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IntroductionMechanisms underlying sudden unexpected death in epilepsy (SUDEP) are unclear, but autonomic disorders are thought to play a critical role. However, those dysfunctions have mainly been reported in the peri-ictal context of generalized tonic–clonic seizures. Here, we explored whether heart rate variability (HRV), heart rate (HR), and breathing rate (BR) changes could be observed perictally during focal seizures with or without impaired awareness as well as interictally to assess the risk of SUDEP. We report the case of a 33-year-old patient with drug-resistant bilateral temporal lobe epilepsy who died at home probably from an unwitnessed nocturnal seizure (“probable SUDEP”).MethodsIctal and interictal HRV as well as postictal cardiorespiratory analyses were conducted to assess autonomic functions and overall SUDEP risk. The SUDEP patient was compared to two living male patients from our local database matched for age, sex, and location of the epileptic focus.ResultsInterictal HRV analysis showed that all sleep HRV parameters and most awake HRV parameters of the SUDEP patient were significantly lower than those of our two control subjects with bitemporal lobe epilepsy without SUDEP (p < 0.01). In two focal with impaired awareness seizures (FIAS) of the SUDEP patient, increased postictal mean HR and reduced preictal mean high frequency signals (HF), known markers of increased seizure severity in convulsive seizures, were seen postictally. Furthermore, important autonomic instability and hypersensitivity were seen through fluctuations in LF/HF ratio following two seizures of the SUDEP patient, with a rapid transition between sympathetic and parasympathetic activity. In addition, a combination of severe hypopnea (202 s) and bradycardia (10 s), illustrating autonomic dysfunction, was found after one of the SUDEP patient’s FIAS.DiscussionThe unusual cardiorespiratory and HRV patterns found in this case indicated autonomic abnormalities that were possibly predictive of an increased risk of SUDEP. It will be interesting to perform similar analyses in other SUDEP cases to see whether our findings are anecdotal or instead suggestive of reliable biomarkers of high SUDEP risk in focal epilepsy, in particular focal with or without impaired awareness seizures.

Summary: The World Health Assembly approved the Intersectoral Global Action Plan for epilepsy and neurological disorders. Member states, including those in Southeast Asia, must now prepare to achieve IGAP's strategic targets by embracing novel approaches and strengthening existing policies and practices. We propose and present evidence to support four such processes. The opening course should engage all stakeholders to develop people-centric instead of outcome-centric approaches. Rather than caring for convulsive epilepsy alone, as currently done, primary care providers should also be skilled in diagnosing and treating focal and non-motor seizures. This could reduce the diagnostic gap as over half of epilepsies present with focal seizures. Currently, primary care providers lack knowledge and skills to manage focal seizures. Technology-enabled aids can help overcome this limitation. Lastly, there is need to add newer “easy to use” epilepsy medicines to Essential Medicines lists in light of emerging evidence for better tolerability, safety and user-friendliness.

Introduction: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods: BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1–2 (early add-on) and ≥ 3 (late add-on) prior antiseizure medications. Results: A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100–200) mg in the early add-on group and 200 (100–200) in the late add-on group (p < 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p < 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p < 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion: Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Eslicarbazepine acetate (ESL) is a once‐daily (QD), oral anti‐seizure medication for the treatment of focal (partial‐onset) seizures. Here, we evaluate risk factors for the development of psychiatric treatment‐emergent adverse events (TEAEs) in clinical trials of adjunctive ESL in adults with focal seizures. Methods: This post‐hoc analysis evaluated data pooled from three Phase III, randomized, double‐blind, placebo‐controlled trials (BIA‐2093‐301, ‐302, ‐304). After an 8‐week baseline period, patients were randomized equally to receive placebo, ESL 400 mg (not reported here), 800 mg, or 1200 mg QD (up to 2‐week titration; 12‐week maintenance; optional open‐label extension [OLE]). Incidences of psychiatric TEAEs were evaluated according to three separate criteria: medical history of psychiatric disorders (yes/no); baseline use of psychotropic drugs (yes/no); Montgomery–Åsberg Depression Rating Scale (MADRS) score at baseline (0–6: normal; 7–19: mild depression; 20–34: moderate depression). Results: The analysis populations comprised 1251 patients for the controlled study period and 1137 patients for the 1‐year OLE. Psychiatric TEAE incidence was similar between patients taking ESL and placebo in the controlled and OLE study periods and was not related to ESL dose. Psychiatric TEAEs generally occurred more frequently in patients with a medical history of psychiatric disorders, using psychotropic drugs, or with depressive symptoms than in those without a history, not using psychotropic drugs, or with no depressive symptoms. Depression and anxiety were the most frequently reported psychiatric TEAEs. Significance: Overall, in clinical trials of ESL in adults with focal seizures, incidences of psychiatric events were not statistically different between patients taking ESL and placebo, were not related to ESL dose, and generally occurred more frequently in patients with baseline psychiatric symptoms or a history of psychiatric disorders. Long‐term exposure to ESL was not associated with a marked increase in the incidence of psychiatric TEAEs. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetic striatopathy is a rare neurological manifestation of nonketotic hyperglycemia that presents with contralateral hemichorea-hemiballismus. Presentation with concurrent seizures is rarely reported. Clinical presentation We report a case of diabetic striatopathy presenting with focal and generalized tonic-clonic seizures (GTCS) with right hemichorea-hemiballismus induced by a ketotic hyperglycemic state. Head MRI showed high T1-weighted signal intensity in the left lentiform nucleus with no significant diffusion restriction or postcontrast enhancement. The patient’s condition gradually improved, with seizure control on AEDs. Hemichorea-hemiballismus significantly improved with adequate blood sugar control and resolved with low-dose haloperidol. Conclusions Diabetic striatopathy presenting with hemichorea-hemiballismus and concurrent GTCS has been reported previously in two cases; however, it has never been reported in ketotic hyperglycemia. To the best of our knowledge, we herein report the first case report of focal and generalized seizures in a ketotic hyperglycemic state and mesial temporal sclerosis.

