Idiopathic Generalized Epilepsy (IGE) patients may not achieve optimal seizure control with monotherapy. Our goal was to evaluate the efficacy of combination therapy in a retrospective series of IGE patients receiving different antiseizure medication (ASM) regimens. We retrospectively identified all patients with adolescence onset IGE with typical clinical and EEG features from a single epilepsy specialist clinic from 2009 to 2020. We evaluated long-term seizure control, for VPA, LEV, LTG mono and combination therapy. We studied 59 patients. VPA was more commonly used in men (84%) than in women (44%) (p < 0.05). VPA was the initial drug of choice in 39% of patients, followed by LEV (22%) and LTG (14.9%). Thirty-nine patients (66.1%) achieved complete seizure control for at least one year. Fifty patients (84.7)% had partial control, without GTC occurrence, for at least one year. VPA was superior to LTG for complete seizure control (p = 0.03), but not for minor seizure control or pseudoresistance (p > 0.05). Combination therapy was superior to LEV and LTG monotherapy for complete control (p = 0.03), without differences for minor seizures and pseudoresistance outcomes (p > 0.05). Combination therapy not including VPA was also non-inferior to VPA monotherapy in all settings. Combination therapy was superior to LTG and LEV monotherapy in IGE, and may be equally effective including or not VPA. Combination therapy including LTG, LEV, and/or VPA is an effective treatment option after monotherapy failure with one of these ASM in IGE. Dual therapy with LEV–LTG should be considered in monotheraphy failure, to avoid fetal effects of in utero VPA exposure.
Introduction: The association between preeclampsia (PE), known as a disorder of pregnancy characterized by the onset of systemic arterial hypertension, and the promotion of neurodevelopmental disorders has been hypothesized by several studies. Indeed, it is believed that multifactorial psychiatric conditions may arise after a compromised anatomical and functional brain development due to low oxygen levels. However, a solid relation between intrauterine hypoxia and potential subsequent neurodevelopmental deficits remains unknown. Therefore, studies in animal models of PE become essential for understanding this specific cause and effect from a behavioral perspective. The aim of this study was to evaluate behavioral alterations in 2-month-old (P60) male rats from females Wistars treated with L-NAME, a hypertensive agent that inhibits nitric oxide synthase (NOS). In addition, we sought to identify a possible protective effect of Sildenafil Citrate (CS), a potent vasodilator, against PE. Methodology: Firstly, pregnant female Wistar rats were treated by gavage, daily, from the 1st to the 18th day of pregnancy (DP) with L-NAME (50 mg/kg) and with CS (10 mg/kg) from the 7th to the 18th DP. Control animals were treated with similar volumes of pure water. The pups were then divided accordingly: 1) Control; 2) L-NAME; 3) CS; 4) L-NAME+CS. The behavioral tests were performed in P60 animals; the male rats were subjected to open field, social interaction, sucrose preference and contextual fear conditioning tests. The results were analyzed by One Way ANOVA with Bonferroni’s post-hoc. Data are presented as mean ± SD (in % of Control group). Results: As expected, the SBP (Systolic Blood Pressure) was significantly elevated in L-NAME treated rats than in controls (149.40 ± 15.45 versus 100.40 ± 2.37, p<0.0001). Still, it was possible to notice a reduction in SBP after the concomitant administration of L-NAME and CS in comparison to L-NAME group (117.00 ± 17.79 versus 149.40 ± 15.45, p<0.0001). No significant differences were verified among all groups evaluated in the open field or social interaction tests (p>0.05). However, the L-NAME group showed a decrease in sucrose preference test (64.12 ± 10.98, p<0.05). Lastly, the results of contextual fear conditioning test pointed towards a reduction in freezing time in L-NAME animals in comparison to the Control group (33.89 ± 33.96 versus 193.00 ± 122.00, p<0.01). Discussion: L-NAME administration induces an increase in SBP that possibly can lead to intrauterine hypoxia and may explain anhedonia and cognitive impairments observed in preeclampsia-like rats. Curiously, such phenotypes are important features of several neurodevelopmental disorders, like Intellectual Disability, Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder, as well as the prodromal phase of Schizophrenia. Our study also indicates that CS administration reverses part of the behavioral alterations observed after PE. Conclusion: Increased SBP during pregnancy promotes intrauterine hypoxia, which seems to be a crucial factor in triggering behavioral alterations that are consistent with neurodevelopmental disorders.
Introduction Intracranial aneurysm (IA) is a major healthcare concern. The use of statin to reduce serum cholesterol has shown evidence to reduce cardiovascular risk in various diseases, but the impact on IA has not been described. This study aims to determine whether statin use, and serum cholesterol levels interfere with outcomes after IA event. Methods A cohort of patients with IA was analyzed. Patients social and demographics data were collected. Modified Rankin scale (mRS) score after 6 months of follow-up was the endpoint. The data regarding statins use, presence or not of atherosclerotic plaque in radiological images and serum cholesterol of 35 patients were included in our study. Linear regression models were used to determine the influence of those 6 variables in the clinical outcome. Results The prevalence of atherosclerotic plaque, high cholesterol and use of statins was 34.3%, 48.5%, and 14.2%, respectively. Statins and serum cholesterol did not impact the overall outcome, measured by mRS after 6 months (p > 0.05), but did show different tendencies when separated by IA rupture status. Serum cholesterol shows an important association with rupture of aneurysm (p = 0.0382). High cholesterol and use of statins show a tendency for worse outcome with ruptured aneurysm, and the opposite is true for unruptured aneurysm. The presence of atherosclerotic plaques was not related with worse outcomes. Conclusions Multiple and opposite mechanisms might be involved in the pathophysiology of IA. Ruptured aneurysms are associated with higher levels of serum cholesterol. Serum cholesterol and statins use were not correlated with worse outcomes, but further studies are important to clarify these relationships.
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