Overview of therapeutic options for epilepsy.

Tuberous sclerosis (TSC) epilepsy includes infantile spasms and focal seizures before the age of 2 years, whereas focal seizures are predominant over 2 years and generalized seizures may occasionally be part of Lennox-Gastaut syndrome. The better and earlier the seizure control, the better the child's subsequent cognitive and behavioral prognosis. As for epilepsy of other causes, therapeutic options depend on the type of seizure/epilepsy, age and drug resistance, but there are significant specificities for TSC. (1) As first-line treatment, vigabatrin is unanimously recommended for infantile spasms and focal seizures before 2 years and is also widely used for seizures over 2 years, as are levetiracetam and carbamazepine. (2) If seizures persist (about 40% of children and adolescents), cannabidiol and everolimus, an inhibitor of the mTOR pathway, have recently been approved as adjunctive therapy to the arsenal of antiseizure medications authorized for this age group and to the ketogenic diet. (3) Surgery is an essential treatment option in cases of drug resistance and should be discussed as soon as two treatments have failed. Presurgical investigations and operating techniques have recently progressed spectacularly, for example laser thermocoagulation with stereotactic location. A particularity of TSC is the possibility of sequential interventions on several epileptogenic tubers. (4) Finally, the innovative principle of initiating "pre-seizure" treatment with vigabatrin from the first months of life has just proven effective on the subsequent development of epilepsy in TSC. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Safety considerations selecting antiseizure medications for the treatment of individuals with Dravet syndrome.

Introduction: Management of individuals with Dravet Syndrome has evolved significantly over the past 10 years. Progress has been made in understanding the pathophysiology, the long-term outcome and possible consequences of inappropriate therapies, new drugs have been approved by the regulatory authorities and patients and families expressed their needs beyond seizures' control.Areas covered: The authors aimed at providing an overview of the main antiseizure medications used in Dravet syndrome with a particular focus on safety considerations. As the highly active phase of seizures takes place before the age of 5 years, the characteristics of antiseizure medications in infancy and childhood have also been considered due to their impact on antiseizure medication safety.Expert opinion: Recent treatments, evaluated via randomized clinical trials, are promising in terms of efficacy and safety in individuals with DS. However, the balance between expected benefits and risks taken must be accurately assessed on an individual basis. There is a lack of data to understand the needs of patients and families, a major point particularly in this population, where the evaluation of efficacy and safety beyond seizures is difficult due to cognitive delay and behavioral disorders and where this evaluation is coming almost exclusively from caregivers.

Flow cytometry: a versatile technology for specific quantification and viability assessment of micro-organisms in multistrain probiotic products.

AIMS: Classical microbiology techniques are the gold standard for probiotic enumeration. However, these techniques are limited by parameters of time, specificity and incapacity to detect viable but nonculturable (VBNC) micro-organisms and nonviable cells. The aim of the study was to evaluate flow cytometry as a novel method for the specific quantification of viable and nonviable probiotics in multistrain products. METHODS AND RESULTS: Custom polyclonal antibodies were produced against five probiotic strains from different species (Bifidobacterium bifidum R0071, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium longum ssp. longum R0175, Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011). Evaluation of specificity confirmed that all antibodies were specific at least at the subspecies level. A flow cytometry method combining specific antibodies and viability assessment with SYTO® 24 and propidium iodide was applied to quantify these strains in three commercial products. Analyses were conducted on two flow cytometry instruments by two operators and compared with classical microbiology using selective media. Results indicated that flow cytometry provides higher cell counts than classical microbiology (P < 0·05) in 73% of cases highlighting the possible presence of VBNC. Equivalent performances (repeatability and reproducibility) were obtained for both methods. CONCLUSIONS: This study showed that flow cytometry methods can be applied to probiotic enumeration and viability assessment. Combination with polyclonal antibodies can achieve sufficient specificity to differentiate closely related strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Flow cytometry provides absolute and specific quantification of viable and nonviable probiotic strains in a very short time (<2 h) compared with classical techniques (>48 h), bringing efficient tools for research and development and quality control.

Cortical Auditory-Evoked Responses in Preterm Neonates: Revisited by Spectral and Temporal Analyses.

Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization.

Dynamic changes of depolarizing GABA in a computational model of epileptogenic brain: Insight for Dravet syndrome.

