OBJECTIVES: To evaluate the evolution of interhemispheric coherences (ICo) in background and spindle frequency bands during childhood and use it to identify individuals with corpus callosum dysgenesis (CCd). METHODS: A monocentric cohort of children aged from 0.25 to 15 years old, consisting of 13 children with CCd and 164 without, was analyzed. The ICo of background activity (ICOBckgrdA), sleep spindles (ICOspindles), and their sum (sICO) were calculated. The impact of age, gender, and CC status on the ICo was evaluated, and the sICO was used to discriminate children with or without CCd. RESULTS: ICOBckgrdA, ICOspindles and sICO increased significantly with age without any effect of gender (p < 10-4), in both groups. The regression equations of the different ICo were stronger, with adjusted R2 values of 0.54, 0.35, and 0.57, respectively. The ICo was lower in children with CCd compared to those without CCd (p < 10-4 for all comparisons). The area under the precision recall curves for predicting CCd using sICO was 0.992 with 98.9 % sensitivity and 87.5 % specificity. DISCUSSION: ICo of spindles and background activity evolve in parallel to brain maturation and depends on the integrity of the corpus callosum. sICO could be an effective diagnostic biomarker for screening children with interhemispheric dysfunction.
OBJECTIVE: This study aims to detect the seizure onset, in childhood absence epilepsy, as early as possible. Indeed, interfering with absence seizures with sensory simulation has been shown to be possible on the condition that the stimulation occurs soon enough after the seizure onset. METHODS: We present four variations (two supervised, two unsupervised) of an algorithm designed to detect the onset of absence seizures from 4 scalp electrodes, and compare their performance with that of a state-of-the-art algorithm. We exploit the characteristic shape of spike-wave discharges to detect the seizure onset. Their performance is assessed on clinical electroencephalograms from 63 patients with confirmed childhood absence epilepsy. RESULTS: The proposed approaches succeed in early detection of the seizure onset, contrary to the classical detection algorithm. Indeed, the results clearly show the superiority of the proposed methods for small delays of detection, under 750 ms from the onset. CONCLUSION: The performance of the proposed unsupervised methods is equivalent to that of the supervised ones. The use of only four electrodes makes the pipeline suitable to be embedded in a wearable device. SIGNIFICANCE: The proposed pipelines perform early detection of absence seizures, which constitutes a prerequisite for a closed-loop system.
BACKGROUND AND PURPOSE: Sturge-Weber syndrome is a rare congenital neuro-oculo-cutaneous disorder. Although the principal mechanism of Sturge-Weber syndrome is characterized by a leptomeningeal vascular malformation, few data regarding perfusion abnormalities of the brain parenchyma are available. Therefore, the aim of this study was to assess the diagnostic performance of arterial spin-labeling perfusion imaging in the early stage of Sturge-Weber syndrome before 1 year of age until 3.5 years of age. We hypothesized that a leptomeningeal vascular malformation has very early hypoperfusion compared with controls with healthy brains. MATERIALS AND METHODS: We compared the CBF using arterial spin-labeling perfusion imaging performed at 3T MR imaging in the brain parenchymal regions juxtaposing the leptomeningeal vascular malformation in patients with Sturge-Weber syndrome (n = 16; 3.5 years of age or younger) with the corresponding areas in age-matched controls with healthy brains (n = 58). The analysis was performed following two complementary methods: a whole-brain voxel-based analysis and a visual ROI analysis focused on brain territory of the leptomeningeal vascular malformation. RESULTS: Whole-brain voxel-based comparison revealed a significant unilateral decrease in CBF localized in the affected cortices of patients with Sturge-Weber syndrome (P < .001). CBF values within the ROIs in patients with Sturge-Weber syndrome were lower than those in controls (in the whole cohort: median, 25 mL/100g/min, versus 44 mL/100g/min; P < .001). This finding was also observed in the group younger than 1 year of age, emphasizing the high sensitivity of arterial spin-labeling in this age window in which the diagnosis is difficult. CONCLUSIONS: Arterial spin-labeling perfusion imaging in the early stage of Sturge-Weber syndrome can help to diagnose the disease by depicting a cortical hypoperfusion juxtaposing the leptomeningeal vascular malformation.
