mTOR-therapy and targeted treatment opportunities in mTOR-related epilepsies associated with cortical malformations.

Dysregulation of the mTOR pathway is now well documented in several neurodevelopmental disorders associated with epilepsy. Mutations of mTOR pathway genes are involved in tuberous sclerosis complex (TSC) as well as in a range of cortical malformations from hemimegalencephaly (HME) to type II focal cortical dysplasia (FCD II), leading to the concept of "mTORopathies" (mTOR pathway-related malformations). This suggests that mTOR inhibitors (notably rapamycin (sirolimus), and everolimus) could be used as antiseizure medication. In this review, we provide an overview of pharmacological treatments targeting the mTOR pathway for epilepsy based on lectures from the ILAE French Chapter meeting in October 2022 in Grenoble. There is strong preclinical evidence for the antiseizure effects of mTOR inhibitors in TSC and cortical malformation mouse models. There are also open studies on the antiseizure effects of mTOR inhibitors, as well as one phase III study showing the antiseizure effect of everolimus in TSC patients. Finally, we discuss to which extent mTOR inhibitors might have properties beyond the antiseizure effect on associated neuropsychiatric comorbidities. We also discuss a new way of treatment on the mTOR pathways.

A simple novel approach for detecting blood-brain barrier permeability using GPCR internalization.

AIMS: Impairment of blood-brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist-induced internalization of a neuronal G protein-coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2). METHODS: The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor. RESULTS: We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging-guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development. CONCLUSIONS: This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.

Lennox-Gastaut syndrome: New treatments and treatments under investigation.

There are currently five compounds (clobazam, felbamate, lamotrigine, topiramate, rufinamide) available for prescription with a demonstrated efficacy on drop seizures for Lennox-Gastaut syndrome (LGS). There are also currently new and under-investigation compounds. This paper gives an overview on these novel developments for LGS based on the lecture given at the French Chapter meeting of the International League Against Epilepsy (ILAE) held in Paris in October 2019. Five compounds were discussed. Epidiolex (cannabidiol) has been approved recently based on positive randomized control trials in LGS patients. Four drugs are under investigation according to a search on the 'clinicaltrials.gov' database. Perampanel and fenfluramine are both being studied in ongoing phase 3 studies. Two compounds are in an earlier stage of development with ongoing phase 1 and 2 studies: carisbamate and OV953. We summarized the publicly available data. Based on these drug development programs, we can expect that new compounds will become available for LGS in the next years, possibly resulting in new treatment paradigms.

Pharmacological treatment of attention-deficit/hyperactivity disorder in children and adolescents with epilepsy.

Attention-deficit/hyperactivity disorder (ADHD) is the most frequent comorbidities in children with epilepsy with an increased risk of other psychiatric comorbidities and academic underachievement. In children with epilepsy, the attentive form is the most common clinical presentation in pediatric epilepsies. A systemic review and a consensus from the ILAE have been recently published on diagnosis, screening and management of ADHD in children with epilepsy. We give an overview of the pharmacological treatment of ADHD in children with epilepsy based on the lecture given at the International League Against Epilepsy (ILAE) French Chapter meeting, (October 2018, Lyon). Although only class II and class III studies are available, methylphenidate is the most appropriate pharmacological option for the treatment of ADHD in children with epilepsy with a limited risk of seizure worsening. The medical treatment should be used in combination of the global management including optimal antiepileptic drug treatment avoiding polytherapy, management of psychiatric comorbidities and support at school.

[Evaluating a child after a febrile seizure: Insights on three important issues]. / Évaluation d'un enfant après une crise fébrile : focus sur trois problèmes de pratique clinique.