Abnormal reemergence of depolarizing GABAA current during postnatal brain maturation may play a major role in paediatric epilepsies, Dravet syndrome (DS) being among the most severe. To study the impact of depolarizing GABA onto distinct patterns of EEG activity, we extended a neural mass model as follows: one sub-population of pyramidal cells was added as well as two sub-populations of interacting interneurons, perisomatic-projecting interneurons (basket-like) with fast synaptic kinetics GABAA (fast, I1) and dendritic-projecting interneurons with slow synaptic kinetics GABAA (slow, I2). Basket-like cells were interconnected to reproduce mutual inhibition mechanisms (I1➔I1). The firing rate of interneurons was adapted to mimic the genetic alteration of voltage gated sodium channels found in DS patients, SCN1A(+/-). We implemented the "dynamic depolarizing GABAA" mediated post-synaptic potential in the model, as some studies reported that the chloride reversal potential can switch from negative to more positive value depending on interneuron activity. The "shunting inhibition" promoted by GABAA receptor activation was also implemented. We found that increasing the proportion of depolarizing GABAA mediated IPSP (I1➔I1 and I1➔P) only (i.e., other parameters left unchanged) was sufficient to sequentially switch the EEG activity from background to (1) interictal isolated polymorphic epileptic spikes, (2) fast onset activity, (3) seizure like activity and (4) seizure termination. The interictal and ictal EEG patterns observed in 4 DS patients were reproduced by the model via tuning the amount of depolarizing GABAA postsynaptic potential. Finally, we implemented the modes of action of benzodiazepines and stiripentol, two drugs recommended in DS. Both drugs blocked seizure-like activity, partially and dose-dependently when applied separately, completely and with a synergic effect when combined, as has been observed in DS patients. This computational modeling study constitutes an innovative approach to better define the role of depolarizing GABA in infantile onset epilepsy and opens the way for new therapeutic hypotheses, especially in Dravet syndrome.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

Treatment of dilute methylene blue-containing wastewater by coupling sawdust adsorption and electrochemical regeneration.

In the present work, the coupling of adsorption and electrochemical oxidation on a boron-doped diamond (BDD) electrode to treat solutions containing dyes is studied. This coupling may be convenient for the treatment of diluted pollutant that is limited by the low rate of electrooxidation due to mass-transfer limitation. A pre-concentration step by adsorption could minimize the design of the electrochemical reactor. The adsorbent chosen was mixed with softwood sawdust, and methylene blue was chosen as the model dye molecule. Isotherms of adsorption and kinetics were investigated as well as the effects of current density and regeneration time. The BDD electrochemical oxidation of methylene blue adsorbed onto sawdust led simultaneously to its degradation and sawdust regeneration for the next adsorption. It was observed that multiple adsorption and electrochemical regeneration cycles led to an enhancement of adsorption capacity of the sawdust. This study demonstrated that adsorption­electrochemical degradation coupling offers a promising approach for the efficient elimination of organic dyes from wastewater.

Treatment strategies.

There has been important progress in the identification of antiepileptic compounds and their indications in children over the past 15 years: their number has doubled and specific pediatric trials are being performed to document their effect according to seizures and syndromes as well as their tolerability in pediatrics. The improved understanding of pharmacokinetics and drug-drug interactions has helped to optimize treatment. Specific issues specific of infants have also been studied although new antiepileptic drugs are still dramatically lacking for this age group. Before reaching a syndromic diagnosis, the choice of a first- line agent goes to compounds with the largest range of efficacy and least identified risks. Subsequent choices are mainly based on the epilepsy syndrome and seizure type in addition to good clinical practice to determine dose, adverse effect profile, risk of aggravating seizures and drug interactions, clinician's experience, cultural habits, and availability of drugs. If there are several options, preference is given to the compound that exhibits the best risk/benefit ratio, or the most rapid titration when seizure frequency is the major issue. For new antiepileptic compounds, price is often a limiting factor in countries with poor insurance coverage. Third generation anti-epileptic drugs are emerging which also seem to be promising.

Advanced structural and functional MRI in childhood epilepsies.

