Risk of breakthrough seizures depends on type and etiology of epilepsy.

OBJECTIVE: This study was undertaken to analyze whether the rate of breakthrough seizures in patients taking antiseizure medication (ASM) who have been seizure-free for at least 12 months varies among different types and etiologies of epilepsy. Given the relative ease of achieving seizure freedom with ASM in patients with post-ischemic stroke epilepsy, we hypothesized that this etiology is associated with a reduced risk of breakthrough seizures. METHODS: We defined a breakthrough seizure as an unprovoked seizure occurring while the patient was taking ASM after a period of at least 12 months without seizures. Data were analyzed retrospectively from a tertiary epilepsy outpatient clinic. Patients were eligible for inclusion if they either had a breakthrough seizure at any time or a seizure-free interval of at least 2 years. Our primary endpoint was rate of breakthrough seizures. We conducted univariable and multivariable analyses to identify variables associated with breakthrough seizures. RESULTS: Of 521 patients (53% females, median age = 49 years) included, 29% had a breakthrough seizure, which occurred after a median seizure-free interval of 34 months (quartiles = 22, 62). When controlling for clinically relevant covariates, breakthrough seizures were associated with post-ischemic stroke epilepsy (odds ratio [OR] = .267, 95% confidence interval [CI] = .075-.946), genetic generalized epilepsy (OR = .559; 95% CI = .319-.978), intellectual disability (OR = 2.768, 95% CI = 1.271-6.031), and the number of ASMs previously and currently tried (OR = 1.203, 95% CI = 1.056-1.371). Of the 151 patients with breakthrough seizures, 34.3% did not reachieve terminal 12-month seizure freedom at the last visit. SIGNIFICANCE: This is the first study to show an association between type and etiology of epilepsy and risk of breakthrough seizures. Our data suggest that epilepsies in which seizure freedom can be obtained more easily also exhibit a lower risk of breakthrough seizures. These findings may help to better counsel seizure-free patients on their further seizure prognosis.

Non-discontinuation of antiseizure medication in seizure-free epilepsy patients.

BACKGROUND AND PURPOSE: In patients with epilepsy and sustained seizure freedom, guidelines recommend considering discontinuation of antiseizure medication (ASM) based on shared decision-making. This study aims to identify factors associated with non-discontinuation of ASM in seizure-free patients. METHODS: Retrospective data from three sites of an academic outpatient clinic were analyzed. Adult patients with epilepsy who have been seizure-free for ≥24 months on ASM monotherapy were included. The primary end-point was non-discontinuation of ASM, defined as no discontinuation or no dose reduction of ≥25% at the last outpatient clinic visit in the ultimate seizure-free interval. Secondary end-points included frequency of discussion on discontinuation attempts between patients and physicians, adherence to ASM discontinuation decisions, and post-discontinuation seizure outcomes. RESULTS: Out of 338 included patients, 81.7% did not discontinue ASM and did not reduce its dose, 11.5% discontinued ASM and 6.8% had a significant dose reduction. Factors independently associated with non-discontinuation of ASM were history of focal to bilateral or generalized tonic-clonic seizures (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.08-5.06), history of breakthrough seizures (OR 3.32, 95% CI 1.10-10.04), history of failed attempts to discontinue or reduce the ASM dose (OR 4.67, 95% CI 1.03-21.11) and higher ASM load at the index visit (OR 6.10, 95% CI 2.09-17.78). Discontinuation attempts were made during the entire period of seizure freedom and were most commonly undertaken ≥10 years after the last seizure. CONCLUSIONS: This study provides insights into factors associated with the shared decision-making process regarding ASM discontinuation in seizure-free patients and highlights the importance of considering individual patient characteristics and seizure history.

Etiology-specific response to antiseizure medication in focal epilepsy.

