UNASSIGNED: Recently, case reports of priapism associated with the use of some anti-seizure medications began to emerge in the literature. We aimed to investigate if there is a potential safety signal of priapism among individual anti-seizure medications and to search the literature for relevant published cases.
UNASSIGNED: We conducted a disproportionality analysis using OpenVigil 2.1 to query the United States Food and Drug Administration\'s Adverse Event Reporting System (FAERS) database. Literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science up to 12 July 2023.
UNASSIGNED: We identified positive signal of priapism for valproic acid and its derivatives (n = 23, chi-squared = 59.943, PRR = 4.566), gabapentin (n = 20, chi-squared = 9.790, PRR = 2.060), lamotrigine (n = 16, chi-squared = 8.318, PRR = 2.120), levetiracetam (n = 16, chi-squared = 10.766, PRR = 2.329), topiramate (n = 14, chi-squared = 28.067, PRR = 3.972) and carbamazepine (n = 8, chi-squared = 6.147, PRR = 2.568), as well as published cases of priapism associated with these drugs. We also found published cases of priapism for pregabalin and phenytoin in the literature and FAERS, and at least one reported adverse event of priapism in FAERS for clonazepam, lacosamide, ethosuximide, oxcarbazepine, and vigabatrin in which they were considered primary suspect.
UNASSIGNED: Our study identified signals for priapism for several anti-seizure medications, but these results need to be confirmed in well-designed pharmacoepidemiological studies.

Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such \"rational polytherapy\" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors\' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients\' clinical characteristics on a scale to identify those who may require long-or short-term use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment.

Ketogenic diet therapy (KDT) is a nonpharmacological treatment that has been demonstrated to be effective in reducing seizures in patients with drug-resistant epilepsy. As the majority of patients on KDT are also receiving anti-seizure medications (ASMs), questions about their combination often arise. KDT is typically implemented as an add-on, and not a substitute for ASMs. Drug monitoring and specific laboratory studies may be helpful in specific cases of cotherapy. Valproate, topiramate, zonisamide, and lamotrigine may be potentially problematic with KDT, but the evidence for this is not conclusive. ASM reduction is usually attempted after 1 month of KDT if a child is showing seizure reduction (but weaning ASMs does not require seizure freedom). Failure to wean an ASM does not mean KDT has failed and adding a new ASM may be beneficial in those cases after several months of KDT fine-tuning. The purpose of this review was to discuss the evidence for possible negative (or positive) pharmacodynamic interactions between KDT and ASMs. In addition, practical suggestions for the weaning or adding of ASMs in patients on KDT are provided.

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Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.

Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment, and social activities. Management of BTRE is complex due to the higher incidence of drug resistance and the potential for interaction between anti-cancer therapy and anti-seizure medications (ASMs). Neurologists, neurosurgeons, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current literature and to outline specific recommendations for the optimal treatment of BTRE, encompassing both Primary Brain Tumours (PBT) and Brain Metastases (BM). A comprehensive search of the literature since 1995 on BTRE was carried out in PubMed, MEDLINE and EMCARE. A broad search strategy was used, and the evidence evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Seizure frequency varies between 10 and 40% in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) in patients with PBT. In patients with BM, risk factors include number of BM and melanoma histology. In patients with PBT, BTRE is more common in patients with lower grade histology, frontal and temporal tumours, presence of an IDH mutation and cortical infiltration. All patients with BTRE should be treated with ASMs. Non-enzyme inducing ASMs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant. There is no proven benefit for the use of prophylactic ASMs, although there are no randomised trials testing newer agents. Surgical and oncological treatments i.e. radiotherapy and chemotherapy improve BTRE. Vagus Nerve Stimulation has been used with partial success. The review highlights the relative dearth of high-quality evidence for the management of BTRE and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for ASMs.KEY POINTSOffer levetiracetam or lamotrigine to all patients with primary or metastatic brain tumours who have seizure(s), irrespective of whether these are partial or generalised.ASM withdrawal for patients in remission is not recommended due to high rates of seizure recurrence.ASM prophylaxis is not generally recommended in the management of seizure-naïve patients.Both levetiracetam and lamotrigine are safe in pregnancy and breastfeeding.

Rare case reports describe genetic generalized epilepsy (GGE) starting de novo in people ≥50 years of age (older adults and the elderly). We aimed to provide comprehensive detail of electro-clinical findings of this extremely late-onset GGE using a retrospective, single-center cohort design and a systematic review of the literature. People with de novo seizure onset ≥50 years of age with EEG and clinical history consistent with GGE were included. These 12 individuals (9; 75% females) with a median age of 56 years at seizure onset accounted for 7.9% of 152 older adults and the elderly with generalized epilepsy. Three patients only had absence seizures. A family history of epilepsy was present in 5 individuals. They had tried a median of 2 anti-seizure medications. More than 90% (11 of 12) were seizure-free for >1 year at the last follow-up, including four requiring monotherapy. Valproate was used in only two patients and levetiracetam in 75% of them. A systematic literature review revealed six papers with 10 extreme late-onset GGE cases. They similarly had good seizure outcomes but a majority were on valproate. Our study shows that rarely, late-onset epilepsy can be GGE, which mostly has a good prognosis.

Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.

To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV.
A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively.
A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%). *Denotes only 1 study.
This systematic review characterizes the incidences of irritability, anger, and aggression with BRV, LEV, PER, and TPM, and it provides robust real-world evidence demonstrating that switching from LEV to BRV may improve BAEs. While additional data remain valuable due to differences in methodology (which make comparisons difficult), these results improve understanding of the real-world incidences of discontinuations due to these BAEs in clinical practice and can aid in discussions and treatment decision-making with PWE.