Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society.

Probability of Remission of the Main Epileptic Syndromes in Childhood.

AIM: To determine the long-term probability of remission without antiepileptic treatment of common epileptic syndromes and of children without a specific syndromic diagnosis. PATIENTS AND METHODS: All children less than 14 years old with 2 or more unprovoked seizures seen at our hospital between June 1, 1994, and March 1, 2011 (n = 680), were included and prospectively followed up until August 15, 2020. Syndromic diagnosis was made retrospectively but blinded to subsequent evolution, employing the data available at 6 months after diagnosis and under predefined operational criteria. RESULTS: The Kaplan-Meier estimate of the probability of achieving a remission period of at least 5 years, with neither seizures nor antiepileptic treatment at 14 years was 97% for well-defined childhood epilepsy with centrotemporal spikes, 82% for uncertain childhood epilepsy with centrotemporal spikes, 85% for well-defined Panayiotopoulos syndrome, 88% for uncertain Panayiotopoulos syndrome, 93% for nonfamilial self-limited infantile epilepsy, 100% for familial self-limited infantile epilepsy, 86% for absence epilepsy, 6% for juvenile myoclonic epilepsy, 71% for cryptogenic West syndrome, 72% for patients with no associated neurologic deficits and no specific syndromic diagnosis, 65% for symptomatic West syndrome, and 40% for patients with associated neurologic deficits and no specific syndromic diagnosis. CONCLUSIONS: The study results highlight the long-term outcomes of the main epileptic syndromes and also of the patients with no syndromic diagnosis.

[New anti-epileptic drugs in Paediatrics]. / Nuevos fármacos antiepilépticos en Pediatría.

It is estimated that about 70 million people all over the world suffer from epilepsy, half of which are children, in whom the prevalence is around 0.5 to 0.8%. Although there are several therapies, the treatment of epilepsy is based mainly on drugs, which, depending on the year of coming onto the market are classified as first, second, or third generation. In this article, a description is presented on the main characteristics of the latest generation of anti-epileptic drugs (lacosamide, eslicarbazepine acetate, brivaracetam, perampanel, retigabine, everolimus and cannabidiol). These, with the exception of retigabine (is not yet on the market), are considered safe and effective in the paediatric population. Everolimus and cannabidiol have very specific indications (tuberous sclerosis, Dravet syndrome, and Lennox Gastaut syndrome), while the rest are indicated in the management of seizures of focal origin in children from 4 years-old. These new molecules have been developed in order to provide a pharmaceutical profile and tolerance superior to the previously available drugs, and it is forecast that as their use increases, their true potential and profile will widen. Furthermore, for the first time in Paediatric Epileptology, the extrapolation of the efficacy data in adults have been used (together with specific safety and pharmacokinetic studies in the paediatric population), in order to speed up their approval for use in the child population.

Neuropsychological assessment and perinatal risk: A study amongst very premature born 4- and 5-year old children.

BACKGROUND: Prematurity and its consequences are serious problems that can result in numerous neurosensory disabilities and cerebral cognitive dysfunctions. The Perinatal Risk Index (PERI) might provide a predictive measure of these problems. AIM: This study compared the cognitive development of prematurely born children at 4 and 5 years of age with age-matched peers born at term. The secondary objective was to determine whether a correlation exists between perinatal risk and performance on neuropsychological tests among premature children. METHODS: A total of 54 children between four and five years of age were evaluated; 27 were born very premature (premature group; PG), and 27 were born at term (term group; TG). Executive function, attention, memory, language, visual perception, and spatial structuring were evaluated. Subtests from the Kaufman Assessment Battery for Children, the Rey Complex Figure Test, the McCarthy Scales of Children's Abilities, the Peabody Picture Vocabulary Test, Test A, Trails A and B, the spatial structuring questionnaire from the Child Neuropsychological Maturity Questionnaire, and the Wechsler Intelligence Scale for Children were used. A PERI score was also obtained for the PG. RESULTS: The PG showed significantly lower scores than the TG in all the studied cognitive domains. Visual-perceptive scores were significantly and negatively correlated with the PERI scores of the PG. CONCLUSIONS: The PG showed neurocognitive deficits compared with the TG. The PERI can be used to predict the development of visual-perceptive abilities in children between four and five years of age.

Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.

