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Background: The risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up., Methods: The study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy., Results: We included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE. A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13-4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03-4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07-3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40-5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3-84.3 %, p < 0.001)., Conclusions: The AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Possible long-term consequences of status epilepticus (SE) include cognitive and behavioral impairment and the development of chronic epilepsy. However, these aspects have not been systematically studied in clinical practice. We aimed to evaluate long-term seizure recurrence after SE and the potential risk factors for their development., Methods: Data were obtained from a prospective registry of all SE episodes occurring in adult patients who attended our center from February 2011 to April 2022. Clinical data, electroencephalographic findings, treatment, and long-term data were prospectively recorded. We performed a cross-sectional study of consecutive SE patients without previous epilepsy diagnosis, and analyzed the development of unprovoked remote seizures., Results: A total of 849 patients were registered in the database. After excluding in-hospital mortality (198/849, 23.3%) and patients with prior epilepsy history (291/849, 44.7%), 360 patients (42.4%) with a first SE episode were included. The median age was 68 years (interquartile range [IQR] = 56-79), and 176 patients (48.9%) were women. The median time to first-line treatment initiation was 2 h (IQR = .7-7.4), and it was correlated with SE duration (R = .375, p < .001). One hundred nine patients (30.3%) presented unprovoked seizures during a median follow-up of 1.8 years (IQR = .5-4.3). After adjusting for identifiable confounders in a multivariable Cox regression analysis, progressive symptomatic etiology (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.33, p = .011), time to first-line treatment initiation > 1.5 h (HR = 1.89, 95% CI = 1.25-2.87, p = .003), and superrefractory SE (HR = 2.34, 95% CI = 1.26-4.33, p = .007) were independently associated with a greater risk of unprovoked seizure recurrence. In contrast, older patients (HR = .99, 95% CI = .97-.99, p = .021) and an acute symptomatic etiology (HR = .44, 95% CI .28-.68, p < .001) were at lower risk of unprovoked seizure recurrence., Significance: The etiology of SE, the delay in initiating SE treatment, and the presence of superrefractoriness have been identified as potentials factors associated with unprovoked remote seizures following a new onset SE. Therefore, prompt and appropriate management should be applied to avoid seizure recurrence., (© 2023 International League Against Epilepsy.)

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk., Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures., Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022., Exposures: Type of acute symptomatic seizure., Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke)., Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy., Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Objective: To investigate the response to various antiseizure medications (ASMs) in the treatment of focal status epilepticus (SE) in the established phase, and the effect of administering several ASMs prior to sedation., Methods: All SE cases in patients aged > 16 years treated with non-BZDs ASMs were prospectively collected in our centre from February 2011 to April 2019. In total, 281 episodes were analysed., Results: Median age at SE onset was 65.1 years; 47 % were focal motor and 53 % focal non-motor episodes. SE cessation was achieved in 79 % episodes with second-line drugs, whereas a third line (anesthetics) was required in 47 episodes. SE cessation was achieved in only 27 % with the first ASM, 48 % with the second, and 51 % with the third. Prompt resolution of the SE episode with a first or second ASM was associated with a better outcome than episodes requiring a larger number of drugs (p = 0.024). The first option in our sample was levetiracetam in 70 % of cases. Among the total of non-responding SE cases treated with levetiracetam as the first ASM option, 107 were subsequently given lacosamide (seizure cessation in 53.3 %) and 34 valproic acid (seizure cessation in 29.4 %) (p = 0.015)., Conclusion: Our findings further support the notion that early termination of SE with a first or second ASM confers a better functional outcome. The large difference in response between the first ASM and consecutive ones suggests that the sum of different ASMs might be the key to resolving focal SE., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Diagnosis of epileptic seizures, particularly regarding status epilepticus (SE), may be challenging in an emergency room setting. The aim of the study was to study the diagnostic yield of perfusion computed tomography (pCT) in patients with single epileptic seizures and SE., Methods: We retrospectively reviewed the records of patients who followed an acute ischemic stroke pathway during a 9-month period and who were finally diagnosed with a single epileptic seizure