New noninvasive MR imaging techniques are currently deeply changing the exploration of epileptic and functional networks in childhood epilepsies, as well as of the normally developing brain. While DTI can be used to look at the anatomical connectivity and at the microstructural changes that reflect the organization of an epileptic network, in addition to other techniques such as SPECT and PET, functional MRI is nowadays used routinely in the presurgical planning of focal epilepsies to assess the cortical organization of motor and language networks, helping to select surgical patients and plan the resection. Precise and robust motor mapping can be obtained in children comparably to adults. The assessment of language dominance by fMRI has reduced the need for invasive techniques such as the Wada test, provided age-related paradigms are being used in cooperating children (from 5 to 6 years of developmental age, with IQs of at least 60, and without behavioral disorders). Recent data indicate that the localizing value of language fMRI might be good when compared to cortical stimulation, and memory fMRI is emerging in children. However, invasive techniques are still necessary in difficult cases with high risk of postoperative deficit.

A prospective open-labeled trial with levetiracetam in pediatric epilepsy syndromes: continuous spikes and waves during sleep is definitely a target.

Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel of refractory epilepsy syndromes has not been entirely evaluated prospectively. In order to study the efficacy and safety of LVT as adjunctive therapy according to syndromes, we included 102 patients with refractory seizures (6 months to 15 years) in a prospective open-labeled trial. The responder rate was respectively 36% and 32% at 3 and 6 months with 6% and 7% patients becoming seizure free. Among the responders at 6 months (n=33), seizure frequency decreased by 66% and 79% at 3 and 6 months LVT compared to baseline. The highest benefit was for CSWS patients with 2/3 responders, 50% seizure free and no aggravation. LVT provided respectively 39% and 42% responders in focal and absence epilepsies. Infantile spasms and Dravet syndrome experienced the lowest efficacy. No patient with myoclonic-astatic epilepsy or Lennox-Gastaut syndrome was aggravated. LVT dose over 40 mg/kg/d was associated with a lower response rate. Tolerability was excellent. In spite of a small sample, we assume that CSWS is a good candidate for a randomized-controlled trial with LVT.

FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical dysplasias.

OBJECTIVE: To determine the diagnostic accuracy and prognostic value of ¹8FDG-PET in a recent series of patients operated for intractable partial epilepsy associated with histologically proven Taylor-type focal cortical dysplasia (TTFCD) and negative MRI. METHODS: Of 23 consecutive patients (12 male, 7-38 years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had strictly normal MRI. FDG-PET was analyzed both visually after coregistration on MRI and using SPM5 software. Metabolic data were compared with the epileptogenic zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome. RESULTS: Visual PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%) corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9). PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13 cases. Location of PET abnormalities was extratemporal in all cases, involving eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic findings (n = 20) demonstrated that single hypometabolic gyri (n = 11) corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus. Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex but were more extensive. Following limited cortical resection (mean follow-up 4 years), seizure freedom without permanent motor deficit was obtained in 20/23 patients (87%). CONCLUSIONS: ¹8FDG-PET coregistered with MRI is highly sensitive to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients with negative MRI.

Unusual consequences of status epilepticus in Dravet syndrome.

Although status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected.

[Structural and functional imaging: particularities in children]. / Imagerie morphologique et fonctionnelle: particularités chez l'enfant.

Surgery of partial epilepsies in childhood has largely benefited from the recent advances of imaging techniques, which carry a triple goal: (1) to contribute to the localization of the epilepsy onset zone, (2) to detect and delineate an underlying lesion, and (3) to study the spatial relationship between the epileptogenic zone and the neighboring functional cortex, in order to select patients and plan the resection. This noninvasive presurgical imaging workup must be compared to clinical and electrical data to estimate the postoperative prognosis, while invasive techniques such as SEEG, cortical stimulations, and IAT often remain indispensable in difficult cases, i.e., in cryptogenic epilepsies. As in adults, advances in MRI allow us to detect more and more subtle underlying lesions, but this requires repeating MR studies during early childhood and using adapted sequence parameters to account for ongoing myelination. Ictal SPECT and PET imaging prove especially useful in planning depth electrode placement when video-EEG is not contributive, when MRI looks normal or shows multiple abnormalities, or in cases of discrepant findings. Multimodal imaging greatly enhances the sensitivity of all of these techniques. Finally, functional MRI of motor and language functions provide noninvasive cortical mapping of essential functions, using age-adapted paradigms, in cooperating children from age five to six and from IQs around 60.

[Positron emission tomography: which indications, which benefits?]. / Tomographie par émission de positons (TEP): quelles indications, quels bénéfices ?