• An ECG wearable helps investigate cardiorespiratory disturbances in FIA seizures. • Ictal tachycardia and bradypnea characterize FIA seizures. • We proposed new methods to study HRV and RSA. • FIA seizures have decreased RSA before the electroclinical seizure onset. • No differences in HRV and RSA occurred between temporal and extratemporal seizures. Seizures are characterized by periictal autonomic changes. Wearable devices could help improve our understanding of these phenomena through long-term monitoring. In this study, we used wearable electrocardiogram (ECG) data to evaluate differences between temporal and extratemporal focal impaired awareness (FIA) seizures monitored in the hospital and at home. We assessed periictal heart rate, respiratory rate, heart rate variability (HRV), and respiratory sinus arrhythmia (RSA). We extracted ECG signals across three time points — five minutes baseline and preictal, ten minutes postictal — and the seizure duration. After automatic Rpeak selection, we calculated the heart rate and estimated the respiratory rate using the ECG-derived respiration methodology. HRV was calculated in both time and frequency domains. To evaluate the influence of other modulators on the HRV after removing the respiratory influences, we recalculated the residual power in the high-frequency (HF) and low-frequency (LF) bands using orthogonal subspace projections. Finally, 5-minute and 30-second (ultra-short) ECG segments were used to calculate RSA using three different methods. Seizures from temporal and extratemporal origins were compared using mixed-effects models and estimated marginal means. The mean preictal heart rate was 69.95 bpm (95 % CI 65.6 – 74.3), and it increased to 82 bpm, 95 % CI (77.51 – 86.47) and 84.11 bpm, 95 % CI (76.9 – 89.5) during the ictal and postictal periods. Preictal, ictal and postictal respiratory rates were 16.1 (95 % CI 15.2 – 17.1), 14.8 (95 % CI 13.4 – 16.2) and 15.1 (95 % CI 14 – 16.2), showing not statistically significant bradypnea. HRV analysis found a higher baseline power in the LF band, which was still significantly higher after removing the respiratory influences. Postictally, we found decreased power in the HF band and the respiratory influences in both frequency bands. The RSA analysis with the new methods confirmed the lower cardiorespiratory interaction during the postictal period. Additionally, using ultra-short ECG segments, we found that RSA decreases before the electroclinical seizure onset. No differences were observed in the studied parameters between temporal and extratemporal seizures. We found significant increases in the ictal and postictal heart rates and lower respiratory rates. Isolating the respiratory influences on the HRV showed a postictal reduction of respiratory modulations on both LF and HF bands, suggesting a central role of respiratory influences in the periictal HRV, unlike the baseline measurements. We found a reduced cardiorespiratory interaction during the periictal period using other RSA methods, suggesting a blockade in vagal efferences before the electroclinical onset. These findings highlight the importance of respiratory influences in cardiac dynamics during seizures and emphasize the need to longitudinally assess HRV and RSA to gain insights into long-term autonomic dysregulation. [ABSTRACT FROM AUTHOR]

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare syndrome characterized with specific clinical and radiological findings due to involvement of the developing brain with cerebral hemiatrophy of one hemisphere. The syndrome was first described from Dyke, Davidoff and Masson in 1933 in a series of nine patients. Syndrome has two forms, congenital and acquired forms and etiological factors vary due to involvement of the brain. Most common clinical symptom are focal or secondary generalized seizures. Hemiparesis, facial asymmetry, intellectual disability, mental retardation, and hemihypertrophy also seen in clinical process. In magnetic resonance imaging (MRI) DDMS has unique radiological findings. Seizures are commonly refractory to treatment and aim of the treatment is to control seizures and improve mental and intellectual capabilities. Prognosis is good when clinical findings occur after two years old.

Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs. This review summarizes the mechanism of action, efficacy, and safety of Cenobamate. The authors provide their expert opinions on the use of this drug. The aim of this paper is to report on the Italian preliminary experience with the use of cenobamate, focusing on treatment goals, optimal dosing and titration schedules, strategies to minimize adverse effects, and identification of suitable candidates for treatment. There was agreement that slow titration may improve tolerability, and that clinically significant benefit can be achieved in many patients at relatively low doses. A favorable response to relatively low doses of cenobamate could be an early predictor of ultimate responsiveness. Overall, cenobamate is a welcome new treatment for adults with focal seizures resistant to conventional ASMs. [ABSTRACT FROM AUTHOR]

Seizures are not common in cases with chronic liver disease. Overall seizures have been reported in 20-30% of cases in chronic liver disease associated with hepatic encephalopathy. We report two cases of chronic liver disease patients who presented with new-onset refractory focal status epilepticus (SE). Both patients had encephalitis and seizures which responded only when acyclovir was added to the treatment with antiepileptic medication. Herpes encephalitis should be considered as a possible diagnosis in new-onset focal seizures or focal SE in patients with chronic liver disease with or without hepatic encephalopathy, pending further investigations. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to propose a diagnostic algorithm for autoimmune epilepsy in a retrospective cohort and investigate its clinical utility. Methods: We reviewed 60 patients with focal epilepsy with a suspected autoimmune etiology according to board-certified neurologists and epileptologists. To assess the involvement of the autoimmune etiology, we used the patients' sera or cerebrospinal fluid (CSF) samples to screen for antineuronal antibodies using rat brain immunohistochemistry. Positive samples were analyzed for known antineuronal antibodies. The algorithm applied to assess the data of all patients consisted of two steps: evaluation of clinical features suggesting autoimmune epilepsy and evaluation using laboratory and imaging findings (abnormal CSF findings, hypermetabolism on fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging abnormalities, and bilateral epileptiform discharges on electroencephalography). Patients were screened during the first step and classified into five groups according to the number of abnormal laboratory findings. The significant cutoff point of the algorithm was assessed using a receiver-operating characteristic curve analysis. Results: Fourteen of the 60 patients (23.3%) were seropositive for antineuronal antibodies using rat brain immunohistochemistry. Ten patients had antibodies related to autoimmune epilepsy/encephalitis. The cutoff analysis of the number of abnormal laboratory and imaging findings showed that the best cutoff point was two abnormal findings, which yielded a sensitivity of 78.6%, a specificity of 76.1%, and an area under the curve of 0.81. Conclusion: The proposed algorithm could help predict the underlying autoimmune etiology of epilepsy before antineuronal antibody test results are available. [ABSTRACT FROM AUTHOR]

