Case report: SLC6A1 mutations presenting with isolated absence seizures: description of 2 novel cases.

We report the clinical and EEG data of two patients harboring heterozygous SLC6A1 mutations, who presented with typical absence seizures at 3 Hz spike and wave as well as with mild cognitive disability. Neuroradiological and other laboratory investigations were normal. Our observations suggest that SLC6A1 mutations can be suspected in children with typical absences as the only seizure type, especially if associated with, even mild, cognitive deficits.

A registry for Dravet syndrome: The Italian experience.

OBJECTIVES: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. METHODS: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. RESULTS: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0-9) while at last follow-up was 11 years (IQR 5-18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). SIGNIFICANCE: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes.

Super-refractory status epilepticus (SRSE): A case series of 22 pediatric patients.

BACKGROUND: Super-refractory Status Epilepticus (SRSE) is a rare condition in which SE persists or recurs ≥24 h after the onset of anesthesia. Although its characteristics are well defined in adulthood, only few studies on children are available. METHODS: we retrospectively analyzed the population of patients with SRSE aged <18 years treated in the Pediatric Intensive Care Unit of the Bambino Gesù Pediatric Hospital. We assessed clinical history, etiology, neuroimaging, electro-clinical features of SRSE, treatments and neurological status after SRSE cessation. RESULTS: We identified 22 children with median age at SRSE onset of 3.1 years (IQR 1.3-7.3) and SRSE duration of 22.0 days (IQR 11.2-30.5) Before SRSE, 17 patients (77.3%) had an abnormal neurological examination, 18 (81.8%) had a diagnosis of epilepsy, 8 of which already presented an episode of SE. Only 4 patients (18.2%) had New Onset SRSE. Eleven patients had a progressive etiology (PE), 9 had a remote etiology (RE) and 2 patients had an acute etiology (AE). Amongst PE the most frequent etiologies were mitochondrial diseases, while among RE they were Developmental Epileptic Encephalopathies of genetic origin. Time to SRSE cessation was significantly longer in PE (p = 0.04). After SRSE, 8 patients, (7 with PE) showed a significant worsening of neurological status. In this group, mean time at SE cessation was significantly longer (p = 0.05). CONCLUSIONS: pediatric SRSE is mostly associated with progressive diseases and remote etiologies. Underlying etiology seems to impact both on SRSE duration and subsequent neurological evolution, however more studies are needed to confirm these findings.

Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study.

PURPOSE: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype-phenotype correlations in patients with MEF2C haploinsufficiency. METHODS: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype. Clinical features (seizure types, onset, evolution, and response to therapy), EEG recordings during waking/sleep, and neuroimaging findings were analyzed. We also performed a detailed literature review using the terms "MEF2C", "seizures", and "epilepsy". RESULTS: Epilepsy was diagnosed in 19 out of 25 (~80%) subjects, with age at onset <30 months. Ten individuals (40%) presented with febrile seizures and myoclonic seizures occurred in ~50% of patients. Epileptiform abnormalities were observed in 20/25 patients (80%) and hypoplasia/partial agenesis of the corpus callosum was detected in 12/25 patients (~50%). Nine patients harbored a 5q14.3 deletion encompassing MEF2C and at least one other gene. In 7 out of 10 patients with myoclonic seizures, MIR9-2 and LINC00461 were also deleted, whereas ADGRV1 was involved in 3/4 patients with spasms. CONCLUSION: The epileptic phenotype of MEF2C-syndrome is variable. Febrile and myoclonic seizures are the most frequent, usually associated with a slowing of the background activity and irregular diffuse discharges of frontally dominant, symmetric or asymmetric, slow theta waves with interposed spike-and-waves complexes. The haploinsufficiency of ADGRV1, MIR9-2, and LINC00461 likely contributes to myoclonic seizures and spasms in patients with MEF2C syndrome.

Directional Goldstone waves in polariton condensates close to equilibrium.

Quantum fluids of light are realized in semiconductor microcavities using exciton-polaritons, solid-state quasi-particles with a light mass and sizeable interactions. Here, we use the microscopic analogue of oceanographic techniques to measure the excitation spectrum of a thermalised polariton condensate. Increasing the fluid density, we demonstrate the transition from a free-particle parabolic dispersion to a linear, sound-like Goldstone mode characteristic of superfluids at equilibrium. Notably, we reveal the effect of an asymmetric pumping by showing that collective excitations are created with a definite direction with respect to the condensate. Furthermore, we measure the critical sound speed for polariton superfluids close to equilibrium.

Self-Trapping of Exciton-Polariton Condensates in GaAs Microcavities.

The self-trapping of exciton-polariton condensates is demonstrated and explained by the formation of a new polaronlike state. Above the polariton lasing threshold, local variation of the lattice temperature provides the mechanism for an attractive interaction between polaritons. Because of this attraction, the condensate collapses into a small bright spot. Its position and momentum variances approach the Heisenberg quantum limit. The self-trapping does not require either a resonant driving force or a presence of defects. The trapped state is stabilized by the phonon-assisted stimulated scattering of excitons into the polariton condensate. While the formation mechanism of the observed self-trapped state is similar to the Landau-Pekar polaron model, this state is populated by several thousands of quasiparticles, in a striking contrast to the conventional single-particle polaron state.

Febrile infection-related epilepsy syndrome (FIRES): prevalence, impact and management strategies.