Febrile seizures (FS) are the most common seizures seen in the paediatric population in the out-of-hospital and emergency department settings, and they account for the majority of seizures seen in children younger than 5 years old. An FS is a seizure accompanied by fever, without central nervous system infection, occurring in children between 6 months and 5 years old. Five criteria have been used and taught to classify any FS as simple or complex FS. These factors do not bear the same significance for clinical practice, in particular, the decision to perform a lumbar puncture for cerebrospinal fluid analysis to rule out an intracranial infection. Moreover, epidemiological studies have illustrated that some factors are predictive of febrile seizure recurrence while others are predictive of epilepsy occurrence. On this basis, a workshop was organized to provide an answer to three clinical practice questions: when should a lumbar puncture be performed in a child who has experienced a seizure during a fever episode, is the prescription of a rescue drug required with a risk of a prolonged febrile seizure recurrence, when should a neurological consultation be requested (risk of later epilepsy)? Based on a review of the literature and on a 1-day workshop, we report here the conclusion of the working group. A lumbar puncture is required in any child with meningitis symptoms or septic signs or behaviour disturbance. A lumbar puncture should be discussed based on the clinical symptoms and their progression over time when a child has experienced a focal FS or repetitive FSs without signs of meningitis or sepsis or behaviour disturbance. The lumbar puncture is not necessary in case of simple FS without signs of meningitis, including in infants between 6 and 12 months old. An early clinical evaluation (at least 4 h after the first clinical assessment) could be helpful, in particular in infants younger than 12 months of age. A rescue drug might be prescribed when there is a high risk of prolonged FS (i.e., risk higher than 20%): age at FS<12months OR a history of a previous febrile status epilepticus OR if the first FS was a focal seizure OR abnormal development/neurological exam/MRI OR a family history of nonfebrile seizure. A neurological consultation should be requested for any child who has experienced a prolonged FS before the age of 1 year, for children who have experienced prolonged and focal FS or repetitive (within 24h) focal FS, for children who have experienced multiple complex (focal or prolonged or repetitive) FS, for children with an abnormal neurological exam or abnormal development experiencing a FS. Although childhood febrile seizures in most cases are benign, witnessing such seizures is always a terrifying experience for the child's parents. Most parents feel that their child is dying or could have severe brain injury related to the episode. Therefore, the group also suggests a post-FS visit with the primary care physician.

[Therapeutic management of neonatal arterial cerebral infarction and neuroprotection perspectives]. / Prise en charge thérapeutique des convulsions associées à l'accident vasculaire cérébral du nouveau-né et perspectives de neuroprotection à la phase aiguë.

Neonatal seizure related to stroke is a common diagnostic feature. Their treatment, although widely debated even today must be initiated in case of status epilepticus, clinical seizures of more than 5 minutes duration or short (> 30 secondes) and repeated clinical seizures (2 or more per hour). The treatment of neonatal seizures is a challenge that remains only partially solved. It should take into account the etiology of seizures, type of brain lesions and clinical/electrical response to treatment after the first line treatment. It is based on using a single anti-epileptic at its maximum dosage, and if needed, on the association with another anti-epileptic drug with a different mechanism of action. Phenobarbital remains the most commonly used drug for initial treatment of neonatal seizures and for which the most clinical experience has been accumulated. The lack of randomized controlled trials makes difficult recommendations about the optimal duration of treatment, but most experts agree that once arrested seizures, the duration of treatment should be as short as possible because of its potential risk on the developing brain. Novel neuroprotective strategies for reducing impact of neonatal stroke or promoting brain repair remain for the moment the concept stage, pre-clinical or parcel clinical data.

[Neonatal arterial ischemic stroke: Review of the current guidelines]. / Accidents vasculaires cérébraux ischémiques artériels néonatals : synthèse des recommandations.

Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended.

[Childhood absence epilepsy: An update]. / Épilepsie absence de l'enfant : actualités diagnostiques et thérapeutiques.

Childhood absence epilepsy (CAE) is a common pediatric epilepsy syndrome accounting for 10% of all pediatric epilepsies. The aim of this review is to provide an updated overview of this epilepsy syndrome to pediatricians. Most of the patients can be initially managed in private practice or in general pediatric settings. Absence seizures are the only seizure type observed at the time of diagnosis in these patients. An electroencephalogram recording and a clinical evaluation lead to the diagnosis. The underlying mechanisms are not yet fully understood. CAE is considered a self-limited epilepsy syndrome since most of the patients will become seizure free. Only a few patients (5-10%) have resistant CAE. However, CAE, as well as any pediatric epilepsy syndrome, should not be considered a "benign" epilepsy. Attention deficit is observed in about one third of the patients. There is also an increased risk of academic difficulties related to specific cognitive disorders. Therefore, the early detection of children at risk of developing neuropsychological problems can be helpful for preventing school underachievement and poor psychosocial outcome. Recently, several studies including a large randomized controlled trial indicated that ethosuximide should be considered as a first-line treatment and valproate as a second-line treatment. Cognitive side effects should be an important factor in the selection of the antiepileptic drug and should be specifically assessed during the follow-up. This review concludes by discussing the criteria that might lead to referring the patient to a specialist.