This post-hoc analysis of the PERMIT Extension study compared the effectiveness and safety/tolerability of perampanel (PER) between Asian and non-Asian participants. Retention rates, adverse events (AEs), seizure frequency, responder rate (≥50% seizure frequency reduction), and seizure freedom rate (no seizures since at least the prior visit) were assessed. Retention was assessed after 3, 6 and 12 months. Effectiveness assessments were evaluated at 3, 6 and 12 months and the last visit by seizure type (total, focal and generalised). PERMIT Extension included 730 Asian and 1662 non-Asian individuals. Significant differences in demographic/baseline characteristics were reported for the Asian versus non-Asian subgroups including higher median age at epilepsy onset, longer median duration of epilepsy, higher mean number of previous and concomitant ASMs and lower mean monthly seizure frequency (total, focal and generalised). Retention rates were similar between the two subgroups at 3 and 12 months, but significantly lower in the Asian versus non-Asian subgroup at 6 months (65.6% vs. 71.8%; p = 0.004). At last visit, seizure freedom rate was significantly higher in the Asian versus non-Asian for total (35.9% vs. 25.4%; p = 0.001) and focal seizures (32.4% vs. 18.9%; p = 0.001) as was responder rate for both total (63.9% vs. 52.3%; p = 0.001) and focal seizures (62.2% vs. 44.7%; p < 0.001). Seizure freedom and responder rates for generalised seizures were similar between the two subgroups at the last visit. Rates of AEs were similar between the two subgroups (Asian, 47.6%; non-Asian, 45.4%). PER was effective and generally well-tolerated in Asian and non-Asian individuals., Competing Interests: Declaration of competing interest TA has received consultancy fees, speaker fees, and research grants from Novartis, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, Hikma and AbbVie. KK has received consultant fees and speaker fees from Eisai, UCB Japan and Daiichi-Sankyo. AD is an employee of Eisai Singapore Pte. Ltd. SC is an employee of Eisai, Inc. VV has participated in advisory boards and symposia organised by Angelini, Bial, Biocodex, Eisai Inc., Jazz Pharmaceuticals, Novartis, Takeda, UCB and Xenon. DWK, HG, YC and TW have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To investigate the effects of vagus nerve stimulation (VNS) on the seizure frequency in patients with drug-resistant epilepsy (DRE) and bilateral temporal lobe epilepsy (bi-TLE). Additionally, we aimed to determine the safety of VNS and its side effects., Methods: Our retrospective study included 17 patients with bi-TLE who underwent VNS-device implantation at our center from 1997 to 2019. The main outcome was a reduction in seizure frequency. Bitemporal cases were confirmed using scalp electroencephalography (EEG) or invasive electroencephalography (iEEG)., Results: The median age at seizure onset was 18 years. Bi-TLE was confirmed by scalp EEG in 47 % and by iEEG in 53 % of the patients. The median follow-up period was 36 months. The median seizure frequency per month before and after VNS was 9.5 (IQR = 4.3-35.3) and 2 (IQR = 0.8-4.2), respectively. Compared to baseline, 70.5 % of the patients achieved ≥ 50 % reduction in seizure frequency, whereas 35.3 % experienced either no or minimal reduction in seizure frequency. The response rate (>50 % reduction in seizure frequency) was 87.5 % in patients who underwent scalp EEG and 55.5 % in those who underwent iEEG. For VNS treatment, the median follow-up was at 36 months (IQR = 17-46.5). Adverse effects were observed in 59 % of the patients, including cough and hoarseness., Discussion: Therapeutic choices are limited in cases of drug-resistant bi-TLE. Our study on VNS-device implantation in bi-TLE suggests a positive outcome., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JGB holds the Jack Cowin Chair in Epilepsy Research at Western University and received funding for education from Eisai and Sunovion. The remaining authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Focal seizures (FS) have previously been described before or after infantile spasm (IS) clusters, but FS occurring simultaneously with an IS cluster has been rarely reported in the EEG literature. We present three cases where focal seizures (FS) occurred concurrently during an infantile spasm (IS) cluster on VEEG. On VEEG, onset of IS cluster preceded FS in all three patients; however, patient three was diagnosed with FS prior to the onset of IS. FS duration ranged from 10-90 s and was electrographic-only in two out of the three patients. Unfortunately, the first two patients are now deceased, and for patient two no etiology was ever identified. Currently, patient three is free of spasms as well as seizures but has global developmental delay; no definite etiology has been identified for their presentation. Concurrent FS with IS suggests that the seizure types may be generated in different brain areas with one seizure type potentially triggering the other and is generally reflective of multifocal or diffuse cerebral disease with a poor prognosis as was seen in at least two of our patients. Our three cases of IS where FS occurred concurrently contribute to the limited existing data describing this phenomenon on VEEG., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We report two cases of temporo-perisylvian epilepsy with habitual seizures consistently inducible by hyperventilation (HV). One case was non-lesional, while the other was a lesional temporo-perisylvian epilepsy. Both underwent surgical resection and were seizure-free or nearly seizure-free thereafter. We discuss the pathophysiological changes evoked by HV in healthy brains, and those with generalized and focal epilepsy. We provide a comprehensive and critical review of the literature on the role of HV in focal epilepsy. We suggest HV should be considered an activation method for patients with focal epilepsy during epilepsy monitoring unit admissions and may help in the localization of the epileptogenic network/zone., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Gaetano Zaccara,1 Simona Lattanzi,2 Antonio Leo,3 Emilio Russo3 1Regional Health Agency of Tuscany, Firenze, Italy; 2Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy; 3Science of Health Department, University Magna Grecia of Catanzaro, Catanzaro, 88100, ItalyCorrespondence: Gaetano ZaccaraRegional Health Agency of Tuscany, via Pietro Dazzi 1, Firenze, 50141, ItalyTel +39 055 2336851Email gaetanozaccara@yahoo.itAbstract: Cenobamate (CNB) is the latest antiseizure medication (ASM) authorized for the treatment of focal-onset seizures in adults. Although the precise mechanism of action of CNB is not yet fully understood, this drug inhibits the persistent, rather than transient, voltage-gated sodium channel currents and is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, differently from benzodiazepines. CNB has a non-linear pharmacokinetic with a terminal half-life range of about 50/60 hours within the therapeutic dose range, which allows once daily administration. Cenobamate inhibits cytochrome P450 (CYP) 2C19 and induces CYP3A4 and 2B6, and hence can potentially interact with ASMs (eg, phenytoin, carbamazepine and clobazam) and no-ASMs drugs. In two randomized, double-blind, placebo-controlled trials in patients with focal epilepsies, CNB has shown a particularly good efficacy with a rate of seizure freedom of about 20% during the maintenance period in participants treated with the dose of 400 mg/day. The most common treatment-emergent adverse effects include central nervous system-related symptoms, like dizziness, diplopia, somnolence, and gait disturbances. Safety issues of particular interest are severe skin reactions (drug reaction with eosinophilia and systemic symptoms) and QT shortening, which contraindicates its use in subjects with familial short QT syndrome or in combination with other QT-shortening drugs. The recommended starting dose is 12.5 mg/day, which can be gradually titrated to the target dose (200 mg/day) and further increased up to 400 mg/day. There are several aspects of CNB that need to be still addressed, including the long-term efficacy and the efficacy in patients with generalized seizures. Ongoing studies will clarify these issues. The clinical relevance of the peculiar pharmacokinetics and the pattern of drug–drug interactions also require further investigation.Keywords: cenobamate, focal seizures, antiseizure medications, drug–drug interactions, safety, efficacy

Focal neuronal lipofuscinosis (FNL) is an uncommon epileptic disorder related to an excess of lipofuscin accumulation within dysmorphic-appearing neurons (DANs), whose epileptogenic mechanisms are still poorly understood. It shares some clinical and neuroimaging similarities with focal cortical dysplasia of type IIb (FCDIIb), but it represents a different pathological entity. Here, we identified two patients with FNL among a 10-year cohort of 323 patients who underwent neurosurgery for a focal pharmacoresistant epilepsy. We describe the electroclinical, metabolic and neuropathological features of both patients with FNL who benefited from a comprehensive presurgical investigation. While the previous reports showed frontal lobe localization of the lesion, FNL was identified in the temporal lobe, in one of our patients. EEG investigations in both patients showed striking focal and rich interictal activity resembling that described in FCDIIb. Besides focal intraneuronal lipofuscin accumulation, the neuropathological analysis demonstrated that somata of DANs were surrounded by a large amount of GABAergic presynaptic buttons, suggesting the involvement of interneurons in the epileptogenicity of FNL. To further explore the role of GABAergic transmission in the generation of epileptiform activity in FNL, we performed in vitro multi-electrode array recordings on the post-surgery tissue from one patient. Spontaneous interictal-like discharges (IILDs) were identified only in the restricted area displaying the highest density of lipofuscin-containing DANs, suggesting a close correlation between the density of lipofuscin-containing neurons and epileptogenicity. Moreover, IILDs were blocked by the GABAA receptor antagonist gabazine. All together, these findings showed how GABA signaling may contribute to the generation of interictal-like activity in FNL tissue. [ABSTRACT FROM AUTHOR]

