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Epilepsy is a common neurological disease in tropical countries, particularly in sub-Saharan Africa. Previous work on epilepsy in sub-Saharan Africa has shown that many cases are severe, partly a result of some specific causes, that it carries a stigma, and that it is not adequately treated in many cases. Many studies on the epidemiology, aetiology, and management of epilepsy in sub-Saharan Africa have been reported in the past 10 years. The prevalence estimated from door-to-door studies is almost double that in Asia, Europe, and North America. The most commonly implicated risk factors are birth trauma, CNS infections, and traumatic brain injury. About 60% of patients with epilepsy receive no antiepileptic treatment, largely for economic and social reasons. Further epidemiological studies should be a priority to improve understanding of possible risk factors and thereby the prevention of epilepsy in Africa, and action should be taken to improve access to treatment.

Background As the data on the association of mental disorders and chronic physical diseases in developing and emerging countries is heterogeneous, this study aims to produce the first meta-analysis of these comorbidities. Methodology The meta-analysis protocol was registered in PROSPERO (N°CRD42017056521) and was performed in accordance with PRISMA guidelines. Initially, an article search was conducted on Medline, Embase, Lilacs and the Institut d’Epidémiologie et de Neurologie Tropicale database [Institute of Epidemiology and Tropical Neurology], as well as manually, with no restriction on language or date focusing on mental disorders, chronic diseases and neurotropic diseases. Two independent investigators assessed the quality of the studies which met the inclusion criteria using the Downs and Black assessment grid. The pooled estimates were calculated out using a random-effects method with CMA software Version 3.0. A meta-regression was then performed, and the significance level was set at 0.05. Results Of the 2604 articles identified, 40 articles involving 21,747 subjects met the inclusion criteria for co-morbidities between mental disorders and chronic physical diseases. Thirty-one articles were included in the meta-analysis of prevalence studies and 9 articles in that of the analytical studies. The pooled prevalence of mental disorders in patients with chronic physical diseases was 36.6% (95% CI, 31.4–42.1) and the pooled odds ratio was 3.1 (95% CI, 1.7–5.2). There was heterogeneity in all the estimates and in some cases, this was explained by the quality of the studies. Conclusion Some estimates regarding the prevalence of mental disorders in people with chronic physical diseases living in developing and emerging countries were similar to those in developed countries. Mental disorders are a burden in these countries. In order to respond effectively and efficiently to the morbidity and mortality associated with them, mental health care could be integrated with physical care.

Background To review how the phenotype and outcome of amyotrophic lateral sclerosis (ALS) change with variations in population ancestral origin (PAO). Knowledge of how PAO modifies ALS phenotype may provide important insight into the risk factors and pathogenic mechanisms of the disease. Methods We performed a systematic review and metaanalysis of the literature concerning differences in phenotype and outcome of ALS that relate to PAO. Results A review of 3111 records identified 78 population-based studies. The 40 that were included covered 40 geographical areas in 10 subcontinents. Around 12,700 ALS cases were considered. The results highlight the phenotypic heterogeneity of ALS at time of onset [age, sex ratio (SR), bulbar onset], age at diagnosis, occurrence of comorbidities in the first year after diagnosis, and outcome (survival). Subcontinent is a major explanatory factor for the variability of the ALS phenotype in population-based studies. Some markers of ALS phenotype were homogeneously distributed in western countries (SR, mean age at onset/diagnosis) but their distributions in other subcontinents were remarkably different. Other markers presented variations in European subcontinents (familial ALS, bulbar onset) and in other continents. As a consequence, ALS outcome strongly varied, with a median survival time from onset ranging from 24 months (Northern Europe) to 48 months (Central Asia). Discussion This review sets the scene for a collaborative study involving a wide international consortium to investigate, using a standard methodology, the link between ancestry, environment, and ALS phenotype.