Non-pharmacological medical treatment in pediatric epilepsies.

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a non-pharmacologic therapy for refractory epilepsy. Several multicenter and two randomized studies have demonstrated the efficacy of the ketogenic diet and the modified Atkins diet for children and adolescent with pharmacoresitant epilepsy. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non-fat components and the initiation of the diet with or without fasting. The modified Atkins diet is now used as an alternative diet. A randomized trial establishing the efficacy of the modified Atkins diet is now available. More recently, the low glycemic index diet seems to be used successfully for pharmacoresistant epilepsy but there are currently only open studies. Looking at the clinical efficacy of dietary treatments, the studies usually report a greater than 50% reduction in seizure frequency in about half of patients at 3 months under diet. Most of the patients who are responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Efficacy of the ketogenic diet has also been reported for teenager and adult patients. Dietary treatment of epilepsy should not be considered as a last chance treatment. It can be used during the investigation for epilepsy surgery even in case of structural abnormalities. In some epilepsy syndromes such as infantile spasms, myoclonic-astatic epilepsy and refractory status epilepticus, an early use seems helpful. The exact underlying mechanisms are unknown and remain a topic of active research.

Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

OBJECTIVE: Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. METHOD: Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. RESULTS: The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. SIGNIFICANCE: Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.

[Prolonged convulsive seizures in children: how are they managed outside the hospital?]. / Survenue d'une crise d'épilepsie prolongée chez l'enfant : quelle prise en charge en dehors du milieu hospitalier ?

CONTEXT AND OBJECTIVES: Guidelines recommend that any epileptic seizure that lasts more than 5 min (prolonged seizures) be treated immediately with benzodiazepines in order to prevent progression to status epilepticus. However, there is very little published information on how such seizures are managed outside of the hospital setting, for example in schools or at home. This paper presents the initial results, specific to France, of the Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy (PERFECT) Initiative, which was set up in 2011 to gain a better understanding of how prolonged convulsive seizures are managed and rescue medication is administered in out-of-hospital settings across Europe. METHODS: The PERFECT Initiative was conducted in six countries (France, Germany, Italy, Spain, Sweden, the United Kingdom) and consists of three phases. This paper reports on the first two phases of this study and focuses on findings for France. Phase I of the PERFECT initiative consisted of a review of existing clinical guidelines, guidance to schools, and relevant policy and legal frameworks in France, from both published and web-based sources. Phase II consisted in a telephone survey of 20 pediatricians, pediatric neurologists, and neurologists who treat children with prolonged convulsive seizures in France in order to obtain their views on how prolonged seizures are managed outside of hospitals. Phase III is ongoing and consists of a survey of children with prolonged seizures and their caregivers. RESULTS: Existing clinical guidelines pertain mainly to the hospital setting and contain very little informations on how prolonged seizures should be managed outside the hospital. Guidance to schools is unclear as to whether teachers are allowed to administer rescue medication to children and legal frameworks are full of contradictions. As a result, whether or not children who experience prolonged seizures receive their rescue medication during school hours depends mostly on the resources and training available in each school. Healthcare professionals stated that lack of information on prolonged seizures and their management, as well as a lack of up-to-date guidance specific to schools were considerable obstacles to a systematic approach to managing prolonged seizures outside of the hospital. DISCUSSION: In France and elsewhere, there has been growing recognition of substantial gaps in the provision of care to children with epilepsy in recent years. However, the issues that arise for children who require rescue medication for prolonged seizures outside of hospitals are conspicuously absent from policy documents or clinical guidelines. This lack of information, combined with insufficient training in schools on epilepsy, and inadequate guidelines create a situation in which schools are likely to call an ambulance every time a child has a prolonged seizure, therefore risking delays in treatment, and putting the child at risk of status epilepticus and clinical sequelae, not to mention stigmatization at school. CONCLUSION: There is a need for more explicit guidance covering educational and healthcare settings, clearer information to parents and schools, and more systematic training to be made available to caregivers in order to ensure that all children at risk of prolonged seizures receive their prescribed rescue medication as quickly as possible, regardless of where their seizure occurs.