or SE. Perfusion maps were visually analyzed for the presence of hyperperfusion and hypoperfusion. Clinical data, EEG patterns, and neuroimaging findings were compared., Results: We included 47 patients: 20 (42.5%) with SE and 27 (57.5%) with single epileptic seizure. Of 18 patients who showed hyperperfusion on pCT, 12 were ultimately diagnosed with SE and eight had EEG findings compatible with an SE pattern. Focal hyperperfusion on pCT had a sensitivity of 60% (95% CI 36.4-80.2) and a specificity of 77.8% (95% CI 57.2-90.6) for predicting a final diagnosis of SE. The presence of cerebral cortical and thalamic hyperperfusion had a high specificity for predicting SE presence. Of note, 96% of patients without hyperperfusion on pCT did not show an SE pattern on early EEG., Conclusions: In acute settings, detection by visual analysis of focal cerebral cortical hyperperfusion on pCT in patients with epileptic seizures, especially if accompanied by the highly specific feature of thalamic hyperperfusion, is suggestive of a diagnosis of SE and requires clinical and EEG confirmation. The absence of focal hyperperfusion makes a diagnosis of SE unlikely., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: The point after which non-convulsive status epilepticus (NCSE) can cause permanent damage remains to be elucidated. The aim of this study was to analyze the association between time to resolution and long-term outcomes in NCSE., Methods: We performed a retrospective study of all patients with focal NCSE without consciousness impairment at two tertiary care hospitals in Spain. All the data were registered prospectively and the study period was December 2014-May 2018. We collected information on demographics, SE etiology, time to administration of different lines of treatment, time to NCSE resolution, and outcomes at discharge, 1 year, and 4 years. Clinical outcome was prospectively categorized as good (return to baseline function) or poor (new disability and death)., Results: Seventy-four patients with a mean (±SD) age of 63.4 ± 17.5 years and a mean follow-up time of 2.4 ± 2.2 years were studied. A poor outcome at discharge was associated with a potentially fatal etiology (p < 0.001), EMSE score (Epidemiology-based Mortality Score in Status Epilepticus) (p = 0.012), lateral periodic discharges on EEG (p = 0.034), and occurrence of major complications during hospitalization (p = 0.007). An SE duration of >100 h was clearly associated with a worse outcome (p < 0.001). In the multiple regression analysis, the only independent predictors of a poor outcome at discharge were an SE duration of >+100 hours (p = 0.001), a potentially fatal etiology (p = 0.001), and complications during hospitalization (p = 0.010). An SE duration of >100 hours retained its value as the optimal cutoff point for predicting poor outcomes at both 1 year (p = 0.037) and 4 years (p = 0.05). Other predictors of poor long-term outcomes were a potentially fatal etiology (p < 0.001) and EMSE score (p = 0.034) at 1 year, and progressive symptomatic etiology at 4 years (p = 0.025)., Significance: In patients with focal NCSE without consciousness impairment, a potentially fatal etiology and an SE duration of >100 h were associated with poor short-term and long-term outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate factors related to benzodiazepine (BZD) resistance in status epilepticus (SE) with a focus on their relationship with the etiology of the episode., Methods: All SE cases in patients aged >16 years treated with BZDs were prospectively collected in our center from February 2011 to April 2019. The registry included demographics, SE type and etiology, the timing and duration of BZD administration, and the outcome. In total, 371 episodes were analyzed., Results: Median age at SE onset was 61.3 years; the most frequent etiology was acute symptomatic (55.8%). SE with prominent motor symptoms occurred in 63.3%. Median time to BZD administration was 2 h. We studied the correlation between two-time variables: time from SE onset to BZD administration and time from BZD administration to resolution of SE (response); we observed that timely administration correlated with a faster response in patients with prominent motor symptoms (p = 0.017), SE due to a chronic structural cerebral lesion (p = 0.004), and patients with a history of seizures (p = 0.013). In these subgroups (prominent motor symptoms or chronic structural lesion) BZD administration within the first 4.5 h was highly associated with shorter post-BZD SE duration (p < 0.001)., Significance: The relationship between prompt BZD administration and subsequent duration of SE was found to depend to some extent on the etiology of the episode: patients with chronic structural lesions and those with previous epilepsy responded faster to BZDs. Semiology may have also its impact, as the presence of prominent motor symptoms showed also a faster response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Tumor-associated status epilepticus (TASE) follows a relatively benign course compared with SE in the general population. Little, however, is known about associated prognostic factors., Methods: We conducted a prospective, observational study of all cases of TASE treated at a tertiary hospital in Barcelona, Spain between May 2011 and May 2019. We collected data on tumor and SE characteristics and baseline functional status and analyzed