BACKGROUND: People with epilepsy who became seizure-free while taking antiepileptic drugs might consider discontinuing their medication, with the possibility of increased quality of life because of the elimination of adverse events. The risk with this action, however, is seizure recurrence. The objectives of our study were to identify predictors of seizure recurrence and long-term seizure outcomes and to produce nomograms for estimation of individualised outcomes. METHODS: We did a systematic review and meta-analysis, and identified eligible articles and candidate predictors, using PubMed and Embase databases with a last update on Nov 6, 2014. Eligible articles had to report on cohorts of patients with epilepsy who were seizure-free and had started withdrawal of antiepileptic drugs; articles also had to contain information regarding seizure recurrences during and after withdrawal. We excluded surgical cohorts, reports with fewer than 30 patients, and reports on acute symptomatic seizures because these topics were beyond the scope of our objective. Risk of bias was assessed using the Quality in Prognosis Studies system. Data analysis was based on individual participant data. Survival curves and proportional hazards were computed. The strongest predictors were selected with backward selection. Models were converted to nomograms and a web-based tool to determine individual risks. FINDINGS: We identified 45 studies with 7082 patients; ten studies (22%) with 1769 patients (25%) were included in the meta-analysis. Median follow-up was 5·3 years (IQR 3·0-10·0, maximum 23 years). Prospective and retrospective studies and randomised controlled trials were included, covering non-selected and selected populations of both children and adults. Relapse occurred in 812 (46%) of 1769 patients; 136 (9%) of 1455 for whom data were available had seizures in their last year of follow-up, suggesting enduring seizure control was not regained by this timepoint. Independent predictors of seizure recurrence were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations. INTERPRETATION: We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom. FUNDING: Epilepsiefonds.

[Combined treatment with antiepileptic drugs. Andalusian Epilepsy Guide 2015]. / Tratamiento combinado con fármacos antiepilépticos. Guía Andaluza de Epilepsia 2015.

AIMS: The aim of this study was to draw up a set of recommendations based on scientific evidence and in agreement with authors and reviewers, which address fundamental issues concerning the combination of antiepileptic drugs. DEVELOPMENT: A committee of 11 experts belonging to the Sociedad Andaluza de Epilepsia (SAdE--Andalusian Epilepsy Society), of whom seven were neurologists, three were neuropaediatricians and one was a neurologist-neurophysiologist, all of them with long experience in epilepsy, promoted a comprehensive literature review among 55 experts in epilepsy who were members of the SAdE, with the aim of searching for any evidence that might be available on diagnostic or therapeutic matters in epilepsy. The guidelines were set out in 35 chapters. One of the chapters addressed the combination of antiepileptic drugs in the treatment of epilepsy. Taking 77 bibliographical references and the consensus view of authors and reviewers as their starting point, a set of easily applicable recommendations were drawn up. CONCLUSIONS: Combining antiepileptic drugs in patients with epilepsy whose seizures are not controlled with a single drug can, on many occasions, result in their going back into remission. There are a series of factors related with the type of epilepsy and characteristics of the patient and with the antiepileptic drugs to be used in combination that may favour a successful therapeutic outcome. Over-treatment with the combination of antiepileptic drugs must be avoided as far as possible. The results of this review provide a set of recommendations regarding combined treatment with antiepileptic drugs, based on scientific evidence and the agreement of authors, that are simple, useful and easy to apply at the different levels of healthcare.

TITLE: Tratamiento combinado con farmacos antiepilepticos. Guia Andaluza de Epilepsia 2015.Objetivo. Elaborar unas recomendaciones basadas en evidencias cientificas y en consenso de los autores y revisores, que aborden las cuestiones basicas acerca de la combinacion de farmacos antiepilepticos. Desarrollo. Un comite de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia (SAdE), constituido por siete neurologos, tres neuropediatras y un neurologo-neurofisiologo, todos con especial competencia en epilepsia, promovieron la realizacion de una revision bibliografica exhaustiva entre 55 expertos en epilepsia pertenecientes a la SAdE, en busca de evidencias disponibles relacionadas con temas diagnosticos o terapeuticos en epilepsia. La guia se estructuro en 35 capitulos. Uno de los capitulos abordo la combinacion de farmacos antiepilepticos en el tratamiento de la epilepsia. Basandose en 77 citas bibliograficas y en la opinion consensuada de autores y revisores, se confecciono una serie de recomendaciones de facil aplicacion. Conclusiones. La combinacion de farmacos antiepilepticos en los pacientes con epilepsia cuyas crisis no estan controladas con un solo farmaco puede conseguir en numerosas ocasiones que entren en remision. Existe una serie de factores relacionados con el tipo de epilepsia y caracteristicas del paciente y con los farmacos antiepilepticos que se van a utilizar en combinacion que pueden favorecer el exito terapeutico. Se debe evitar en lo posible el sobretratamiento con la combinacion de farmacos antiepilepticos. Los resultados de esta revision proveen unas recomendaciones sobre el tratamiento combinado con farmacos antiepilepticos, basadas en evidencias cientificas y en el consenso de los autores, utiles, sencillas y aplicables en los diferentes niveles asistenciales.

