OBJECTIVE: To document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE).
METHODS: Patients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes.
RESULTS: We identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence.
CONCLUSIONS: All-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life.

BACKGROUND: Approximately two thirds of patients with epilepsy become seizure-free with antiseizure medication (ASM). A central question is whether and when ASM can be discontinued.
OBJECTIVE: To present an overview of the current knowledge about risks and benefits of discontinuation of ASM.
METHODS: Review of the current literature, discussion of data on and recommendations for discontinuation of ASM.
RESULTS: The risk of seizure recurrence after discontinuation of ASM is approximately 40-50% and thus twice as high as continuing with ASM. Guidelines recommend considering discontinuation of ASM at earliest after a seizure-free period of 2 years. Predictive variables for seizure recurrence after stopping ASM include longer duration of epilepsy and higher number of seizures until remission, a shorter seizure-free interval until stopping ASM, older age at epilepsy onset, developmental delay or IQ < 70, febrile seizures in childhood, absence of a self-limiting epilepsy syndrome, and evidence of epileptiform activity in the electroencephalograph (EEG). The individual risk of seizure recurrence after stopping ASM can be estimated using an online prediction tool.
CONCLUSIONS: Discontinuation of ASM should be discussed with patients at the earliest after 2 years of seizure freedom in a shared decision-making process weighing up the risks and benefits. The risk of a seizure recurrence depends on a number of clinical variables. Psychosocial aspects, such as impact on driving and occupational issues must be taken into consideration as well as individual fears and concerns of patients about seizure recurrence or the long-term use of ASM.
UNASSIGNED: HINTERGRUND: Etwa zwei Drittel der Patient*innen mit Epilepsie werden unter der Einnahme anfallssuppressiver Medikamente (ASM) anfallsfrei. Eine zentrale Frage ist, ob und wann ASM wieder abgesetzt werden können.
UNASSIGNED: Überblick zum aktuellen Kenntnisstand über Risiken und Nutzen des Absetzens von ASM.
METHODS: Zusammenfassung der aktuellen Literatur, Diskussion der Datenlage und Ableitung von Therapieempfehlungen.
UNASSIGNED: Das Risiko für Anfallsrezidive nach dem Absetzen von ASM ist mit 40–50 % ungefähr doppelt so hoch wie unter der weiteren Einnahme von ASM. Leitlinien empfehlen, das Absetzen von ASM frühestens nach 2‑jähriger Anfallsfreiheit zu erwägen. Prädiktive Faktoren für ein Anfallsrezidiv nach dem Absetzen von ASM umfassen eine längere Dauer der Epilepsie und eine höhere Anzahl epileptischer Anfälle bis zur klinischen Remission, ein kürzeres anfallsfreies Intervall bis zum Absetzen, ein höheres Alter bei Erstmanifestation, eine Entwicklungsverzögerung bzw. ein IQ < 70, Fieberkrämpfe in der Kindheit, das Nichtvorliegen eines selbstlimitierenden Epilepsiesyndroms und der Nachweis epilepsietypischer Muster im EEG. Mithilfe einer webbasierten Prognosesoftware kann das individuelle Risiko eines Anfallsrezidivs nach dem Absetzen von ASM abgeschätzt werden.
UNASSIGNED: Ein Absetzen von ASM sollte frühestens nach 2 Jahren Anfallsfreiheit in einer gemeinsamen Entscheidungsfindung von Ärzt*innen und Patient*innen unter Abwägung von Nutzen und Risiken besprochen werden. Das Risiko eines erneuten Anfalls wird durch eine Reihe klinischer Variablen beeinflusst. Psychosoziale Aspekte wie Fahreignung und die berufliche Situation müssen ebenso berücksichtigt werden wie individuelle Ängste und Sorgen der Patient*innen vor einem Anfallsrezidiv oder der dauerhaften Einnahme von ASM.

BACKGROUND: Although there are models predicting epilepsy recurrence under different clinical conditions, few studies have examined blood biomarkers. Inflammation plays a crucial role in the occurrence and development of epilepsy. We analyzed inflammatory mediators in a regional hospital-based epilepsy cohort and investigated their relationship with subsequent epilepsy recurrence.
METHODS: Interictal inflammatory mediators were measured in 128 patients diagnosed with epilepsy participating in a prospective study. Inflammatory mediators were compared during the follow-up period between patients who experienced epilepsy recurrence and those who did not. We also assessed the correlation between inflammatory mediators and the time interval until the next recurrence.
RESULTS: Over a median 4-month follow-up period, 41 patients experienced seizure recurrence. Differences in interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels were observed between seizure recurrence and non-recurrence groups. After adjusting for covariates through multivariate Cox regression analysis, the patients in the third IL-6 tertile (>2.31 pg/mL; HR: 2.49; 95 % CI: 1.00-6.16; P = 0.049) and in the third TNF-α tertile (>0.74 pg/mL; HR: 2.80; 95 % CI: 1.13-6.92; P = 0.026) had higher risk of seizure recurrence. The time until the next recurrence was negatively correlated with IL-6 level (ρ =  - 0.392, P = 0.011).
CONCLUSIONS: High levels of IL-6 and TNF-α are associated with a higher possibility of seizure recurrence. Future predictive models should also include inflammatory mediators in addition to clinical variables.

OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is a clinic radiological disorder characterized by headache, epileptic seizure, encephalopathy, visual impairment, and focal neurological deficits. Gestational hypertension, which is a significant risk factor for PRES, may cause significant morbidity and mortality among pregnant women.
METHODS: Twenty-four patients with PRES caused by eclampsia who were admitted to our hospital in the last 5 years were included in this study.
METHODS: Blood pressure at admission, the number of regions with vasogenic edema in the brain, and recurrent seizures were noted. Patients were divided into three groups: mild, moderate, and severe.
RESULTS: Using Kruskal-Wallis and Pearson χ2 tests, there was no statistical significance between the groups in terms of cranial involvement (p = 0.471). However, binary logistic regression analysis showed that seizure recurrence increased in correlation with blood pressure (p = 0.04).
CONCLUSIONS: PRES is a rare syndrome associated with several etiologies. In our study, only patients with PRES due to eclampsia were included. Therefore, the number of included patients was limited (24 participants).
CONCLUSIONS: PRES may occur in eclamptic patients with mild, moderate, or severe blood pressure values. Evaluation by magnetic resonance imaging is needed to confirm the diagnosis. Early and rapid treatment is essential for reducing morbidity and mortality among pregnant women.

BACKGROUND: Cognitive dysfunction has been correlated with seizure control in chronic epilepsy and in newly diagnosed epilepsy, which potentially makes it a good marker for predicting disease course and seizure control. However, there is a lack of prospective studies examining the role of cognitive dysfunction in predicting seizure recurrence at the earliest stages of the disease, such as following the first unprovoked seizure (UFS) or new onset epilepsy (NOE).
METHODS: Thirty three adult participants (FS=18, NOE=15) from the Halifax First Seizure Clinic (HFSC) completed a cognitive screening assessment at baseline (typically 3 months following diagnosis); seizure-recurrence was evaluated one year after the initial HFSC visit.
RESULTS: Cognitive impairment, defined as at least one z-score in the impaired range (≤-1.5) relative to published test norms, was documented in 76% of the patients with seizure recurrence at follow-up and in 55% without seizure recurrence. Speed/executive functions and Memory were the most frequently affected domains, with impaired performance noted in 35% and 29% of the entire sample, respectively. Although the seizure recurrence vs. non-recurrence groups did not differ significantly on likelihood of impairment in any specific cognitive domains, a regression model of seizure recurrence that included years of education, baseline mood and anxiety scores, normal vs. abnormal baseline MRI, and impaired (vs. unimpaired) function in six cognitive domains was significant overall (Χ2 (10) = 24.04, p =.007*, R2N =.77). The regression model was no longer significant with the cognitive variables removed.
CONCLUSIONS: Subtle cognitive dysfunction, especially in the domains of executive functions and memory are prevalent in individuals at the earliest stages of epilepsy. In addition to abnormal MRI and EEG findings at baseline, which are far less prevalent in FS and NOE, cognitive factors show promise in helping predict seizure recurrence in these populations.

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.

BACKGROUND: Management of status epilepticus (SE) is focused on the early seizure termination. Refractory SE is an indication for sedation in patients with SE, but up to 75% of patients may be ventilated due to a neurological or respiratory failure. In patients requiring sedation, the clinical assessment is not sufficient to assess seizure control. Identifying those at risk of recurrent seizures could be useful to adapt their management. On the other hand, patients with low risk could benefit from an early withdrawal of sedation to avoid the impact of inappropriate sedation on outcome.
OBJECTIVE: To determine the prevalence and the predictors of uncontrolled SE and its impact on outcome in patients with generalized convulsive SE (GCSE) requiring mechanical ventilation (MV).
METHODS: We retrospectively included patients admitted to the intensive care unit with GCSE requiring MV. Uncontrolled SE was defined as persistent or recurrent seizures during sedation or within 24hours following withdrawal. A multivariable logistic regression model was used to assess the associated factors.
RESULTS: Uncontrolled SE occurred in 37 out of 220 patients (17%). Persistent seizures at admission, higher SAPS II and central nervous system infection were associated with a higher risk of uncontrolled SE. Acute toxic or metabolic etiologies were associated with a decreased risk of uncontrolled SE. In a supplementary analysis, decrease of albumin blood levels was associated with uncontrolled SE. Uncontrolled SE was associated with a poor functional outcome and mortality at 90 days.
CONCLUSIONS: Seventeen percent of patients with a GCSE requiring MV suffered from uncontrolled SE. Etiology and persistent seizures at admission were the main predictors of uncontrolled SE. Patients with uncontrolled SE had a longer duration of sedation and MV, a poor functional outcome and a higher mortality. Further studies are required to determine the impact of continuous electroencephalogram monitoring on the clinical course.

OBJECTIVE: The 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.
METHODS: We 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.
RESULTS: This 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.
CONCLUSIONS: ASM 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.

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.

OBJECTIVE: To analyze the clinical characteristics of acute symptomatic seizures and predict the risk factors for seizure recurrence in patients with anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), and anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis.
METHODS: In this retrospective study, we included hospitalized patients who had been diagnosed with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis between November 2014 and April 2021. Binary logistic regression analysis was performed to identify the potential risk factors for seizure recurrence.
RESULTS: In total, 262 patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were included, 197 (75.2%) of whom presented with acute symptomatic seizures. During follow-up, 42 patients exhibited seizure recurrence. In anti-NMDAR encephalitis, frontal lobe abnormality on brain magnetic resonance imaging, delayed immunotherapy, early seizures, and focal motor onset were associated with seizure recurrence.
CONCLUSIONS: Acute symptomatic seizure is a common clinical feature observed in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis, with 50% of patients presenting with seizures as an initial symptom. The prognosis of patients with acute symptomatic seizures can be improved after receiving immunotherapy. Nevertheless, a minority of patients will experience seizure recurrence; therefore, restarting immunotherapy is recommended.