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• Most patients responded to ketamine without subsequent recurrence. • The rate of adverse effects of ketamine was low. • Super-refractory status epilepticus was associated with worse response to ketamine. • Delayed ketamine administration was associated with worse response to ketamine. • Ketamine was also effective in patients without mechanical ventilation. There is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl- d -aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. Adult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. This study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. Ketamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised. [ABSTRACT FROM AUTHOR]

• Cenobamate was effective and safe in a cohort of patients with highly refractory focal epilepsy. • The percentage of hyper-responder patients (> 90% of seizure reduction or seizure-free) was exceptionally high. • The introduction of cenobamate allowed the reduction of other concomitant ASM, particularly other sodium channel blockers, maintaining effectivity and reducing adverse events. To determine the effectiveness and safety outcomes of cenobamate in a cohort of patients with highly refractory focal epilepsy in routine clinical practice. Observational, retrospective, phase 4 study on subjects receiving cenobamate in three Spanish centers. The primary endpoint was the retention rate at the last follow-up. The main secondary endpoints were the 50%-responder and seizure-free rates at three months and the last follow-up. Other secondary endpoints were Global Clinical Impressions-Improvement (CGI-I) scores and treatment-emergent adverse events (TEAEs). Fifty-one patients with highly refractory focal epilepsy with 24.7 years of disease evolution, ten previously tried ASM, and a 23.5% of previous epilepsy surgery were included. The retention rate at the last follow-up was 80.4%. The 50% responder rate in focal seizures at three months was 56.5% (median reduction per month 51%, 0–74.6; p < 0.0001) and in focal to bilateral tonic-clonic seizures was 63.6% (median reduction per month 89%, 0–100; p = 0.022). A total of 54.3% of subjects reported a reduction in the intensity of focal seizures, and 66% manifested clinically significant satisfaction. Cenobamate allowed a significant decrease in concomitant ASM, especially sodium channel blockers. TEAEs were reported in 43.1% of individuals, 85% of whom resolved or improved, with no new safety findings. In this analysis of patients with highly refractory focal epilepsy treated with cenobamate according to standard clinical practice, there was evidence of a high reduction in both seizure frequency and intensity, with a manageable safety profile. [ABSTRACT FROM AUTHOR]

• Levetiracetam broad-spectrum and drug features led to a "one-for-all" overprescription. • Levetiracetam seems to be an optimal choice in some clinical scenarios, such as childbearing-aged and pregnant female patients with idiopathic generalized epilepsies and in Alzheimer's and down Syndrome-related epilepsies, as well as in some genetic epilepsies. • Levetiracetam is scarcely effective or even harmful in other clinical scenarios, such as in epilepsies related to malformations of cortical development, or patients with variants in PRRT2 or SV2A, as well as SCN8A with gain-of-function. Levetiracetam (LEV) is an antiseizure medication (ASM) whose mechanism of action involves the modulation of neurotransmitters release through binding to the synaptic vesicle glycoprotein 2A. It is a broad-spectrum ASM displaying favorable pharmacokinetic and tolerability profiles. Since its introduction in 1999, it has been widely prescribed, becoming the first-line treatment for numerous epilepsy syndromes and clinical scenarios. However, this might have resulted in overuse. Increasing evidence, including the recently published SANAD II trials, suggests that other ASMs are reasonable therapeutic options for generalized and focal epilepsies. Not infrequently, these ASMs show better safety and effectiveness profiles compared to LEV (partially due to the latter's well-known cognitive and behavioral adverse effects, present in up to 20% of patients). Moreover, it has been shown that the underlying etiology of epilepsy is significantly linked to ASMs response in particular scenarios, highlighting the importance of an etiology-based ASM choice. In the case of LEV, it has demonstrated an optimal effectiveness in Alzheimer's disease, Down syndrome, and PCDH19-related epilepsies whereas, in other etiologies such as malformations of cortical development, it may show negligible effects. This narrative review analyzes the current evidence related to the use of LEV for the treatment of seizures. Illustrative clinical scenarios and practical decision-making approaches are also addressed, therefore aiming to define a rational use of this ASM. [ABSTRACT FROM AUTHOR]

Purpose: There is scarce evidence of effective treatments for the chronic phase of Febrile infection-related epilepsy syndrome (FIRES). This study aimed to analyze the outcomes of treatment with anakinra and tocilizumab.Methods: Retrospective study including patients receiving either anti-interleukin-1 (anti-IL-1, anakinra) or anti-IL-6 (tocilizumab) during the chronic phase of FIRES. We evaluated seizure outcomes, non-seizure comorbidities, and adverse events. Additionally, an indirect control group including patients during the chronic phase of FIRES non-treated with-IL therapies was evaluated.Results: Five patients were included; three females. Median age at FIRES: 8 years (IQR: 6-10). Five patients received anakinra; one patient switched to tocilizumab after ineffectiveness. Median treatment duration was 9months (IQR: 7-20). While no patients became seizure-free, 20-50% reduction in seizure frequency was reported in 3/5 patients after 6 months with anakinra. Retention rate was 100% at 6 months and 40% at 12months. Three patients reported reduced seizure intensity and rescue medication needed, and better behavior/communication. Similar improvement was reported for the patient switching to tocilizumab. Patients with the best response received anti-IL a median of 9 years after acute phase. All discontinuations were due to ineffectiveness. There were none relevant adverse events apart from one patient presenting transient seizure aggravation. Nine patients were included in the control group; none of them showed relevant improvement in seizure outcomes or cognitive/behavioral comorbidities. Only one presented mild improvement in seizure frequency during the 6-months follow-up.Conclusion: This study provides promising data on effectiveness/safety of anakinra and tocilizumab in the chronic phase of FIRES. These findings warrant prospective/larger studies. [ABSTRACT FROM AUTHOR]