Sturge-Weber Syndrome , Vascular Malformations , Humans , Child, Preschool , Sturge-Weber Syndrome/diagnostic imaging , Brain/diagnostic imaging , Brain/blood supply , Perfusion , Perfusion Imaging
INTRODUCTION: The COVID-19 pandemic caused a state of alarm in Spain in March 2020. The necessary approach to the care of patients with Dravet syndrome (DS) makes them and their caregivers a vulnerable group in emergency situations. OBJECTIVES: To explore the impact of the COVID-19 pandemic on the management and condition of Spanish patients with DS and their caregivers and families. MATERIALS AND METHODS: Analysis of data belonging to Spanish families taken from a European online survey (14 April-17 May 2020). It included data on DS patients, on the disease and on caregivers before and after lockdown during the state of alarm. RESULTS: Sixty-nine Spanish families participated; average age of patients: 12.6 years. Except in 19% of the cases that were isolated, protective/isolation measures for patients were followed without increasing. Epilepsy remained stable, with no medication or resource/personnel availability issues. Sleep-wake pattern (61%) and behavior (41%) of patients changed. Behavior change was associated with seizures during lockdown and with caregiver emotional state (changes in 76%). Psychological support was offered to only 9% of caregivers. Thirty-eight per cent of patients did not receive remote care. CONCLUSIONS: The experience gathered during the lockdown has allowed the detection of points of improvement to ensure the proper management of DS and to keep the situation of patients and caregivers stable. All of this with a prominent role of telemedicine.
TITLE: Impacto de la COVID-19 en pacientes españoles con síndrome de Dravet y sus cuidadores: consecuencias del confinamiento.Introducción. La pandemia por COVID-19 implicó el estado de alarma en España en marzo de 2020. El abordaje necesario para el cuidado de los pacientes con síndrome de Dravet (SD) los convierte, junto con sus cuidadores, en un grupo vulnerable en situaciones de emergencia. Objetivos. Explorar el impacto de la pandemia por COVID-19 en el manejo y la condición de los pacientes españoles con SD, y de sus cuidadores y familias. Materiales y métodos. Análisis de los datos pertenecientes a familias españolas extraídos de una encuesta en línea europea (14 de abril-17 de mayo de 2020). Incluía datos de los pacientes con SD, de la enfermedad y de los cuidadores antes y después del confinamiento, durante el estado de alarma. Resultados. Participaron 69 familias españolas; edad media de los pacientes: 12,6 años. Excepto en el 19% de los casos que fueron aislados, las medidas de protección/aislamiento del paciente continuaron sin incrementar. La epilepsia se mantuvo estable, sin problemas de medicación ni disponibilidad de recursos/personal. Cambió el patrón de sueño/vigilia (61%) y la conducta (41%) de los pacientes. El cambio de conducta se asoció con las crisis durante el confinamiento y el estado anímico del cuidador (cambios en el 76%). Sólo se ofreció apoyo psicológico al 9% de los cuidadores. El 38% de los pacientes no recibió atención telemática. Conclusiones. La experiencia recogida durante el confinamiento ha permitido detectar puntos de mejora para asegurar el apropiado manejo del SD y mantener estable la situación de los pacientes y cuidadores, todo ello con un papel destacado de la telemedicina.
COVID-19 , Epilepsies, Myoclonic , Caregivers , Child , Communicable Disease Control , Humans , Pandemics , SARS-CoV-2 , Spain/epidemiology
Introducción: La pandemia por COVID-19 implicó el estado de alarma en España en marzo de 2020. El abordaje necesario para el cuidado de los pacientes con síndrome de Dravet (SD) los convierte, junto con sus cuidadores, en un grupo vulnerable en situaciones de emergencia. Objetivos: Explorar el impacto de la pandemia por COVID-19 en el manejo y la condición de los pacientes españoles con SD, y de sus cuidadores y familias. Materiales y métodos: Análisis de los datos pertenecientes a familias españolas extraídos de una encuesta en línea europea (14 de abril-17 de mayo de 2020). Incluía datos de los pacientes con SD, de la enfermedad y de los cuidadores antes y después del confinamiento, durante el estado de alarma. Resultados: Participaron 69 familias españolas; edad media de los pacientes: 12,6 años. Excepto en el 19% de los casos que fueron aislados, las medidas de protección/aislamiento del paciente continuaron sin incrementar. La epilepsia se mantuvo estable, sin problemas de medicación ni disponibilidad de recursos/personal. Cambió el patrón de sueño/vigilia (61%) y la conducta (41%) de los pacientes. El cambio de conducta se asoció con las crisis durante el confinamiento y el estado anímico del cuidador (cambios en el 76%). Sólo se ofreció apoyo psicológico al 9% de los cuidadores. El 38% de los pacientes no recibió atención telemática. Conclusiones: La experiencia recogida durante el confinamiento ha permitido detectar puntos de mejora para asegurar el apropiado manejo del SD y mantener estable la situación de los pacientes y cuidadores, todo ello con un papel destacado de la telemedicina.(AU)
