are likely to have them anyway, but on no account may it be the cause of the epilepsy.

It is important to keep in mind that infectious diseases such as measles, rubella, mumps, pertussis, and influenza may be severe trigger seizures and even cause neurological complications. If vaccination is a way to prevent an infection, then it should not be excluded.

Vaccination may be followed by seizures even when there is no change in temperature, although the mechanisms driving this remain obscure. It occured in one third of the vaccine-related seizures in a study of 19 patients. For this reason, prevention is not currently possible.

  • With regards to recommendations for vaccination of Dravet syndrome children, the Dravet syndrome chapter in the “Epileptic syndromes in infancy childhood and adolescence” book, states to “not inject vaccine when the child is ill or
    febrileWith fever
    and to give antipyretics before and after the vaccination, associated with benzodiazepines for one week”.

b/ Other seizure-triggering factors

Dravet syndrome patients are sensitive to various stimuli that may trigger seizures.


1- Photosensivity

Some Dravet syndrome patients may have seizures triggered by bright flashing lights, such as strobe lights, sun reflected from the water at the beach, or moving through the branches of trees. For others, flashing colours and shapes may be important, such as from video games or cartoons.

The following remarks may be useful for these patients:

  • Avoid bright lights that flicker.
  • Limit the time spent in front of television and other electronic screens and reduce their contrast. Sit as far away from the screen as possible and keep the lights on in the room. Avoid watching screens in the dark.
  • Regular sunglasses may be helpful outside but not sufficient.

A Japanese study hypothesized that there were certain wavelengths that would cause the triggering of seizures. This study on Dravet syndrome patients with photosensitivity and self-induced seizures showed that an appropriate filter of 600-700 nm light waves gradually reduced photosensitivity and inhibited flickering hand movement and forced eye closure-induced seizures. These results were confirmed by a large Italian study of photosensitive patients with various types of epilepsy.

According to these data, we strongly suggest that patients who are light sensitive and even more those with self-induced seizures wear glasses that stop the patient’s specific seizure-triggering light wave. It is also important that these glasses provide lateral protection to stop side lights from reaching the eye.

This suggestion is also valid for patients who are sensitive to non-flickering environmental light and experience seizures when they go outside or in a well-illuminated place.

2- Pattern sensitivity

Visual patterns may trigger seizures in some patients. They consist of various designs such as regular geometric patterns, lines, dots, or contrasted surfaces, which are largely found in the environment: clothes, roof tiles, escalators, pavements, windows, letters in books for children, TV screens, etc. Affected patients may or may not also be photosensitive. Pattern sensitivity is generally not suppressed but only attenuated by wearing special glasses for photosensitivity.

Although it is not always easy to avoid patterns, another solution exists which involves completely masking one eye. It is not, however, well tolerated by patients and can only be used for short periods of time to facilitate some activities (e.g. reading).

3- Temperature sensivity

A slight increase in body temperature can be a seizure-triggering factor. It is often provoked by infectious diseases.

However increased body temperature may occur in other situations: excessive or prolonged physical activity, immersion in hot water, environmental heat. It may be sensible to avoid intensive sports, hot environments (hot rooms, hot cars etc.), hot baths and to opt for air-conditioned environments. But parents cannot always restrain the hyperactivity of their child.
Control of body temperature through the use of cooling vests has no established value.

4- Other situations

Excitation and emotions can be included in triggering factors.

They are reported by many parents who are afraid when their child participates in celebrations such as birthdays, Christmas, school parties, etc.

Stress situations may also be responsible for seizures: separation, change of people and environment, first days at school, criticism, etc. Sometimes this can disrupt education and promote a tendency to misbehave, or even become “little tyrants”!

The role of doctors and of the medical team is to reassure parents by putting the risk of such provoked seizures in perspective.

c/ Other disorders

  • Every child affected by Dravet syndrome is unique. He/she may experience one or more of the following disorders :
  • Cognitive decline
  • Behavioural and psychological issues
  • Gait difficulties
  • Sleeping and/or feeding disorders

1- Cognitive functions

  • Even though the evolution of Dravet syndrome is very individual,
    cognitive functions Any mental process that involves symbolic operations such as: perception, memory, creation of imagery, and thinking.
    are nearly always impacted.

