Experienced Seizure Recurrence Research Articles

Efficacy and safety of phenytoin and levetiracetam for acute symptomatic seizures in children with acute encephalitis syndrome: an open label, randomised controlled trial

IntroductionSeizures represent a significant comorbidity in children with acute encephalitis syndrome (AES). Despite this, there is a notable absence of randomized controlled trials (RCTs) directly comparing antiseizure medications (ASMs) in children with AES. Materials and MethodsThis RCT aimed to assess the efficacy and safety of phenytoin and levetiracetam in controlling seizures among children with AES. Both ASMs were administered with a loading followed by maintenance dose. After a 12-week period, children exhibiting a normal electroencephalogram and no seizure recurrence underwent tapering and discontinuation of ASM. Clinical follow-up occurred daily for the first week, and subsequently at 4, 12, and 24 weeks, evaluating seizure recurrence, incidence of status epilepticus, cognition, behavior, functional status, ASM acquisition cost, and adverse effects. ResultsA total of 100 children (50 in each group) were enrolled. Within the first week, 5 and 3 children in the phenytoin and levetiracetam groups expired. Up to 1 week or death (whichever occurred earliest), 46 (92 %) and 44 (88 %) children remained seizure-free. Intention-to-treat analysis for both best and worst-case scenarios showed insignificant differences (p=0.52 and 1.0). No children experienced seizure recurrence after 1 week in either group. The number of patients with breakthrough status epilepticus, need for mechanical ventilation, duration of hospital stay, presence of epileptiform abnormalities in repeat electroencephalogram at 12 weeks, functional outcomes at 1, 12, and 24 weeks, as well as cognition and behavioral profiles at 24 weeks, were comparable in both groups (p>0.05 for all). However, the incidence of treatment-emergent adverse events (TEAEs) causally related to study medications was significantly higher in the phenytoin group (p=0.04). ConclusionLevetiracetam and phenytoin are comparable in efficacy in terms of achieving clinical seizure control in children with acute encephalitis syndrome, although levetiracetam group demonstrated fewer adverse effects.

Assessing the outcome of drug therapy in adult patients with epilepsy who have experienced seizure recurrence after remission

Background. Remission in general sense means disappearance of signs and symptoms of the disease. The risk of recurrence of seizures is usually evaluated only in terms of the risk of a second unprovoked seizure after the first one or the risk of recurrence of seizures after discontinuation of therapy. There are no studies that assess the probability of achieving a second remission in patients with recurrent seizures.Aim. To develop a tool for assessing the probability of favorable and unfavorable treatment outcomes after recurrent seizures in adult patients with different forms of epilepsy.Materials and methods. We analyzed data from 215 patients with recurrent seizures after achieving remission, followed up for 12 or more months, and analyzed disease outcomes.Results and conclusion. At the end of the study, repeat remission was observed in 67 patients, improvement in 48, and no effect in 100. Patients with remission and improvement were combined into a “favorable outcome” group (n = 115), while patients with no effect from therapy formed an “unfavorable outcome” group (n = 100).Patients with an unfavorable outcome were statistically significantly more likely to have factors such as longer disease duration, coexisting serious somatic diseases, structural etiology of epilepsy, bilateral tonic-clonic seizures with focal onset, focal forms of epilepsy, daily seizures, epileptogenic changes on neuroimaging, and regional epileptiform activity on EEG (p <0.05). In turn, patients with a favorable outcome were statistically significantly more likely to have factors such as genetic etiology of epilepsy, generalized tonic-clonic seizures, absences, myoclonic seizures, generalized forms of epilepsy, no pathology on neuroimaging, diffuse epileptiform activity on electroencephalogram, and no pathology on electroencephalogram (p <0.05).Based on the obtained data using the results of constructing contingency tables, a scale for assessing the probability of achieving repeat remission in patients with recurrent epileptic seizures was developed, consisting of 9 sections. To assess the effectiveness of the model, ROC analysis was performed, confirming statistically significant sensitivity and specificity of the obtained scale.Further research is needed to develop more accurate predictors of epilepsy outcomes to understand the peculiarities of the disease pathogenesis.

