86 research outputs found

    Dravet syndrome as epileptic encephalopathy: Evidence from long-term course and neuropathology

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    Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20–66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy

    Tides in colliding galaxies

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    Long tails and streams of stars are the most noticeable upshots of galaxy collisions. Their origin as gravitational, tidal, disturbances has however been recognized only less than fifty years ago and more than ten years after their first observations. This Review describes how the idea of galactic tides emerged, in particular thanks to the advances in numerical simulations, from the first ones that included tens of particles to the most sophisticated ones with tens of millions of them and state-of-the-art hydrodynamical prescriptions. Theoretical aspects pertaining to the formation of tidal tails are then presented. The third part of the review turns to observations and underlines the need for collecting deep multi-wavelength data to tackle the variety of physical processes exhibited by collisional debris. Tidal tails are not just stellar structures, but turn out to contain all the components usually found in galactic disks, in particular atomic / molecular gas and dust. They host star-forming complexes and are able to form star-clusters or even second-generation dwarf galaxies. The final part of the review discusses what tidal tails can tell us (or not) about the structure and content of present-day galaxies, including their dark components, and explains how tidal tails may be used to probe the past evolution of galaxies and their mass assembly history. On-going deep wide-field surveys disclose many new low-surface brightness structures in the nearby Universe, offering great opportunities for attempting galactic archeology with tidal tails.Comment: 46 pages, 13 figures, Review to be published in "Tidal effects in Astronomy and Astrophysics", Lecture Notes in Physics. Comments are most welcom

    Study of the doubly charmed tetraquark T+cc

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    Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar T+cc tetraquark with a quark content of ccu⎯⎯⎯d⎯⎯⎯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector T+cc state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the T+cc state. In addition, an unexpected dependence of the production rate on track multiplicity is observed

    Sudden, unexpected death in epilepsy in children

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    Sudden, unexpected death in epilepsy (SUDEP) remains a controversial and enigmatic syndrome, particularly in children where the incidence, prevalence and risk factors may, and probably do, differ from adults. This study demonstrates (and further reinforces) the difficulties and inability of retrospective and coroner/death certificate-derived data in identifying the frequency of SUDEP in children

    The biochemical investigation of epilepsy in childhood

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    Metabolic disorders are a relatively uncommon, but important, cause of childhood seizures. Routinely searching for a metabolic disorder in epilepsy is usually unrewarding. Children and adolescents with epilepsy can be selected for appropriate biochemical investigation by considering the seizure type, age of onset, EEG appearance, family history, clinical findings and the results of brain imaging. A limited number of biochemical screening tests can be used to categorize the more common metabolic disorders associated with seizures

    Epilepsy in a children's hospital: an out-patient survey

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    Epilepsy, a common childhood condition, is largely managed by general paediatricians. To assess whether recent management guidelines are being met, we undertook a prospective questionnaire-based survey of children with epilepsy, attending the general paediatric out-patient clinic, at the Royal Liverpool Children's Hospital, Alder Hey. Ninety-one children were identified over seven months—giving a prevalence of epilepsy in this out-patient population of 13.7/1000. Fifty-four per cent were diagnosed as having tonic-clonic, 16% partial and 5% typical absence seizures. Forty-two per cent received carbamazepine and 33% sodium valproate, as monotherapy, and 7% were treated with multiple antiepileptic drugs (AEDs).Correlation between AED and seizure type was often inappropriate as was the routine measurement of blood level of AEDs. Correlation between seizure frequency and clinic visits was generally acceptable with those children experiencing frequent seizures attending most often. Specialist paediatric neurologist advice was sought in only 14% of children; 19 of the 28 children with the most poorly controlled seizures were not referred for a specialist opinion.This study has demonstrated a poor understanding of seizure/syndrome classification: the frequent inappropriate use of AEDs and their blood level measurement and inadequate referral for specialist advice. Recognized guidelines are not being followed, nor are standards being met by many general paediatricians. There is a clear indication for more extensive education and the need to provide clear recommendations for the management of epilepsy in children

    Fits, faints and funny turns

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    Myotubular myopathy in a female

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    Managing the teenager with epilepsy: paediatric to adult care

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    Epilepsy starting in childhood frequently persists through adolescence and into adult life, and an onset in adolescence itself is common. The management of the teenager with epilepsy is important but often inadequate. In 1991, a specific clinic for teenagers with epilepsy was established in Liverpool to address the unique needs and concerns of this age group and, importantly, to facilitate a smooth handover of specialist epilepsy care from paediatric to adult services. An additional and crucial benefit of this clinic has been to provide a further, and hopefully final, screen to confirm (or refute) the diagnosis of epilepsy, to corroborate, or correctly identify, the specific epilepsy syndrome and to ensure that the most appropriate antiepileptic drug (AED) is being prescribed and when, if possible, the drug can be withdrawn. Of 120 consecutive patients referred to the teenager clinic, 12 (10%) did not have epilepsy, and 26 (22%) were being treated with an inappropriate AED. The main issues and concerns voiced by the teenagers included choices of further education and career, the possibility and risks of withdrawing anticonvulsants, driving regulations, the inheritance of epilepsy and pregnancy/contraception. This teenager clinic could serve as a model for both other ‘epilepsy centres’ and also for managing other chronic disorders with an onset in childhood
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