The degree of severity and the nature of the cognitive decline should be documented by aged-adapted standardised testing. This testing allows an understanding of the specific deficits, but also the real abilities of the child and the respective roles of epilepsy and treatment. It can be carried out as soon as the diagnosis is established and at intervals throughout the patient’s life. The results are taken into account by the family and the medical team for school integration and implementation of rehabilitative therapies: speech therapy, psychomotricity, and ergotherapy.

If available in your country, the help of a cognition specialist can be valuable to develop an early appropriate management plan and optimize cognitive progression.

2- Behavioural and psychological issues

Behavioural and psychological issues are always observed in Dravet syndrome patients and impact their family and social life.

These factors vary from one child to another and may include hyperactivity, repetitive behaviour, opposition behaviour and problems with social interaction.

A short attention span especially when associated with hyperactivity can make life dangerous for these patients – they may not perceive a situation as risky.

Stereotypic activities are repetitive movements and behaviours that may interfere with structured play as well as with learning activities.

Oppositional behaviour may make Dravet patients difficult to manage at home and in public. Some oppositional behaviour may be linked to language impairment and poor communication.

For the same reasons, many Dravet syndrome patients have difficulties interacting appropriately with children of their own age, which can lead to withdrawal and isolation. They may prefer the company of adults. Overly trusting and friendly behaviour towards adults may lead them to danger.

These problems often worsen in adolescence, particularly in patients who do not have severe cognitive impairment and become aware of their differences with those of the same age.

  • Pharmacological treatments are rarely necessary, except for some children with
    hyperkinesis Said of a child who can’t stay still, always moving.
    and depressed adults.

Pedagogic, behavioural and psychological measures that can be used depend on the structures and specialists in different countries.

Special classes, individual help in mainstream classes, out-of-school social and educational settings, sport practice, and group leisure activities, are some of the possible solutions.

Either psychotherapy or, at least, psychological support should also be offered.

In adulthood, few patients can engage in simple work in a sheltered structure. Specialized institutions for mentally retarded patients, when possible, can be positively received by patients and alleviate the burden for the family.

In all cases it is important that physicians and professionals are aware of all these problems, take time to listen to patients and families, without forgetting siblings, to help them find the best possible solutions and, finally, to accompany them in the acceptance of the disease.

3- Sleeping and/or feeding disorders

Sleeping disorders

Dravet patients may experience difficulties with sleep. Problems may include excessive sleepiness or difficulty falling asleep, maintaining sleep or awakening very early.

There are many causes, including unrecognized seizures or side effects from some anti-epileptic drugs, which may be improved through dose adjustment and spreading out doses during the day. Sleep-inducer drugs may help falling asleep.

Feeding disorders

Most feeding disorders such as anorexia or loss of appetite are a consequence of anti-epileptic drug treatment. Dose adjustments may not be easy because of the risk of more seizures. Sometimes a psychologist can be helpful.

In rare patients, anorexia, failure to thrive or loss of weight are independent from antiepileptic drugs and are so worrying that gastrostomy becomes necessary.

4- Gait and Fine Motor Skills

Dravet syndrome patients are often subject to motor impairment and postural change. These issues may become particularly important during adolescence.

Fine motor skills are impacted from the first years, making children clumsy, especially if they have ictal and interictal myoclonic jerks. Difficulties with fine motor skills may impact all daily life activities and also reading, writing and drawing. They can be attenuated by psychomotricity therapy.

Gait tends to deteriorate from about nine to ten years of age, associated with pes planus-valgus and, sometimes, cyphoscoliosis. From adolescence, the most severely affected patients gradually develop a special crouch pattern when they walk. These patients may have difficulty walking long distances, although usually they maintain the ability to walk around the house and for short distances.

Motor impairment can be attenuated by physiotherapy but needs to be followed up by an orthopaedist who will possibly prescribe custom orthesis and, rarely, surgical intervention.