Using scalp EEG to predict seizure recurrence and electrical status epilepticus in children with idiopathic focal epilepsy

PurposeSome individuals with idiopathic focal epilepsy (IFE) experience recurring seizures accompanied by the evolution of electrical status epilepticus during sleep (ESES). Here, we aimed to develop a predictor for the early detection of seizure recurrence with ESES in children with IFE using resting state electroencephalogram (EEG) data. MethodsThe study group included 15 IFE patients who developed seizure recurrence with ESES. There were 17 children in the control group who did not experience seizure recurrence with ESES during at least 2-year follow-up. We used the degree value of the partial directed coherence (PDC) from the EEG data to predict seizure recurrence with ESES via 6 machine learning (ML) algorithms. ResultsAmong the models, the Xgboost Classifier (XGBC) model achieved the highest specificity of 0.90, and a remarkable sensitivity and accuracy of 0.80 and 0.85, respectively. The CATC showed balanced performance with a specificity of 0.85, sensitivity of 0.73, and an accuracy of 0.80, with an AUC equal to 0.78. For both of these models, F4, Fz and T4 were the overlaps of the top 4 features. ConclusionsConsidering its high classification accuracy, the XGBC model is an effective and quantitative tool for predicting seizure recurrence with ESES evolution in IFE patients. We developed an ML-based tool for predicting the development of IFE using resting state EEG data. This could facilitate the diagnosis and treatment of patients with IFE.

High-density electric source imaging patterns and outcomes following temporal lobectomy in patients with hippocampal sclerosis.

The objective of this study was to ascertain specific patterns of electrical source imaging (ESI) that are associated with a good surgical outcome (no seizure recurrence) using 256-channel high-density (HD) electroencephalography (EEG) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) who underwent temporal lobectomy. Adult patients (age ≥ 18 years) were prospectively recruited from September 2016 to May 2020 at the authors' center. All patients underwent phase I presurgical evaluation and were subsequently advised to proceed with surgery based on consensus from a multidisciplinary epilepsy conference, without knowing HD-ESI results. All recruited patients were followed for at least 12 months after surgery. The outcome of interest was a status of no seizure recurrence, which was assessed at the end of the study. The association between ESI patterns and outcome was assessed using the chi-square or Fisher exact test. Associated p values as well as odds ratios and 95% CIs were reported. The diagnostic performance of the significant pattern associated with the outcome was also evaluated. Fifty-eight patients with known predictors for either good or worse surgical outcomes were recruited. The mean postoperative follow-up period was 33.34 (SD 13.88) months. Forty-seven patients had sufficient interictal epileptiform discharges for HD-ESI analysis. Thirteen of these 47 patients experienced seizure recurrence. The most common source localizations were at Brodmann area (BA) 20 (inferior temporal area) and BA 21 (middle temporal area). A specific ESI pattern of BA 21 without extratemporal sources was significantly associated with no seizure recurrence (p = 0.047). This pattern had a high positive predictive value of 100% and false-positive rate of 0% associated with no seizure recurrence following the surgery. A specific ESI pattern that was highly associated with no seizure recurrence following surgery was demonstrated by a 256-channel HD-EEG. If this pattern can be reproducibly proven in further studies, some TLE-HS patients may be able to proceed with surgery without further investigations.

Causes and prognosis of adults experiencing a first seizure in adulthood: A pilot cohort study conducted in five countries in Latin America.

There are limited data on first seizure (FS) among adults in low and middle-income countries. We describe findings from a prospective cohort study involving 180 adults presenting with seizures in emergency departments in five Latin American countries. Overall, 102 participants (56.7%) had acute symptomatic seizures (ASyS) while 78 (43.3%) had unprovoked seizures (UPS). Among patients with ASyS, 55 (53.9%) had structural causes, with stroke (n = 24, 23.5%), tumor (n = 10, 9.8%), and trauma (n = 3, 3%) being the most frequent. Nineteen patients (18.6%) had infectious causes, including four (4%) with meningoencephalitis, three (3%) neurocysticercosis, and two (2%) bacterial meningoencephalitis. Twenty patients (19.6%) had metabolic/toxic evidence, including four (4%) with uremic encephalopathy, two (2%) hyponatremia, and three (3%) acute alcohol intoxication. Immune dysfunction was present in seven (7%) patients and neurodegenerative in two (2%). Among participants with UPS, 45 (57.7%) had unknown etiology, 24 (30.7%) had evidence of structural disorders (remote symptomatic), four (5%) were related to infectious etiology (>7 days before the seizure), and five (6.4%) had genetic causes. During the 3- and 6-month follow-up, 29.8% and 14% of patients with UPS, respectively, experienced seizure recurrence, while 23.9% and 24.5% of patients with ASyS had seizure recurrence. Longer follow-up is necessary to assess seizure recurrence for patients with ASyS after the acute cause is resolved and to determine the 10-year risk of recurrence, which is part of the definition of epilepsy. PLAIN LANGUAGE SUMMARY: We monitored 180 adults who presented with their first seizure in emergency departments across five Latin American countries. Among these patients, 57% had acute symptomatic seizures, with structural causes such as stroke (23%), infection (17%), or tumor (10%) being more prevalent. Among the 43% with unprovoked seizures, 58% showed no identifiable acute cause, while 6.4% were due to genetics. Within 3 months after their initial seizure, 26.6% of individuals experienced a second seizure, with 11.9% continuing to have seizures in Months 3-6. Between Months 3 and 6, an additional 20% of patients encountered a second seizure. Research is needed to better understand the cause and prognosis of these patients to improve outcomes.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