associations with outcomes at discharge and 1-year follow-up., Results: Eighty-two patients were studied; 58.5% (n = 48) had an aggressive tumor (glioblastoma or brain metastasis). Fifty-one patients (62.2%) had a favorable outcome at discharge compared with just 30 patients (25.8%) at 1-year follow-up. Fourteen patients (17.1%) died during hospitalization. Lateralized period discharges (LPDs) on the baseline electroencephalography (EEG), presence of metastasis, and SE severity were significantly associated with a worse outcome at discharge. The independent predictors of poor prognosis at 1-year follow-up were SE duration of at least 21 h, an aggressive brain tumor, and a nonsurgical treatment before SE onset. Lateralized period discharges, super-refractory SE, and an aggressive tumor type were independently associated with increased mortality., Conclusions: Status epilepticus duration is the main modifiable factor associated with poor prognosis at 1-year follow-up. Accordingly, patients with TASE, like those with SE of any etiology, should receive early, aggressive treatment., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The pharmacokinetics of brivaracetam (BRV), added to its effectiveness observed in animal models of status epilepticus (SE), makes this drug attractive for use in emergency situations. Our objective was to evaluate the use of intravenous BRV in a multicenter study., Methods: A retrospective multicenter registry of SE cases treated with BRV was created. These patients were evaluated between January and December 2018 at seven hospitals in Spain. Demographic variables, SE characteristics, concomitant drugs, loading doses, and response to treatment were collected., Results: Forty-three patients were registered. The mean age was 56 ± 23.1 years, 51.2% were male, 29 had previous epilepsy, 24 (55.8%) had prominent motor symptoms, and 19 had nonconvulsive symptoms. Regarding the etiology, 19 (44.2%) were considered acute symptomatic, 16 (17.2%) remote symptomatic, four (9.3%) progressive symptomatic, and four (9.3%) cryptogenic. Regarding concomitant antiepileptic drugs (AEDs), 17 had previously received levetiracetam (LEV). In 14 patients, BRV was used early (first or second AED). The median loading dose was 100 mg (range = 50-400), and the weight-adjusted dose was 1.8 mg/kg (range = 0.4-7.3). BRV was effective in 54% (n = 23), and a response was observed in <6 hours in 13 patients. We observed a tendency for it to be more effective when administered earlier (P = 0.09), but there were no differences regarding SE type and the concomitant use of LEV. In those with the fastest responses, we observed that both the total administered dose (300 mg vs 100 mg, P = 0.008) and the weight-adjusted dose (3.85 mg vs 1.43 mg, P = 0.006) were significantly higher. The receiver operating characteristic curve showed that the best cutoff point for a faster response was 1.82 mg/kg., Significance: BRV is useful for the treatment of SE, even when patients are already being treated with LEV. The response rate seems higher when it is administered earlier and at higher doses (>1.82 mg/kg)., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Status epilepticus (SE) is a neurological emergency that requires urgent antiepileptic therapies, and a rapid treatment of its cause. In recent years, its definition has been updated to adapt it to all types of SE; this update helps to standardise the treatment. The new definition is based on two times: point t1, after which the event will not spontaneously cease, and period t2, after which neuronal damage may appear. There are three lines of treatment: first, benzodiazepines; second, antiepileptic drugs; and third, intravenous anaesthetics. The application of the different lines of treatment raises still unanswered questions, since the prognosis also depends on the aetiology, age and duration. For this reason, different prognostic scales are being developed to help us to assess its evolution and in turn, adapt the aggressiveness of the treatment to each patient., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Purpose: The risk of developing epilepsy at long term after post-stroke status epilepticus (PSSE) is unknown. We aimed to evaluate post-stroke epilepsy (PSE) after early-onset PSSE and its associated factors., Method: All consecutive patients with early-onset PSSE and no history of epilepsy admitted to our hospital between February 2011 and April 2017 were included. We analysed status epilepticus (SE) and stroke-related factors in relation to the development of PSE., Results: Fifty patients with early-onset PSSE were analysed. Mean age was 74.8 ± 14.3 years and 22 (44%) were women. Median NIHSS at the onset of PSSE was 11 (IQR 4-16) and median PSSE duration was 12 h (IQR 4.69-57). Median follow-up was 214 days (IQR 7.5-747). Ten patients (20%) developed PSE at a median delay of 153 days (IQR 20-334). On multivariate analysis, NIHSS > 4 (p = 0.019; hazard ratio: 15.757; 95% CI, 1.564-158.799) and PSSE > 16 h (p = 0.023; hazard ratio: 7.483; 95% CI, 1.325-42.276) were independently associated with a greater risk of PSE. The mean time from PSSE to onset of recurrent seizures was 142 days (IQR 19-153) in patients with PSSE > 16 h and 310 days (IQR 147-480) in PSSE < 16 h (p = 0.094)., Conclusions: NIHSS score >4 at the stroke presentation and PSSE duration >16 h may predict of PSE in patients with