Status epilepticus in Auckland, New Zealand: Treatment patterns and determinants of outcome in a prospective population-based cohort.

OBJECTIVE: Determination of the real-world performance of a health care system in the treatment of status epilepticus (SE). METHODS: Prospective, multicenter population-based study of SE in Auckland, New Zealand (NZ) over 1 year, with data recorded in the EpiNet database. Focus on treatment patterns and determinants of SE duration and 30-day mortality. The incidence, etiology, ethnic discrepancies, and seizure characteristics of this cohort have been published previously. RESULTS: A total of 365 patients were included in this treatment cohort; 326 patients (89.3%) were brought to hospital because of SE, whereas 39 patients (10.7%) developed SE during a hospital admission for another reason. Overall, 190 (52.1%) had a known history of epilepsy and 254 (70.0%) presented with SE with prominent motor activity. The mean Status Epilepticus Severity Score (STESS) was 2.15 and the mean SE duration of all patients was 44 min. SE self-terminated without any treatment in 84 patients (22.7%). Earlier administration of appropriately dosed benzodiazepine in the pre-hospital setting was a major determinant of SE duration. Univariate analysis demonstrated that mortality was significantly higher in older patients, patients with longer durations of SE, higher STESS, and patients who developed SE in hospital, but these did not maintain significance with multivariate analysis. There was no difference in the performance of the health care system in the treatment of SE across ethnic groups. SIGNIFICANCE: When SE was defined as 10 continuous minutes of seizure, overall mortality was lower than expected and many patients had self-limited presentations for which no treatment was required. Although there were disparities in the incidence of SE across ethnic groups there was no difference in treatment or outcome. The finding highlights the benefit of a health care system designed to deliver universal health care.

Critical care EEG monitoring: improving access and unravelling potentially epileptic patterns.

PURPOSE OF REVIEW: The major advances in critical care EEG have been the development of rapid response EEG, major revision of the American Clinical Neurophysiology Society's (ACNS) standardized critical care EEG terminology, and the commencement of treatment trials on rhythmic and periodic patterns (RPPs) that do not qualify as seizures. RECENT FINDINGS: Rapid response EEG (rEEG) has proven an important supplement to full montage continuous EEG monitoring (cEEG). This EEG can be applied in a few minutes and provides excellent ability to exclude seizures, selecting those where conversion to cEEG would have the greatest diagnostic yield. Once cEEG has been commenced, the durations required to adequately exclude seizures have been refined. The ACNS provided major revision and expansion to the standardized critical care EEG terminology, which paved the way for determining with great accuracy the RPPs that are associated with seizures and that are capable of causing neurologic symptoms and/or secondary neuronal injury. The current limitations to multicenter treatment trials of these patterns have been highlighted. SUMMARY: Novel methods of EEG in critical care have been expanding access to all patients where clinically indicated. Standardized EEG terminology has provided the framework to determine what patterns in which presenting causes warrant treatment vs. those that do not.

Clinical and Electroencephalographic Predictors of Seizures and Status Epilepticus in 12,450 Critically Ill Adults: A Retrospective Cohort Study.

OBJECTIVES: Status epilepticus (SE) is associated with significantly higher morbidity and mortality than isolated seizures. Our objective was to identify clinical diagnoses and rhythmic and periodic electroencephalogram patterns (RPPs) associated with SE and seizures. DESIGN: Retrospective cohort study. SETTING: Tertiary-care hospitals. SUBJECTS: Twelve thousand four hundred fifty adult hospitalized patients undergoing continuous electroencephalogram (cEEG) monitoring in selected participating sites in the Critical Care EEG Monitoring Research Consortium database (February 2013 to June 2021). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We defined an ordinal outcome in the first 72 hours of cEEG: no seizures, isolated seizures without SE, or SE (with or without isolated seizures). Composite groups included isolated seizures or SE (AnySz) and no seizure or isolated seizures. In this cohort (mean age: 60 ± 17 yr), 1,226 patients (9.8%) had AnySz and 439 patients (3.5%) had SE. In a multivariate model, factors independently associated with SE were cardiac arrest (9.2% with SE; adjusted odds ratio, 8.8 [6.3-12.1]), clinical seizures before cEEG (5.7%; 3.3 [2.5-4.3]), brain neoplasms (3.2%; 1.6 [1.0-2.6]), lateralized periodic discharges (LPDs) (15.4%; 7.3 [5.7-9.4]), brief potentially ictal rhythmic discharges (BIRDs) (22.5%; 3.8 [2.6-5.5]), and generalized periodic discharges (GPDs) (7.2%; 2.4 [1.7-3.3]). All above variables and lateralized rhythmic delta activity (LRDA) were also associated with AnySz. Factors disproportionately increasing odds of SE over isolated seizures were cardiac arrest (7.3 [4.4-12.1]), clinical seizures (1.7 [1.3-2.4]), GPDs (2.3 [1.4-3.5]), and LPDs (1.4 [1.0-1.9]). LRDA had lower odds of SE compared with isolated seizures (0.5 [0.3-0.9]). RPP modifiers did not improve SE prediction beyond RPPs presence/absence ( p = 0.8). CONCLUSIONS: Using the largest existing cEEG database, we identified specific predictors of SE (cardiac arrest, clinical seizures prior to cEEG, brain neoplasms, LPDs, GPDs, and BIRDs) and seizures (all previous and LRDA). These findings could be used to tailor cEEG monitoring for critically ill patients.

Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

Case Report: Focal, generalized, or both: does generalized network involvement preclude successful epilepsy surgery?

We present two cases with focal seizures where scalp electroencephalography (EEG) had prominent features of a developmental and epileptic encephalopathy (DEE): Case 1: a 17-year-old male with complex motor seizures whose EEG demonstrated a slow spike-and-wave pattern and generalized paroxysmal fast activity (GPFA). Case 2: a 12-year-old male with startle-induced asymmetric tonic seizures whose EEG also had a slow spike-and-wave pattern. Both patients had intracranial EEG assessment, and focal cortical resections resulted in long-term seizure freedom and resolution of generalized findings. These cases exemplify patients with focal epilepsy with networks that share similarities to generalized epilepsies, and importantly, these features did not preclude curative epilepsy surgery.

The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy.

Introduction: Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Methods: Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. Results: There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. Discussion: The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

Rapid response EEG with needle electrodes in an intensive care unit with limited resources.

Objective: Continuous EEG (cEEG) is the gold standard for detecting seizures and rhythmic and periodic patterns (RPPs) in critically ill patients but is often not available in health systems with limited resources. The current study aims to determine the feasibility and utility of low-cost, practical, limited montage, sub-dermal needle electrode EEG in a setting where otherwise no EEG would be available. Methods: The study included all adult patients admitted to the intensive care unit of a single center over a 24-month period. Members of the existing ICU care team, mostly nurses, were trained to place 8 sub-dermal needle EEG electrodes to achieve rapid, limited montage-EEG recording. Clinical outcomes were recorded, including any reported major complications; and the EEG findings documented, including background characterization, RPPs, and seizures. Results: One hundred twenty-three patients, mean age 68 years, underwent an average of 15.6 min of EEG recording. There were no complications of electrode placement. Overall, 13.0% had seizures (8.1% qualifying as status epilepticus [SE]), 18.7 % had generalized periodic discharges (GPDs), 4.9% had lateralized periodic discharges (LPDs), and 11.4 % sporadic epileptiform discharges (sEDs). Greater mortality was observed in patients with worse background EEGs, seizures, LPDs, or sEDs. Conclusions: Rapid, limited montage EEG could be achieved safely and inexpensively in a broad population of critically ill patients following minimal training of existing care teams. Significance: For resource poor centers or centers outside of major metropolitan areas who otherwise have no access to EEG, this may prove a useful method for screening for non-convulsive seizures and status epilepticus.

Quantitative assessment of burst suppression as a predictor of seizure recurrence in refractory status epilepticus.