ObjectiveThe study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes...

Early antiseizure medication withdrawal and risk of seizure recurrence in children after epilepsy surgery: A retrospective study

ObjectiveThe timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. MethodsWe retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. ResultsThis study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SignificanceASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.

Molecular subtypes of epilepsy associated with post-surgical seizure recurrence.

Approximately 50% of individuals who undergo resective epilepsy surgery experience seizure recurrence. The heterogenous post-operative outcomes are not fully explained by clinical, imaging and electrophysiological variables. We hypothesized that molecular features may be useful in understanding surgical response, and that individuals with epilepsy can be classified into molecular subtypes that are associated with seizure freedom or recurrence after surgical resection. Pre-operative blood samples, brain tissue and post-operative seizure outcomes were collected from a cohort of 40 individuals with temporal lobe epilepsy, 23 of whom experienced post-operative seizure recurrence. Messenger RNA and microRNA extracted from the blood and tissue samples were sequenced. The messenger RNA and microRNA expression levels from the blood and brain were each subjected to a novel clustering approach combined with multiple logistic regression to separate individuals into genetic clusters that identify novel subtypes associated with post-operative seizure outcomes. We then compared the microRNAs and messenger RNAs from patient blood and brain tissue that were significantly associated with each subtype to identify signatures that are similarly over- or under-represented for an outcome and more likely to represent endophenotypes with common molecular aetiology. These target microRNAs and messenger RNAs were further characterized by pathway analysis to assess their functional role in epilepsy. Using blood-derived microRNA and messenger RNA expression levels, we identified two subtypes of epilepsy that were significantly associated with seizure recurrence (clusters A1 and B4) (adjusted P < 0.20). A total of 551 microRNAs and 2486 messenger RNAs were associated with clusters A1 and B4, respectively (adjusted P < 0.05). Clustering of brain-tissue messenger RNA expression levels revealed an additional subtype (C2) associated with seizure recurrence that had high overlap of dysregulated messenger RNA transcripts with cluster B4. Clusters A1, B4 and C2 also shared significant overlap of subjects, which altogether suggests a coordinated mechanism by which microRNA and messenger RNA transcripts may be related to seizure recurrence. Epileptic subtypes A1, B4 and C2 reveal both known and novel microRNA and messenger RNA targets in seizure recurrence. Furthermore, targets identified in A1 and B4 are quantifiable in pre-operative blood samples and could potentially serve as biomarkers for surgical resection outcomes.

Hemispherectomy Outcome Prediction Scale: a validity study.

Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score. The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity. The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score. While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Sensorimotor outcomes after resection for perirolandic drug-resistant epilepsy: a systematic review and individual patient data meta-analysis.

