PURPOSE OF THE REVIEW:Perimenopause and menopause are reproductive stages marked by fluctuating and subsequent permanent loss of ovarian estrogen and progesterone production. There are important considerations in these life stages for people with epilepsy including the influence of hormonal changes and use of menopausal hormone therapy (HT) on seizure control and on antiseizure medication (ASM) metabolism. This narrative review summarizes the currently available information about this topic to increase provider awareness and identify gaps in knowledge for future research. RECENT FINDINGS:Menopause is associated with symptoms that can negatively affect quality of life, including vasomotor and genitourinary symptoms, mood and sleep disturbances, and cognitive changes. HT is the most effective treatment for menopause symptoms, but data on HT use in women with epilepsy are limited. HT may influence seizure control and the metabolism of some ASMs, such as lamotrigine. These observations and the limited available data may be a deterrent to the use of HT in women with epilepsy. SUMMARY:Data are largely lacking to guide the management of epilepsy during perimenopause and menopause. This review summarizes existing data and discusses HT and nonhormone therapies for management of menopause symptoms, highlighting unique considerations for those with epilepsy during the menopause transition.

OBJECTIVE:Capillary microsampling offers a minimally invasive alternative to venipuncture for therapeutic drug monitoring (TDM) of anti-seizure medications (ASMs). We evaluated the feasibility and reliability of volumetric absorptive microsampling (VAMS) and quantitative dried blood spot (qDBS) devices for ambulatory self-collection and at-home use in persons with epilepsy (PwE). METHODS:PwE attending the Epilepsy Centre of the IRCCS-Istituto delle Scienze Neurologiche di Bologna (Italy) were enrolled between October 2023 and October 2024. Participants performed supervised self-collection using VAMS and qDBS in ambulatory setting and at-home self-collection with VAMS devices. Sample quality, delivery success, and patient-reported outcomes (ease, pain, and clarity of instructions) were recorded. Carbamazepine, lacosamide, lamotrigine, and levetiracetam were quantified using a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Reliability was assessed by comparing at-home VAMS with ambulatory VAMS and cross-validating qDBS with VAMS and venous plasma samples using Bland-Altman analysis and linear regression. RESULTS:A total of 105 PwE (66% female, mean age 41 years) performed at-home and ambulatory self-collection using VAMS and qDBS devices. Most at-home VAMS samples (88%) were received by the laboratory within 7 days, and 86.8% met high-quality criteria. For lacosamide, lamotrigine, and levetiracetam, we found strong correlations between at-home and ambulatory VAMS (Pearson's r ranging from .88 to .98) and low mean bias (<1.0 μg/mL). Conversely, carbamazepine showed lower reliability (r = .31; p = .49; bias = 2.05 μg/mL). Cross-validation of qDBS vs plasma confirmed good agreement (slope = .92, .63-1.21) with no significant systematic bias. Patient feedback indicated that self-collection was easy and minimally painful, although age>60 years impacted sampling quality, particularly for qDBS (p = .04). SIGNIFICANCE:VAMS-based self-collection is feasible and reliable for at-home TDM, provided that high-quality sampling is ensured. qDBS represents a reliable alternative for ambulatory monitoring. Future work should focus on optimizing sampling procedures for older adults and improving logistics for home-based microsampling.