Objective: Motivated by the challenges raised by diagnosing poststroke epilepsy (PSE), especially in nonmotor onset seizure (non‐MOS), we aimed to investigate the features of non‐MOS, including seizure sequences, patient characteristics, and electrophysiological and imaging findings in PSE. Methods: This observational cohort study enrolled patients with PSE whose seizure onset was witnessed. According to the International League Against Epilepsy (ILAE) 2017 seizure classification, we classified seizure‐onset symptoms into the non‐MOS and MOS groups. We compared the different clinical characteristics between the two groups. Results: Between 2011 and 2018, we enrolled 225 patients with PSE (median age, 75 years), consisting of 97 (43%) with non‐MOS and 128 (57%) with MOS. Overall, 65 (67%) of the patients without MOS had no subsequent convulsions. Multivariable logistic regression analysis showed significant associations of non‐MOS with absence of poststroke hemiparesis (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.03–3.42), frontal stroke lobe lesions (OR, 2.11; 95% CI, 1.14–3.91), and putaminal stroke lesions (OR, 2.51; 95% CI, 1.22–5.18) as negative indicators. Postictal single‐photon emission computed tomography (SPECT) detected prolonged hyperperfusion in the temporal lobe more frequently in the non‐MOS than in the MOS group (48% vs 31%; p =.02). The detection rate was higher than spikes/sharp waves in scalp electroencephalography, both in the non‐MOS group (72% vs 33%; p <.001) and the MOS group (68% vs 29%; p <.001). Significance: This study provides the clinical features of non‐MOS in patients with PSE. Compared with the patients with MOS, patients with non‐MOS showed less likely subsequent convulsive seizures, highlighting the clinical challenges. Postictal perfusion imaging and negative indicators of the non‐MOS type may help diagnose and stratify PSE. [ABSTRACT FROM AUTHOR]

Anti-seizure medications (ASMs) represent the pillar of the treatment of epilepsy. The rate of drug-resistant epilepsy remained substantially unchanged over time and there is still the need for new and more effective treatment options. Brivaracetam, cenobamate, eslicarbazepine acetate, lacosamide and perampanel are 'third-generation' ASMs. The aim of this article is to summarize the currently available evidence about the relative efficacy and tolerability of the 'third-generation' ASMs as adjunctive treatment of focal-onset seizures in adults. So far, no randomized controlled study directly compared these ASMs, and their comparative efficacy and tolerability have been indirectly evaluated by one network meta-analysis. Sixteen trials were included in the network meta-analysis. The efficacy endpoints were the rates of seizure response and seizure freedom, defined as ≥ 50% and 100% reduction in baseline monthly seizure frequency. The tolerability endpoints were the rate of patients who developed any treatment emergent adverse events (TEAEs) and any TEAE leading to drug discontinuation. Cenobamate had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction. Brivaracetam and lacosamide had the greatest likelihood to rank as the best-tolerated treatments for the occurrence of any TEAE and TEAE leading to discontinuation. Although network meta-analyses are not substitutes of direct comparisons, they can provide valuable evidence about the hierarchy of interventions. Additional real-world data can be useful complement to characterize the clinical profile and therapeutic potentialities of third-generation ASMs. [ABSTRACT FROM AUTHOR]

Case series summary: Seven cases of feline hippocampal and piriform lobe necrosis (FHN) are described, with particular emphasis on clinical, radiographic and histopathological correlations. FHN is an uncommon acute epileptic condition resembling human autoimmune limbic encephalitis and temporal lobe epilepsy. Seizures are typically focal and feature uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalisation and motionless staring, with inter-ictal behavioural changes such as unprovoked aggression and rapid running. Emerging evidence supports an autoimmune aetiology, although disruption of hippocampal architecture secondary to brain neoplasia has also been recognised. Most commonly, however, the underlying cause remains unknown. Diagnosis is achieved clinically and with brain MRI; electroencephalography and voltage-gated potassium channel-complex autoantibodies are currently the subject of research. Affected cats are frequently refractory to conventional antiepileptic treatment. Relevance and novel information: Following a review of the literature, including potential complicating factors and comparisons with human medicine, the hippocampus and piriform lobe are proposed as the neuroanatomical localisation for focal seizures with orofacial involvement in cats, regardless of aetiology. [ABSTRACT FROM AUTHOR]

On March 18, 2021, an online council of experts in the field of epilepsy treatment was held, dedicated to the use of perampanel in the additional therapy of focal seizures (FS) and primary generalized tonic-clonic seizures (PGTCS) in children 4–12 years old. During the event, the features of the use of perampanel in this group of patients were discussed, considering the specifics of everyday clinical practice, current possibilities of PGTCS and FS therapy in children, its goals, as well as unsolved problems in the treatment of pediatric patients with PGTCS and FS. Particular attention was paid to the role of perampanel in the treatment of PGTCS and FS in children and its effectiveness in specific types of focal seizures.

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

Anti-seizure medications (ASMs) represent the pillar of the treatment of epilepsy. The rate of drug-resistant epilepsy remained substantially unchanged over time and there is still the need for new and more effective treatment options. Brivaracetam, cenobamate, eslicarbazepine acetate, lacosamide and perampanel are ‘third-generation’ ASMs. The aim of this article is to summarize the currently available evidence about the relative efficacy and tolerability of the ‘third-generation’ ASMs as adjunctive treatment of focal-onset seizures in adults. So far, no randomized controlled study directly compared these ASMs, and their comparative efficacy and tolerability have been indirectly evaluated by one network meta-analysis. Sixteen trials were included in the network meta-analysis. The efficacy endpoints were the rates of seizure response and seizure freedom, defined as ≥ 50% and 100% reduction in baseline monthly seizure frequency. The tolerability endpoints were the rate of patients who developed any treatment emergent adverse events (TEAEs) and any TEAE leading to drug discontinuation. Cenobamate had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction. Brivaracetam and lacosamide had the greatest likelihood to rank as the best-tolerated treatments for the occurrence of any TEAE and TEAE leading to discontinuation. Although network meta-analyses are not substitutes of direct comparisons, they can provide valuable evidence about the hierarchy of interventions. Additional real-world data can be useful complement to characterize the clinical profile and therapeutic potentialities of third-generation ASMs.

