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Aims: The prognosis of Infantile epileptic spasm syndrome (IESS), relates to the underlying etiology and delay in controlling epileptic spasms. Based on the spasm-free rate, a randomized controlled trial has demonstrated the superiority of combining oral steroids and vigabatrin over oral steroids alone but confirmation in real-life conditions is mandatory., Methods: We compared two real-life IESS cohorts: a multicenter, retrospective cohort of 40 infants treated with vigabatrin followed by a sequential (ST) addition of steroids, and a prospective, single-center cohort of 58 infants treated with an immediate combination of vigabatrin and steroids (CT)., Results: The two cohorts were similar. When the rate of spasm-free infants in the two cohorts was compared on day 14, a significant difference was observed between the ST (27,5 %) and CT cohorts (64 %) (p < 0.0004). This difference remained significant on day 30, with 55 % spasm-free patients in the ST cohort compared to 76 % in the CT cohort (p = 0.03). After the infants had received both vigabatrin and steroids, without taking into account the time point after treatment initiation, no significant difference was observed in the spasm-free rate between the two cohorts (p = 0.38)., Interpretation: Real-life data confirm the interest of combination therapy as a first-line treatment for IESS., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Children with tuberous sclerosis complex (TSC), may experience a variety of seizure types in the first year of life, most often focal seizure sand epileptic spasms. Drug resistance is seen early in many patients, and the management of TSC associated epilepsy remain a major challenge for clinicians. In 2018 clinical recommendations for the management of TSC associated epilepsy were published by a panel of European experts. In the last five years considerable progress has been made in understanding the neurobiology of epileptogenesis and three interventional randomized controlled trials have changed the therapeutic approach for the management of TSC associated epilepsy. Pre-symptomatic treatment with vigabatrin may delay seizure onset, may reduce seizure severity and reduce the risk of epileptic encephalopathy. The efficacy of mTOR inhibition with adjunctive everolimus was documented in patients with TSC associated refractory seizures and cannabidiol could be another therapeutic option. Epilepsy surgery has significantly improved seizure outcome in selected patients and should be considered early in all patients with drug resistant epilepsy. There is a need to identify patients who may have a higher risk of developing epilepsy and autism spectrum disorder (ASD). In the recent years significant progress has been made owing to the early identification of risk factors for the development of drug-resistant epilepsy. Better understanding of the mechanism underlying epileptogenesis may improve the management for TSC-related epilepsy. Developmental neurobiology and neuropathology give opportunities for the implementation of concepts related to clinical findings, and an early genetic diagnosis and use of EEG and MRI biomarkers may improve the development of pre-symptomatic and disease-modifying strategies., Competing Interests: Declaration of competing interest We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. N Specchio has served on scientific advisory boards for GW Pharma, BioMarin, Arvelle, Marinus and Takeda; has received speaker honoraria from Eisai, Biomarin, Livanova, Sanofi; has served as an investigator for Zogenix, Marinus, Biomarin, UCB, Roche. R Nabbout has served as principal investigators in clinical trials for Novartis, Nutricia, Eisai, UCB, GW Pharma, Livanova. She received consulting and lecturer honoraria from Biogene, BioMarin, Praxis, GW Pharma, Zogenix, Novartis, Nutricia, Stoke, Ionis, Targeon, Neuraxpharma, Takeda, Nutricia, Biocodex, Advicennes and Eisai. She received unrestricted research grants from Eisai, UCB, Livanova and GW Pharma and academic research grants from EJP-RD (horizons 2020). E Aronica has nothing to disclose. S Auvin is a deputy editor at Epilepsia and has received support from, and/or has served as a paid consultant for Biocodex, Eisai, Encoded, Jazz Pharmaceuticals, GRIN Therapeutics, Neuraxpharm, Nutricia, Orion Pharma, Supernus Pharmaceuticals, Takeda Pharmaceutical Company, UCB Pharma, Vitaflo, Xenon Pharmaceuticals, and Zogenix. M Feucht received speaker and advisory board honoraria as well as scientific grants from Biocodex, Eisai, Gerot, Livanova, Novartis, Nutricia, Shire, UCB and GW Pharma. F Jansen has served as a consultant for Jazz Pharmaceuticals, Nutricia, Novartis and UCB. She was an investigator of the GWEPCARE 1512 trial. L Lagae received grants and is a consultant and/or speaker for Zogenix; LivaNova, UCB, Shire, Eisai, Novartis, Takeda/Ovid, NEL, Epihunter. A Benvenuto, K Kotulska, S Jozwiak, P Curatolo report no conflicts of interest., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