Understanding how prevalence, incidence, and mortality of motor neuron diseases change over time and by location is crucial for understanding the causes of these disorders and for health-care planning. Our aim was to produce estimates of incidence, prevalence, and disability-adjusted life-years (DALYs) for motor neuron diseases for 195 countries and territories from 1990 to 2016 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. The motor neuron diseases included in this study were amyotrophic lateral sclerosis, spinal muscular atrophy, hereditary spastic paraplegia, primary lateral sclerosis, progressive muscular atrophy, and pseudobulbar palsy. Incidence, prevalence, and DALYs were estimated using a Bayesian meta-regression model. We analysed 14 165 site-years of vital registration cause of death data using the GBD 2016 cause of death ensemble model. The 84 risk factors quantified in GBD 2016 were tested for an association with incidence or death from motor neuron diseases. We also explored the relationship between Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility) and age-standardised DALYs of motor neuron diseases. In 2016, globally, 330 918 (95% uncertainty interval [UI] 299 522–367 254) individuals had a motor neuron disease. Motor neuron diseases have caused 926 090 (881 566–961 758) DALYs and 34 325 (33 051–35 364) deaths in 2016. The worldwide all-age prevalence was 4·5 (4·1–5·0) per 100 000 people, with an increase in age-standardised prevalence of 4·5% (3·4–5·7) over the study period. The all-age incidence was 0·78 (95% UI 0·71–0·86) per 100 000 person-years. No risk factor analysed in GBD showed an association with motor neuron disease incidence. The largest age-standardised prevalence was in high SDI regions: high-income North America (16·8, 95% UI 15·8–16·9), Australasia (14·7, 13·5–16·1), and western Europe (12·9, 11·7–14·1). However, the prevalence and incidence were lower than expected based on SDI in high-income Asia Pacific. Motor neuron diseases have low prevalence and incidence, but cause severe disability with a high fatality rate. Incidence of motor neuron diseases has geographical heterogeneity, which is not explained by any risk factors quantified in GBD, suggesting other unmeasured risk factors might have a role. Between 1990 and 2016, the burden of motor neuron diseases has increased substantially. The estimates presented here, as well as future estimates based on data from a greater number of countries, will be important in the planning of services for people with motor neuron diseases worldwide. Bill & Melinda Gates Foundation.

Background Clomiphene citrate is an ovulation inductor for which inadvertent post-conceptional exposures may occur in early pregnancy. In preclinical studies, post-conceptional exposures showed a teratogenic effect in different species. In humans, to date, little is known about the outcomes of inadvertently post-conceptionally exposed pregnancies. Objectives The objectives of our study were to assess the association between post-conceptional exposures to clomiphene citrate and major and minor congenital malformations in the offspring. Methods A retrospective cohort study of prospectively ascertained cases was undertaken, based on clinical data from the Centre de Référence sur les Agents Tératogènes (CRAT), Paris, France. Women with post-conceptional exposure to clomiphene citrate ( n = 309), and unexposed pregnant women ( n = 1236, 1:4 ratio) with prospectively collected data, known pregnancy outcome and delivery date prior to 01/02/2022, were matched by calendar year. An adjudication committee classified major and minor congenital malformations according to the EUROCAT (European Registration of Congenital Anomalies and Twins) classification. Results Among post-conceptional exposed women, no increased risk of major malformation was found (crude relative risk = 0.64, 95% confidence interval 0.19–2.15) as compared to unexposed women. Three major and ten minor congenital malformations were reported in the exposed group. An increased risk of minor malformations was found (crude relative risk = 4.05, 95% confidence interval 1.70–9.64) although there was no specific clinical pattern. Conclusions Post-conceptional exposure to clomiphene citrate was not associated with an increased risk of major congenital malformations. Given potential confounding and information biases, the results about minor malformations should be interpreted with caution as no specific clinical pattern was identified.

To evaluate the association between worldwide ALS incidence rates and age, using a dose-response meta-analysis. We reviewed Medline and Embase up to July 2016 and included all population-based studies of newly-diagnosed cases, using multiple sources for case ascertainment. A dose-response meta-analysis was performed. A meta-regression investigated potential sources of heterogeneity. Of 3254 articles identified in the literature, we included 41 incidence studies covering 42 geographical areas. Overall, the fit between observed and predicted age-specific rates was very good. The expected variation of ALS incidence with age was characterized, in each study, by a progressive increase in the incidence from the 40s leading to a peak in the 60s or 70s, followed by a sharp decrease. Cochran's Q test suggested a significant heterogeneity between studies. Overall, estimated patterns of ALS age-specific incidence (at which the peak was reached) were similar among subcontinents of Europe and North America: peak of ALS incidence ranged in these areas between 6.98 and 8.17/100,000 PYFU, which referred to age in the range 71.6-77.4 years. The relationship between age and ALS incidence appeared different for Eastern Asia which was characterized by a peak of ALS incidence at 2.20/100,000 PYFU around 75 years of age. This study confirms the consistency of the age-specific ALS incidence pattern within different subcontinents. Age-specific incidence appears lower in Eastern Asia as compared to Europe and North America.

We reviewed studies that analyzed cysticercosis (CC), neurocysticercosis (NCC) and epilepsy across Latin America, Asia and Sub-Saharan Africa, to estimate the odds ratio and etiologic fraction of epilepsy due to CC in tropical regions. We conducted a systematic review of the literature on cysticercosis and epilepsy in the tropics, collecting data from case-control and cross-sectional studies. Exposure criteria for CC included one or more of the following: serum ELISA or EITB positivity, presence of subcutaneous cysts (both not verified and unverified by histology), histology consistent with calcified cysts, and brain CT scan consistent with NCC. A common odds-ratio was then estimated using meta-analysis. 37 studies from 23 countries were included (n = 24,646 subjects, 14,934 with epilepsy and 9,712 without epilepsy). Of these, 29 were case-control (14 matched). The association between CC and epilepsy was significant in 19 scientific articles. Odds ratios ranged from 0.2 to 25.4 (a posteriori power 4.5-100%) and the common odds ratio was 2.7 (95% CI 2.1-3.6, p <0.001). Three subgroup analyses performed gave odds ratios as: 2.2 (EITB-based studies), 3.2 (CT-based studies), 1.9 (neurologist-confirmed epilepsy; door-to-door survey and at least one matched control per case). Etiologic fraction was estimated to be 63% in the exposed group among the population. Despite differences in findings, this meta-analysis suggests that cysticercosis is a significant contributor to late-onset epilepsy in tropical regions around the world, and its impact may vary depending on transmission intensity.

