Background: Stroke is one of the leading causes of acquired epilepsy in adults. An

Other isotype-selective estrogen receptor (ER) agonists, the selective ER␣ agonist 3,17-dihydroxy-19-nor-17␣-pregna-1,3,5 (10)-triene-21,16␣-lactone and the selective ER␤ agonist 8-vinylestra-1,3,5 (10)-triene-3,17␤-diol, were used in hypophysectomized rats, gonadotropin-releasing hormone antagonist-treated mice, as well as intact rats to elucidate the effects of isotype-selective estrogens on the physiology of folliculogenesis and ovulation. In hypophysectomized rats and gonadotropin-releasing hormone antagonisttreated mice, the ER␤ agonist caused stimulation of early folliculogenesis, a decrease in follicular atresia, induction of ovarian gene expression, and stimulation of late follicular growth, accompanied by an increase in the number of ovulated oocytes similar to 17␤-estradiol (E2). In contrast, the ER␣ agonist had little or no effect on these parameters, implying that direct estrogen effects on ovarian follicular development are mediated by ER␤. In intact rats, E2 and the ER␣ agonist dose-dependently inhibited ovulation, in contrast to the ER␤ agonist. On the other hand, the ER␤ agonist did not stimulate uterine weight in intact rats, in contrast to E2 and the ER␣ agonist. This finding is in line with the assumption that estrogen mediated ovulation inhibition and stimulation of uterine growth are mediated by ER␣ but not by ER␤.pharmacology ͉ folliculogenesis ͉ endocrinology E strogens play a central role in the development and maintenance of female reproductive organs, mammary glands, and sexual behavior. In addition, estrogen's involvement in the function of a number of other tissues such as the bone, the cardiovascular, and the CNS has also been recognized (1, 2).Estrogens exhibit most of their physiological effects through nuclear receptor proteins, the estrogen receptors (ERs). Until recently, it had been assumed that there is only one ER. In 1996, a second ER was detected (3-5), which shares a high degree of homology with the ''classic'' counterpart, specifically in the DNA-and ligand-binding domains. The newly detected receptor is called ER␤, the classic counterpart being renamed as ER␣. The expression pattern of the two ER isotypes is different: ER␤ is predominantly expressed in the ovary and prostate but also other organs not subserving reproduction-related functions. In contrast, its expression is low in the pituitary, the thymus, the uterus, and the liver; these organs express ER␣ at high levels (6, 7). A distinct tissue distribution of ER␣ and ER␤ suggests specific biological functions of ER␣ and ER␤.ER␤ is the predominant ER in ovarian follicles in rodents and nonrodents (8-10). The hypothesis that ER␤ plays an important role in the control of ovarian function is supported by data from various lines of ER␤ knockout mice showing different degrees of female subfertility due to reduced follicular maturation and ovulation rate (11).The stimulatory activity of estrogens on ovarian cell growth, especially folliculogenesis, has been demonstrated in rodent models (12,13). It is suggested that estroge...

The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. Methods: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. Results: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and

ImportanceAcute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk.ObjectiveTo compare mortality and risk of epilepsy following different types of acute symptomatic seizures.Design, Setting, and ParticipantsThis cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022.ExposuresType of acute symptomatic seizure.Main Outcomes and MeasuresAll-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke).ResultsA total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy.Conclusions and RelevanceIn this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Background: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. Methods: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0–2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. Results: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). Conclusion: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.