The prevalence of long-term postoperative sensorimotor deficits in children undergoing perirolandic resective epilepsy surgery is unclear. The risk of developing these deficits must be weighed against the potential reduction in seizure frequency after surgery. In this study, the authors investigated the prevalence of sensorimotor deficits after resective surgery at ≥ 1 year postoperatively. A systematic review and individual patient data meta-analysis was conducted using PubMed, Embase, and Scopus databases. Subgroups of patients were identified and categorized according to their outcomes as follows: group A patients were denoted as seizure free with no postoperative sensorimotor deficits; group B patients experienced seizure recurrence with no deficit; group C patients were seizure free with deficits; and group D patients were not seizure free and with deficits. Rates of sensory deficits were examined in patients undergoing postcentral gyrus resection, and rates of motor deficits were aggregated in patients undergoing precentral gyrus resection. Of 797 articles resulting from the database searches, 6 articles including 164 pediatric patients at a mean age of 7.7 ± 5.2 years with resection for drug-resistant perirolandic epilepsy were included in the study. Seizure freedom was observed in 118 (72.9%) patients at a mean follow-up of 3.4 ± 1.8 years. In total, 109 (66.5%) patients did not develop sensorimotor deficits at last follow-up, while 55 (33.5%) had permanent deficits. Ten (14.3%) of 70 patients with postcentral gyrus resection had permanent sensory deficits. Of the postcentral gyrus resection patients, 41 (58.6%) patients were included in group A, 19 (27.1%) in group B, 7 (10.0%) in group C, and 3 (4.3%) in group D. Forty (37.7%) of 106 patients with precentral resections had permanent motor deficits. Of the precentral gyrus resection patients, 50 (47.2%) patients were in group A, 16 (15.1%) in group B, 24 (22.6%) in group C, and 16 (15.1%) in group D. Patients without focal cortical dysplasia were more likely to have permanent motor deficits relative to those with focal cortical dysplasia in the precentral surgery cohort (p = 0.02). In total, 58.6% of patients were seizure free without deficit, 27.1% were not seizure free and without deficit, 10.0% were seizure free but with deficit, and 4.3% were not seizure free and with deficit. Future studies with functional and quality-of-life data, particularly for patients who experience seizure recurrence with no deficits (as in group B in the present study) and those who are seizure free with deficits (as in group C) after treatment, are necessary to guide surgical decision-making.

Psychomotor development and seizure features in idiopathic myoclonic epilepsy in infancy.

Myoclonic epilepsy in infancy (MEI) is a rare syndrome characterized by generalized myoclonic seizures (MS) that occur within the first 3 years of life. In the present study, the form of onset, and clinical and electroencephalogram (EEG) features were analyzed. A retrospective chart review was conducted for 16 MEI patients between March 2009 and July 2022 in Peking Union Medical College. The clinical and video EEG (VEEG) characteristics, treatment strategy, and follow-up information were analyzed. Four cases presented with afebrile generalized tonic-clonic seizures (GTCS) at the onset of MEI (GTCS at onset or atypical MEI), while 12 cases presented with MS at onset (MS at onset or typical MEI). The 24-hour VEEG revealed a generalized discharge of polyspike (or spike)-and-wave complexes that lasted for 1–3 seconds in the ictal phase. All patients were treated with valproic acid monotherapy, and none of the patients experienced seizure recurrence. Furthermore, all patients had normal psychomotor development at the end of the follow up period. Typical MEI (MS at onset) and atypical MEI (GTCS at onset) were described in the present study. These 2 groups differed in form of onset, but there were no significant differences in clinical or EEG features.

Timing matters: there are significant differences in short-term outcomes between two time points of status epilepticus

BackgroundIn 2015, the International League Against Epilepsy proposed a new conceptual definition of status epilepticus (SE) with two operational dimensions (t1 and t2) to guide emergency treatment. The purpose of this study was to compare clinical characteristics and prognoses of patients at these two different time points.MethodsWe conducted a prospective observational cohort study of consecutive adults diagnosed with SE. In case of convulsive SE, t1 is 5 min and t2 is 30 min, whereas in case of focal SE with impaired consciousness, t1 is 10 min, t2 is 60 min. Data on clinical characteristics, including age, gender, history of prior seizures, neuroimaging, semiology, duration, and etiology of SE, were collected. The primary outcome was mortality, with seizure recurrence as a secondary measure, and functional status as tertiary outcome of enrolled patients at 3 months after SE onset.ResultsWe screened one hundred patients with SE, with a median age of 66 years and 61% were male. Fifty-six (56.0%) patients reached t1 of SE, while 44 (44.0%) reached t2 of SE. Convulsive SE (52.0%, n = 52) was more common than focal SE with impaired consciousness (48.0%, n = 48). Status epilepticus secondary to an acute symptomatic process was the most common (50%, n = 50). Patients meeting t2 of SE demonstrated a remarkably increased risk of mortality (unadjusted analysis-RR 3.606, 95%CI 1.552–8.376, p = 0.003; adjusted analysis-RR 2.924, 95%CI 1.221–7.003, p = 0.016) and unfavorable functional status (unadjusted analysis-RR 1.803, 95%CI 1.280–2.539, p = 0.001; adjusted analysis-RR 1.664, 95%CI 1.184–2.340, p = 0.003) at 3 months compared to those who only reached t1 of SE. Patients reaching t2 of SE were more likely to experience seizure recurrence, however, there was no significant difference between the two cohorts.ConclusionsOur study provides strong support for the new definition of SE. Patients meeting t2 of SE tend to have a remarkably increased risk of mortality and unfavorable functional outcomes compared to those who only reached t1 of SE. Furthermore, patients were likely to experience seizure recurrence after undergoing an episode of SE. Physicians must be educated about prompt recognition and appropriate management of SE.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy.