Positron emission tomography (PET) is currently used in the presurgical workup for drug-resistant partial epilepsies in addition to MRI. Interictal metabolism is studied in clinical practice using (18)fluoro-desoxy-glucose ((18)FDG). In medial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis, hypometabolism ipsilateral to the epileptogenic focus is found in 70-90% of cases. However, hypometabolism is larger than the structural lesion observed on MRI and includes the epileptogenic zone and ictal discharge spread areas. Hypometabolism is related to surgical outcome and cognitive disturbances in MTLE. Although the usefulness of PET appears less well-established in extratemporal lobe epilepsy and in children, its sensitivity may be improved by coregistration and superimposition of PET on MRI at any age. Focal hypometabolism can be easily detected by visual analysis, allowing detection of minor gyral abnormalities that may correspond to focal cortical dysplasias. Moreover, in cases of negative MRI, focal hypometabolism findings may help invasive monitoring planning and deep electrode placement for SEEG, and finally improve surgical outcome.

Long term response to steroid therapy in Rasmussen encephalitis.

Rasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term. We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9+/-2 years. Age at onset of RE ranged from 2 to 14 years. Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate. Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection.

New locus for febrile seizures with absence epilepsy on 3p and a possible modifier gene on 18p.

OBJECTIVE: To report a clinical and genetic study of a large family with febrile seizures (FS) and childhood absence epilepsy (CAE). METHODS: This family was identified through a French campaign for familial epilepsies. It spans four generations and consists of 51 members, 13 of whom were affected. The medical history of all members was obtained by personal information and by consulting the medical files of affected members. All family members gave written consent to participate in the study. RESULTS: All affected members presented FS, with CAE in five and temporal lobe epilepsy (TLE) in one. FS stopped before age 6 years in all but one patient. FS were simple, except in one patient who had a long-lasting complex FS at 8 months of age. He later presented pharmacoresistant TLE and left hippocampal sclerosis was visible on brain MRI. Patients presenting CAE had recorded absences and characteristic EEGs with 3 Hz spike waves. After exclusion of reported loci for FS and generalized epilepsy with FS plus, a genome-wide search allowed us to map a new locus for FS on 3p. We could not exclude another genomic segment on chromosome 18p and all patients presenting epilepsy (CAE and TLE) shared a common haplotype at this locus in addition to the haplotype on 3p. CONCLUSION: These findings emphasize the genetic heterogeneity of febrile seizures. Furthermore, epilepsy in association with febrile seizures might result in this family from an interaction between at least two genes: the gene on 3p and a possible modifier gene on 18p.

Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis.

PURPOSE: To describe the characteristics of a previously overlooked devastating epileptic encephalopathy that presents as intractable bilateral perisylvian epilepsy starting with prolonged status epilepticus (SE) in normally developing school-aged children. METHODS: Retrospective study over 7 years of all normally developing children admitted in our institution for a prolonged SE following non-specific febrile illness with at least one seizure recorded on EEG. RESULTS: Fourteen children were included at a median age of 7.5 years (4-11) (median follow-up of 4 years (1-7)). Intractable SE lasted 4-60 days (median 30). CSF cell count was normal in five cases and moderately increased in the others. During SE, seizures were recorded in 11 patients and involved temporal lobes in 7; the other 4 patients exhibited perisylvian clinical features with secondary generalization. Intractable epilepsy followed SE in all cases without any latent period. Persisting seizures were recorded in 10 patients and involved temporo-perisylvian regions in 8, frontal regions in 2; 3 others had perisylvian ictal semiology. Spiking was bilateral in 10 cases. MRI showed bilateral hippocampal hypersignal and/or atrophy in 10 cases (extended to the neocortex in 3). All children had major cognitive sequelae. When feasible (six patients), detailed neuropsychology suggested fronto-temporal impairment. CONCLUSIONS: Among so called grey matter encephalitis patients, we identified a recognizable pattern we propose to call Devastating Epileptic encephalopathy in School-age Children (DESC) that begins with prolonged SE triggered by fever of unknown cause, and persists as intractable perisylvian epilepsy with severe cognitive deterioration.

Topiramate in the treatment of highly refractory patients with Dravet syndrome.