Introduction: The COVID-19 pandemic caused a state of alarm in Spain in March 2020. The necessary approach to the care of patients with Dravet syndrome (DS) makes them and their caregivers a vulnerable group in emergency situations. Objectives: To explore the impact of the COVID-19 pandemic on the management and condition of Spanish patients with DS and their caregivers and families. Materials and methods: Analysis of data belonging to Spanish families taken from a European online survey (14 April-17 May 2020). It included data on DS patients, on the disease and on caregivers before and after lockdown during the state of alarm. Results: Sixty-nine Spanish families participated; average age of patients: 12.6 years. Except in 19% of the cases that were isolated, protective/isolation measures for patients were followed without increasing. Epilepsy remained stable, with no medication or resource/personnel availability issues. Sleep-wake pattern (61%) and behavior (41%) of patients changed. Behavior change was associated with seizures during lockdown and with caregiver emotional state (changes in 76%). Psychological support was offered to only 9% of caregivers. Thirty-eight per cent of patients did not receive remote care. Conclusions: The experience gathered during the lockdown has allowed the detection of points of improvement to ensure the proper management of DS and to keep the situation of patients and caregivers stable. All of this with a prominent role of telemedicine.(AU)
Humans , Male , Female , /complications , 50230 , Telemedicine , Caregivers , Epilepsy , Spain , Neurology , Nervous System Diseases , /epidemiology , Surveys and Questionnaires
PURPOSE: Analyzing parents' and physicians' opinions regarding phone-based encounters in emergency shifts of a French pediatric epilepsy center compared to traditional face-to-face encounters during the first lockdown of the COVID-19 pandemic METHODS: Prospective monocentric study on remote encounters at Necker rare epilepsy reference center from March 20th, 2020 to April 23rd, 2020 due to lockdown measures. This study was conducted with a survey based on 5-point Likert scales (LS-2/2) designed for both parents and physicians. We compared first versus follow-up encounters as well as physicians' and parents' opinions. RESULTS: We had a total of 224 responses, among which 204 were completed by physicians (91%) and 173 (84,4%) by parents. Twenty five were first encounters (14,2%). Physicians pointed out the need for clinical examination (42.6%), mainly for first encounters (p=0.0004). Physicians rated the quality of communication lower (p=0.003) as their capacity to answer parents' questions (p=0.004). They were significantly less satisfied with remote encounters compared to parents (p<10-4). We identified six urgent (2.9%) and 50 semi-urgent (24%) situations requiring programming face-to-face encounter during or shortly after the lockdown. CONCLUSION: Remote encounters could be a helpful practice for pediatric patients with epilepsy in emergency situations such as pandemics. It allowed the identification and prioritization of emergency situations. Physicians were less positive than parents. We raised the possible use of remote encounters in association to face-to-face encounters for routine follow-up of pediatric patients with epilepsy.
COVID-19 , Epilepsy , Physicians , Telemedicine , Child , Communicable Disease Control , Epilepsy/epidemiology , Epilepsy/therapy , Humans , Outpatients , Pandemics , Patient Satisfaction , Prospective Studies , SARS-CoV-2
OBJECTIVE: We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). METHODS: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.o to 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis. RESULTS: Seventy video-EEGs were analyzed (1-16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15 (8 m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7 m.o to 12 y.o, median 15 m). Epilepsy: 6 West syndrome (WS) (2intdup15, 4idic15); 4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-band rapid-rhythms (RR): present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age. CONCLUSION: WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay. SIGNIFICANCE: This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.
Beta Rhythm , Chromosome Disorders/physiopathology , Epilepsy/physiopathology , Intellectual Disability/physiopathology , Trisomy/physiopathology , Adolescent , Child , Child, Preschool , Chromosome Aberrations , Chromosomes, Human, Pair 15 , Epilepsy/genetics , Female , Humans , Infant , Male , Sleep , Wakefulness
OBJECTIVES: The purpose of this study was to describe and compare the initial management, including clinical/biological investigation and treatment, of new-onset seizures and status epilepticus (SE) in children versus seizures and SE in those with known epilepsy. METHODS: This was a retrospective, single-center, observational study conducted in an urban pediatric hospital in Paris. All patients, aged from 1 month to 18 years, admitted to the pediatric intensive care unit, the high-dependency care unit, and those who required hospitalization in the short-term unit of the emergency department between January 1 and December 31, 2014 for seizures and/or SE were included. RESULTS: We analyzed the data of 190 children: new-onset seizures (N=118; group A) versus those with known epilepsy (N=72; group B). At least one diagnostic test was performed on 156 patients (82.1%) (group A, N=104, 88.1%; group B, N=52, 72.2%; P=0.05). In group B, blood levels of antiepileptic drugs were measured in 14 of the 38 patients with SE, of whom six were under dosed. Treatments were: first line, diazepam (group A, 80%; group B, 46%; P<0.001); second line, diazepam (group A, 56%; group B, 34%; P=0.02) or clonazepam (group A, 24%; group B, 46%; P=0.001); third line, phenytoin (group A, 54%; group B, 22%; P<0.001) or clonazepam (group A, 18%; group B, 61%; P<0.001). CONCLUSION: Diagnostic evaluation and treatment should be individualized for children with known epilepsy.
