Epilepsy Research 125 (2016) 42–46
Contents lists available at www.sciencedirect.com
Epilepsy Research
journa l h om epa ge: www.elsevier.com/locate/epilepsyres
Patients with dravet syndrome in the era of stiripentol: A French
cohort cross-sectional study
Paola De Liso
a,b
, Nicole Chemaly
a,c,d,e
, Jacques Laschet
c,d,e
, Christine Barnerias
a
,
Marie Hully
a,c,d,e
, Dorothée Leunen
a,c,d,e
, Isabelle Desguerre
a,e
, Catherine Chiron
a,c,d
,
Olivier Dulac
a,c,d
, Rima Nabbout
a,c,d,e,*
a
Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, 149 Rue de Sevres, 75015
Paris, France
b
Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
c
Inserm U1129, Hôpital Necker-Enfants Malades, 149 Rue de Sèvres, 75015 Paris, France
d
CEA, Gif Sur Yvette, France
e
Paris Descartes University, Department of Pediatrics, Hôpital Necker-Enfants Malades, 149 Rue de Sèvres, 75015 Paris, France
a r t i c l e i n f o
Article history:
Received 3 January 2016
Received in revised form 26 April 2016
Accepted 27 May 2016
Available online 28 May 2016
Keywords:
Dravet syndrome
Outcome
Seizure frequency
Seizure duration
Status epilepticus
Stiripentol
Combined therapy
SCN1A
a b s t r a c t
Objective: The aim of this study was to assess outcome and seizure response to treatment with stiripentol
(STP) associated to valproate (VPA) and clobazam (CLB), which we have used in our center since the
1990s, in patients with Dravet syndrome (DS).
Methods: We performed a cross-sectional study of all DS patients with SCN1A mutations who had at least
one visit to our center in 2013. A total of 54 patients were included (32 males, 22 females), whose ages
ranged from 2.5 to 22 years.
Results: Seizure onset ranged from 2 to 9 months (mean 5 months). Treatment started at a mean age
of 7 months with valproate (VPA) as first therapy in 83% of patients. STP was prescribed in 96% at an
average age of 20 months. At last follow-up (up to 22 years, median 8 years), 96% were still receiving
STP, with VPA and clobazam (CLB) in 91%. Additional therapies were prescribed in 72% of patients. Most
patients (96%) continued to have clonic or tonic-clonic seizures but they were brief (<5 min, with last
status epilepticus (SE) episode being before 4 years of age). Seizures occurred weekly (>3/month) in 38%
of patients, monthly (1–3/month) in 40%, and yearly in the remaining patients. None presented with daily
seizures. Seizure frequency at last visit was related to the age of treatment initiation, the age of last SE,
and SCN1A mutation type.
Conclusions: Triple therapy with STP, VPA, and CLB was maintained long-term by 96% of this large DS
cohort because the reduced frequency and severity of seizures STP provided when added to CLB and VPA
was durable. Nevertheless, only a few patients achieved seizure freedom and persisting seizures remains
a concern in the majority of patients.
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
Dravet syndrome (DS) (OMIM 607208), is a serious, intractable
epilepsy syndrome that is characterized by prolonged febrile and
afebrile, often unilateral, tonic-clonic (TC) seizures beginning in the
first year of life. Later, focal seizures, myoclonic jerks, and atypical
absences may develop with TC seizures and susceptibility to fever.
*
Corresponding author at: Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, 149 Rue de Sevres,
75015 Paris, France.
E-mail addresses: paola.deliso@uniroma1.it (P. De Liso), nicole.chemaly@aphp.fr (N. Chemaly), jacques.laschet@inserm.fr (J. Laschet), christine.barnerias@aphp.fr
(C. Barnerias), marie.hully@aphp.fr (M. Hully), dorothee.leunen@aphp.fr (D. Leunen), isabelle.desguerre@aphp.fr (I. Desguerre), catherine.chiron@aphp.fr (C. Chiron),
olivier.dulac@aphp.fr (O. Dulac), rima.nabbout@aphp.fr, rimanabbout@yahoo.com (R. Nabbout).
These seizures persist long-term, often life-long, and achieving
seizure freedom is rarely reported (Takayama et al., 2014). Status
epilepticus (SE) in DS patients is frequent during early childhood
(Dravet and Oguni, 2013), despite the fact that electroencephalo-
gram (EEG) readings are initially normal. From the second year of
life onward, EEGs show the development of background slowing
with focal spikes, generalized spikes, and polyspike waves (Dravet
and Oguni, 2013). Psychomotor outcome is typically poor, mani-
festing with gait disorders, developmental delays,
http://dx.doi.org/10.1016/j.eplepsyres.2016.05.012
0920-1211/© 2016 Elsevier B.V. All rights reserved.