Darshan Mehta,1 Matthew Davis,2 Andrew J Epstein,3 Brian Wensel,1 Todd Grinnell,4 G Rhys Williams1 1Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 2Medicus Economics, LLC, Milton, MA, USA; 3Medicus Economics, LLC, Philadelphia, PA, USA; 4Medical Affairs, Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Darshan MehtaAssociate Director, Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc, 84 Waterford Drive, Marlborough, MA, 01752, USATel +1-774-369-7913Email Darshan.Mehta@sunovion.comObjective: To examine the association between initiating first-line (1L) monotherapy with eslicarbazepine acetate (ESL) vs a generic antiseizure drug (ASD) and healthcare resource utilization (HCRU) and charges in adults with treated focal seizures (FS).Methods: This was a retrospective analysis of Symphony Health’s Integrated Dataverse® open-source claims data. Two cohorts were identified as having initiated 1L monotherapy with ESL or literature-defined generic ASDs. Linear regression models with person fixed effects and inverse probability treatment weights assessed the relative additional changes in HCRU and charges among patients who received ESL compared to generic ASD.Results: A total of 250 and 43,220 patients initiated ESL (48.3 years; 57.2% female) or a generic ASD (54.5 years; 58.1% female), respectively. Compared to patients initiating a generic ASD, patients treated with ESL had additional reductions of 11.8 percentage points in the likelihood of any all-cause outpatient visits (P< 0.001), 7.4 percentage points in the likelihood of any emergency department (ED) visits (P=0.013), and 22.7 percentage points in the likelihood of any FS-related outpatient visits (P< 0.001). Patients initiating ESL had greater reductions in mean charges for all-cause medical ($2620; P=0.002), outpatient ($1995; P=0.005), and non-FS-related medical ($2708; P< 0.001) services. Patients initiating ESL had greater relative increases in mean total prescription ($1368; P< 0.001) and ASD-related prescription ($1636; P< 0.001) charges, but greater relative reductions in non-ASD prescription ($269; P=0.032) charges. The increases in prescription charges were of a lower magnitude than the decreases in medical charges.Conclusion: Initiation of ESL as 1L monotherapy was associated with statistically significantly greater reductions in any use of several all-cause and FS-related services, number of visits, and charges compared to initiation of a generic ASD as 1L monotherapy in patients with FS. Initiation of a generic ASD as 1L monotherapy was associated with significantly smaller increases in total prescription charges and ASD-related prescription charges.Keywords: eslicarbazepine acetate, focal seizures, healthcare resource utilization, medical charges

Abstract Objective This post hoc analysis assessed the efficacy and safety of adjunctive perampanel in patients (aged ≥ 12 years) with focal seizures (FS), with/without focal to bilateral tonic‐clonic seizures (FBTCS), or generalized tonic‐clonic seizures (GTCS) in India. Methods Centers in India were identified from six double‐blind, randomized, Phase II and Phase III studies of adjunctive perampanel (2–12 mg/day) and their open‐label extensions (OLEx). Efficacy assessments included median percent change in seizure frequency per 28 days, 50% and 75% responder and seizure‐freedom rates. Treatment‐emergent adverse events (TEAEs) were monitored. Results Overall, 128 patients (placebo, n = 39; perampanel, n = 89) were included in the double‐blind Safety Analysis Set and 126 (FS, n = 113 [placebo, n = 32; perampanel, n = 81]; FBTCS, n = 35 [placebo, n = 14; perampanel, n = 21]; GTCS, n = 13 [placebo, n = 6; perampanel, n = 7]) comprised the Full Analysis Set. Median percent reductions in seizure frequency per 28 days for placebo vs perampanel for Indian patients were as follows: 34.8% vs 49.8% (FS; not significant [NS]) and 43.1% vs 60.5% (FBTCS; NS) at 4–12 mg/day, respectively, and −22.4% vs 8.2% (GTCS; NS) at 8 mg/day, respectively. Fifty‐percent responder rates were 37.5% vs 55.1% (FS; NS), 42.9% vs 60.0% (FBTCS; NS), and 16.7% vs 42.9% (GTCS; NS), respectively; seizure‐freedom rates were 0.0% vs 5.8%, 7.1% vs 10.0%, and 0.0% vs 14.3%, respectively (all NS). Overall, 110 patients entered OLEx studies (FS, n = 99; GTCS, n = 11). Perampanel was efficacious for up to four years for FS and FBTCS and two years for GTCS. Across double‐blind and OLEx studies, TEAEs occurred in 58.4% and 83.6% of Indian perampanel‐treated patients, respectively; dizziness was most common. Efficacy and safety outcomes were generally similar overall between Indian and non‐Indian patients. Significance These data suggest adjunctive perampanel (up to 12 mg/day) may be a suitable anti‐seizure medication for patients (aged ≥ 12 years) with FS, with/without FBTCS, or GTCS in India.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real‐world practice. Patients with focal epilepsy prescribed add‐on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12‐month follow‐up. Nine hundred ninety‐four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1‐year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure‐free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy. [ABSTRACT FROM AUTHOR]

Objective: To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo‐controlled, phase 3 trial in patients with drug‐resistant epilepsy associated with tuberous sclerosis complex (TSC). Methods: Patients received plant‐derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4‐week titration, 12‐week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC‐associated seizure (countable focal or generalized) count was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. Results: Of 224 patients, 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo. Median (range) age was 11.3 (1.1–56.8) years. Patients had discontinued a median (range) of 4 (0–15) antiseizure medications and were currently taking 3 (0–5). Difference in seizure reduction between CBD and placebo emerged on Day 6 (titrated dose, 15 mg/kg/day) and became nominally significant (p <.049) by Day 10. Separation between placebo and CBD in ≥50% responder rate also emerged by Day 10. Onset of AEs occurred during the first 2 weeks of the titration period in 61% of patients (CBD25, 61%; CBD50, 67%; placebo, 54%). In patients with an AE, resolution occurred within 4 weeks of onset in 42% of placebo and 27% of CBD patients and by end of trial in 78% of placebo and 51% of CBD patients. Significance: Onset of treatment effect occurred within 6–10 days. AEs lasted longer for CBD than placebo, but the most common (diarrhea, decreased appetite, and somnolence) resolved during the 16‐week trial in most patients. [ABSTRACT FROM AUTHOR]

Fasting is the basis for the ketogenic diet, and intermittent fasting is emerging as a treatment for epilepsy. There are no available data about the role of Islamic fasting on seizure control. This study aims to assess the effect of Ramadan fasting on the frequency of different seizure types. This was a prospective observational study on Muslim patients with active epilepsy intending to fast during Ramadan in the year 2019, with an average of 16 fasting hours per day. Seizure frequency for each seizure type was followed over three months, one month before (Shaaban), during Ramadan and one month after (Shawwal), after ensuring drug compliance. Three hundred and twenty one Muslim patients with active epilepsy with median age of 33 years were included (some patients had more than one type of seizure). In Ramadan, 86 out of 224 patients with focal seizures, 17 out of 38 patients with myoclonic seizures and 6 out of 10 patients with absence seizures showed ≥ 50% reduction. In Shawaal, such improvement continued to include 83, 13 and 4 patients with focal, myoclonic and absence seizures. Focal and myoclonic seizures were significantly improved in the months of Ramadan and Shawaal compared to Shaaban. However, absence seizures were significantly improved only in Ramadan compared with Shaaban. The frequency of generalized tonic-clonic seizures did not significantly differ between the three months. Ramadan fasting may have an improving effect, as well as a post-fasting effect, on active focal, myoclonic and absence seizures. [ABSTRACT FROM AUTHOR]

Background: Diabetic striatopathy is a rare neurological manifestation of nonketotic hyperglycemia that presents with contralateral hemichorea-hemiballismus. Presentation with concurrent seizures is rarely reported.Clinical Presentation: We report a case of diabetic striatopathy presenting with focal and generalized tonic-clonic seizures (GTCS) with right hemichorea-hemiballismus induced by a ketotic hyperglycemic state. Head MRI showed high T1-weighted signal intensity in the left lentiform nucleus with no significant diffusion restriction or postcontrast enhancement. The patient's condition gradually improved, with seizure control on AEDs. Hemichorea-hemiballismus significantly improved with adequate blood sugar control and resolved with low-dose haloperidol.Conclusions: Diabetic striatopathy presenting with hemichorea-hemiballismus and concurrent GTCS has been reported previously in two cases; however, it has never been reported in ketotic hyperglycemia. To the best of our knowledge, we herein report the first case report of focal and generalized seizures in a ketotic hyperglycemic state and mesial temporal sclerosis. [ABSTRACT FROM AUTHOR]

