Case studies

A paediatric case of adjunctive fenﬂuramine for the management of Dravet syndrome

Dr. Rocío Sánchez-Carpintero Abad
Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain

Key takeaways and learning points

Fenfluramine can be effective in controlling seizures in young children with Dravet syndrome.

In this clinical case, the child with Dravet syndrome has achieved long lasting periods of seizure freedom under treatment with fenfluramine.

The observed antiseizure effect of fenfluramine was dose related and was generally well tolerated.

Treatment with adjunctive fenfluramine should be considered early in the management of Dravet syndrome.

Patient profile

Management of adverse events

Explore the case timeline below

0-12
months

First febrile seizure

(4 months)

Diagnosis of Dravet syndrome

genetically confirmed

(11 months)

First febrile seizure (4 months)

Diagnosis of Dravet syndrome genetically confirmed (11 months)

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic	Status epilepticus (4)
Seizure type(s)

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic	Status epilepticus (4)
Seizure type(s)

Antiseizure medication(s)

At 4 months: Generalised clonic febrile seizure
By age 1: 7 generalised clonic seizures
(4 status epilepticus)

Epilepsy description

13-24
months

First presented

(18 months)

First presented (18 months)

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (1-3 mins)	Status epilepticus (1)
Seizure type(s)

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (1-3 mins)	Status epilepticus (1)
Seizure type(s)

Antiseizure medication(s)

25-36
months

First non-febrile seizure

(25 months)

Stiripentol and Ketogenic diet
added to treatment

First non-febrile seizure (25 months)

Stiripentol and Ketogenic diet added to treatment

24
+
>100^*

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (30 secs)	Absence
Seizure type(s)

*>100 absence seizures

24
+
>100^*

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (30 secs)	Absence
Seizure type(s)

*>100 absence seizures

Antiseizure medication(s)

Seizures became more frequent but shorter. Between 33-36 months frequency reached 20-30 absence seizures per day, which disappeared after 4 months on ketogenic diet

Epilepsy description

37-48
months

Fenfluramine introduced to antiseizure medication

Stiripentol stopped due to cognitive side effects

(43 months)

Fenfluramine introduced to antiseizure medication
Stiripentol stopped due to cognitive side effects (43 months)

15
+
21^*

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (30 secs)

Seizure type(s)

*21 seizures occurred after stopping treatment with stiripentol.

15
+
21^*

Total seizures

Longest seizure-free
period (days)

Generalised tonic-clonic (30 secs)

Seizure type(s)

*21 seizures occurred after stopping treatment with stiripentol.

Antiseizure medication(s)

21 seizures occurred after stopping treatment with stiripentol. 50 days seizure-free after first dose of fenfluramine.

Epilepsy description

49-60
months

Fenfluramine dose gradually
increased to 0.4 mg/kg/day
over 12 months

Fenfluramine dose gradually increased to 0.4 mg/kg/day over 12 months

Total seizures

44
+
82

Longest seizure-free
period (days)

Generalised tonic-clonic

Seizure type(s)

Total seizures

44
+
82

Longest seizure-free
period (days)

Generalised tonic-clonic

Seizure type(s)

Antiseizure medication(s)

Following introduction of fenfluramine, 10 generalised tonic-clonic seizures with 20–30 absence seizures/day over 4 months, which then stopped.

Epilepsy description

61-76
months

Ketogenic diet stopped due

to lack of efficacy

(66 months)

Ketogenic diet stopped due to lack of efficacy (66 months)

Total seizures

515

Longest seizure-free
period (days)

Total seizures

515

Longest seizure-free
period (days)

Antiseizure medication(s)

Discussion

Add-on treatment with fenfluramine has achieved 100% seizure control in this 5 year old child with Dravet syndrome

Epilepsy in children with Dravet syndrome is usually drug resistant, although avoidance of contraindicated medication has already improved seizure control in comparison with historical cases

The use of sodium valproate + clobazam + stiripentol demonstrated efficacy in two randomised clinical trials and helped this child by shortening his seizures

However, amongst all medications tried in this case, only fenfluramine has achieved total remission of generalised clonic seizures

Titration was very slow in this case. Fenfluramine was well tolerated. No cardiovascular side effects were seen

Developmental quotient during the first 5 years of life

Observations from a case study (n=1); causal effect cannot be established

Total remission of seizures under fenfluramine treatment in combination with sodium valproate and clobazam was accompanied by an important improvement in language development, although we cannot exclude it was coincidental.