RNA sequencing (RNA-seq) provides a powerful complement to DNA sequencing for uncovering pathogenic defects affecting gene expression and splicing in individuals with genetically undiagnosed rare disorders. However, as large rare disease consortia adopt RNA-seq, challenges arise due to cohort heterogeneity, variability in tissues and sample sizes, and differences in interpretation practices. Here, we present a harmonized analytical and interpretation framework developed by the pan-European Solve-RD consortium to address these challenges. We analyzed 521 RNA-seq samples from whole blood, fibroblasts, muscle and peripheral blood mononuclear cells collected across more than 30 clinics and five European Reference Networks. Aberrant expression and splicing events were identified using OUTRIDER and FRASER 2.0 and analysed through a standardized four-level scoring framework that encompassed RNA-seq outlier reliability, phenotype relevance, variant mechanism, and segregation evidence, captured in structured reports for interpretation. Regular meetings, and collaborative Solvathon workshops were used to evaluate variant pathogenicity. This effort resulted in molecular diagnoses for 19 families out of 248 (7.7%) for whom DNA analyses had been inconclusive. Furthermore, three cases diagnosed using DNA analyses were confirmed, and 49 candidate events and five novel candidate disease genes were identified in the remaining families. Our results demonstrate the feasibility and impact of large-scale, standardized RNA-seq analysis in a transnational research setting. This framework provides a model for other international initiatives such as the Undiagnosed Diseases Network and ERDERA, paving the way for broader clinical implementation of transcriptome-based rare disease diagnostics. ### Competing Interest Statement V.A.Y., F.B., and C.M., are founders, shareholders and managing directors of OmicsDiscoveries. The other authors declare no competing interests. ### Clinical Trial NCT03491280 ### Funding Statement The SolveRD project has received funding from the European Union Horizon 2020 research and innovation programme under grant agreement No 779257. SolveRD research is supported (not financially) by ERN ITHACA (project ID no. 101085231), ERN RND (project ID no. 101155994), ERN EURO NMD (project ID no. 101156434), ERN EpiCARE (project ID 101156811), and ERN RITA (project ID 101155878). All ERNs are cofunded by the European Union within the framework of the Third Health Programme. ERDERA has received funding from the European Union Horizon Europe research and innovation programme under grant agreement 101156595. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or any other granting authority, who cannot be held responsible for them. VAY, RL, CM and JG were supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) via the project NFDI 1/1 GHGA German Human Genome Phenome Archive(441914366). The TUM IT infrastructure was cofunded via the Deutsche Forschungsgemeinschaft (German Research Foundation, project ID 461264291). BEA was supported by the predoctoral program Joan Oro of the Secretary of Universities and Research of the Department of Research and Universities of the Government of Catalonia with codes 2024 FI1 00075 and 2025 FI2 00075, cofinanced by the European Union. HM was supported by the Wellcome Trust grant 220906/Z/20/Z and UCL Global Engagement Fund scheme (2022/23 GEF project). HL receives support from the Canadian Institutes of Health Research (CIHR) for Foundation Grant FDN167281 (Precision Health for Neuromuscular Diseases), Transnational Team Grant ERT 174211 (ProDGNE) and Network Grant OR2 189333 (NMD4C), from the Canada Foundation for Innovation (CFI JELF 38412), the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950 232279), the European Commission (101080249) and the Canada Research Coordinating Committee New Frontiers in Research Fund (NFRFG 2022 00033) for SIMPATHIC, and from the Government of Canada First Research Excellence Fund (CFREF) for the Brain-Heart Interconnectome (CFREF 2022 00007). KP is a recipient of a Canadian Institutes of Health Research (CIHR) postdoctoral fellowship award under award no: MFE 491707. JP was supported by the Else Kroener Fresenius Stiftung Clinician Scientist program precise.net and by the intramural TUFF program (3049 0 0). AP has received funding from the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia (2021SGR00899), and the Instituto de Salud Carlos III (ISCIII) (FIS PI23/00835) Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, una manera de hacer Europa. ASC was supported by the grants FPU20/06692 and EST23/00463 from Ministerio de Universidades, Spain. AH was supported by a ZonMW (The Netherlands Organization for Health Research and Development) Vici grant (No. 09150182310053). KL receives support from the German Research Foundation (DFG, LO1555/10 1). DNdB was supported by Instituto de Salud Carlos III (Grant CP22/00141). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of University Hospital of Tuebingen gave ethical approval for this work (ClinicalTrials.gov ID: [NCT03491280][1], https://clinicaltrials.gov/study/[NCT03491280][1]). Informed consent for data sharing, including indirect identifiers within Europe for research, was obtained from all recruited individuals. All data submitters confirmed the code of conduct of RD-connect GPAP. This study adheres to the principles set out in the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Raw data will be available at the European Genome-Phenome Archive (https://ega-archive.org/datasets/) under the Solve-RD study EGAS00001003851, and can be accessed following approval from the Solve-RD Data Access Committee. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03491280&atom=%2Fmedrxiv%2Fearly%2F2026%2F02%2F14%2F2026.02.10.26345954.atom