Background: Following approval by the US Food and Drug Administration (FDA) in late 2019, cenobamate (Xcopri) has been utilized to treat adults with focal seizures. Based on its robust efficacy from the phase 2 trials, we began using cenobamate in our adolescent and young adult patients whose seizures were not controlled with previously available options. This study expanded its real-world application to this cohort with focal epilepsy and a history of drug-related rash.Methods: We conducted a retrospective study of our patients exposed to cenobamate (n = 45). We evaluated dosage and serum levels, efficacy, drug interactions, and adverse effects.Results: After gradually increasing cenobamate to clinical effect using the FDA-approved dosing protocol, 60% (n = 22) of patients were responders. Adolescents were treated with an average daily dose of 204.0 mg, and adults with 223.4 mg cenobamate, and had serum levels of 20.5 μg/mL and 26.7 μg/mL, respectively. The side effect profile observed was similar to that seen in the phase 2/3 registry trials. Importantly, patients with a prior history of rash to other medications or antiseizure medications (n = 5) experienced no rashes related to cenobamate.Conclusions: This real-world study supports the findings of prior controlled studies regarding the efficacy of cenobamate as a treatment for focal seizures in adolescents and suggests that patients with a history of rash may benefit from this medication. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and safety of vigabatrin in focal epilepsy associated with tuberous sclerosis complex by retrospectively reviewing patients with focal epilepsy and tuberous sclerosis complex treated with vigabatrin at a pediatric epilepsy center over an 8-year period. Of 85 patients, 20 (23.5%) were seizure-free for >12 months, 45 (52.9%) were responders (≥50% seizure reduction), and 20 (23.5%) were nonresponders. The median age (in months) at seizure onset in the seizure-free group (median, 15; interquartile range [IQR], 6-23.3) was higher than that of responders (median, 5; IQR, 3-14) and nonresponders (median, 6; IQR, 2-12). Fewer patients in the seizure-free group had calcification in their largest tubers, but the presence of tuber calcification did not differ among groups. Vigabatrin is more likely to result in seizure freedom in children with tuberous sclerosis complex who have later infantile onset of focal seizures and no calcification in their largest tuber. [ABSTRACT FROM AUTHOR]

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting.Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure-freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs.Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases.Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE. [ABSTRACT FROM AUTHOR]

Purpose: To assess how efficacy and safety outcomes were affected when cenobamate was co-administered with antiseizure medications (ASMs) that use either sodium channel blocker (SCB) or non-sodium channel blocker (non-SCB) mechanisms of action (MoAs) in patients with uncontrolled focal seizures.Methods: An exploratory post-hoc analysis of a randomized, double-blind, placebo-controlled clinical study (YKP3089C017) was conducted. Baseline concomitant ASMs were grouped as either those that employed an SCB or non-SCB MoA. Efficacy was examined by cenobamate dose (100 mg, 200 mg, and 400 mg/day) and concomitant ASM group using responder rates (≥50%, ≥75%, ≥90% seizure reduction; 100% seizure reduction/seizure freedom) during the maintenance phase and median percentage seizure reduction during the double-blind period. Treatment-emergent adverse events (TEAEs) were examined in the double-blind period.Results: When co-administered with SCBs or non-SCBs, significantly higher percentages of patients achieved ≥50%, ≥75%, and ≥90% responder rates with cenobamate 200 mg/day and/or 400 mg/day versus placebo. Additionally, significantly higher percentages of patients achieved seizure freedom with cenobamate 400 mg/day versus placebo (SCB group, 17.5% versus 1.2%; non-SCB group, 40.0% versus 0.0%). Patients receiving 200 mg/day and 400 mg/day and concomitant SCBs and all patients taking cenobamate combined with non-SCB concomitant ASMs had significantly greater median percentage reductions in focal seizure frequency versus placebo. TEAEs were similar across groups; however, dizziness was more frequently reported in the SCB group.Conclusion: Cenobamate is a highly effective new treatment option for patients with uncontrolled focal seizures when co-administered with SCB or non-SCB ASMs. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term safety and efficacy of add‐on cannabidiol (CBD) in patients with seizures associated with tuberous sclerosis complex (TSC) in the open‐label extension (OLE) of the randomized, placebo‐controlled phase 3 trial GWPCARE6 (NCT02544763). Results of an interim (February 2019 data cut) analysis are reported. Methods: Patients who completed the randomized trial enrolled to receive CBD (Epidiolex® in the United States; Epidyolex® in the EU; 100 mg/mL oral solution). The initial target dose was 25 mg/kg/day, which, based on response and tolerability, could be decreased or increased up to 50 mg/kg/day. The primary end point was safety. Key secondary end points included percentage reduction in TSC‐associated (countable focal and generalized) seizures, responder rates, and Subject/Caregiver Global Impression of Change (S/CGIC). Results: Of 201 patients who completed the randomized phase, 199 (99%) entered the OLE. Mean age was 13 years (range, 1–57). At the time of analysis, 5% of patients had completed treatment, 20% had withdrawn, and 75% were ongoing. One‐year retention rate was 79%. Median treatment time was 267 days (range, 18–910) at a 27 mg/kg/day mean modal dose. Most patients (92%) had an adverse event (AE). Most common AEs were diarrhea (42%), seizure (22%), and decreased appetite (20%). AEs led to permanent discontinuation in 6% of patients. There was one death that was deemed treatment unrelated by the investigator. Elevated liver transaminases occurred in 17 patients (9%) patients; 12 were taking valproate. Median percentage reductions in seizure frequency (12‐week windows across 48 weeks) were 54%–68%. Seizure responder rates (≥50%, ≥75%, 100% reduction) were 53%–61%, 29%–45%, and 6%–11% across 12‐week windows for 48 weeks. Improvement on the S/CGIC scale was reported by 87% of patients/caregivers at 26 weeks. Significance: In patients with TSC, long‐term add‐on CBD treatment was well tolerated and sustainably reduced seizures through 48 weeks, with most patients/caregivers reporting global improvement. [ABSTRACT FROM AUTHOR]

Background: Seizure is a common problem evaluated in pediatric emergency departments. Seizure disorders are among the most frequent neurologic problems that occur in childhood. Around 4 to 10% of children experience at least one episode of seizure in the first 16 years of their life. Objectives: To study clinical and etiological profile of children presenting with seizures. Material and Methods: A total of 126 consecutive children aged 1 month to 18 years presenting with seizures defined as per international league against epilepsy classification, participated in this study. A detailed history was taken, and clinical examination was done, along with the investigation for the aetiology of seizures with routine and specific tests, computerized tomography (CT) scan and/or magnetic resonance imaging (MRI) and electroencephalography (EEG) as and when needed. Results: In our present study, we recorded the highest incidence of seizures in the age group of 1year to 5 years. The incidence of seizures in our study was more in males, accounting for 73 cases (57.4%) while females were 53 cases (42.06%). Generalized seizures were the commonest, among them GTCS accounting for 88 cases (69.84). The identified major etiologic factors were febrile convulsions followed by CNS infections. Conclusion: The incidence of convulsions is highest in the age group of 1 month to 5 years and in males. The commonest type of seizure is generalized tonic-clonic (40.6%).The most common cause of convulsion is febrile seizures. Milestones were achieved normally in majority of cases. [ABSTRACT FROM AUTHOR]