early-onset PSSE. Recurrence may develop earlier in PSSE patients with longer duration of the episode., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: The prognosis of status epilepticus (SE) depends on the time between onset and the diagnosis and start of treatment. Our aim was to design a scale with predictive value for pre-hospital diagnosis of SE., Methods: This was a retrospective study of 292 patients who attended the emergency department for an epileptic seizure. A total of 49 patients fulfilled the criteria for SE. We recorded the patients' history and clinical features. Variables independently associated with SE were combined to design a clinical scale. The performance of the scale was evaluated in a validation dataset of 197 patients., Results: A total of 50.3% of the patients were male and the mean age was 55.9 years. The following features were more prevalent in patients with SE: abnormal speech (79.6% vs. 18.9%, P < 0.001), eye deviation (69.4% vs. 14.0%, P < 0.001), automatism (22.4% vs. 6.3%, P < 0.001), hemiparesis (24.5% vs. 10.9%, P = 0.011), state of stupor/coma (46.9% vs. 4.2%, P < 0.001) and number of pre-hospital seizures, i.e. two (34.7% vs. 4.5%, P < 0.001) or more than two (51.0% vs. 0.4%, P < 0.001). Based on these findings, we designed a scale that scored 1 point each for presence of abnormal speech, eye deviation, automatism and two seizures, and 2 points for more than two seizures. The predictive capacity of the scale for identifying SE in the validation dataset was 98.7% (95% confidence interval, 97.3%-100%) and 85.4% of patients with a score >1 had SE., Conclusions: A score >1 on the ADAN scale is a robust predictor of the diagnosis of SE in patients who experience an epileptic seizure. This scale may be a useful tool for clinical use and warrants further investigation., (© 2018 EAN.)

Background: The health expenditure related to status epilepticus (SE) is high because of lengthy hospitalization requirements and possible sequelae. We aimed to study the factors associated with this cost including the different timings of the treatment and SE duration., Methods: We evaluated retrospectively all SE recorded in 2 hospitals. The factors studied included the mean cost of hospitalization, demographics, clinical data, duration of hospitalization, in-hospital/out-of-hospital debut, time from onset to treatment, duration of SE, and destination at discharge., Results: Three hundred five patients were evaluated (December/2012-July/2017), 195 with out-of hospital and 110 with in-hospital debut. The cost of SE with out-of-hospital onset was significantly lower (6559€ vs 15,174€; p = 0.0001). In out-of-hospital cases, the factors independently related to expenditure were the level of consciousness (p < 0.001), presence of complications (p = 0.005), a potentially fatal etiology (p = 0.008), and duration of the episode (p = 0.003). Duration was significantly higher in patients discharged to a convalescence center (p = 0.006); this variable was significantly related to the time SE onset-arrival to hospital, and SE onset-administration of the treatment. In the in-hospital cases, cost was related to male sex (p = 0.002), the development of complications (p = 0.003), and the etiology (p = 0.016) but was not directly related to the SE duration or to the time onset-treatment., Conclusions: The duration of SE and the speed with which proper management is applied have a direct impact on the healthcare expenditure resulting from out-of-hospital SE. In contrast, the etiology and development of complications are the main factors responsible for expenditure related to in-hospital SE., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate the prognosis of patients with status epilepticus (SE) following stroke, focusing on the timing of SE after the event and other unexplored variables., Methods: All consecutive patients experiencing post-stroke SE (PSSE) in our center were included (2011-2016). We analyzed SE- and stroke-related factors in relation to the patients' outcome., Results: 95 patients with PSSE (54 ischemic and 41 hemorrhagic stroke) were analyzed; 40 were women (42.1%) and mean age was 72.7 ± 13.56 years. 51(53.7%) showed prominent motor symptoms, 49(51.6%) needed >2 antiepileptic drugs, and 27(28.4%) required anesthetics. Median duration of SE was 12 h (1-240). Median time from stroke to SE was 15 days (0-532). At discharge, logistic regression identified SE within 72 h after stroke (p = 0.004), baseline mSTESS (p = 0.009), and lesion volume (p = 0.001) as independent factors predicting mortality. Female sex (p = 0.019), SE duration >12 h (p = 0.005), temporal lobe involvement (p = 0.029), and stroke-to-SE time <90 days (p < 0.0001) were independent predictors of functional decline. At long-term follow-up, SE occurring within 72 h after stroke (p = 0.0001), SE duration (p = 0.004), and baseline mSTESS score (p = 0.012) remained as predictive of mortality., Conclusions: The timing of SE after stroke is associated with different consequences: mortality was higher when SE occurred within the first 72 h after stroke and this risk persisted at follow-up, whereas risk of functional decline was higher when SE occurred during the first 3 months. Other factors such as the mSTESS score and SE duration were associated with outcome at both discharge and long-term follow-up., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)