BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE).
METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure\'s onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments.
RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as \"Responder with Relapse\", 11 as \"Resistant\", 6 as \"Pyridoxine First Approach\", and 2 as \"Responders\". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up.
CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

OBJECTIVE: To evaluate and synthesize the evidence and knowledge gaps on primary prevention and treatment of post-stroke acute symptomatic seizures (ASSs) using antiseizure medications (ASMs).
METHODS: We systematically searched of EMBASE, MEDLINE (accessed from PubMed), and the Cochrane Central Register of Controlled Trials (CENTRAL) to include randomized, double- or single-blinded trials (RCTs) on primary prophylaxis and treatment of post-stroke ASSs with ASMs. The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS: Two placebo-controlled RCTs (totaling 114 participants) evaluating valproate or levetiracetam as primary prophylaxis of ASSs due to hemorrhagic stroke were included. In one RCT, post-stroke ASS occurred in 1/36 patients (2.7%) on valproate and in 4/36 patients (7%) on placebo (p = 0.4). In the other RCT, ASSs were only electrographic and occurred in 3/19 (16%) with levetiracetam and in 10/23 (43%) with placebo (p = 0.043). We found no RCTs on the treatment of post-stroke ASSs or discontinuation of ASMs administered for the treatment of post-stroke ASSs.
CONCLUSIONS: Evidence to support primary prophylaxis of ASSs is sparse and of very low quality and is insufficient to recommend it routinely. Secondary prevention of post-stroke ASSs is usually not recommended except in selected cases (the most relevant being acute symptomatic status epilepticus, which carries a high risk of subsequent poststroke seizures (PSE)). The choice of which ASM to administer and for how long is not based on solid RCT evidence. Management of post-stroke PSE should be done according to an evidence-based framework, considering the individuality of the patient and the pharmacological properties of the drugs.

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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OBJECTIVE: Triple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome.
METHODS: We retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported.
RESULTS: Our case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy.
CONCLUSIONS: According to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG.

OBJECTIVE: The aim of this retrospective study was to analyze the incidence of lower urinary tract infections (LUTI) and antibiotic prescriptions within 12 months after initial prescription of anti-seizure medication (ASM) between January and December 2020 (index date) and to investigate the association between a broad spectrum of ASMs and the risk of LUTI in patients with epilepsy.
METHODS: This retrospective cohort study included a total of 9186 adult patients (≥18 years) with an initial diagnosis of epilepsy and a prescription of an ASM treated in 1284 general practices in Germany between January 2010 and December 2020 (index date). Six frequently prescribed ASMs with at least 1000 available patients were analyzed. Patients treated with one of six ASMs were matched to each other by propensity scores based on sex, age, and secondary diagnoses. Cox regression models were used to analyze the association between the use of ASM and LUTI risk.
RESULTS: The cumulative LUTI incidence 12 months after the start of therapy was highest in patients treated with pregabalin (16.7%), followed by valproate (11.6%) and gabapentin (10.2%). A similar trend was observed for LUTI with antibiotic prescription (9.2% pregabalin, 6.8% valproate, 6.8% gabapentin). Conditional regression analyses revealed that pregabalin therapy was significantly positively associated with LUTI (HR: 1.76; 95% CI 1.29-2.39) and LUTI-based antibiotic prescription (HR: 2.16; 95% CI 1.43-3.27). Carbamazepine was associated with a significantly lower incidence of LUTI in women (HR: 0.47; 95% CI: 0.30-0.75), but not in men. No significant associations were observed for other ASMs.
CONCLUSIONS: The present study identifies a significant positive association between ASM and LUTI incidence and antibiotic prescriptions in patients with epilepsy treated with pregabalin, whereas a protective effect was found for carbamazepine in women only. No significant associations were observed for the four remaining ASMs.

Background: Little is known regarding the non-inferiority of new anti-seizure medications (ASMs) in terms of replacing valproic acid (VPA) in patients with idiopathic generalized epilepsy (IGE). We hypothesized that replacement of VPA with new ASMs would offer non-inferior or better control of seizure frequency. The purpose of this study was to compare epileptic seizure frequency between the subset of patients with IGE who were on VPA and the subset of patients with IGE who replaced VPA with new ASMs. Methods: Patients with IGE who were on or had been on VPA between January 2016 and March 2022 were divided into a group that replaced VPA with new ASMs (VPA-replace group) and a group that remained on VPA (VPA-continue group). We then compared the groups in terms of seizure frequency and myoclonus. Results: Of the 606 patients on VPA between January 2016 and March 2022, 156 patients with IGE were enrolled to this study (VPA-replace group, n = 68; VPA-continue group, n = 88). The VPA-replace group included significantly more females than the VPA-continue group (p < 0.001). The VPA-replace group also showed significantly higher seizure frequency before replacement (p < 0.001), but not after replacement (p = 0.074). Patients on monotherapy displayed improved seizure frequency with new ASMs (p < 0.001). Among the new ASMs, perampanel (PER) significantly improved seizure frequency (p = 0.002). Forty-two patients in the VPA-replace group who had myoclonus achieved significant improvements (p < 0.001). Among these, patients on PER monotherapy (p < 0.001) or PER + lamotrigine (0.016) showed significantly improved myoclonus scale scores. Conclusions: This study shows the non-inferiority of new ASMs compared to VPA, with better seizure control using new ASMs in subsets of patients with IGE on monotherapy.

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.