Seizure clusters (SCs) are an acute and transient increase in seizure frequency relative to an individual patient’s baseline and are associated with an increased risk of injury, morbidity, and potentially mortality if not promptly and adequately treated. Despite their clinical importance, the management of SCs remains highly heterogeneous, primarily due to the absence of a universally accepted definition, which is determined also by the wide variability in seizure semiology and baseline individual burden;, as well as by differences in care settings. Outpatient treatment relies largely on caregivers’ ability to recognize SCs and administer rescue medication, whereas inpatient management may also involve invasive routes of administration. We conducted a literature review identifying 32 original articles addressing the treatment of SCs. The analysis focused on definitions, efficacy outcomes, and adverse events across three clinical scenarios: outpatient, Emergency Department (EDs) and Epilepsy Monitoring Units. The results show that in the outpatient setting, the available evidence suggests that diazepam nasal spray (DZP-NS), midazolam nasal spray (MDZ-NS), and oral lorazepam (LZP) solution may demonstrate comparable efficacy and safety. However, comparisons are limited by heterogeneity in studies’ designs, patient populations and outcome definitions, as well as by the absence of head-to-head trials. Moreover, geographic differences in drug availability (e.g., USA vs. Europe) limit the development of universally applicable treatment protocols. Consequently, the off-label use of oral benzodiazepines, including clobazam, clonazepam, and lorazepam, remains common when oral therapy is feasible, despite limited evidence. The implementation of a patient-specific Acute Seizure Action Plan (ASAP) incorporating an individualized SC definition is recommended. In contrast, inpatient management shows greater consensus, largely reflecting first-line treatment paradigms for status epilepticus. These include prompt intravenous benzodiazepine administration, followed by the intravenous loading of antiseizure medications such as brivaracetam or lacosamide in cases of seizure recurrence. In ED settings, “empirical” definitions of SCs (i.e., more than three seizures within 24 h) may facilitate timely intervention.

In a clinical setting, exome sequencing (ES) with copy number variant (CNV) analysis is currently the most effective approach for developmental and epileptic encephalopathies (DEE). However, trio-based ES is often not feasible in adults, its costs remain prohibitive in certain health care settings, and computational tools for CNV calling still lack sufficient accuracy. Chromosomal microarray (CMA) is indicated as a first-tier test for CNV detection in patients with DEE, dysmorphisms, and comorbidities. We investigate the role of CNVs in the etiology of DEE in an adult cohort, to define the most appropriate diagnostic approach in this population. A total of 219 patients (male/female: 104/115) with undiagnosed DEE underwent array-based comparative genomic hybridization/single nucleotide polymorphism arrays as adults. Causative CNVs were identified in 18 patients (8.2%); 14 were deletions (mean size ≈ 2.96 Mb), and four were duplications/triplications (mean size ≈ 3.63 Mb). Thirteen were responsible for known deletion/microduplication syndromes, and four were deletions involving haploinsufficient genes associated with epilepsy/neurodevelopmental disorders. For one deletion, population evidence, reports with overlapping deletions, and clinical databases support a likely pathogenic role. The mean age at CMA diagnosis was 32.4 ± 13 years. An additional 46 patients (21%) then received a molecular diagnosis through alternative approaches. Despite a diagnostic delay of 24.2 ± 14.5 years, CMA enabled a genetic diagnosis in 8.2% of our adult DEE patients, especially in those with dysmorphisms. The diagnostic yield rises to 10.4% when excluding patients diagnosed using other methods. A total of 66.7% of solved cases had direct implications from the diagnosis, supporting the clinical utility of CNV analysis inclusion in the diagnostic workflow for adult patients with DEE.

To evaluate the long-term efficacy of vagus nerve stimulation (VNS) in reducing tonic-clonic seizures (TCS), drop attacks, and seizure clusters in adults with drug-resistant epilepsy (DRE). This retrospective, single-center study included adults with DRE who received VNS and had ≥ 12 months of follow-up. Data were collected pre-implantation (T0), at 12 months (T1), and last follow-up (T2). Outcomes included reduction in total seizure frequency and severity, frequency of TCS and drop attacks, and frequency/duration of seizure clusters. Battery replacement and tolerability were also assessed. Eighty-seven subjects (51 males, median age 33 at T0) with a mean follow-up of 8 years were analyzed. At T2, 54