Anticonvulsants/therapeutic use , Epilepsy/diagnosis , Seizures/drug therapy , Seizures/etiology , Status Epilepticus/drug therapy , Status Epilepticus/etiology , Adolescent , Anticonvulsants/blood , Child , Child, Preschool , Clonazepam/blood , Clonazepam/therapeutic use , Diazepam/blood , Diazepam/therapeutic use , Epilepsy/complications , Epilepsy/drug therapy , Female , Hospitalization , Humans , Infant , Male , Phenytoin/blood , Phenytoin/therapeutic use , Retrospective Studies
Hamartoma/diagnosis , Retinal Diseases/diagnosis , Tuberous Sclerosis/diagnosis , Ultrasonography/methods , Early Diagnosis , Female , Follow-Up Studies , Fundus Oculi , Hamartoma/complications , Humans , Infant , Monitoring, Physiologic , Retinal Diseases/complications , Tuberous Sclerosis/complications
Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.
Calcinosis/genetics , Malformations of Cortical Development/genetics , Occludin/genetics , Polymicrogyria/genetics , Basal Ganglia/metabolism , Basal Ganglia/pathology , Brain/metabolism , Brain/pathology , Calcinosis/pathology , DNA Copy Number Variations/genetics , Female , Gray Matter/metabolism , Gray Matter/pathology , Humans , Infant , Male , Malformations of Cortical Development/pathology , Microcephaly/genetics , Microcephaly/pathology , Mutation , Phenotype , Polymicrogyria/epidemiology , Polymicrogyria/pathology , Tight Junctions/pathology
This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns.
Congresses as Topic , Epilepsy/diagnosis , Epilepsy/therapy , Transition to Adult Care/trends , Adolescent , Adult , Child , Child, Preschool , Encephalitis/diagnosis , Encephalitis/therapy , Epilepsy, Absence/diagnosis , Epilepsy, Absence/therapy , Hashimoto Disease/diagnosis , Hashimoto Disease/therapy , Humans , Infant , Myoclonic Epilepsy, Juvenile/diagnosis , Myoclonic Epilepsy, Juvenile/therapy , Rett Syndrome/diagnosis , Rett Syndrome/therapy , Spasms, Infantile/diagnosis , Spasms, Infantile/therapy , Treatment Outcome , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/therapy , Young Adult
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 (I1âI1). 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 (I1âI1 and I1âP) 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.
Brain/pathology , Computer Simulation , Epilepsies, Myoclonic/pathology , Models, Neurological , Pyramidal Cells/drug effects , gamma-Aminobutyric Acid/pharmacology , Adolescent , Animals , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Brain/physiopathology , Brain Waves/physiology , Child , Child, Preschool , Electroencephalography , Epilepsies, Myoclonic/genetics , Female , Humans , Male , Membrane Potentials/drug effects , Mutation/genetics , NAV1.1 Voltage-Gated Sodium Channel/genetics , Neural Inhibition/drug effects , Synaptic Transmission/drug effects
INTRODUCTION: Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis. STATE OF ART: Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy. CONCLUSION: Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death.
Epilepsy/etiology , Mitochondrial Diseases/complications , Adult , Ataxia/complications , Child , DNA Polymerase gamma , DNA-Directed DNA Polymerase/genetics , Diffuse Cerebral Sclerosis of Schilder/genetics , Epilepsy/diagnosis , Epilepsy/therapy , Humans , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/genetics , Mitochondrial Diseases/therapy , Muscle Weakness/complications , Mutation , Phenotype , Ubiquinone/deficiency
STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern on EEG, in patients with infantile spasms and in a few patients with nonsyndromic mental retardation without epilepsy. We report a patient who presented late onset infantile spasms. Epilepsy was controlled but the patient developed severe mental delay. A first diagnosis of mitochondrial disease was based on clinical presentation and on a partial deficit of respiratory chain complex IV, but molecular screening for mitochondrial genes was negative. The sequencing of STXBP1 gene found a de novo nonsense mutation (c.585C>G/p.Tyr195X). This observation widens the clinical spectrum linked to STXBP1 mutations with the description of a patient with late onset infantile spasms. It raises the question of the value of epilepsy genes screening in patients with uncertain, partial or unconfirmed mitochondrial dysfunction.