The ketogenic diet is the treatment of GLUT1 deficiency syndrome that provides an alternative energy source for the brain. However, there are some limitations, including compliance issues as well as patients who do not respond to the ketogenic diet. We report the case of two patients that were not on any particular diet. Both experienced infrequent paroxysmal non-epileptic events (acute ataxia and exercise-induced dystonia). Intermittent glucose intake prior to physical activity for exercise-induced symptoms and at the onset of symptoms for acute ataxia showed consistent and reproducible improvement of the symptoms. Our observations raised the question of developing a new treatment strategy with the induction of a sustained increase in blood glucose. For now, the use of this strategy should be limited to a small group of GLUT1-DS patients who are not on a ketogenic diet., Competing Interests: Declaration of competing interest Stéphane Auvin is Deputy Editor for Epilepsia. He has served as consultant or gave lectures for Angelini, Biocodex, Eisai, Encoded, Grintherapeutics, Jazz Pharmaceuticals, Neuraxpharm, Orion, Nutricia, Proveca, UCB Pharma, Vitaflo, Xenon, Zogenix. He has been investigator for clinical trials for Eisai, Marinus, Proveca, Takeda, UCB Pharma and Zogenix. Blandine Dozières-Puyrvale has given lectures for Biomarin, Eisai, Jazz Pharmaceuticals, Neuraxpharm, UCB Pharma. She has been investigator for clinical trials for Eisai, Proveca, Takeda, UCB Pharma and Zogenix. The other authors don't have any interest to declare., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Aim: Neurological disorders, in particular seizure, are one of the reasons for admission in pediatric emergency departments (PED). We aimed to evaluate the frequency and the relevance of each investigation for seizure management in the PED., Methods: We conducted a one-year retrospective study. Based on predefined criteria, we evaluate the appropriateness of the investigations. Logical regression was used to study the risk factors for acute symptomatic seizure (ASS)., Results: We identified 691 visits to the PED for an epileptic event over an annual volume of 80,320 visits. Seizures occurring in Children with epilepsy were the most frequent epileptic events seen in the PED (42%). Looking at the investigation performed in the PED, a blood electrolytes analysis was performed in 26%, neuroimaging in 9%, electroencephalography recording in 9% and LP in 5% of patients. ASSs represented 2.1% of the seizures and 0.6% of PED neurological visits. In the multivariate analysis, an initial abnormal neurological examination (OR, 20.92 [4.87; 89.81, p<0.0001) was the only risk factor that remained significantly associated with ASS. A seizure occurring in an epilepsy patient was significantly associated with an unprovoked seizure (OR, 0.12 [0.02; 0.57], p<0.008)., Interpretation: All ASSs were associated with a positive or abnormal examination. Moreover, there is a significant proportion of investigations requested in cases of an epileptic event that did not lead to a diagnosis or modification of the management. Based on our methods, there seems to be an overuse of investigations for seizure in children with epilepsy., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest with the content of this manuscript., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Aim: Neurological disorders are one of the reasons for admission in pediatric emergency departments (PEDs). We aimed to evaluate the frequency of neurological disorders seen in a large tertiary PED., Methods: We conducted a one-year retrospective study that included 1471 medical records. Inclusion was based on the main complaint recorded by nurses at triage. We also retrieved the final diagnoses and the investigations performed in the PED., Results: About 3.4% of the yearly admissions was based on a neurologic complaint on arrival. The final diagnosis was of a neurologic disorder in 1237 children, 2% of which were admitted to the pediatric intensive care unit. An opinion from a child neurologist was requested for 33% of the children. Seizures were the most frequent reason for admission, followed by headaches. A previous visit to the PED in the past six months was a frequent finding (40%), and about one third of the patients with a neurologic diagnosis (except headaches) was already being followed by a child neurologist., Interpretation: Neurological disorders are frequent in our PED and are mainly represented by seizures and headaches. Appropriate training in epileptology might be helpful for healthcare professional working in PEDs., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Neuronal Ceroid Lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal disease which leads to early dementia and death without treatment. The recently available therapy consists of intracerebroventricular enzyme substitution: cerliponase alfa. In this report, we describe the evolution of the first French children treated with cerliponase alfa., Method: CLN2 Clinical Rating Scale Motor-Language (CLN2 ML) assesses the motor and language evolution of CLN2 patients. We retrospectively studied patients' medical records: clinical symptoms, MRI conclusions, gene mutation, side effects of infusions, patient's age and CLN2 ML scores at diagnosis, at the beginning of enzyme replacement therapy (ERT) and at the last evaluation. Seven patients were included., Results: Average age at diagnosis was 50 months ( ±10) with CLN2 ML score equal to 3.6 [1.5-5]. Average age at the beginning of ERT was 56 months ( ±13) with CLN2 ML score equal to 3.1 [1-5]. At the last available evaluation, average age was 82 months ( ±20) with CLN2 ML score equal to 2.8 [0-5]. Thus, in 26 months, the mean CLN2 ML score only decreased by 0.3 points. However, patients with a CLN2 ML score greater than three at the onset of ERT experienced