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy with a yet undefined etiology, affecting healthy children. It is characterized by acute manifestation of recurrent seizures or refractory status epilepticus preceded by febrile illness, but without evidence of infectious encephalitis. To date, the absence of specific biomarkers poses a significant diagnostic challenge; nonetheless, early diagnosis is very important for optimal management. FIRES is mostly irreversible and its sequelae include drug-resistant epilepsy and neuropsychological impairments. The treatment of FIRES represents a significant challenge for clinicians and is associated with low success rates. Early introduction of ketogenic diet seems to represent the most effective and promising treatment. This review aims to highlight the most recent insights on clinical features, terminology, epidemiology, pathogenesis, diagnostic challenges and therapeutic options.

Network characteristics in benign epilepsy with centro-temporal spikes patients indicating defective connectivity during spindle sleep: A partial directed coherence study of EEG signals.

OBJECTIVE: To investigate the changes in EEG connectivity in children with the typical presentation of benign epilepsy with centro-temporal spikes (BECTS). METHODS: We compared awake and spindle-sleep EEG recordings obtained by a standard electrode array in patients with lateralised (10 Right, 9 Left-BECTS) or bilateral spikes (10 MF-BECTS) and in 17 age-matched controls. We analysed EEG activity using partial directed coherence, an estimator of connectivity based on the multivariate autoregressive models and calculated in- and out-degrees, strength, clustering coefficient and betweenness centrality. RESULTS: In comparison with the controls, the awake EEG recordings of the patients with lateralised BECTS showed a minimal increase in out-degrees on F4 and F3. The greater differences, found during sleep, included significant reductions in both in- and out-degrees and strength in all of the patient groups, but in T4 or T3 showing increased out-degrees and strength in Right and Left-BECTS. Betweenness centrality was significantly reduced on C3 and C4 in the patients with MF-BECTS. CONCLUSIONS: Our observations suggest that the main finding in BECTS patients is widely reduced local connectivity. SIGNIFICANCE: The network changes in BECTS can be interpreted as a permissive condition occurring in a developmental window that predisposes to seizure generation during spindle-sleep.

CHD2-epilepsy: Polygraphic documentation of self-induced seizures due to fixation-off sensitivity.

CHD2 gene has been described in association with different types of childhood myoclonic epilepsy and is emerging as a gene involved in photosensitivity alone or combined with epilepsy. Recent studies suggest that CHD2 could be responsible for a proper phenotype characterized by infantile-onset generalized epilepsy, intellectual disability, and photosensitivity and in particular with self-induced seizures. We report the case of a child with CHD2 mutation and mild developmental impairment that since the age of 3 years started with myoclonic seizures apparently well responding to antiepileptic drugs and that subsequently developed intractable self-induced seizures. Through an accurate Video-EEG polygraphic analysis, we demonstrated that seizures are related to an abnormal increase of epileptiform activity after eye-closure or loss of fixation as observed in the Fixation-Off Sensitivity (FOS) phenomenon. In conclusion our study adds relevant features of the CHD2-epilepsy phenotype and confirms that CHD2 mutations produce a distinctive form of myoclonic epilepsy with visual-sensitive seizures.

Topological order and thermal equilibrium in polariton condensates.

The Berezinskii-Kosterlitz-Thouless phase transition from a disordered to a quasi-ordered state, mediated by the proliferation of topological defects in two dimensions, governs seemingly remote physical systems ranging from liquid helium, ultracold atoms and superconducting thin films to ensembles of spins. Here we observe such a transition in a short-lived gas of exciton-polaritons, bosonic light-matter particles in semiconductor microcavities. The observed quasi-ordered phase, characteristic for an equilibrium two-dimensional bosonic gas, with a decay of coherence in both spatial and temporal domains with the same algebraic exponent, is reproduced with numerical solutions of stochastic dynamics, proving that the mechanism of pairing of the topological defects (vortices) is responsible for the transition to the algebraic order. This is made possible thanks to long polariton lifetimes in high-quality samples and in a reservoir-free region. Our results show that the joint measurement of coherence both in space and time is required to characterize driven-dissipative phase transitions and enable the investigation of topological ordering in open systems.

Cerebellar fits in the 2000s.

Acute compression on the brainstem or acute increase in intracranial pressure may induce non-epileptic events varying from tonic seizures to axial rigidity with motor automatism, sometimes clearly characterized by decerebrate or decorticate paroxysmal posturing. The EEG correlate is characterized by diffuse asynchronous slow waves of variable amplitude. The mechanism behind such events, known as "cerebellar seizures or fits", is linked to cerebellar herniation and brainstem compression and is not of cortical origin. Misrecognition of such entity may entail an incongruous therapeutic intervention in a life-threatening situation. We describe two emblematic paediatric cases of cerebellar fits caused by diffuse oedema and brainstem compression: a 10-year-old girl with acute disseminated encephalomyelitis (ADEM) and a 2-year-old girl with severe respiratory distress symptomatic of Fallot tetralogy. We also describe the EEG correlate recorded during the events.

Macroscopic Two-Dimensional Polariton Condensates.

We report a record-size, two-dimensional polariton condensate of a fraction of a millimeter radius free from the presence of an exciton reservoir. This macroscopically occupied state is formed by the ballistically expanding polariton flow that relaxes and condenses over a large area outside of the excitation spot. The density of this trap-free condensate is <1 polariton/µm^{2}, reducing the phase noise induced by the interaction energy. Moreover, the backflow effect, recently predicted for the nonparabolic polariton dispersion, is observed here for the first time in the fast-expanding wave packet.

Symptomatic and presumed symptomatic focal epilepsies in childhood: An observational, prospective multicentre study.

OBJECTIVE: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance. METHODS: In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses. RESULTS: Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy. SIGNIFICANCE: In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.