OBJECTIVE: In focal epilepsy, data on the etiology-specific response to antiseizure medication (ASM) are surprisingly sparse. In this study, we sought to reappraise whether seizure outcome of pharmacological treatment is linked to the underlying etiology. Furthermore, we assessed ASM load with respect to the cause of epilepsy. METHODS: Data were retrospectively obtained from the electronic database of the three sites of an academic adult epilepsy outpatient clinic. For each patient, presumed cause of epilepsy was categorized into one of nine etiological groups. Individual drug loads were calculated according to the 2020 World Health Organization Center for Drug Statistics Methodology ATC/DDD Index. Univariate and multivariate analyses were conducted to explore the association between different etiologies and outcome regarding 12-month seizure freedom as well as ASM load. RESULTS: A total of 591 patients with focal epilepsy were included in the final analysis. Ischemic stroke was the etiology with the highest rate of 12-month terminal seizure freedom (71.2%, 95% confidence interval [CI] = 57.9-82.2) and, considering all etiological groups, was an independent predictor of seizure freedom (odds ratio = 2.093, 95% CI = 1.039-4.216). The lowest rates of seizure freedom were observed in patients with hippocampal sclerosis (28.2%, 95% CI = 15.0-44.9) and malformation of cortical development (16.7%, 95% CI = 2.1-48.4). In patients with ischemic stroke, median ASM load (1.0, interquartile range [IQR] = .5-1.8) was significantly lower compared to that in patients with hippocampal sclerosis (median = 1.8, IQR = 1.2-3.0, p = .008) and brain tumors (median = 1.7, IQR = .7-3.2, p = .049). SIGNIFICANCE: Response to treatment with ASM is highly etiology-specific and best in patients with epilepsy due to ischemic stroke. Interestingly, this most favorable treatment outcome can be achieved by the lowest ASM load considering all etiological groups. In focal epilepsy, etiology should be taken into account when counseling patients about their expected seizure outcome with pharmacological treatment and when tailoring initial ASM doses.

Predictive value of acute EEG measurements for seizures and epilepsy after stroke using a dry cap electrode EEG system - Study design and proof of concept.

The development of seizures is a common complication in patients with stroke. A recent study suggests that electroencephalography (EEG) could be useful to predict the occurrence of seizures after stroke. However, EEG is not routinely performed in the follow-up after stroke. We present the design and proof of concept of a large prospective cohort study in which we seek to evaluate the predictive usefulness of a single dry cap EEG measurement in the acute phase after stroke or transient ischemic attack (TIA) with respect to the development of poststroke epilepsy (PSE). In patients with ischemic stroke (IS), TIA, or intracerebral hemorrhage (ICH), an acute EEG measurement using a dry cap electrode EEG (dEEG) system is performed within 7 days of symptom onset. Electroencephalography data will be analyzed quantitatively and qualitatively looking for background asymmetry, different band power ratios, and epileptiform activity. The development of seizures will be assessed repeatedly during the first 2 years after stroke or TIA using a validated questionnaire. Results from the pilot phase of 11 patients showed that the dry cap EEG measurements in patients with acute stroke and TIA are feasible. In comparison with conventional EEG, a higher proportion of noise and artifacts was detected. This article is part of the Special Issue "Seizure & Stroke".

Epileptogenicity of white matter lesions in cerebral small vessel disease: a systematic review and meta-analysis.

BACKGROUND: The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions. METHODS: Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model. RESULTS: Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38-3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55-6.16) but not WML volume (OR 1.30, 95% CI 0.91-1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD. CONCLUSIONS: This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure.

Acute symptomatic seizures in the emergency room: predictors and characteristics.

BACKGROUND: When treating patients with epileptic seizures in the emergency room (ER), it is of paramount importance to rapidly assess whether the seizure was acute symptomatic or unprovoked as the former points to a potentially life-threatening underlying condition. In this study, we seek to identify predictors and analyze characteristics of acute symptomatic seizures (ASS). METHODS: Data from patients presenting with seizures to highly frequented ERs of two sites of a university hospital were analyzed retrospectively. Seizures were classified as acute symptomatic or unprovoked according to definitions of the International League Against Epilepsy. Univariate and multivariate analysis were conducted to identify predictors; furthermore, characteristics of ASS were assessed. RESULTS: Finally, 695 patients were included, 24.5% presented with ASS. Variables independently associated with ASS comprised male sex (OR 3.173, 95% CI 1.972-5.104), no prior diagnosis of epilepsy (OR 11.235, 95% CI 7.195-17.537), and bilateral/generalized tonic-clonic seizure semiology (OR 2.982, 95% CI 1.172-7.588). Alcohol withdrawal was the most common cause of ASS (74.1%), with hemorrhagic stroke being the second most prevalent etiology. Neuroimaging was performed more often in patients with the final diagnosis of ASS than in those with unprovoked seizures (82.9% vs. 67.2%, p < 0.001). Patients with ASS were more likely to receive acute antiseizure medication in the ER (55.9% vs. 30.3%, p < 0.001). CONCLUSIONS: In one quarter of patients presenting to the ER after an epileptic fit, the seizure had an acute symptomatic genesis. The independently associated variables may help to early identify ASS and initiate management of the underlying condition.