[A national framework for educational programs in epileptic patients, children and adults]. / Un référentiel national pour l'éducation thérapeutique des patients atteints d'épilepsie(s), enfants et adultes.

Epilepsy is a chronic disease with a wide range of presentations occurring at any age. It affects the patient's quality of life, implying a need for numerous healthcare services. Therapeutic education programs (TEPs) are designed to match patient age, disease course, and individual learning abilities. In France, these programs are proposed by the national health authorities (Superior Health Authority), and authorized by the Regional Health Agencies. Two years ago, a Therapeutic Education Programs Commission (TEPC), supported by the French League against Epilepsy (FLAE), was created. The goal was to bring together representative healthcare professionals in a working group in order to standardize practices. This led to the creation of a national reference of healthcare skills specific for children and adults with epilepsy. Five tables, for five "life periods", outline the framework of this professional reference tool. Program personalization, an essential part of TEPs, is necessary to develop a creative atmosphere. This slow process is specific to the various stages of life and can be influenced by the occurrence of various handicaps. Family and caregivers make key contributions to the process. The national framework for therapeutic education in epilepsy serves as a central crossroad where professions can find essential information to create or adapt their own TEPs. In the near future, regional experiences will be documented and collected for regular updates. This professional therapeutic education network will help promote therapeutic education programs and facilitate standard practices. Finally, several TEP files and tools will be shared on the FLAE website available for professional access. Today, the group's goal is to achieve national deployment of this "referential" framework.

[Quality of health information about epilepsy on the Internet: Evaluation of French websites]. / Lisibilité et qualité des sites Internet français sur l'épilepsie.

UNLABELLED: The Internet is now the single largest source of health information and is used by many patients who are affected by epilepsy and their families. METHODS: To assess the quality of information provided by French website on the different forms of epilepsy and their treatment, we used search engines (French pages from Bing, Google and Yahoo) to look for information using the French equivalent of three keywords epilepsy (Épilepsie); epilepsy treatment (Épilepsie traitement) and seizure (Convulsions). The websites were evaluated for content quality by using an adaptation of the validated DISCERN rating instrument. Each website was evaluated by three investigators (a naive observer, a pediatric neurologist and a neurologist). RESULTS: Most of the information on epilepsy and its treatment were from community websites. We found six French websites which were scored higher than half of the maximal value of our scoring system (≥27.5/55): www.passeportsante.net; fr.wikipedia.org; www.fondation-epilepsie.fr; www.epilepsie-france.fr; www.doctissimo.fr; www.caducee.net. CONCLUSION: This study provides a list of French websites that have been evaluated for the quality of their information. We did not observe any correlation between the quality of the information and priority on search engine listings. Websites sponsored by patients associations and by institutions should update their content more frequently or work on their search engine indexation to appear higher on search engine listings.

[Assessment of education needs of adolescents and parents of children with epilepsy]. / Évaluation des besoins en éducation thérapeutique auprès des parents d'enfants et d'adolescents ayant une épilepsie.

INTRODUCTION: Education program for patients (EPP) is now a part of the management of patients with chronic disease. According to WHO, the EPP is designed to help patients to maintain or gain self-care skills and adaptive skills necessary to improve their health and their quality of life. Patient education programs have been developed in recent years in several chronic diseases such as diabetes and asthma. In the field of epilepsy, however, adult and child programs have been developed only recently in France. We evaluate the interests for the establishment of an EPP and the topics that the parents and the adolescents would like to be discussed in such courses. METHODS: We conducted a qualitative survey, based on interviews of parents of epileptic children and adolescents. The survey was conducted between April and November 2010 in pediatric neurology services of four French university hospitals: Amiens, Nancy, Marseille, and in Robert Debré (Paris) hospital. We investigated the following issues: treatment and self-management, and seizure management, psychosocial difficulties related to epilepsy, anatomical and physiological knowledge of epilepsy and lifestyle. RESULTS: Two topics seem to have the greatest interest for parents of children with epilepsy and adolescents: knowledge about seizures and knowledge of anatomy and physiology of the brain. Adolescents involved in this study gave consistently lower scores in all items compare to parents of children. CONCLUSION: The medical management of children and adolescents with epilepsy, and their caregivers, is a comprehensive care including the EPP in order to provide a full management of all issues raised by epilepsy. The survey identified key-points that parents and their children would like to learn in an EPP. These data would be helpful to design an EPP.