BackgroundEpilepsy significantly impacts on morbidity and mortality. Understanding hospitalization and mortality risks in persons with epilepsy (PWE) is essential for improving healthcare strategies. We aimed to investigate the risk and causes of hospitalization and mortality in PWE compared to a matched general population cohort.MethodsThe EpiLink Bologna historical cohort study analyzed adult PWE in the period 2018-2019. A general population control cohort was used for comparison. Clinical data were linked with health administrative data. PWE were grouped into persons with focal epilepsy, idiopathic generalized epilepsy, and developmental and/or epileptic encephalopathy (PDEE). The primary outcome was the hospitalization rate. Emergency department (ED) visit rate and the risk of death for any cause were also assessed.ResultsThe study included 1438 PWE and 14,096 controls. PWE had higher incidence rate ratio (IRR) for ED visit (IRR 1.26, 95% CI 1.20-1.32), hospital admission (IRR 2.05, 95% CI 1.83-2.29), and death (IRR 1.5, 95% CI 1.1-2.2) compared to control cohort. The highest hospitalization risk was in the PDEE group (IRR 4.70; 95% CI 3.28-6.74). The increased hospitalization rate among PWE was due to both their higher ED visit and elective hospital admission rates. PWE on polytherapy were at higher risk of hospitalization for inflammation of jaw, acid-base/electrolyte imbalances, chronic cerebrovascular disease, major traumas and infections.ConclusionsDuring a 2-year-period, PWE in Bologna had a doubled risk of hospitalization and 50% higher risk of death compared to a matched general population cohort. Hospitalization risks varied significantly by epilepsy type and antiseizure therapy.

OBJECTIVES:Epileptic seizures can present with various clinical manifestations, often resembling other conditions-referred to as "imitators of epileptic seizures"-making differential diagnosis challenging. Among them, psychogenic non-epileptic seizures (PNES) or functional/dissociative seizures (FDS) are particularly prevalent in females. This study aimed to evaluate the ability of various non-epileptologist physicians to distinguish epileptic seizures from imitators by viewing video recordings of several paroxysmal events. We also assessed whether variables, such as medical specialty and years of professional experience, could impact diagnostic accuracy. MATERIALS AND METHODS:Ten video recordings of authorized informational material were presented to non-epileptologist physicians. Five videos depicted non-epileptic events, including syncope, hyperkinetic movement disorder episodes, cataplexy, PNES/FDS, and REM behavior disorder. The remaining videos featured focal and generalized seizures. Participants completed an anonymous questionnaire to classify each event as epileptic or non-epileptic. RESULTS:Seventy specialists (44 men, 26 women) from psychiatry (12.9%), internal medicine (12.9%), neurosurgery (14.3%), neurology (14.3%), emergency (18.6%), anesthesiology. (18.6 %) and others (7.1 %) were enrolled. The mean age was 49.9 ± 8.7 years; years of work experience were 0-20 years for 53 % and 21-40 years for 47 %. Epileptic seizures were correctly. recognized in 50.3% of cases, whereas non-epileptic paroxysmal events were. misdiagnosed in 49.7% of cases. The most accurately recognized event was tonic-clonic seizure (88.6%), while the most frequently misdiagnosed was PNES/FDS (94.3%). DISCUSSION AND CONCLUSION:Correctly diagnosing epileptic and non-epileptic paroxysmal events can be challenging when relying solely on video recordings. This study highlights the importance of implementing training for adequate diagnosis and subsequent correct management of these conditions.

OBJECTIVE:This study aimed to identify prescribing behaviors in women of childbearing potential (WOCP) with epilepsy already taking valproate (VPA), and to investigate the relationship between VPA maintenance, substitution, reduction, or withdrawal as part of polytherapy, and seizure worsening or relapse. METHODS:We retrospectively reviewed the prescription behaviors and seizure outcomes in WOCP (16-50 years of age) with epilepsy, referred to eight Italian epilepsy centers, who were taking VPA for at least 1 year between 2014 and 2019. RESULTS:Among 750 women (~12% of all WOCP), 528 (70.4%) maintained VPA unchanged throughout the observation period, 103 (13.7%) replaced VPA with another antiseizure medication (ASM), 90 (12%) reduced VPA, and 29 (3.9%) discontinued VPA in polytherapy. Focal epilepsy was most strongly associated with VPA withdrawal (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.38-6.38), whereas generalized epilepsy was most associated with its non-withdrawal (reduction/switch/maintenance) (OR .31, 95% CI .14-.68). Intellectual disability, higher seizure frequency, and higher VPA doses were linked to VPA continuation. VPA withdrawal from polytherapy was associated with a higher risk of tonic-clonic seizure worsening (OR 2.91, 95% CI 1.09-7.77) compared to non-withdrawal. SIGNIFICANCE:VPA was rarely withdrawn or substituted in WOCP with epilepsy, in secondary and tertiary care settings following European regulatory restrictions. This likely reflects a population with severe epilepsies where VPA is difficult to replace; whereas women with milder epilepsies likely discontinued VPA earlier, as evidenced by its low overall prescription frequency. Withdrawal of VPA from a polytherapy regimen was associated with a threefold increased risk of seizure exacerbation.