Objectives: To identify semiologic features of automatisms correlating to different seizure onset zones (SOZ).Methods: In total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG).Results: Four clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p = .017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p = .011).Conclusion: The distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare healthcare resource utilization (HCRU) before and after initiation of eslicarbazepine acetate (ESL) in the long-term care (LTC) setting (rehabilitation center, mental health center, LTC non-skilled nursing facility/assisted-living facility, home health, assisted living, nursing home, other/unknown). Methods: This retrospective analysis used IQVIA's New Data Warehouse, which includes deterministically linked LTC, prescription, and professional fee claims data and IQVIA Hospital Charge Data Master database. The study period was 1 April 2013 to 31 December 2019. The index date was the date of ESL initiation in the LTC setting. Inclusion criteria were: (1) ≥ 1 new ESL prescription between 1 April 2014 and 31 December 2018; (2) diagnosis of focal seizure (FS) during the 12 months pre-index date; and (3) no ESL prescription during the 12-month period pre-index. A 12-month pre-post analysis compared epilepsy-specific and all-cause HCRU before and after ESL initiation. Categorical variables were compared with McNemar's tests. Results: A total of 307 patients (mean age 52.2 years, 57.7% male) with FS were included, of whom 24.8% were in nursing homes. Patients used a mean of 3.1 antiseizure drugs prior to initiation of ESL, and 87.9% of patients initiated ESL as adjunctive treatment. There were significant reductions in proportion of patients with epilepsy specific physician office visits, emergency department (ED) visits, hospitalizations, and all-cause physician office visits and hospitalizations in the post-index period compared to the pre-index period (P < 0.05). Similar results were observed in sensitivity (patients with an epilepsy diagnosis) and subgroup analyses [presence or absence of intellectual developmental disorders or age (≥ 65 and < 65 years)]. Conclusion: Proportion of patients with epilepsy-specific physician office visits, ED visits, hospitalizations, and all-cause physician office visits and hospitalizations were significantly reduced following initiation of ESL in patients with FS in LTC. [ABSTRACT FROM AUTHOR]

Epilepsy is a worldwide neurological disease with a characteristic feature of the seizure development activity in one or both brain hemispheres, which can be suppressed by antiepileptic drugs. The main intention of pharmacotherapy is to improve the life quality of patients by partially or completely reducing the number of seizures and minimizing side effects, drug interactions and contraindications. These demands are met by a newer generation of antiepileptic drugs including perampanel (PER). The aim of the study was to analyse a group of 43 outpatients treated with PER. PER has been used as the first adjuvant antiepileptic drug during 12 months and the gathered data were evaluated focusing on the efficacy and drug safety. Our results indicated that the highest effect of PER was achieved after a maximum of one previous monotherapy (88.4 % of patients). The results have also shown a high PER potential as the 1st add-on antiepileptic drug in complete or partial seizure reduction during polytherapy with the correctly indicated antiepileptic drug in optimal dose, especially for the treatment of drug-resistant epilepsy already after 6 month therapy. Twenty patients (47.3 %) showed seizure-free status after 12 months of PER therapy and a seizure reduction by more than 50 % was indicated in fifteen patients (34.1 %). The most commonly concomitant antiepileptic drug with PER was levetiracetam (51.2 %). PER has showed a broadspectrum effect on both focal and generalized seizures with one tablet per day being sufficient. The concomitant use of dietary supplements with magnesium during PER therapy is recommended as an additional treatment of epilepsy (68.8 % of patients in our study). PER could be indicated as the drug with a safe profile and minimal side effects reported in 14 % of our patients. PER is considered a quality antiepileptic drug helping patients to live actively despite the diagnosis of epilepsy. [ABSTRACT FROM AUTHOR]

Purpose of Review: Diagnostic delay is an increasingly recognized issue in epilepsy. At the same time, there is a clear disparity between public awareness of epilepsy and that of other public health issues. A contributing factor for this seems to be a lack of studies testing interventions designed to improve seizure recognition. In this review, we summarize the main findings from recent studies investigating diagnostic delay in epilepsy, highlighting causes, consequences, and potential interventions in future research that may improve quality of care in this population. Recent Findings: Building on prior evidence, diagnostic delay in patients with new-onset focal epilepsy has been identified as an important problem for patients with epilepsy. Such delay in diagnosis can lead to delayed treatment and potentially preventable morbidity and mortality including motor vehicle accidents. Nonmotor seizure semiology appears to be a major contributor for delay; such seizures are largely unrecognized when patients present to emergency departments for care. Improving recognition and diagnosis of recurrent nonmotor seizures in emergency departments represents a significant opportunity for improving time to diagnosis, particularly when patients present following a first lifetime motor seizure and meet diagnostic criteria for epilepsy. Summary: Diagnostic delay in epilepsy is a significant public health issue and recent studies have highlighted potential areas for intervention. [ABSTRACT FROM AUTHOR]

Abstract Introduction This study assessed the association between early initiation of eslicarbazepine acetate (ESL) as first-line therapy (1L cohort) or as first adjunctive regimen to either levetiracetam (LEV) or lamotrigine (LTG) (add-on cohort), and healthcare resource utilization (HCRU) and charges among adults with treated focal seizures (FS). Methods This retrospective, longitudinal cohort analysis used Symphony Health’s Integrated Dataverse (IDV®) claims data to identify patients aged ≥ 18 years with a diagnosis of FS who had a new prescription for ESL between April 2015 and June 2018. Baseline was the 90-day period immediately prior to the date of the first-dispensed claim for ESL (index date) with a follow-up of 1–4 consecutive 90-day periods. Linear regression models were estimated to assess changes in HCRU and charge outcomes. Results There were 274 and 153 patients who received ESL in the 1L cohort and add-on cohort, respectively. The 1L cohort experienced significant reductions from baseline during follow-up in all-cause inpatient (IP; P

Abstract Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice.

Background. Comparative study of antiepileptic drugs allows to make the optimal choice in therapy.The aim of the study: a comparative analysis of the administration of two similar by chemical structure antiepileptic drugs (zonisamide and topiramate) in the outpatient practice in epilepsy in children, taking into account the efficacy and tolerability.Materials and methods. A retrospective analysis of outpatient charts of equal in number (n = 18) groups of patients with different forms of epilepsy treated with zonisamide and topiramate in monotherapy and in combined therapy was carried out.Results. In general, no statistically significant difference in the efficacy of zonisamide and topiramate was obtained (p = 0.692). Efficacy in structural focal epilepsy was also comparable (absence of seizures 54.6 % and 45.5 %, respectively). With comparable efficacy, zonisamide was administered to patients much later in the antiepileptic drugs (Me = 5) than topiramate (Me = 3). Side effects on zonisamide were registered in 27.8 %, side effects on topiramate – in 38.9 % (p = 0.480). The difference in the effect of these drugs on cognitive functions was noted.Conclusions. Zonisamide shows its effectiveness in different forms of epilepsy in children, despite the later appointment in practice. The drug is well tolerated and probably has less negative effect on children’s cognitive functions than topiramate.

