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

Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring

The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring

CHANGES IN RED-BLOOD-CELLS WITH VALPROATE THERAPY

Increase in the red blood cell mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH) values in patients receiving Valproate as mono or polytherapy was noted. To investigate this situation 41 epileptic patients were studied on Valproate alone (Group 1) and 20 patients on Valproate added to another antiepileptic drug (AED), (Group 4), and compared with 19 patients on carbamazepine (CBZ) (Group 2) and 12 patients on phenytoin (PHT), (Group 3). The results showed significant rise in MCV values in Groups 1 and 4. The peripheral blood smear and other tests including reticulocyte counts of the patients with abnormal values ruled out macrocytic anemias. We postulate a generalized effect which is the result of alteration in erythrocyte membrane phospholipids