IMPORTANCE: Women with idiopathic generalized epilepsy (IGE) face challenges in treatment due to limited options that are both effective and safe. OBJECTIVE: To evaluate the effectiveness and safety of substitution monotherapy vs add-on therapy as second-line options for women who might become pregnant with IGE after failure of first-line antiseizure medications (ASMs) other than valproic acid. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective comparative effectiveness cohort study at 18 primary, secondary, and tertiary adult and children epilepsy centers across 4 countries, analyzing data from 1995 to 2023. Participants were women aged 10 to 50 years diagnosed with IGE who were prescribed a second line of ASM. MAIN OUTCOMES AND MEASURES: Treatment failure (TF), defined as the replacement or addition of a second ASM due to ineffectiveness, was compared between patients receiving ASM add-on or substitution monotherapy using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression. Exploratory analyses were also conducted to assess the effectiveness of individual ASMs and various ASM combinations. RESULTS: This study included 249 women with a median (IQR) age of 18.0 (15.5-22.0) years. Among them, 146 (58.6%) received an add-on regimen, and 103 (41.4%) received substitution monotherapy. During follow-up, TF occurred in 48 patients (32.9%) receiving add-on therapy and 36 (35.0%) using substitution monotherapy, with no significant differences between groups (IPTW-adjusted hazard ratio [HR], 0.89; 95% CI, 0.53-1.51; P = .69). ASM discontinuation due to ineffectiveness or adverse effects occurred in 36 patients (24.7%) receiving add-on therapy and 29 (28.2%) receiving substitution monotherapy, showing no significant differences (IPTW-adjusted HR, 0.97; 95% CI, 0.57-1.65; P = .92). Rates of ASM discontinuation due to adverse effects only were low in both groups, occurring in 13 patients (9.0%) receiving add-on therapy and 9 (8.7%) receiving a substitution monotherapy. Among add-on regimens other than valproic acid, the combination of levetiracetam and lamotrigine demonstrated a lower risk of TF compared with other combinations with levetiracetam plus other ASM (adjusted HR, 2.41; 95% CI, 1.12-5.17; P = .02) and lamotrigine plus other ASM (adjusted HR, 4.03; 95% CI, 1.73-9.39; P = .001). However, valproic acid remained the most effective second-line ASM when considering individual agents. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of second-line treatment strategies for women with IGE, no significant differences were observed between substitution monotherapy and add-on therapy.

BACKGROUND:Therapeutic drug monitoring (TDM) of Antiseizure Medications (ASMs) is an essential tool for persons with epilepsy (PwE). Compared to traditional venipuncture, microsampling requires lower blood volume through less painful and invasive fingerprick offering a sampling methodology potentially performed at-home. This study aimed to validate the extraction method of ASMs from Capitainer®-qDBS microsampling. Five ASMs were considered. According to EMA guidelines, through technical and clinical validation, ASMs' quantification from qDBS device was performed by UHPLC-MS/MS. Extraction parameters were optimized by Design of Experiment. Clinical validation was performed to compare ASMs concentrations in Capitainer®-qDBS with those in plasma in 30 PwE. RESULTS:The method used in the chosen extraction procedure was proven to be accurate and precise. Intra and inter-assay reproducibility analyses showed accuracy and precision ≤15 % across the calibration range. Recovery was >75 %, and matrix effect >75 %, for most of the ASMs analyzed. Stability was tested at 7, 15, and 30 days of storage, showing mutual robustness at 30 days at room temperature. No hematocrit effect was observed over a range of 20-70 %. Linear regression and Bland-Altman analysis indicated a good correlation for the ASMs considered. SIGNIFICANCE:A UHPLC-MS/MS assay was developed and validated according to EMA guidelines for quantifying ASMs from qDBS devices. This validation has the advantage of allowing the potential to utilize the new microsampling qDBS device, providing a patient-friendly approach to blood sampling eventually even at-home.

