Application of recent international epidemiological guidelines to a prospective study of the incidence of first seizures, newly-diagnosed epilepsy and seizure mimics in a defined geographic region in Ireland

Studies adherent to international guidelines and epilepsy classification are needed to accurately record the incidence of isolated seizures, epilepsy and seizure-mimics within a population. Because the diagnosis of epilepsy is largely made through clinical assessment by experienced physicians, seizures and epilepsy are susceptible to misdiagnosis. Previous epidemiological studies in epilepsy have not captured â seizure mimicsâ . We therefore sought to quantify the incidence of isolated seizures, epilepsy and seizure-mimics using the International League Against Epilepsy (ILAE) classification system. In this study multiple overlapping methods of case ascertainment were applied to a defined geographic region from January 1 to March 31, 2017 to identify all patients presenting with first seizures (provoked and unprovoked), new diagnoses of epilepsy and seizure mimics. Over a 3 month period, from a population of 542,869 adults and children, 442 potential presentations were identified, and 283 met the inclusion criteria. Radiology databases were the source of the largest number of individual cases (n = 153, 54%), while electroencephalogram (EEG) databases were the source of the highest number of unique-to-source cases (those not identified elsewhere, n = 60, 21%). No single case was picked up in every method of ascertainment. Among the 283 included presentations, 38 (13%) were classed as first provoked seizures, 27 (10%) as first unprovoked seizures, 95 (34%) as new diagnosis of epilepsy and 113 (40%) as seizure mimics. Ten (3%) presentations were indeterminate. We present and apply a rigorous study protocol for investigation of the incidence of first seizures, new diagnosis of epilepsy and seizure mimics in a geographically defined region which is adherent to recently published international guidelines for epidemiologic studies and epilepsy classification. We highlight the challenges in making a diagnosis of new-onset epilepsy in patients presenting with a first seizure using the current ILAE definition of epilepsy, when epilepsy can be diagnosed in situations where the treating physician anticipates the risk of further seizures exceeds 60%

The incidence of first seizures, epilepsy and seizure mimics in a geographically defined area.

To determine the incidence of first seizures, epilepsy and seizure mimics in a geographically defined area using the updated 2014 International League Against Epilepsy (ILAE) definition which allows an epilepsy diagnosis following a single seizure where risk of further seizures over the next 10 years is approximately 60% or more. This replaced the 1993 definition where epilepsy was diagnosed when a person had two or more seizures separated by 24 hours. Using multiple overlapping methods of case ascertainment followed by individual case classification by an epileptologist we identified all first seizures, new diagnosis of epilepsy, and seizure mimics occurring in a defined geographical area (population 542,868) 01/01/2017-12/31/2017. Incidence was age-standardised to the Standard European Population. We compared incidence rates when using the 2014 and 1993 ILAE definitions. When applying the 2014 ILAE definition of epilepsy the incidence of new diagnosis of epilepsy was 62 per 100,000 (age-standardised 74), compared to 41 per 100,000 (age-standardised 48) when applying the 1993 definition, and the difference was more pronounced at older ages. The incidence of all first seizures and of seizure mimics was 102 per 100,000 (age-standardised 123) and 94 per 100,000 (age-standardised 111), respectively. The most frequently encountered seizure mimic was syncope. Application of the 2014 ILAE definition of epilepsy resulted in higher incidence of new diagnosis of epilepsy compared to the 1993 definition. The incidence of seizure mimics almost equals that of all first seizures. Seizures, epilepsy and seizure mimics represent a significant burden to healthcare systems

Prediagnostic plasma metabolomics and the risk of amyotrophic lateral sclerosis

Objective: To identify prediagnostic plasma metabolomic biomarkers associated with amyotrophic lateral sclerosis (ALS). Methods: We conducted a global metabolomic study using a nested case-control study design within 5 prospective cohorts and identified 275 individuals who developed ALS during follow-up. We profiled plasma metabolites using liquid chromatography–mass spectrometry and identified 404 known metabolites. We used conditional logistic regression to evaluate the associations between metabolites and ALS risk. Further, we used machine learning analyses to determine whether the prediagnostic metabolomic profile could discriminate ALS cases from controls. Results: A total of 31 out of 404 identified metabolites were associated with ALS risk (p < 0.05). We observed inverse associations (n = 27) with plasma levels of diacylglycerides and triacylglycerides, urate, purine nucleosides, and some organic acids and derivatives, while we found positive associations for a cholesteryl ester, 2 phosphatidylcholines, and a sphingomyelin. The number of significant associations increased to 67 (63 inverse) in analyses restricted to cases with blood samples collected within 5 years of onset. None of these associations remained significant after multiple comparison adjustment. Further, we were not able to reliably distinguish individuals who became cases from controls based on their metabolomic profile using partial least squares discriminant analysis, elastic net regression, random forest, support vector machine, or weighted correlation network analyses. Conclusions: Although the metabolomic profile in blood samples collected years before ALS diagnosis did not reliably separate presymptomatic ALS cases from controls, our results suggest that ALS is preceded by a broad, but poorly defined, metabolic dysregulation years before the disease onset

Association between social deprivation and incidence of first seizures and epilepsy: A prospective population-based cohort