a stabilisation or improvement of clinical signs, whereas patients with a CLN2 ML score less than three at baseline continue to deteriorate., Conclusion: For patients starting ERT at an early stage of the disease, cerliponase alfa changes the natural history of the disease with a halt in disease progression or even a slight improvement in clinical symptoms., Competing Interests: Declaration of competing interest AC, SP, DS, ID, SA, BC reports grants personal fees from BioMarin independent of the submitted work. All other authors report no competing interests., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Epileptic encephalopathy with continuous spikes-and-waves during sleep (EE-CSWS) is a rare childhood epilepsy syndrome characterized by a regression in cognitive, behavioral and psychiatric functioning, seizures and a specific electroencephalographic pattern. An early recognition and an appropriate treatment might play a key role in the outcome of this epileptic encephalopathy. We conducted a case-control study to evaluate if there is any clinical or electroencephalographic sign suggestive of EE-CSWS after the first seizure. We retrospectively identified 10 EE-CSWS patients with available EEG recordings at time of the first seizure. We matched them with 10 controls from our first seizure clinics. All EEG recording were analyzed for the study. We did not find any clinical or EEG features that would suggest later development of EE-CSWS. As reported by others, the occurrence of multiple seizures types and a seizure worsening during the follow-up is more frequent in the cases than in the controls. These clinical criteria might be used as a red flag in clinical practice to identify the very few patients with EE-CSWS among the frequent patients with BECTS., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: The ketogenic diet (KD) is an established, effective non-pharmacologic treatment for drug resistant childhood epilepsy. For a long time, the KD was not recommended for use in infancy (under the age of 2 years) because this is such a crucial period in development and the perceived high risk of nutritional inadequacies. Indeed, infants are a vulnerable population with specific nutritional requirements. But current research shows that the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is often achieved and maintained in this specific patient group. There is a need for standardised protocols and management recommendations for clinical use., Method: In April 2015, a project group of 5 experts was established in order to create a consensus statement regarding the clinical management of the KD in infants. The manuscript was reviewed and amended by a larger group of 10 international experts in the KD field. Consensus was reached with regard to guidance on how the diet should be administered and in whom., Results: The resulting recommendations include patient selection, pre-KD counseling and evaluation, specific nutritional requirements, preferred initiation, monitoring of adverse effects at initiation and follow-up, evaluation and KD discontinuation., Conclusion: This paper highlights recommendations based on best evidence, combined with expert opinions and gives directions for future research., (Copyright © 2016 European Paediatric Neurology Society. All rights reserved.)

The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed., (Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015. Published by Elsevier Ltd.)

Background: Zonisamide has recently been approved in Europe for the adjunctive treatment of partial seizures (with or without secondary generalisation) in adolescents and children aged ≥6 years., Aim: To further assess the safety of adjunctive zonisamide in paediatric epilepsy patients., Methods: A pooled analysis of data from 17 studies (including four randomised, double-blind trials) was conducted. The safety population comprised patients aged ≤16 years receiving at least one dose of study drug. Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs and electrocardiography., Results: The analysis included 398 patients treated with zonisamide (<12 years, n = 191; 12-16 years, n = 207). All but seven patients received zonisamide as adjunctive therapy. Mean duration of exposure was 318.7 days (mean dose, 253.1 mg/day). Most TEAEs were of mild or moderate intensity. The most frequently reported treatment-related TEAEs were decreased appetite (15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight (5.8%), irritability (5.8%) and headache (5.3%). Incidence of serious zonisamide-related TEAEs was low (3.5% overall). TEAEs most commonly leading to discontinuation were lethargy (1.0%) and fatigue (1.0%). TEAEs of decreased weight and decreased appetite occurred in 28 (7.0%) and 78 (19.6%) patients, respectively. Twenty-eight patients had decreased bicarbonate levels, but there were no reports of respiratory alkalosis or metabolic acidosis. No changes in vital signs of clinical concern were observed and there were no reports of clinically significant electrocardiogram abnormalities with zonisamide treatment., Conclusion: Zonisamide demonstrated an acceptable safety profile when used as adjunctive treatment in paediatric patients., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Mutation of the X-linked methyl CpG binding protein 2 (MECP2) has been first identified as the cause of Rett syndrome. More recently, MECP2 gene duplication syndrome has been identified in males. The