Abstract Objective To assess feasibility and efficacy of subtraction ictal SPECT coregistered to MRI (SISCOM) for epilepsy localization in children who are candidates for resective surgery. Methods We retrospectively reviewed all patients ≤16 years with drug‐resistant epilepsy screened for epilepsy surgery in the University Hospital of Leuven from January 2009 to January 2018. Fifty‐eight hospitalizations for ictal SPECT and 51 SISCOM analyses in 44 patients were included. Mean age was 9.1 years. Hospitalizations for SISCOM were analyzed in terms of multiple variables affecting feasibility and efficacy. The localization of SISCOM was compared with the localization of the presumed epileptogenic zone (PEZ) as determined by video‐EEG. Results SISCOM was feasible in terms of chronic medication management, rescue antiepileptic therapy during hospitalization, and operative timings. Radiotracer injection occurred within 30 seconds from seizure onset in 91.4% of the patients. ictal SPECT imaging was performed within two hours from injection in 100% of the patients (mean: 40 minutes). SISCOM was able to localize the PEZ in 51.0% (26/51) and to additionally lateralize the PEZ in 17.6% (9/51), achieving better localizations than ictal SPECT, FDG‐PET, and MRI (P

Epilepsy is one of the most common diseases of the nervous system, characterized by the occurrence of recurrent and unprovoked seizures, which are an expression of abnormal brain activity associated with sudden and excessive bioelectric discharges. Partial seizures come from specific areas of the brain. They can run with motor, autonomic, sensory, and psychological symptoms. Currently, new active substances are sought that can be used in the treatment of drug-resistant partial seizures. The aim of the study is to evaluate the safety and efficacy of cenobamate in the treatment of patients with uncontrolled, partial seizures. Our study material consisted of publications, which were found in PubMed, Google Scholar, and Embase databases. In order to find the proper publications, the search has been conducted with the use of a combination of keywords like: “cenobamate”, “focal seizures”, “cenobamate in epilepsy”. The first step was to find proper publications from the last 10 years. The second step was to carry out an overview of the found publications. Studies have shown that treatment with cenobamate significantly improved seizure control in adults with uncontrolled focal seizures. Long-term use of cenobamate is safe and well-tolerated by patients. Most adverse events are mild or moderate.

Eating epilepsy is a rare condition in children where seizures are triggered by the act of eating. An eight-year-old girl presented with seizures occurring primarily during mealtimes, characterized by a fixed gaze, jaw hypotonia, and impaired awareness. These seizures began at age seven, were initially uninvestigated, and progressively worsened over the year, reaching up to 20-30 episodes per meal. Diagnostic tests, including blood work, upper gastrointestinal endoscopy, psychiatric evaluation, and magnetic resonance imaging (MRI), were normal. The EEG showed generalized epileptiform activity, suggesting a seizure disorder, but the exact cause was unclear. After ruling out more common conditions with similar symptoms, such as gastroesophageal reflux disease, Sandifer syndrome, and psychogenic non-epileptic seizures, the diagnosis of reflex eating epilepsy was made in the end through a process of elimination, combining clinical features with EEG findings and through reviewing the literature. Treatment with oral sodium valproate monotherapy led to significant symptomatic improvement, reducing the frequency of seizures during meals., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Chandrasekhar et al.)

Aims: To study the association between initiation of first adjunctive therapy with eslicarbazepine acetate (ESL) vs. brivaracetam (BRV) on healthcare resource utilization (HCRU) and charges among patients with treated focal seizures (FS). Materials and methods: Symphony Health's Integrated Dataverse (IDV) claims data (1 April 2015 to 30 June 2018) were used to identify two cohorts as first adjunctive therapy with ESL or BRV following a generic anti-seizure drug (ASD). The index date was the earliest claim for a new ESL or BRV prescription. Key inclusion criteria were only 1 generic ASD in the 12months before the index date; ≤1 medical claim with an FS diagnosis. Unit of analysis was the 90-day person-time-block. Changes in HCRU and charges were assessed using a difference-in-differences framework. Both unadjusted and adjusted analyses were performed. The adjusted model utilized person-specific fixed effects and propensity score-based weighting to control for differences in baseline covariates. Bias-corrected bootstrap confidence intervals (CIs) were calculated for charge outcomes. Results: 208 and 137 patients initiated first adjunctive therapy with ESL (43.7 years, 51.9% female) or BRV (39.3 years, 51.8% female). Patients in the ESL cohort had numerically larger reductions in all-cause and FS-related inpatient hospitalizations and outpatient visits and FS-related emergency department visits. Compared to patients initiating BRV, patients treated with ESL had significantly larger reductions in total charges (-$3,446, CI: -$13,716, -$425), all-cause (-$3,166, CI: -$13,991, -$323) and FSrelated (-$2,969, CI: -$21,547, -$842) medical charges, all-cause (-$3,397, CI: -$15,676, -$818) and FS-related (-$2,863, CI: -$19,707, -$787) outpatient charges, and non-ASD-related prescription charges (-$420, CI: -$1,058, -$78). Limitations: Claims may be missing, or miscoded; outcomes may be influenced by variables not accounted for in the analysis; only information on submitted charges was included. Conclusions: Among patients with FS, initiation of first adjunctive therapy with ESL was associated with significantly larger reductions in medical and non-ASD-related prescriptions charges compared to BRV. [ABSTRACT FROM AUTHOR]

Objectives: To compare the evidence on efficacy, safety, tolerability, and impact on short term/long functional outcome of lacosamide (LCM) and phenytoin (PHT) in patients with status epilepticus. Materials & Methods: We conducted a systematic literature search of relevant electronic databases using a suitable search strategy to identify studies directly comparing PHT and LCM, irrespective of dose and duration in patients with convulsive and/or nonconvulsive status epilepticus (SE). We used a standardized assessment form to extract information on the study design, data sources, methodologic framework, efficacy, and adverse events attributed to PHT and LCM from included studies and compared the efficacy and safety outcomes, using a fixed/random effect model. Results: Five studies were found to be eligible for inclusion out of 192 search items, enrolling a total of 115 and 166 participants (predominantly with SE) in LCM and PHT arm, respectively. Baseline characteristics were comparable between both arms. The proportion with seizure control was comparable between both arms (57.3% in LCM vs. 45.7% in PHT arm, p = 0.28) and even in the subgroup analysis separately for convulsive and non‐convulsive SE. Proportion with treatment‐emergent adverse events (TEAE) were comparable in both (17.6% vs. 12.2%, p = 0.20), but serious adverse events (SAE) were higher in PHT arm (5.1% vs. 0.8%, p = 0.049). The proportion with all‐cause mortality and survival with moderate‐severe disability were comparable between both arms (p = 0.23 and 0.37, respectively). Conclusion: LCM has comparable efficacy with fewer SAEs as compared to PHT for achieving seizure control in patients with SE. [ABSTRACT FROM AUTHOR]