The functional outcome and mortality of patients with poststroke epilepsy (PSE) have not been assessed in a prospective study. Previous reports have suggested that patients with PSE may suffer from prolonged functional deterioration after a seizure. In this study, we prospectively investigated the functional outcome and mortality of patients with PSE and analyzed the effect of seizure recurrence on the outcomes. This is part of the Prognosis of Post-Stroke Epilepsy study, a multicenter, prospective observational cohort study, where 392 patients with PSE (at least 1 unprovoked seizure more than 7 days after the onset of the last symptomatic stroke) were followed for at least 1 year at 8 hospitals in Japan. This study included only PSE patients with a first-ever seizure and assessed their functional decline and mortality at 1 year. Functional decline was defined as an increase in modified Rankin Scale (mRS) score at 1 year compared with baseline, excluding death. The associations between the seizure recurrence and the outcomes were analyzed statistically. A total of 211 patients (median age of 75 years; median mRS score of 3) were identified. At 1 year, 50 patients (23.7%) experienced seizure recurrence. Regarding outcomes, 25 patients (11.8%) demonstrated functional decline and 20 (9.5%) had died. Most patients died of pneumonia or cardiac disease (7 patients each), and no known causes of death were directly related to recurrent seizures. Seizure recurrence was significantly associated with functional decline (odds ratio [OR] 2.96, 95% CI 1.25-7.03, p = 0.01), even after adjusting for potential confounders (adjusted OR 3.26, 95% CI 1.27-8.36, p = 0.01), but not with mortality (OR 0.79, 95% CI 0.25-2.48, p = 0.68). Moreover, there was a significant trend where patients with more recurrent seizures were more likely to have functional decline (8.7%, 20.6%, and 28.6% in none, 1, and 2 or more recurrent seizures, respectively; p = 0.006). One-year functional outcome and mortality of patients with PSE were poor. Seizure recurrence was significantly associated with functional outcome, but not with mortality. Further studies are needed to ascertain whether early and adequate antiseizure treatment can prevent the functional deterioration of patients with PSE.

Risk factors and consequences of self-discontinuation of treatment by patients with newly diagnosed epilepsy

ObjectivePatients with epilepsy not uncommonly self-discontinue treatment with antiseizure medications (ASM). The rate, reasons for this, and consequences have not been well studied. MethodsWe analyzed self-discontinuation of ASM treatment in patients with recently diagnosed epilepsy via review of clinic letters and hospital correspondence in a prospective cohort of first seizure patients. ResultsWe studied 489 patients with newly diagnosed and treated epilepsy (median age 41, range 14–88, 62% male), followed up for a median duration of 3.0 years (interquartile range [IQR]: 1.2–6.0). Seventy eight (16.0%) self-discontinued ASM therapy after a median treatment duration of 1.4 years (IQR: 0.4–2.9), and after a median duration of seizure freedom of 11.8 months (IQR: 4.6–31.8).Patients commonly self-discontinued treatment due to adverse effects (41%), perception that treatment was no longer required (35%), and planned or current pregnancy (12%). Patients who self-discontinued were less likely to have epileptogenic lesions on neuroimaging (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.23–0.83), presentation with seizure clusters (HR = 0.32, 95% CI: 0.14–0.69) and presentation with tonic-clonic seizures (HR = 0.36, 95% CI: 0.19–0.70). Patients with shorter interval since the last seizure (HR = 0.76, 95% CI: 0.66–0.86) were more likely to self-discontinue treatment.Sleep deprivation prior to seizures before diagnosis (HR = 1.80, 95% CI: 1.05–3.09) and significant alcohol or illicit drug use (HR = 2.35, 95% CI: 1.20–4.59) were also associated with higher rates of discontinuation.After discontinuation, 51 patients (65%) experienced seizure recurrence, and 43 (84%) restarted treatment. Twenty two patients (28%) experienced a seizure-related injury after treatment discontinuation. SignificanceSelf-initiated discontinuation of ASM treatment was not uncommon in patients with newly treated epilepsy. Reasons for discontinuation highlight areas for improved discussion with patients, including the chronicity of epilepsy and management strategies for current or potential adverse effects.