OBJECTIVE: To determine whether quantitative EEG analysis of burst suppression can predict seizure recurrence in patients with refractory status epilepticus (RSE) being treated with anesthetic doses of continuous IV antiseizure medications (cIVASM). METHODS: Quantitative assessment of burst suppression (including epileptiform discharges [EDs] and evolution) in 31 occasions (from 27 patients), and correlation with seizure recurrence up to 48 hours post sedative wean. RESULTS: Occasions resulting in seizure recurrence (vs. no seizure recurrence) had lower burst (8.4 vs. 10.6 µV) and interburst interval (IBI) (4.2 vs. 4.8 µV) average amplitude, duration (bursts 2.8 vs. 3.6 s: IBIs 3.6 vs. 4.4 s); and burst total power (0.4 vs. 0.7 µV2). Bursts (0.86 vs. 0.60) and IBIs (0.28 vs. 0.07) with EDs, higher number of EDs within bursts (mean 2.1 vs. 1.4) and IBIs (0.6 vs. 0.2), and positive evolution measures all predicted seizure recurrence, although EDs had the greatest adjusted odds ratio on multivariate analysis. CONCLUSIONS: For patients in burst suppression, successful wean of cIVASM was not determined by classical burst suppression measures, but instead how "epileptiform" bursts and IBIs were, as determined by EDs in both bursts and IBIs and surrogates for evolution within bursts. SIGNIFICANCE: If confirmed, these objective measures could be used during clinical care to help determine when to wean cIVASM in patients with RSE.

The Significance of LRDA With Bilateral Involvement Compared With GRDA on EEG in Critically Ill Patients.

PURPOSE: Lateralized rhythmic delta activity (LRDA) is highly associated with seizures but generalized rhythmic delta activity (GRDA; symmetric by definition) has no known seizure association. A subset of LRDA includes patterns that are "bilateral asymmetric LRDA" (LRDA-ba), falling between purely unilateral LRDA and GRDA. The significance of this finding has not been previously addressed. METHODS: Clinical, EEG, and imaging findings were reviewed in all patients with >6 hours of continuous EEG and LRDA-ba between 2014 and 2019. They were compared with a control group of patients with GRDA, matched 1:1 for prevalence, duration, and frequency of the predominant rhythmic pattern. RESULTS: Two hundred fifty-eight patients with LRDA-ba and 258 matched controls with GRDA were identified. Statistically significant findings included that patients with LRDA-ba were more likely to have presented with an ischemic stroke (LRDA-ba 12.4% vs. GRDA 3.9%) or subdural hemorrhage (8.9% vs. 4.3%); those with GRDA were more likely to have a metabolic encephalopathy (GRDA 10.5% vs. LRDA-ba 3.5%) or "altered mental state" without clear etiology (12.5% vs. 4.3%). Patients with LRDA-ba were significantly more likely to have a background EEG asymmetry (LRDA-ba 62.0% vs. GRDA 25.6%) or focal (arrhythmic) slowing (40.3% vs. 15.5%), and acute (65.5% vs. 46.1%) or focal (49.6% vs. 28.3%) abnormalities on computed tomography scan. Patients with LRDA-ba were more likely to have focal sporadic epileptiform discharges (95.4% vs. 37.9%), lateralized periodic discharges (32.2% vs. 5.0%), and focal electrographic seizures (33.3% vs. 11.2%); however, patients with LRDA-ba alone (i.e., without sporadic epileptiform discharges or PDs) showed only a trend toward increased seizures (17.3%) compared with a matched group of patients with GRDA alone (9.9%, P = 0.08). CONCLUSIONS: Patients with LRDA-ba had a higher proportion of acute focal abnormalities compared with a matched group of patients with GRDA. The LRDA-ba was associated with additional evidence of focal cortical excitability on EEG (sporadic epileptiform discharges and lateralized periodic discharges) and seizures but with only a trend toward increased seizures when other signs of focal excitability were absent.

Hemisphere-Dependent Ictal Tachycardia Versus Ictal Bradycardia in a Critically Ill Patient.

SUMMARY: Tachycardia is a common ictal phenomenon; however, ictal bradycardia is less commonly reported and rarely presents as ictal asystole/syncope. In critically ill patients, seizures are much less likely to manifest with overt clinical signs, i.e., are more likely to be subtle or nonconvulsive. In this setting, changes in heart rate may be the only clue that seizures are occurring. The authors report an exemplary case of a 78-year-old right-handed man who presented with spontaneous left frontal intraparenchymal hemorrhages. During standard clinical monitoring in the Neuro-Intensive Care Unit, the patient had discrete paroxysms of relative sinus tachycardia, independent episodes of sinus bradycardia, and 3 to 4 seconds of sinus pause. The cardiac investigation was unrevealing, but continuous EEG revealed the answer. The episodes of mild tachycardia were associated with seizures from the left temporal region, whereas those with bradycardia were associated with independent seizures from the right temporal region. The case stands as a stark reminder to remain vigilant of seizures in high-risk patients, especially as a cause for paroxysmal autonomic changes.