A study of drug-resistant childhood epilepsy testing the new ILAE criteria.

PURPOSE: To test the new ILAE definition of drug-resistant epilepsy in a cohort study. METHODS: All children younger than 14 with two or more unprovoked seizures observed at our hospital between 1994 and 2008 were included. RESULTS: Five hundred and eight patients were followed for an average of 90 months (range 24-168). The probabilities of achieving seizure freedom, according to the ILAE criteria, with the first, second, third and fourth and subsequent therapeutic regimens were 65%, 29%, 27% and 21%, respectively. In the cohort, 87 patients met the criteria for drug-resistant epilepsy, which represents 19% of the treated patients (n=459) and 17% of the overall sample. The probability of meeting the criteria for drug-resistant epilepsy was 11%, 11% and 13% at 2, 6 and 10 years respectively. Sixty two percent of drug resistant cases were younger than 4 years old, 73% had an associated developmental delay and/or motor deficit, 42% had an identifiable structural cause of epilepsy and 32% had a specific epileptic syndrome. For drug-resistant patients who tried additional therapeutic regimens, the probability of achieving a seizure-free state without further recurrences was 23% and 27% at three and five years, respectively. CONCLUSIONS: Compared with more stringent criteria, the new ILAE criteria classify a greater number of patients with drug-resistant epilepsy. A significantly higher proportion of cases meeting this definition subsequently enter remission. A definition of drug-resistance that includes the additional criteria of failure of a third antiepileptic drug or high seizure frequency may better identify patients with truly drug-resistant epilepsy.

Training with differential outcomes enhances discriminative learning and visuospatial recognition memory in children born prematurely.

Previous studies have demonstrated that discriminative learning is facilitated when a particular outcome is associated with each relation to be learned. When this training procedure is applied (the differential outcome procedure; DOP), learning is faster and more accurate than when the more common non-differential outcome procedure is used. This enhancement of accuracy and acquisition has been called the differential outcome effect (DOE). Our primary purpose in the present study was to explore the DOE in children born with great prematurity performing a discriminative learning task (Experiment 1) or a delayed visuospatial recognition task (Experiment 2). In Experiment 1, participants showed a faster learning and a better performance when differential outcomes were used. In Experiment 2, a significant DOE was also observed. That is, premature children performed the visuospatial recognition task better when they received differential outcomes following their correct responses. By contrast, the overall performance of full-term children was similar in both differential and non-differential conditions. These results are first to show that the DOP can enhance learning of conditional discriminations and recognition memory in children born prematurely with very low birth-weight.

[The use of bibliographic information resources and Web 2.0 by neuropaediatricians]. / Uso de recursos de información bibliográfica y Web 2.0 por neuropediatras.

AIM: To determine the state of knowledge and use of the main sources of bibliographic information and Web 2.0 resources in a sample of pediatricians linked professionally to child neurology. SUBJECTS AND METHODS: Anonymous opinion survey to 44 pediatricians (36 neuropediatric staffs and 8 residents) with two sections: sources of bibliographic information: (25 questions) and Web 2.0 resources (14 questions). RESULTS: The most consulted journals are Revista de Neurología and Anales de Pediatría. All use PubMed database and less frequently Índice Médico Español (40%) and Embase (27%); less than 20% use of other international and national databases. 81% of respondents used the Cochrane Library, and less frequently other sources of evidence-based medicine: Tripdatabase (39%), National Guideline Clearinghouse (37%), Excelencia Clínica (12%) and Sumsearch (3%). 45% regularly receive some e-TOC (electronic table of contents) of biomedical journals, but only 7% reported having used the RSS (really system syndication). The places to start searching for information are PubMed (55%) and Google (23%). The four resources most used of Web 2.0 are YouTube (73%), Facebook (43%), Picasa (27%) and blogs (25%). We don't found differences in response between the group of minus or equal to 34 and major or equal to 35 years. CONCLUSIONS: Knowledge of the patterns of use of information databases and Web 2.0 resources can identify the limitations and opportunities for improvement in the field of pediatric neurology training and information.