MECP2 duplication syndrome is characterized by severe mental retardation, infantile hypotonia, progressive spasticity and recurrent infections. Epileptic seizures are inconstant but poorly described. The aim of the study is to describe the electroclinical features of epilepsy in MECP2 duplication patients in order to refine the epilepsy phenotype and its evolution., Methods: We conducted a retrospective study in four child neurology departments in France. Eight boys with a MECP2 gene duplication and epilepsy were retrospectively studied. We evaluated both clinical and electroencephalographic data before seizure onset, at seizure onset and during the follow-up., Results: The patients started seizures at the median age of 6 years (range: 2.5-17 years). Half exhibits late onset epileptic spasms while the other exhibit either focal epilepsy or unclassified generalized epilepsy. Before seizure onset, EEGs were abnormal in all patients showing a slowing of the background or a normal background with fast activities, while EEG performed in epileptic patients, showed a slowing of the background in 6/8 and localized slow or sharp waves in 7/8. Most patients (6/8) have evolved to drug resistant epilepsy., Conclusion: Although late onset epileptic spasms are common in patients with MECP2 duplication, no specific electroclinical phenotype emerges, probably due to genetic heterogeneity of the syndrome. Further studies are needed to individualize specific epileptic subtype in larger cohort of patients., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Alternating hemiplegia of childhood (AHC) is rare disorder characterised by recurrent attacks of hemiplegia followed by developmental delay. We investigated the parental perceptions and psychosocial issues of AHC. Using a questionnaire sent to the French AHC association, we investigated families' concerns and needs of support. Additionally, we evaluated the impact of this disease., Results: We analysed 47 questionnaires from 30 families. At time of diagnosis, the concern of the parents was highest for the hemiplegic spells and abnormal eye movements. These concerns decreased over time. The highest concern at the time of the study was the outcome of the patients with an emphasis on cognitive consequences and the level of autonomy. The results showed that AHC has a significant impact on families., Interpretation: Our data enhance how the explanation of the disease by healthcare professional is important. This study also highlights the need for family support over time., (Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Hemiconvulsion-Hemiplegia (HH) syndrome is an uncommon consequence of prolonged focal febrile convulsive seizures in infancy and early childhood. It is characterized by the occurrence of prolonged clonic seizures with unilateral predominance occurring in a child and followed by the development of hemiplegia. Neuroradiological studies showed unilateral edematous swelling of the epileptic hemisphere at the time of initial status epilepticus (SE). This acute phase is followed by characteristic cerebral hemiatrophy with subsequent appearance of epilepsy, so called Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome. The etiologies and the underlying mechanisms remain to be understood. Using a review of the literature, we summarized the data of the last 20 years. It appears that idiopathic HH/HHE syndrome is the most common reported form. The basic science data suggest that immature brain is relatively resistant to SE-induced cell injury. Several factors might contribute to the pathogenesis of HH/HHE syndrome: 1. prolonged febrile seizure in which inflammation may worsen the level of cell injury; 2. inflammation and prolonged ictal activity that act on blood-brain-barrier permeability; 3. predisposing factors facilitating prolonged seizure such as genetic factors or focal epileptogenic lesion. However, these factors cannot explain the elective involvement of an entire hemisphere. We draw new hypothesis that may explain the involvement of one hemisphere such as maturation of brain structure such as corpus callosum or genetic factors (CACNA1A gene) that are specifically discussed. An early diagnosis and a better understanding of the underlying mechanisms of HHE are needed to improve the outcome of this condition., (Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Recent data have reported the effectiveness of levetiracetam (LVT) on generalized seizures. Among them, it seems that LVT can be successfully used to treat absence seizures. Many antiepileptic drugs (AEDs) have been occasionally reported to paradoxically aggravate some seizures. We retrospectively identified patients with aggravation of absence seizures using LVT from the databases of 2 pediatric neurology departments (Robert-Debré, Paris and Amiens; France). We also used the prospective data from an open-label clinical trial performed in a third pediatric neurology department (Necker, Paris; France). We included 6 patients: n = 2 childhood absence epilepsy, n = 3 juvenile absence epilepsy and n = 1 epilepsy with myoclonic absences. All of them have had an aggravation of the absences with a causal and temporal relationship between introduction of the drug and the detrimental effect. The aggravation disappeared when LVT was decreased or was withdrawn. This report highlights that LVT may aggravate epilepsy with absence seizures., (Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)