To gain further insight on the association between human toxocariasis and epilepsy in light of the new evidence in the last years. A systematic review was conducted without date and language restriction in the following electronic databases: MEDLINE (PubMed), Ingenta Connect, Science Direct (Elsevier), RefDoc, Scopus, HighWire, Scielo and the database of the Institute of Neuroepidemiology and Tropical Neurology of the Limoges University (IENT). Two investigators independently conducted the search up to November 2017. A pooled odds ratio (OR) was estimated using a random effects model. Meta-regression was conducted to investigate potential sources of heterogeneity. Database search produced 204 publications. Eleven case-control studies were included that were carried out in 13 countries worldwide. A total number of 4740 subjects were considered (2159 people with epilepsy and 2581 people without epilepsy). The overall pooled OR was 1.69 (95% CI 1.42-2.01) for the association between epilepsy and Toxocara spp. seropositivity. A positive association was constantly reported in the restricted analysis (WB as confirmatory or diagnostic test, younger population, and population-based studies). Meta-regression showed no statistically significant association between covariates and outcome. The updated meta-analysis provides epidemiological evidence of a positive association between Toxocara seropositivity and epilepsy. New surveys supported the association, mainly population-based studies. On this basis, health strategies to reduce the impact of Toxocara spp are strongly advised. Further research should be performed to understand the physiopathological mechanisms of toxocara-associated epileptogenesis.

Background Although they are declining worldwide, neurotropic parasitic diseases are still common in developing and emerging countries. The aim of this study was to estimate the pooled prevalence and pooled association measures of comorbidities between mental disorders (anxiety, depression, bipolar disorder, and schizophrenia) and neurotropic parasitic diseases (malaria, cysticercosis, toxoplasmosis, human African trypanosomiasis, Chagas disease, and human toxocariasis) in developing and emerging countries. Methods As the first meta-analysis on this topic, this study was performed in accordance with PRISMA guidelines. The protocol was registered in PROSPERO (N°CRD42017056521). The Medline, Embase, Lilacs, and Institute of Epidemiology and Tropical Neurology databases were used to search for articles without any restriction in language or date. We evaluated the quality of studies independently by two investigators using the Downs and Black assessment grid and pooled estimates using the random-effects method from CMA (Comprehensive Meta Analysis) Version 3.0. Results In total, 18 studies published between 1997 and 2016 met our inclusion criteria. We found that the prevalence of anxiety and depression in people suffering from Chagas disease and/or neurocysticercosis was 44.9% (95% CI, 34.4–55.9). In 16 pooled studies that included 1782 people with mental disorders and 1776 controls, toxoplasmosis and/or toxocariasis were associated with increased risk of schizophrenia and/or bipolar disorders (odds ratio = 2.3; 95% CI, 1.7–3.2). Finally, toxocariasis and/or toxoplasmosis were associated with an increased risk of the onset of schizophrenia (odds ratio = 2.4; 95% CI, 1.7–3.4). Conclusion Our pooled estimates show that the associations between diseases studied are relatively high in developing and emerging countries. This meta-analysis supports the hypothesis that toxoplasmosis could be the cause of schizophrenia. These findings could prove useful to researchers who want to further explore and understand the associations studied.

Despite concerns about the representativeness of patients from ALS tertiary centers as compared to the ALS general population, the extent of referral bias in clinical studies remains largely unknown. Using data from EURALS consortium we aimed to assess nature, extent and impact of referral bias. Four European ALS population-based registries located in Ireland, Piedmont, Puglia, Italy, and Limousin, France, covering 50 million person-years, participated. Demographic and clinic characteristics of ALS patients diagnosed in tertiary referral centers were contrasted with the whole ALS populations enrolled in registries in the same geographical areas. Patients referred to ALS centers were younger (with difference ranging from 1.1 years to 2.4 years), less likely to present a bulbar onset, with a higher proportion of familial antecedents and a longer survival (ranging from 11% to 15%) when compared to the entire ALS population in the same geographic area. A trend for referral bias is present in cohorts drawn from ALS referral centers. The magnitude of the possible referral bias in a particular tertiary center can be estimated through a comparison with ALS patients drawn from registry in the same geographic area. Studies based on clinical cohorts should be cautiously interpreted. The presence of a registry in the same area may improve the complete ascertainment in the referral center.