Prognostic value of 'late' electroencephalography recordings in patients with cardiopulmonal resuscitation after cardiac arrest.

BACKGROUND: Electroencephalography (EEG) significantly contributes to the neuroprognostication after resuscitation from cardiac arrest. Recent studies suggest that the prognostic value of EEG is highest for continuous recording within the first days after cardiac arrest. Early continuous EEG, however, is not available in all hospitals. In this observational study, we sought to evaluate the predictive value of a 'late' EEG recording 5-14 days after cardiac arrest without sedatives. METHODS: We retrospectively analyzed EEG data in consecutive adult patients treated at the medical intensive care units (ICU) of the Charité-Universitätsmedizin Berlin. Outcome was assessed as cerebral performance category (CPC) at discharge from ICU, with an unfavorable outcome being defined as CPC 4 and 5. RESULTS: In 187 patients, a 'late' EEG recording was performed. Of these patients, 127 were without continuous administration of sedative agents for at least 24 h before the EEG recording. In this patient group, a continuously suppressed background activity < 10 µV predicted an unfavorable outcome with a sensitivity of 31% (95% confidence interval (CI) 20-45) and a specificity of 99% (95% CI 91-100). In patients with suppressed background activity and generalized periodic discharges, sensitivity was 15% (95% CI 7-27) and specificity was 100% (95% CI 94-100). GPDs on unsuppressed background activity were associated with a sensitivity of 42% (95% CI 29-46) and a specificity of 92% (95% CI 82-97). CONCLUSIONS: A 'late' EEG performed 5 to 14 days after resuscitation from cardiac arrest can aide in prognosticating functional outcome. A suppressed EEG background activity in this time period indicates poor outcome.

Quantitative and Qualitative EEG as a Prediction Tool for Outcome and Complications in Acute Stroke Patients.

Currently, the relevance of EEG measurements in acute stroke patients is considered low in clinical practice. However, recent studies on the predictive value of EEG measurements after stroke for various outcomes may increase the role of EEG in patients with stroke. We aimed to review the current literature on the utility of EEG measurements after stroke as a tool to predict outcome and complications, focusing on studies in which the EEG measurement was performed in the acute phase after the event and in which long-term outcome measures were reported. In our literature review, we identified 4 different outcome measures (functional outcome, mortality, development of post-stroke cognitive decline, and development of post-stroke epilepsy) where studies on the utility of acute EEG measurements exist. There is a large body of evidence for the prediction of functional outcome, in which a multitude of associated quantitative and qualitative EEG parameters are described. In contrast, only few studies focus on mortality as outcome parameter. We found studies of high methodical quality on the prediction of post-stroke cognitive decline, though the number of patients in these studies often was small. The role of EEG as a prediction tool for seizures and epilepsy after stroke could increase after a recently published study, especially if its result can be incorporated into already existing post-stroke epilepsy prediction tools. In summary, EEG is useful for the prediction of functional outcome, mortality, development of post-stroke cognitive decline and epilepsy, even though there is a discrepancy between the large amount of studies on EEG in acute stroke patients and its underuse in clinical practice.

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage - Results from the Virtual International Stroke Trials Archive.

INTRODUCTION: Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. PATIENTS AND METHODS: Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. RESULTS: A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale ≤ 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6). Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. DISCUSSION: It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. CONCLUSION: Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days.

Frequency, predictive factors and therapy of emergence delirium: data from a large observational clinical trial in a broad spectrum of postoperative pediatric patients.

BACKGROUND: Emergence delirium (ED) is an important postanesthetic complication in children. Although it has been thoroughly studied, data on frequency, predictive factors, and therapy of this phenomenon are inconclusive. In this study, we seek to obtain a better understanding of the frequency of ED and different therapeutic approaches, making use of the large amount of patients in our university hospital. METHODS: After approval by the local ethics committee, patients aged zero to 13 years, who were treated in the post anesthesia care of our hospital, were investigated in this observational study. ED was diagnosed on basis of a clinical evaluation as well as with the Pediatric Anesthesia Emergence Delirium (PAED) Scale. RESULTS: In 86 of 821 patients a PAED-Score≥10 and therefore an ED was detected (10.5%). Based on clinical assessment by the PACU staff only 5.7% experienced an ED. Age