The purpose of this study was to assess the effectiveness and tolerability of topiramate (TPM) as add-on therapy in children with Dravet syndrome and considered unsatisfactorily controlled using stiripentol. All the 36 patients having been treated with TPM in our centre in 2001 were retrospectively evaluated. Seventy percent of them still received stiripentol when TPM was introduced. The association of both drugs did not need any particular adaptation of dosages. The mean TPM follow-up was 13.3 months (4-25 months) and the mean optimal TPM dose was 3.2 mg/kg/d (0.6-9.2 mg/kg/d). Twenty eight children (78 %) showed more than 50 % reduction in the frequency of generalized tonic-clonic seizures and status epilepticus (SE), whereas 8 % had more than 50 % increase. Six patients (17 %) remained seizure-free for at least 4 months. The most frequently reported side-effects were gastrointestinal and behavioural disturbances. TPM had to be stopped in 17 % of patients, because of poor tolerability and/or lack of efficacy. Topiramate seems therefore to be helpful in Dravet syndrome, even in patients not satisfactorily controlled by stiripentol. Both drugs can be easily and safely associated.

[Acceptability and tolerance of sodium valproate, a new sustained-action granule formulation, in monotherapy for epileptic children from 3 years old]. / Acceptabilité et tolérance du valproate de sodium, granules à libération prolongée, en monothérapie chez l'enfant épileptique à partir de trois ans.

UNLABELLED: Sodium valproate (VPA) is an anti-epileptic drug which was until now administered to children as drinkable or injectable form. A new galenic form of this compound has been developed as microgranules with prolonged release (Micropakine)LP; MPK). This new galenic form of VPA allows a greater stability of the plasmatic rates, thus limiting the risk of amount-dependent adverse effects at the time of the peaks, and of less effectiveness at the time of the fall of the circulating rates. The main objective of this study was to evaluate the acceptability of the new galenic form of VPA, in monotherapy, for epileptic children with >or=3 years old. The evaluation was performed at day (D)90 by the patients using a hedonic visual scale. The secondary objectives were to evaluate the acceptability by the parents, the treatment compliance, the percentage of patients free of seizure at D 90, and the tolerance. Finally, the authors compared all these data to those recovered at the baseline in patients already treated by the previous drinkable VPA. A total of 307 patients were involved by 76 hospital neuropediatric physicians. The population was constituted by 110 children <5 years old and 197 children from 5 to 14 years old. MPK was well accepted for total population at D 90 (<5 years old: 83.3%; >or=5 years old: 80%). For patients previously treated by drinkable form of VPA (N=199), MPK was significantly better accepted than the drinkable form at D1 (<5 years, P=0.0189; >or=5 years, P<0.0001). Less difficulties were experienced by the parents to administrate MPK when compared to the drinkable form (P<0.001), mainly due to his neutral taste. Patients free of seizure at D 90 were 77% [70,3; 82,5]. Specially, fewer epileptic seizures were evidenced for all children previously treated at D1 by drinkable form of VPA. The treatment was well respected by the patients, which were compliant in 80% of the cases. The adherence to treatment was good since the treatment compliance was 87%. MPK was well tolerated. CONCLUSION: MPK in the microgranule form significantly improves the treatment acceptability with a good tolerance. Two daily intakes and neutral taste are two major advantages to favour the compliance in children, thus contributing to the efficacy of the antiepileptic treatment.

[Recent advances in pathogenic concepts and therapeutic strategies in Rasmussen's encephalitis]. / Avancées actuelles sur les concepts pathogéniques et thérapeutiques de l'encéphalite de Rasmussen.

Rasmussen's encephalitis (RE) is a rare inflammatory brain disease mainly affecting children and characterised by intractable epilepsy involving a single hemisphere that undergoes progressive atrophy. RE is characterized by refractory focal seizures, often associated with epilepsia partialis continua, progressive unilateral motor defect, slow EEG activity over the entire contralateral hemisphere, with focal white matter hyperintensity and insular cortical atrophy on neuroimaging. Surgical exclusion of the affected hemisphere is the only treatment that interrupts progression of the disease. Pathogenic concepts have considered viruses, autoimmune antibodies and autoimmune cytotoxic T lymphocytes that might contribute to the initiating or perpetuating events in the central nervous system. Based on these concepts, different therapeutic strategies have been pursued, such as antiviral agents, plasmapheresis, immuno-adsorption, immunosuppression or immunomodulation with intravenous immunoglobulins. However, due to the lack of large studies, to date there is no established therapeutic strategy for this devastating condition. In this review, we give an overview of the current state of immunopathogenic concepts for Rasmussen's encephalitis and discuss the different therapeutic options for future perspectives.