Objective: Epidemiologic studies have investigated whether social deprivation is associated with a higher incidence of epilepsy, and results are conflicting, especially in children. The mechanisms underlying a potential association are unclear. This study examines whether there is an association between social deprivation and the incidence of first seizures (unprovoked and provoked) and new diagnosis of epilepsy by comparing incidence across an area-level measure of deprivation in a population-based cohort. Methods: Multiple methods of case identification followed by individual case validation and classification were carried out in a defined geographical area (population 542 868) to identify all incident cases of first provoked and first unprovoked seizures and new diagnosis of epilepsy presenting during the calendar year 2017. An area-level relative deprivation index, based on 10 indicators from census data, was assigned to each patient according to registered address and categorized into quintiles from most to least deprived. Results: The annual incidence of first unprovoked seizures (n = 372), first provoked seizures (n = 189), and new diagnosis of epilepsy (n = 336) was highest in the most deprived areas compared to the least deprived areas (incidence ratios of 1.79 [95% confidence interval (CI) = 1.26–2.52], 1.55 [95% CI = 1.04–2.32], and 1.83 [95% CI = 1.28–2.62], respectively). This finding was evident in both adults and children and in those with structural and unknown etiologies of epilepsy. Significance: The incidence of first seizures and new diagnosis of epilepsy is associated with more social deprivation. The reason for this higher incidence is likely multifactorial

Role of Antihypertensive Treatment and Blood Pressure Control in the Occurrence of Adverse Pregnancy Outcomes:a Population-Based Study of Linked Electronic Health Records

Background: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. Methods: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. Results: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44–6.07]); PTB (aOR, 2.53 [2.39–2.67]); and FGR (aOR, 2.51 [2.31–2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05–1.30]), PTB (1.25 [1.12–1.39]), and FGR (1.80 [1.51–2.14]). Women prescribed methyldopa (versus β-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19–1.73]); PTB (1.59 [1.30–1.93]), but lower odds of FGR (aOR, 0.66 [0.48–0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus β-blockers) except for PTB (aOR, 1.94 [1.15–3.27]). Among women prescribed treatment, lower average blood pressure (<135/85 mm Hg) was associated with better pregnancy outcomes. Conclusions: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. β-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy

Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis

Objective: Limited evidence exists on the role that the cause of chronic kidney disease plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between chronic kidney disease and adverse pregnancy outcomes by the cause and severity of chronic kidney disease where reported. The protocol was registered under the International Prospective Register of Systematic Reviews (CRD42020211925). Data Sources: PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. Study Eligibility Criteria: Studies that compared the pregnancy outcomes in women with or without chronic kidney disease were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. Methods: Data extraction and quality appraisal were performed independently by 3 reviewers. The grading of recommendations, assessment, development, and evaluation approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate the pooled estimates using the generic inverse variance method. The primary outcomes included preeclampsia, cesarean delivery, preterm birth (<37 weeks’ gestation), and small for gestational age babies. Results: Of 4076 citations, 31 studies were included. Prepregnancy chronic kidney disease was significantly associated with a higher odds of preeclampsia (pooled crude odds ratio, 8.13; [95% confidence interval, 4.41–15], and adjusted odds ratio, 2.58; [1.33–5.01]), cesarean delivery (adjusted odds ratio, 1.65; [1.21–2.25]), preterm birth (adjusted odds ratio, 1.73; [1.31–2.27]), and small for gestational age babies (adjusted odds ratio, 1.93; [1.06–3.52]). The association with stillbirth was not statistically significant (adjusted odds ratio, 1.67; [0.96–2.92]). Subgroup analyses indicated that different causes of chronic kidney disease might confer different risks and that the severity of chronic kidney disease is associated with a risk of adverse pregnancy outcomes, as pregnancies with later stages of chronic kidney disease had higher odds of preeclampsia, preterm birth, and small for gestational age babies than those at earlier stages. The grading of recommendations, assessment, development, and evaluation certainty of the evidence overall was “very low”. Conclusion: This meta-analysis quantified the associations between prepregnancy chronic kidney disease and adverse pregnancy outcomes, both overall and according to the cause and severity of the disease. These findings might support the clinicians aiming to counsel women having chronic kidney disease by allowing them to tailor their advice according to cause and severity of the chronic kidney disease. We identified the gaps in the literature, and further studies examining the effect of specific kidney diseases and other clinical characteristics (eg, proteinuria, hypertension) on adverse pregnancy outcomes are warranted

Genetic variants related to urate and risk of Parkinson's disease

Introduction: Higher urate concentrations have been associated with a lower risk of developing Parkinson's disease (PD) and with slower rates of clinical decline in PD patients. Whether these associations reflect a neuroprotective effect of urate is unclear. Our objective was to assess whether genetic variants that modify circulating urate levels are also associated with altered PD risk. Methods: Participants were from three large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Cancer Prevention Study II Nutrition Cohort (CPS-IIN). We examined associations between single nucleotide polymorphisms (SNPs) in SLC2A9 and other genes involved in urate transport and PD risk using conditional logistic regression among 1451 cases and 3135 matched controls. We assessed associations between SNPs and plasma urate levels in a subset of 1174 control participants with linear regression models. Results: We found the expected associations between SNPs in SLC2A9 and plasma urate levels among men and women; however, SNPs in other genes tended not to be associated with urate. Each SNP in SLC2A9 explained less than 7% of the variance in plasma urate. We did not find significant associations between the SNPs in SLC2A9 and PD risk among men or women. Conclusion: Our results do not support an association between genetic variants associated with circulating urate levels and risk of PD, but larger investigations are needed to determine whether the modest genetic effects on blood urate contribute to predict PD risk