Quantitative analysis of visually reviewed normal scalp EEG predicts seizure freedom following anterior temporal lobectomy

ObjectiveAnterior temporal lobectomy (ATL) is a widely performed and successful intervention for drug‐resistant temporal lobe epilepsy (TLE). However, up to one third of patients experience seizure recurrence within 1 year after ATL. Despite the extensive literature on presurgical electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities to prognosticate seizure freedom following ATL, the value of quantitative analysis of visually reviewed normal interictal EEG in such prognostication remains unclear. In this retrospective multicenter study, we investigate whether machine learning analysis of normal interictal scalp EEG studies can inform the prediction of postoperative seizure freedom outcomes in patients who have undergone ATL.MethodsWe analyzed normal presurgical scalp EEG recordings from 41 Mayo Clinic (MC) and 23 Cleveland Clinic (CC) patients. We used an unbiased automated algorithm to extract eyes closed awake epochs from scalp EEG studies that were free of any epileptiform activity and then extracted spectral EEG features representing (a) spectral power and (b) interhemispheric spectral coherence in frequencies between 1 and 25 Hz across several brain regions. We analyzed the differences between the seizure‐free and non–seizure‐free patients and employed a Naïve Bayes classifier using multiple spectral features to predict surgery outcomes. We trained the classifier using a leave‐one‐patient‐out cross‐validation scheme within the MC data set and then tested using the out‐of‐sample CC data set. Finally, we compared the predictive performance of normal scalp EEG‐derived features against MRI abnormalities.ResultsWe found that several spectral power and coherence features showed significant differences correlated with surgical outcomes and that they were most pronounced in the 10–25 Hz range. The Naïve Bayes classification based on those features predicted 1‐year seizure freedom following ATL with area under the curve (AUC) values of 0.78 and 0.76 for the MC and CC data sets, respectively. Subsequent analyses revealed that (a) interhemispheric spectral coherence features in the 10–25 Hz range provided better predictability than other combinations and (b) normal scalp EEG‐derived features provided superior and potentially distinct predictive value when compared with MRI abnormalities (>10% higher F1 score).SignificanceThese results support that quantitative analysis of even a normal presurgical scalp EEG may help prognosticate seizure freedom following ATL in patients with drug‐resistant TLE. Although the mechanism for this result is not known, the scalp EEG spectral and coherence properties predicting seizure freedom may represent activity arising from the neocortex or the networks responsible for temporal lobe seizure generation within vs outside the margins of an ATL.

Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update.

This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up. In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAB R]). All patients were recruited from the Department of Neurology at West China Hospital between October 2011 and June 2019, and data were collected prospectively on their demographic and clinical characteristics, treatment strategy, and seizure outcomes, with a median follow-up of 42months (range = 6-93months). Potential risk factors associated with seizure recurrence were also assessed. Of 320 AE patients, 75.9% had acute seizures, among whom >90% of patients had their last seizure within 12months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABAB R encephalitis had a higher cumulative incidence of seizure recurrence than those with anti-NMDAR (log-rank p=.03) or anti-LGI1/Caspr2 encephalitis (log-rank p=.04). Among patients with anti-NMDAR encephalitis, women had a significantly higher cumulative incidence of seizure recurrence than men (log-rank p=.01). Interictal epileptiform discharges (IEDs) or seizures captured on continuous electroencephalogram (EEG) in the acute phase were identified as potential risk factors for seizure recurrence (p=.04, p=.007). Among 163 patients with ≥24months of follow-up, five (3.1%) showed persistent seizures and required ongoing antiseizure medications despite aggressive immunotherapy. Seizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.

Depressive and Anxiety Symptoms Are Predictors of Seizure Recurrence in Adults With Newly Diagnosed Epilepsy.