Neuroimaging Correlates of Lateralized Rhythmic Delta Activity, Lateralized Periodic Discharges, and Generalized Rhythmic Delta Activity on EEG in Critically Ill Patients.

PURPOSE: The neuroimaging correlates of lateralized rhythmic delta activity (LRDA) are not well defined, and imaging findings between different epileptiform patterns have seldom been compared directly. METHODS: Patients were retrospectively selected from a critical care EEG database between December 2014 and December 2017. Patients were included if they had greater than 6 hours of continuous EEG that contained LRDA, lateralized periodic discharges LPDs), or generalized rhythmic delta activity (GRDA) and had an MRI within 48 hours of the EEG. Clinical, EEG, and MRI characteristics were collected and compared. RESULTS: All the following results showed statistical significance between the groups: Patients with GRDA were more likely to have a normal MRI (LRDA, 0%; LPDs, 0.8%; GRDA, 17.3%), although the majority were abnormal. In patients with LRDA and LPDs, the MRI abnormalities were much more likely lateralized to one side, whereas in those with GRDA, they were more likely to have bilateral or multifocal abnormalities. Across all groups most abnormalities were acute, although this proportion was higher in patients with LRDA and LPDs compared with that in those with GRDA (LRDA, 91.3%; LPDs, 86.0%; GRDA, 70.4%). An MRI abnormality that was concordant with the side of LRDA was present in 66.3%, with 17.3% having discordant findings. These were similar in patients with LPDs (concordant 67.4%; discordant 11.6%). CONCLUSIONS: Patients with LRDA had a similarly high rate of acute focal abnormalities ipsilateral to the EEG pattern compared with those with LPDs. Patients with GRDA were more likely to have a normal MRI, but the majority of patients with GRDA still had acute focal findings.

Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study.

BACKGROUND: Determine the prevalence of seizure clusters (two or more seizures in six hours), use of rescue medications, and adverse outcomes associated with seizure clusters in pediatric patients with a range of epilepsy severities, and identify risk factors predictive of seizure clusters. METHODS: Prospective observational two-center study, including phone call and seizure diary follow-up for 12 months in patients with epilepsy aged one month to 18 years. We classified patients into three risk groups based on seizures within the prior year: high, seizure cluster (two or more seizures within one day); intermediate, at least one seizure but no days with two or more seizures; low, no seizures. RESULTS: One-third (32.3%; high risk, 72.4%; intermediate risk, 30.4%; low risk, 3.1%) of 297 patients had a seizure cluster during the study, including half (46.2%) of the patients with active seizures at baseline (intermediate- and high-risk groups combined). Emergency room visits or injuries were no more likely due to a seizure cluster than an isolated seizure. Rescue medications were utilized in 15.8% of patients in the high-risk group and 19.2% in the intermediate-risk group. History of status epilepticus (adjusted odds ratio [aOR], 2.13; confidence interval [CI], 1.09 to 4.16]), seizure frequency greater than four per month (aOR, 4.27; CI, 1.92 to 9.50), and high-risk group status (aOR, 6.42; CI, 2.97 to 13.87) were associated with greater odds of seizure cluster. CONCLUSIONS: Seizure clusters are common in pediatric patients with epilepsy. High seizure frequency was the strongest predictor of clusters. Rescue medications were underutilized. Future studies should evaluate the applicability and effectiveness of these medications for optimization of pediatric seizure cluster treatment and reduction of seizure-related emergency department visits, injuries, and mortality.

When and How to Treat Status Epilepticus: The Tortoise or the Hare?

Status epilepticus (SE) is a collective term that is used to describe a variety of subtypes. Forgetting this point can be perilous, even resulting in exposing patients to unnecessary harms. This review revisits the foundations of many of our current treatment guidelines, providing context to the ever-growing options in the treatment of SE. It aims to highlight the uncertainties that clinicians and EEGers face when treating SE. Several promising future approaches are raised. These bring hope of transitioning to therapies that are based on correcting maladaptive neuronal responses that are personally tailored using real time measures. All types of SE should be diagnosed as soon as possible, and treatment should be started expeditiously. For convulsive SE, treatment should be aggressive with full doses and cessation of seizures should be confirmed with EEG if patients are not returning to normal rapidly. For most other types of SE, the perennial debate about the tortoise or the hare continues: When should we be more measured and conservative and when should we rapidly escalate therapies to a combination of highly sedating agents?