Effects of Age of Onset of Tonic-Clonic Seizures on Neuropsychological Performance in Children

Forty-eight children (aged 9 to 15 years) with tonic-clonic seizures were administered a neuropsychological test battery. The children with seizures of early onset (before age 5) were significantly impaired relative to the children with later onset on 8 of the 14 measures in the battery. The deficits were seen on tasks whose requirements included the repetition of a simple motor act, attention and concentration, memory, and complex problem solving. These findings emphasize the need for further research to determine the causal factors of the greater dysfunction seen in the early onset group. RÉSUMÉ Quarante huit enfants ÁgÉs de 9 À 15 ans souffrant de crises Épileptiques tonico-cloniques ont ÉtÉÉtudiÉs avec une batterie de tests neuropsychologiques. Pour huit des quatorze mesures de cette batterie de tests les enfants dont les cirses avaient dÉbutÉ prÉcocÉment (avant cinq ans) se sont avÉrÉs Étre signiflcativement dÉtÉriorÉs par rapport À ceux dont les crises avaient dÉbutÉ plus tardivement. Les dÉficits se sont manifestÉs pour des tÁches nÉcessitant la rÉpÉtition d'un acte moteur simple, attention et concentration, mÉmoire et capacitÉÀ rÉsoudre des problÈmes complexes. Ces rÉsultats mettent l'accent sur la nÉcessitÉ de poursuivre les recherches afin de dÉterminer les facteurs responsables de la plus grande dysfonction observÉe chez les enfants dont l'Épilepsie a dÉbutÉ tÔt dans la vie. RESUMEN Se ha aplicado una bateria de tests neuro-psicolÓgicos a 48 niÑos de 9 a 15 aÑos de edad que padecÍan ataques tonico-clÓnicos. Los niÑos con ataques de comienzo precoz (antes de los 5 aÑos) mostraron incapacidades significativas compareÁndolos con niÑos con comienzos mÁs tardios en 8 de los 14 tests de la bateria. Los defectos fueron detectados en las pruebas cuyos requisitos incluÍan la repeticiÓn de un acto motor simple, atenciÓn y concentraciÓn, memoria y resoluciÓn de problemas complejos. Estos hallazgos indican la necesidad de continuar la inves-tigaciÓn para determinar los factores causales de la mayor disfunciÓn observada en el grupo de comienzo precoz. ZUSAMMENFASSUNG 48 Kinder (9 bis 15 Jahre alt) mit tonisch-klonischen KrÄmpfen wurden mit einer neuropsychologischen Testbatterie untersucht. Die Kinder mit einem FrÜhbeginn der AnfÄlle (vor dem Alter von 5 Jahren) zeigten sich bei 8 von 14 Tests der Serie deutlich beeintrÄchtigt im VerhÄltnis zu Kindern mit spÄterem Anfallsbeginn. Die Defekte traten bei Aufgaben auf, die folgende AnsprÜche stellten: Wiederholung einer einfachen motorischen Handlung, Aufmerksamkeit und Konzentration, GedÄchtnis und komplexes ProblemlÖsen. Diese Befunde deuten auf die Notwendigkeit weiterer Untersuchungen, um die ursÄchlichen Faktoren der grÖßeren Funktionseinbuße zu bestimmen, die bei Patienten mit frÜhem Anfallsbeginn beobachtet wird.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65238/1/j.1528-1157.1981.tb04102.x.pd

Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase

Introduction Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. Methods Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. Results There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). Conclusion Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid

Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC

The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK

Squatter settlements and slums and sustainable development

Squatter settlement is defined as a low residential area, which has developed without legal right to the land or permission from the concerned authorities to build, and as a result, of their illegal status, infrastructure and services are usually inadequate (UN-Habitat 2003). On the other hand, slums are contiguous settlements where inhabitants are characterized by insecure residential status, inadequate access to safe water, inadequate access to sanitation and other basic infrastructure and services, poor housing quality, and overcrowding (UN-Habitat 2003). Both are form of informal settlements that are not formally planned

Classification and Lateralization of Temporal Lobe Epilepsies with and without Hippocampal Atrophy Based on Whole-Brain Automatic MRI Segmentation

Brain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishing controls (n = 28) from patients with unilateral temporal lobe epilepsy (TLE), 60 with and 20 without hippocampal atrophy (TLE-HA and TLE-N, respectively), and for determining the presumed side of seizure onset. The framework employs multi-atlas segmentation to estimate the volumes of 83 brain structures. A kernel-based separability criterion was then used to identify structures whose volumes discriminate between the groups. Next, we applied support vector machines (SVM) to the selected set for classification on the basis of volumes. We also computed pairwise similarities between all subjects and used spectral analysis to convert these into per-subject features. SVM was again applied to these feature data. After training on a subgroup, all TLE-HA patients were correctly distinguished from controls, achieving an accuracy of 96 ± 2% in both classification schemes. For TLE-N patients, the accuracy was 86 ± 2% based on structural volumes and 91 ± 3% using spectral analysis. Structures discriminating between patients and controls were mainly localized ipsilaterally to the presumed seizure focus. For the TLE-HA group, they were mainly in the temporal lobe; for the TLE-N group they included orbitofrontal regions, as well as the ipsilateral substantia nigra. Correct lateralization of the presumed seizure onset zone was achieved using hippocampi and parahippocampal gyri in all TLE-HA patients using either classification scheme; in the TLE-N patients, lateralization was accurate based on structural volumes in 86 ± 4%, and in 94 ± 4% with the spectral analysis approach. Unilateral TLE has imaging features that can be identified automatically, even when they are invisible to human experts. Such morphometric image features may serve as classification and lateralization criteria. The technique also detects unsuspected distinguishing features like the substantia nigra, warranting further study