Objective: To investigate whether emerging depressive and anxiety symptoms are predictors of seizure recurrence in a cohort of patients with newly diagnosed epilepsy (PWNDE) who did not have a history of psychiatric diagnosis.Methods: A cohort of 283 PWNDE were psychiatrically assessed before antiseizure medication (ASM) therapy and were followed for 12 months to assess seizure recurrence. The influence of depressive and anxiety symptoms score on seizure recurrence was assessed using univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was utilized.Results: A total of 283 individuals were included in final analysis, and 115 patients (40.6%) experienced seizure recurrence during follow-up. In multivariate logistic regression analysis, NDDI-E and GAD-7 score were associated with an increased risk of seizure recurrence with an adjusted OR of 1.360 (CI: 1.176–1.572; P < 0.001) and 1.101 (CI: 1.004–1.209; P = 0.041), respectively. Additionally, the adjusted OR and 95% CI of seizure recurrence for the “high NDDI-E score and high GAD-7 score” vs. “not high NDDI-E score and not high GAD-7 score” was 7.059 (3.521–14.149) (P for trend < 0.001).Conclusion: We found that an emergence of new psychiatric symptoms including depressive and anxiety symptoms were predictors of seizure recurrence in adults with newly diagnosed epilepsy who did not have psychiatric history.

Prolonged and short epileptiform discharges have an opposite relationship with the sleep–wake cycle in patients with JME: Implications for EEG recording protocols

In a recent study, we found that during 20.55 ± 1.60 h of artifact-free ambulatory EEG recordings, epileptiform discharges (EDs) longer than 2.68 s occurred exclusively in patients with Juvenile Myoclonic Epilepsy (JME) who experienced seizure recurrence within a year after the EEG. Here we expanded this analysis, exploring whether long EDs (>2.68 s), and short ones, were uniformly distributed during the day. Lastly, we evaluated the temporal distribution of seizure relapses.By Friedman test, we demonstrated that hourly frequencies of both short and long EDs were dependent on the hours of day and sleep–wake cycle factors, with an opposite trend. Short EDs were found mostly during the night (with two peaks at 1 AM and 6 AM), and sleep, dropping at the wake onset (p < 0.001). Conversely, long EDs surged at the wake onset (0.001), remaining frequent during the whole wake period, when compared to sleep (p = 0.002). Of note, this latter pattern mirrored that of seizures, which occurred exclusively during the wake period, and in 9 out of 13 cases at the wake onset.We therefore suggested that short and long EDs could reflect distinct pathophysiological phenomena. Extended wake EEG recordings, possibly including the awakening, could be extremely useful in clinical practice, as well as in further studies, with the ambitious goal of predicting seizure recurrences.

Prolonged epileptic discharges predict seizure recurrence in JME: Insights from prolonged ambulatory EEG.

ObjectiveMarkers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features.MethodsWe compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year (“cases”) after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG (“controls”). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the “cases”, or 1‐year seizure freedom for “controls”). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact‐free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods.ResultsBoth the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut‐off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity.SignificanceThe occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.

Microstructural features of the cerebral cortex: Implications for predicting epilepsy relapse after drug withdrawal

A considerable portion of patients with well-controlled seizures and visually normal brain structures experience seizure recurrence after anti-seizure medication is withdrawn. Microstructural abnormalities of the cortex may play an essential role in epilepsy relapse. Patients with idiopathic/cryptogenic epilepsy were registered. At the follow-up endpoint, 18 patients with relapse (PR+ group), 20 patients without relapse (PR− group), and 30 healthy controls were included. High-resolution T1-weighted images were obtained at the time of drug withdrawal. Microstructural features including cortical thickness, surface area, cortical volume and mean curvature in 68 cortical areas were calculated. A general linear model was applied to investigate intergroup differences, and then post hoc analysis was performed. Additionally, factor analysis was conducted to extract components from imaging measures showing a difference between PR− and PR+ groups, and independent associations between components and epilepsy relapse were assessed using a logistic regression model. Cortical thickness of the left paracentral lobule, left temporal pole and right superior frontal gyrus; surface area of the bilateral lingual gyrus and bilateral pericalcarine cortex; and cortical volume of the bilateral pericalcarine cortex had significant intergroup differences (false discovery rate correction, P < 0.05). All measures, except for cortical thickness of the left temporal pole, showed differences between PR− and PR+ groups. Two dominant components were extracted from these measures, and both were independently associated with epilepsy relapse. In conclusion, epilepsy patients with relapse presented distinct microstructural features of cortex at the time of drug withdrawal, which may serve as a potential biomarker for predicting seizure recurrence.