[Use of midazolam for refractory status epilepticus in children]. / Utilisation du midazolam dans l'état de mal épileptique réfractaire de l'enfant.

UNLABELLED: Morbidity and mortality are high in children with refractory status epilepticus (RSE). Here, we assess the efficacy of midazolam for RSE in children. METHODS: This was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008. The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failure. RESULTS: We recorded 29 patients with RSE during the study period: 26 were treated with midazolam, including two where midazolam replaced thiopenthal because of hypotension. Midazolam successfully controlled RSE in 58% of patients. Mean delay to cessation of RSE was 48+/-65 minutes. Hypotension was observed in 8% of midazolam-treated patients and 71% of thiopenthal-treated patients. Overall mortality was 15% (4/26). Two deaths occurred long after the cessation of RSE. None of the deaths occurred in midazolam-treated patients. CONCLUSION: Midazolam is an efficient treatment for RSE in children. Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE.

[Use of injectable lorazepam in status epilepticus: a comparative study in French-speaking hospitals]. / Utilisation du lorazépam injectable dans le traitement de l'état de mal épileptique : étude comparative au sein d'hôpitaux pédiatriques francophones.

BACKGROUND: Injectable lorazepam (IL) is marketed in many countries but in France is only available within the framework of a compassionate use program for refractory status epilepticus. This study aims to evaluate the differences of pediatric use and status of IL in the hospitals of the Mother-Child French-speaking Network (Réseau mère-enfant de la francophonie, i.e., RMEF). METHODS: Inclusion criteria are: firstly, RMEF member; secondly, one site per town; thirdly, all the Assistance publique-Hôpitaux de Paris hospitals. After a phone-recruitment in each selected hospital, a survey was sent by e-mail. The data collected concerned the number of beds in the hospital, the official status of IL, its place in the therapeutic strategy, in hospital consumption in 2008 (in milligram) and the therapeutic alternatives. RESULTS: Among the 18 hospitals selected, 17 were contacted and 12 (70%) replied. IL is not marketed in Tunisia and Lebanon. In Switzerland, Canada and Belgium, IL is marketed and used in all the polled hospitals (6.2 to 48.0mg per bed). In France, only the Robert Debré Hospital uses it (3.2mg per bed). In the countries where it is marketed, IL was firstly prescribed for the studied indication. In the other countries, injectable diazepam was the first line treatment (six out of eight hospitals). DISCUSSION/CONCLUSION: France is the only country where IL is available though not marketed. The pharmacokinetic data favor use of IL instead of its principal therapeutic alternative (injectable diazepam) but no currently available evidence concludes that IL is superior to diazepam in the management of pediatric status epilepticus. The official indication of IL in France (last intention) is in contradiction with its use in the countries where it is marketed and with the data of the literature in favor of the first intention. This works presents the first evaluation on the use of IL in pediatric status epilepticus in the RMEF hospitals. It highlights the discrepancies in the management of status epilepticus in comparable pediatric hospitals.

[Use of ketogenic diet in children in France from 2001 to 2008]. / Evolution de la prescription du régime cétogène en France chez l'enfant entre 2001 et 2008.

INTRODUCTION: The ketogenic diet is an adequate treatment for drug-resistant epilepsy and certain inborn metabolic disorders. The efficacy of the ketogenic diet for the treatment of epilepsy is now well established. In France, and more widely in Europe, there is currently no consensus concerning appropriate initiation of the ketogenic diet and subsequent patient management. METHODS: Using the same questionnaire in 2005 and 2008, we retrospectively recorded the practices of child neurology departments of the French university hospitals during three study periods (2001-2002, 2002-2003 and 2005-2008). The aim was to evaluate the number of ketogenic diets started and how the ketogenic diet was initiated. RESULTS: The ketogenic diet was widely used by pediatric neurologists. The number of patients on a ketogenic diet increased over time. Diet initiation protocols also changed over time, being modified adequately with advances in knowledge of the ketogenic diet. CONCLUSION: The French pediatric neurologists appear to have a good understanding of the ketogenic diet.