OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure.
METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality.
RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence.
CONCLUSIONS: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures.
CONCLUSIONS: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Inter-ictal spikes aid in the diagnosis of epilepsy and in planning surgery of medication-resistant epilepsy. However, the localizing information from spikes can be unreliable because spikes can propagate, and the burden of spikes, often assessed as a rate, does not always correlate with the seizure onset zone or seizure outcome. Recent work indicates identifying where spikes regularly emerge and spread could localize the seizure network. Thus, the current study sought to better understand where and how rates of single and coupled spikes, and especially brain regions with high-rate and leading spike of a propagating sequence, informs the extent of the seizure network. In 37 patients with medication-resistant temporal lobe seizures, who had surgery to treat their seizure disorder, an algorithm detected spikes in the pre-surgical depth inter-ictal EEG. A separate algorithm detected spike propagation sequences and identified the location of leading and downstream spikes in each sequence. We analysed the rate and power of single spikes on each electrode and coupled spikes between pairs of electrodes, and the proportion of sites with high-rate, leading spikes in relation to the seizure onset zone of patients seizure free (n = 19) and those with continuing seizures (n = 18). We found increased rates of single spikes in mesial temporal seizure onset zone (ANOVA, P < 0.001, η2 = 0.138), and increased rates of coupled spikes within, but not between, mesial-, lateral- and extra-temporal seizure onset zone of patients with continuing seizures (P < 0.001; η2 = 0.195, 0.113 and 0.102, respectively). In these same patients, there was a higher proportion of brain regions with high-rate leaders, and each sequence contained a greater number of spikes that propagated with a higher efficiency over a longer distance outside the seizure onset zone than patients seizure free (Wilcoxon, P = 0.0172). The proportion of high-rate leaders in and outside the seizure onset zone could predict seizure outcome with area under curve = 0.699, but not rates of single or coupled spikes (0.514 and 0.566). Rates of coupled spikes to a greater extent than single spikes localize the seizure onset zone and provide evidence for inter-ictal functional segregation, which could be an adaptation to avert seizures. Spike rates, however, have little value in predicting seizure outcome. High-rate spike sites leading propagation could represent sources of spikes that are important components of an efficient seizure network beyond the clinical seizure onset zone, and like the seizure onset zone these, too, need to be removed, disconnected or stimulated to increase the likelihood for seizure control.

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337-450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09-6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93-3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.

UNASSIGNED: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.
UNASSIGNED: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/).
UNASSIGNED: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73).
UNASSIGNED: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools.
UNASSIGNED: MING fonds.

BACKGROUND: To assess the frequency and clinical characteristics of seizures in adult critically ill patients, to identify predictors of recurrent seizures not transforming into status epilepticus and to characterize their effects on course and outcome.
METHODS: ICU patients at a Swiss academic medical center with seizures not transforming into status epilepticus from 2015 to 2020 were included. Recurrent seizures and associated clinical characteristics were primary, death, and return to premorbid neurologic function were secondary outcomes.
RESULTS: Two hundred of 26,370 patients (0.8%) with a median age of 65 years had seizures during ICU stay. Seizure semiology was described in 82% (49% generalized; 33% focal) with impaired consciousness during seizures in 80% and motor symptoms in 62%. Recurrent seizures were reported in 71% (36% on EEG) and associated with longer mechanical ventilation (p = 0.031), higher consultation rate by neurologists (p < 0.001), and increased use of EEG (p < 0.001) when compared to single seizures. The use of EEG was not associated with secondary outcomes. Acidosis at seizure onset and prior emergency operations were associated with decreased odds for seizure recurrence (OR 0.43; 95% CI 0.20-0.94 and OR 0.48; 95% CI 0.24-0.97). Epilepsy had increased odds for seizure recurrence (OR 3.56; 95% CI 1.14-11.16).
CONCLUSIONS: Seizures in ICU patients are infrequent, but mostly recurrent, and associated with higher resource utilization. Whenever seizures are observed, clinicians should be vigilant about the increased risk of seizures recurrence and the need for antiseizure treatment must be carefully discussed. While known epilepsy seems to promote recurrent seizures, our results suggest that both acidosis and previous emergency surgery seem to have protective/antiseizure effects.
BACKGROUND: Clinicaltrials.gov (No. NCT03860467).

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.

The ILAE practical definition of epilepsy has a one seizure possibility to diagnose epilepsy after a first seizure if the recurrence risk is very high. The recurrence risk after a first seizure in brain disorders (first remote seizure) is often high, but varies with etiology, so more specific information is needed for clinical practice. This review describes etiology-specific recurrence risks in adults with a first remote seizure in stroke, traumatic brain injury, infections, dementia, multiple sclerosis, and tumors. Most studies are short, single center, and retrospective. Inclusion criteria, outcome ascertainment, and results vary. Few patient categories are clearly above the epilepsy threshold of recurrence risk, and there are surprisingly little data for important etiologies like brain infections. Beside stroke, severe TBI could have a sufficiently high recurrence risk for early epilepsy diagnosis, but more studies are needed, preferably prospective ones. The literature is uninformative regarding which seizures qualify as remote. The clinical implication of the low level of available evidence is that for other etiologies than stroke, seizure recurrence remains the most appropriate indicator of epilepsy for most patients with a first remote seizure. Nonetheless, there are worrying indications of a diagnostic drift, which puts patients with a preexisting brain disorder at risk of misdiagnosis. Although there are drawbacks to an intermediate term like \"possible epilepsy,\" it could perhaps be useful in cases when the recurrence risk is high, but epilepsy criteria are not definitely met after a first remote seizure.

The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE.
This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens.
Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001).
Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.

Epilepsy prevalence is higher in children with Autism Spectrum Disorder (ASD) and is a contributor to morbidity and mortality. Little is known about the recurrence rate after the first nonfebrile seizure in this population, specifically in regard to seizure type and electroencephalogram (EEG) findings.
We reviewed pediatric medical records at our institution between 2006 and 2016 for subjects with ASD who had a first seizure. We then looked for risk of a recurrent non-provoked seizure within the next two years.
Overall, the recurrence rate in this study was 70.9%. This is much higher than the general population. The recurrence rate was higher in patients who had a generalized convulsion compared to those who had a behavioral arrest. When the first seizure was a generalized convulsion, there was an 84% chance of developing a second convulsion, whereas the recurrence rate was 59% for behavioral arrest type seizures (p = 0.002). The odds of having recurrence when the first seizure is a generalized convulsion was 5.36 higher than when it was a behavioral arrest (95% CI 2.14-13.42, p < 0.001). An abnormal EEG was a strong predictor of seizure recurrence in both seizure types. However, even with a normal EEG, generalized convulsions were more likely to recur within 2 years compared to behavioral arrest (OR 6.3, 95% CI 2.1-19).
The recurrence rate for nonfebrile seizures in children with ASD is much higher than the general population, especially for generalized convulsions. An abnormal EEG has a strong predictive value for seizure recurrence. However, even when the EEG is normal, the recurrence rate for generalized convulsions is quite high. This is an important finding as epilepsy contributes to morbidity and mortality in this group and may impact clinical decisions about when to start anti-seizure medications.

We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis.
Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time.
Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017).
We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.