OBJECTIVES:To understand the extent to which women of childbearing age (WoCBA) are aware of the issues associated with epilepsy and pregnancy and identify unmet reproductive healthcare and information needs. METHODS:WoCBA with epilepsy completed a 34-question online survey (January to March 2021), including sections on demographics, clinical information, and access to reproductive health care. The survey was available in English, Croatian, Czech, Georgian, German, Italian, Polish, Russian and Spanish. RESULTS:Overall, 865 responses were received and included in the analysis. Most respondents were aged 20-39 years (77.0 %), were married (43.6 %) and 63.2 % had been diagnosed with epilepsy for more than 10 years. Over half of respondents (53.9 %) had previously been pregnant, with 75.5 % reporting that they took anti-seizure medication (ASMs) during pregnancy. Most (67.6 %) respondents had received information about epilepsy and pregnancy with 43.4 % of respondents receiving this information before their first pregnancy. Although 71.5 % found the information 'very helpful' or 'somewhat helpful', some respondents found the information frightening, confusing, or difficult to access. Most respondents (74.1 %) had been made aware of the risks of taking some ASMs while pregnant; 59.8 % had been advised to consider pregnancy planning, however, 52.7 % were not provided with information on contraception while taking ASMs. Over half (56.9 %) of respondents felt that clear and concise information was not available for women with epilepsy who were considering becoming pregnant. CONCLUSIONS:There is a need to improve education and support for WoCBA with epilepsy to help them with decision-making, planning and managing pregnancy.

Objectives:To describe the occurrence of secondary sclerosing cholangitis in critically ill patients (SC-CIP) with febrile infection-related epilepsy syndrome (FIRES). Methods:Monocentric retrospective analysis of all adult patients with FIRES admitted from January 2020 to December 2024. Results:Four patients (3 males) with a mean age of 24 years (range: 18-40 years) and no significant medical history presented with cryptogenic FIRES. They required treatment with antiseizure medications (mean: 9; range: 8-10), anesthetics (propofol, midazolam and ketamine in all cases), and immunotherapies. The average duration of status epilepticus (SE) was 57 days (range: 34-90 days), while the mean duration of intensive care unit (ICU) stay was 82 days (range: 58-117 days). All patients developed cholestatic liver disease during their ICU stay, reversible in one case. In the three cases with persistent injury (75%), SC-CIP was diagnosed with MR-colangiography after a mean of 106 days from SE onset. Discussion:The high incidence of SC-CIP in our cohort of patients with FIRES suggests a link between these two rare conditions, likely related to prolonged intensive care, hyperinflammation and polytherapy, including ketamine use. Vigilant monitoring of liver disease progression in critically ill patients with FIRES and similar predisposing factors may allow early recognition of SC-CIP and improved patient outcomes.

As a part of a wider project aimed to assess sex-related differences in adverse effects and efficacy of antiseizure medications (ASMs), we performed a systematic review focusing on differences in response to ASMs between males and females with epilepsy. We conducted a comprehensive literature search in the PubMed database. The search was conducted without restriction on publication date, and all results up to September 2022 were included. We included all the articles written in English, Italian, Spanish, or French language evaluating the response to ASMs in people with epilepsy (PWE), with specific mention of the two sexes. The Newcastle–Ottawa Scale and the Jadad Scale were used to assess study quality. A total of 1778 studies were identified. Of these, 60 studies searched for sex differences and among those, 46 (76

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and real-life feasibility of patient self-collected capillary VAMS for TDM of antiseizure medication (ASMs), using plasma ASMs concentrations from venous blood as a reference standard. Nurses collected venous and capillary blood samples using VAMS. Afterward, persons with epilepsy (PWE) performed VAMS sampling by themselves. All samples were analyzed by UHPLC-MS/MS. We performed a cross-validation study, comparing ASMs concentrations obtained by VAMS nurses and patients' self-collected versus plasma through Bland-Altman analysis and Passing-Bablok regression. We enrolled 301 PWE (M: F 42.5%:57.5%; mean age 44±16 years), treated with 13 ASMs, providing a total of 464 measurements. Statistical analysis comparing VAMS self-collected versus plasma ASMs concentrations showed a bias close to zero and slope and intercept values indicating a good agreement for CBZ, LCS, LEV, LTG, OXC, PB, and PHT, while a systematic difference between the two methods was found for VPA, PMP, TPM and ZNS. This is the first study showing the reliability and feasibility of the real-world application of PWE self-collected VAMS for most of the ASMs considered, giving a promising basis for at-home VAMS applications.