Emerging contaminants are produced globally at high rates and often ultimately find their way into the aquatic environment. These include substances contained in anti-seizure medication (ASM), which are currently appearing in surface waters at increasing concentrations in Germany. Unintentional and sublethal, chronic exposure to pharmaceuticals such as ASMs has unknown consequences for aquatic wildlife. Adverse effects of ASMs on the brain development are documented in mammals. Top predators such as Eurasian otters (Lutra lutra) are susceptible to the bioaccumulation of environmental pollutants. Still little is known about the health status of the otter population in Germany, while the detection of various pollutants in otter tissue samples has highlighted their role as an indicator species. To investigate potential contamination with pharmaceuticals, Eurasian otter brain samples were screened for selected ASMs via high-performance liquid chromatography and mass spectrometry. Via histology, brain sections were analyzed for the presence of potential associated neuropathological changes. In addition to 20 wild otters that were found dead, a control group of 5 deceased otters in human care was studied. Even though none of the targeted ASMs were detected in the otters, unidentified substances in many otter brains were measured. No obvious pathology was observed histologically, although the sample quality limited the investigations.

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[This corrects the article DOI: 10.3389/fphar.2022.832929.].

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Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5-1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk-benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies.

Background: This study aimed to evaluate the efficacy and tolerability of Anti-Seizure medication (ASM) treatment in patients with BECTS. Method: We searched PubMed, Cochrane Library, Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA, and China Science and Technology Journal Database (VIP) between 1 Jan 1990, and 1 Sep 2021, for randomized controlled studies. Data on seizure freedom rate, rate of treatment withdrawal due to serious adverse events, rate of any adverse events and dropout, 50% remission rate, the proportion of patients whose EEG to be normalized, and improvement in cognitive function were extracted by two authors independently. The pooled data were meta-analyzed using a random effects model. Results: A total of 27 studies evaluating 9 ASMs were included, 19 of which were suitable for meta-analysis. Compared with sulthiame (STM), levetiracetam (LEV) was associated with a higher probability of treatment withdrawal due to serious adverse events [RR = 5.12, 95% CI (1.19, 22.01), I 2 = 0.0%], experiencing any adverse events [RR = 5.12, 95% CI (1.19, 22.01)], and dropping out for any reason [RR = 3.17, 95% CI (1.36, 10.11)], while it did not affect the seizure freedom rate [RR = 0.90, 95% CI (0.75, 1.06)]. LEV significantly improved cognitive performance relative to carbamazepine (CBZ) but had no effect on the proportion of any adverse events [RR = 0.62, 95% CI (0.25, 1.59)] and EEG to be normalized [RR = 1.27, 95% CI (0.94, 1.71)]. There was no higher probability of a 50% remission rate when comparing valproic acid (VPA) to LEV [RR = 0.96, 95% CI (0.57, 1.61)] and oxcarbazepine (OXC) [RR = 0.61, 95% CI (0.31, 1.20)]. In addition, STM was related to a higher probability of EEG normalization than placebo [RR = 4.61, 95% CI (2.12, 10.01)]. The included single studies also provided some evidence for the efficacy and/or tolerability of other ASMs in BECTS, including topiramate, lamotrigine, clobazam, and clonazepam. The risk of bias of the included studies was frequently low or unclear. Conclusion: This study indicated some discrepancies in efficacy and tolerability among ASMs used in patients with BECTS. More randomized controlled trials (RCTs) comparing ASMs with larger populations are required to ascertain the optimum antiepileptic drug treatment to guide clinicians.

OBJECTIVE: COVID-19 pandemic has disrupted healthcare services for chronic disorders such as epilepsy. In this study, the impact of COVID-19 pandemic on persons with epilepsy (PWE) with regard to their seizure control, depression status, and medication adherence was assessed.
METHODS: After ethical clearance, 449 PWE who had been previously evaluated for depression at All India Institute of Medical Sciences (AIIMS), New Delhi, India, were telephonically revaluated using Mini International Neuropsychiatric Interview and surveyed for source of medication and medication adherence over past 6 months. The prevalence and the association of depression, suicidality, and seizures during pandemic with different PWE variables were determined.
RESULTS: Out of 449 PWE, 70.6% responded. 19.9% were diagnosed positive for depression as per MINI while suicidal ideation was observed in 5.4%. Seventy six (23.9%) PWE reported seizures during pandemic. The incidence was greater in females, unemployed, previously uncontrolled epilepsy, polytherapy, altered use of medications, and depressed PWE. Seizure during pandemic, increased seizure frequency, previous history of depression, and altered use of medications were all significantly associated with depression during COVID-19 pandemic (2.6-95%CI, 1.45-4.73; 1.9-95%CI, 1.01-3.57; 8.8-95%CI, 4.54-17.21; 2.9-95%CI, 1.19-7.24), and polytherapy (2.9-95%CI, 0.92-9.04), seizures during pandemic (3.9-95%CI, 1.45-10.53) and previous history of depression and suicidality, were related with suicidal ideation.
CONCLUSIONS: COVID-19 pandemic-induced disruptions can be detrimental for PWE, and restoring services to the precovid levels as well as putting appropriate continuity plans in place for care of PWE should be a priority.

Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation. Methods: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance. Results: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs. Significance: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scale.

Treatment of pediatric status epilepticus (SE) remains challenging as up to 50 % of patients are refractory to conventional anti-seizure medications. The glycolytic intermediate, fructose-1,6-bisphosphate (FBP), has been reported to exert significant anticonvulsant effects in both adult animals and in in vitro models of seizures. This study aims to examine FBP efficacy in controlling seizures in a rat model of juvenile SE.
Sprague Dawley rats (P11-P17) were injected with pilocarpine (300 mg/kg, i.p.) to induce SE, which was monitored by video-electroencephalography (v-EEG). Thirty minutes into SE, FBP was administrated (500 or 1000 mg/kg, i.p.). v-EEG recording was continued for ∼60 additional minutes to assess the anticonvulsant effect of FBP, compared with vehicle (saline) treatment.
SE consistently occurred in rat pups 10-15 min after pilocarpine injection and persisted over the 90-min recording period. Neither saline nor a lower dose of FBP (500 mg/kg) treatment stopped behavioral and electrographic seizures. At higher doses (1000 mg/kg), FBP terminated SE in ∼15 min in 60 % (6 of 10) of the rat pups.
The endogenous glycolytic metabolite, FBP, promptly suppresses ongoing seizure activity and represents a potential alternative metabolic therapy to improve the treatment of SE in the juvenile age range.