Search

ObjectiveSmall prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance.MethodsWe used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects.ResultsWe identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (−12.7% less than the control group), mathematics (−12.1%), language (−10.4%) and in science (−12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by −20.7% less than the control group), mathematics (−21.9%), language (−19.3%) and science (−19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group.ConclusionsIn utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.

Hyperekplexia is a rare neurogenetic disorder, frequently misdiagnosed in neonates with a risk of apnoea, asphyxia, and sudden infant death. We present video sequences of a male newborn, admitted on the second day of life to the neonatal intensive care unit, due to tonic‐clonic movements. Following clinical and paraclinical investigations, a final diagnosis of hyperekplexia was made. Genetic analysis revealed a homozygous mutation in GLRA1resulting in a R392H amino acid substitution and altered receptor dynamics, as indicated from previous work. The infant showed a marked improvement of the startle response and muscle hypertonia with clonazepam which is a strong clinical feature of GLRA1‐mediated hyperekplexia. [Published with video sequences] Content available: Video

PurposeWe aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates.MethodsWe performed a retrospective study using population-scale anonymised health records. We identified deaths in people with epilepsy (DPWE), those with a diagnosis of epilepsy, and deaths associ- ated with epilepsy (DAE), where epilepsy was recorded as a cause of death. We compared death rates in 2020 with average rates in 2015–2019 using Poisson models.ResultsThere were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015–2019) for DAE were 1.34 (95%CI 1.14–1.57, p<0.001) and for DPWE were 1.08 (0.99–1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99–1.39, p = 0.06) and for DPWE were 0.96 (0.87–1.05, p = 0.37).ConclusionsThe significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.

ObjectiveTo characterise the Welsh idiopathic intracranial hypertension (IIH) population, epidemiologi- cal trends and healthcare outcomes using routinely collected healthcare data.MethodsWe used primary and secondary care healthcare diagnostic codes within the Secure Anonymised Information Linkage databank to ascertain IIH cases and controls in a retrospective cohort study between 2003–2017. We validated IIH diagnosis codes using anonymised secondary care lists of IIH cases.ResultsWe analysed 35 million patient years of data (2003–2017). There were 1765 cases of IIH in 2017 (85% female). The prevalence and incidence of IIH in 2017 was 76/100,000 and 7.8/100,000, significantly increased from 2003 (prevalence=12/100,000, incidence=2.3/100,000). IIH prevalence is associated with socio-economic deprivation and increasing body mass index (BMI). 9% of people with IIH had CSF shunts with less than 0.2% having bariatric surgery. Unscheduled hospital admissions were significantly higher in the IIH cohort compared to controls; and also in IIH patients with CSF shunts compared to those without.ConclusionsIIH incidence and prevalence is increasing significantly, corresponding to population increases in BMI. This has important implications for healthcare professionals and policy makers given the comor- bidities, complications and increased healthcare utilisation and economic burden associated with IIH.lotif_miah@hotmail.com

There is strong evidence for a genetic contribution to age at onset of schizophrenia, which probably involves both susceptibility loci for schizophrenia and modifying loci acting independent of disease risk. We sought evidence of linkage to loci that influence age at onset of schizophrenia in a sample of 94 affected sibling pairs with DSM-IV schizophrenia or schizoaffective disorder, and age at first psychiatric contact of 45 years or less. Individuals were genotyped for 229 microsatellite markers spaced at approximately 20 cM intervals throughout the genome. Loci contributing to age at onset were sought by a quantitative maximum-likelihood multipoint linkage analysis using MAPMAKER/SIBS. A nonparametric multipoint analysis was also performed. The genomewide significance of linkage results was assessed by simulation studies. There were six maximum-likelihood LOD score peaks of 1.5 or greater, the highest being on chromosome 17q (LOD = 2.54; genomewide P = 0.27). This fulfils Lander and Kruglyak's [1995: Nat Genet 11:241–247] criteria for suggestive linkage in that it would be expected to occur once or less (0.3 times) per genome scan. However, this finding should be treated with caution because the LOD score appeared to be almost solely accounted for by the pattern of ibd sharing at one marker (D17S787), with virtually no evidence of linkage over flanking markers. None of the linkage results achieved genomewide statistical significance, but the LOD score peak on chromosome 13q (LOD = 1.68) coincided with the region showing maximum evidence for linkage in the study by Blouin et al. [1998: Nat Genet 20:70–73] of categorical schizophrenia. © 2001 Wiley-Liss, Inc.

IntroductionMultiple sclerosis (MS) causes long-term disability with broad socioeconomic consequences. This may influence educational attainment in children of affected individuals. We investigated whether having a mother with MS affects performance in Welsh national attainment tests.MethodAnonymised lists of 1584 women with MS diagnosed in two neuroscience centres (Cardiff, Swansea) were linked to population level routinely-collected health and education data. We identified children born to mothers with MS and compared performance in Key Stage (KS) 2–4 tests, taken at ages 11, 14 and 16, to a control group (matched for deprivation score, maternal age, year of birth, gestational age and birth weight). We measured core subject indicator (CSI) as an outcome measure (proportion achieving minimum standard in core subjects).Results525 children from mothers with MS had test results available from 2003–2016; there were 2217 matched controls. There was no significant overall difference in CSI achievement between cases and controls: KS2 (85.3%v84.3%); KS3 (75%v71.5%); KS4 (52.1%v50.5%). Greater Expanded Disability Score Status did not significantly worsen performance but longer time since diagnosis improved performance in KS3 and KS4.ConclusionHaving a mother with MS did not significantly worsen performance in national attainment tests and was associated with improved performance in some subgroups.