Codon, Nonsense , Electron Transport Complex IV/genetics , Intellectual Disability/genetics , Munc18 Proteins/genetics , Spasms, Infantile/genetics , Brain Waves , Humans , Infant , Intellectual Disability/diagnosis , Lennox Gastaut Syndrome , Male , Spasms, Infantile/diagnosis
Sturge-Weber syndrome (SWS) is a rare sporadic neurocutaneous syndrome defined by the association of a facial capillary malformation in the ophthalmic distribution of the trigeminal nerve, with ipsilateral vascular glaucoma and vascular malformation of the eye, and a leptomeningeal angioma. SWS is suspected at birth in the presence of facial angioma in the trigeminal nerve area. MRI with gadolinium enhancement and pondered T1, T2, FLAIR and diffusion sequences is today the technique of choice to visualize the leptomeningeal angioma or to suspect it by indirect signs, even before the development of neurological signs, from the first months of life. The prognosis of SWS with leptomeningeal angioma is related to the severity of neurological signs that are absent at birth and develop later in life (epilepsy, hemiparesis, and mental delay). Seizures are usually the presenting neurological symptom. Status epilepticus might inaugurate the epilepsy and remains frequent in infancy. Repetitive seizures are thought to increase the atrophy of brain tissue in regard to the leptomeningeal angioma. Preventive presymptomatic treatment with antiepileptic drugs is often recommended, and parents are trained to use rescue benzodiazepines in case of seizures. After epilepsy onset, in patients intractable to antiepileptic drugs, surgery should be considered.
Sturge-Weber Syndrome , Brain/pathology , Humans , Sturge-Weber Syndrome/diagnosis , Sturge-Weber Syndrome/physiopathology , Sturge-Weber Syndrome/therapy
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.
Brain/pathology , Epilepsy/pathology , Status Epilepticus/pathology , Anticonvulsants/adverse effects , Barbiturates/adverse effects , Brain/blood supply , Child, Preschool , Developmental Disabilities/etiology , Epilepsy/drug therapy , Epilepsy/genetics , Humans , Infant , Magnetic Resonance Imaging , Mutation , NAV1.1 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/genetics , Sodium Channels/genetics , Status Epilepticus/drug therapy , Status Epilepticus/genetics , Tomography, X-Ray Computed
INTRODUCTION: Mutations in the voltage-gated sodium channel SCN1A gene are the main genetic cause of Dravet syndrome (previously called severe myoclonic epilepsy of infancy or SMEI). OBJECTIVE: To characterise in more detail the mutation spectrum associated with Dravet syndrome. METHODS: A large series of 333 patients was screened using both direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Non-coding regions of the gene that are usually not investigated were also screened. RESULTS: SCN1A point mutations were identified in 228 patients, 161 of which had not been previously reported. Missense mutations, either (1) altering a highly conserved amino acid of the protein, (2) transforming this conserved residue into a chemically dissimilar amino acid and/or (3) belonging to ion-transport sequences, were the most common mutation type. MLPA analysis of the 105 patients without point mutation detected a heterozygous microrearrangement of SCN1A in 14 additional patients; 8 were private, partial deletions and six corresponded to whole gene deletions, 0.15-2.9 Mb in size, deleting nearby genes. Finally, mutations in exon 5N and in untranslated regions of the SCN1A gene that were conserved during evolution were excluded in the remaining negative patients. CONCLUSION: These findings widely expand the SCN1A mutation spectrum identified and highlight the importance of screening the coding regions with both direct sequencing and a quantitative method. This mutation spectrum, including whole gene deletions, argues in favour of haploinsufficiency as the main mechanism responsible for Dravet syndrome.
Epilepsies, Myoclonic/genetics , Mutation , Nerve Tissue Proteins/genetics , Sodium Channels/genetics , Female , Gene Deletion , Gene Rearrangement , Humans , Infant , Infant, Newborn , Male , NAV1.1 Voltage-Gated Sodium Channel , Nucleic Acid Amplification Techniques , Sequence Analysis, DNA
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.
Encephalitis/drug therapy , Steroids/administration & dosage , Adolescent , Child , Drug Administration Schedule , Encephalitis/surgery , Female , Humans , Longitudinal Studies , Male , Time Factors
