Emergent Management of Status Epilepticus.

OBJECTIVE: Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control. LATEST DEVELOPMENTS: Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option. ESSENTIAL POINTS: As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.

Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.

OBJECTIVE: Status epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last decade, mortality is still durably high. Because a gap has emerged between SE management based on clinical practice guidelines (CPGs) and actual clinical practice, we conducted a systematic review of CPGs, assessing their quality, outlining commonalities and discrepancies in recommendations, and highlighting research gaps. METHODS: We searched the PubMed and EMBASE databases and other gray literature sources (nine among guideline registries, evidence-based medicine databases, point-of-care tools; seven websites of governmental organizations and international neurologic societies) in December 2021 (updated in November 2023). The units of analysis were CPGs that included recommendations on the diagnostic and/or therapeutic management of SE in adults. The quality of the CPGs was assessed using the AGREE II tool. RESULTS: Fifteen CPGs were included. The "Applicability" domain was assigned the lowest median score of 10%. The domains "Stakeholder Involvement", "Rigor of Development," and "Editorial Independence" were as well generally underrated. Recommendations on general and diagnostic management and on organizational interventions were fragmented and scattered. Recommendations on pre-hospital and hospital treatment of early-onset and refractory SE were broadly agreed, whereas there was less agreement on the treatment model and medications for established SE and super-refractory SE. SIGNIFICANCE: The CPGs for the management of SE developed in recent years are flawed by several methodological issues and discrepancies in the coverage of important topics. The gap between CPG-based management of SE and actual clinical practice may be due in part to the inherent limitations of the CPGs produced so far.

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.

Health care disparities in morbidity and mortality in adults with acute and remote status epilepticus: A national study.

OBJECTIVE: Although disparities have been described in epilepsy care, their contribution to status epilepticus (SE) and associated outcomes remains understudied. METHODS: We used the 2010-2019 National Inpatient Sample to identify SE hospitalizations using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM codes. SE prevalence was stratified by demographics. Logistic regression was used to assess factors associated with electroencephalographic (EEG) monitoring, intubation, tracheostomy, gastrostomy, and mortality. RESULTS: There were 486 861 SE hospitalizations (2010-2019), primarily at urban teaching hospitals (71.3%). SE prevalence per 10 000 admissions was 27.3 for non-Hispanic (NH)-Blacks, 16.1 for NH-Others, 15.8 for Hispanics, and 13.7 for NH-Whites (p < .01). SE prevalence was higher in the lowest (18.7) compared to highest income quartile (18.7 vs. 14, p < .01). Older age was associated with intubation, tracheostomy, gastrostomy, and in-hospital mortality. Those ≥80 years old had the highest odds of intubation (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.43-1.58), tracheostomy (OR = 2, 95% CI = 1.75-2.27), gastrostomy (OR = 3.37, 95% CI = 2.97-3.83), and in-hospital mortality (OR = 6.51, 95% CI = 5.95-7.13). Minority populations (NH-Black, NH-Other, and Hispanic) had higher odds of tracheostomy and gastrostomy compared to NH-White populations. NH-Black people had the highest odds of tracheostomy (OR = 1.7, 95% CI = 1.57-1.86) and gastrostomy (OR = 1.78, 95% CI = 1.65-1.92). The odds of receiving EEG monitoring rose progressively with higher income quartile (OR = 1.47, 95% CI = 1.34-1.62 for the highest income quartile) and was higher for those in urban teaching compared to rural hospitals (OR = 12.72, 95% CI = 8.92-18.14). Odds of mortality were lower (compared to NH-Whites) in NH-Blacks (OR = .71, 95% CI = .67-.75), Hispanics (OR = .82, 95% CI = .76-.89), and those in the highest income quartiles (OR = .9, 95% CI = .84-.97). SIGNIFICANCE: Disparities exist in SE prevalence, tracheostomy, and gastrostomy utilization across age, race/ethnicity, and income. Older age and lower income are also associated with mortality. Access to EEG monitoring is modulated by income and urban teaching hospital status. Older adults, racial/ethnic minorities, and populations of lower income or rural location may represent vulnerable populations meriting increased attention to improve health outcomes and reduce disparities.

Responsive neurostimulation as a therapy for epilepsy following new-onset refractory status epilepticus: Case series and review of the literature.

OBJECTIVE: To report clinical outcomes of patients who presented with new-onset refractory status epilepticus (NORSE), developed drug-resistant epilepsy (DRE), and were treated with responsive neurostimulation (RNS). METHODS: We performed a retrospective review of patients implanted with RNS at our institution and identified three who originally presented with NORSE. Through chart review, we retrieved objective and subjective information related to their presentation, workup, and outcomes including patient-reported seizure frequency. We reviewed electrocorticography (ECoG) data to estimate seizure burden at 3, 6, 12, and 24 months following RNS implantation. We performed a review of literature concerning neurostimulation in NORSE. RESULTS: Use of RNS to treat DRE following NORSE was associated with reduced seizure burden and informed care by differentiating epileptic from non-epileptic events. CONCLUSIONS: Our single-center experience of three cases suggests that RNS is a safe and potentially effective treatment for DRE following NORSE. SIGNIFICANCE: This article reports outcomes of the largest case series of NORSE patients treated with RNS. Since patients with NORSE are at high risk of adverse neuropsychiatric and cognitive sequelae beyond seizures, a unique strength of RNS over other surgical options is the ability to distinguish ictal or peri-ictal from non-epileptic events.

Super-refractory status epilepticus, rhabdomyolysis, central hyperthermia and cardiomyopathy attributable to spinal anesthesia: a case report and review of literature.

BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear. CASE PRESENTATION: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine. CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.

Can critical care transport be safely reduced in children intubated during emergency management of status epilepticus in the United Kingdom: a national audit with case-control analysis.

OBJECTIVE: This study describes the baseline clinical characteristics, predictors of successful extubation at referring hospitals and short-term outcomes of children intubated for status epilepticus and referred to United Kingdom (UK) paediatric critical care transport teams (PCCTs). DESIGN: Multicentre audit with case-control analysis, conducted between 1 September 2018 and 1 September 2020. SETTING: This study involved 10 UK PCCTs. PATIENTS: Children over 1 month of age intubated during emergency management for status epilepticus (SE), referred to UK PCCTs. Patients with trauma, requiring time-critical neurosurgical intervention or those with a tracheostomy were excluded. INTERVENTIONS: No interventions were implemented. MEASUREMENTS AND MAIN RESULTS: Out of the 1622 referrals for SE, 1136 (70%) were intubated at referral. The median age was 3 years (IQR 1.25-6.54 years). Among the intubated children, 396 (34.8%) were extubated locally by the referring team, with 19 (4.8%) requiring reintubation. Therefore, the overall rate of successful extubation was 33% (377/1136). There was significant variation between PCCTs, with local extubation rates ranging from 2% to 74%. Multivariable analyses showed region/PCCT, contributing diagnosis, acute changes on CT, preceding encephalopathy and type of continuous sedation (midazolam) used postintubation were significantly associated with transfer to a critical care unit. CONCLUSION: This study highlights wide regional variation in early extubation practices. Regions with high successful extubation rates have established extubation guidelines from PCCTs. Successful extubation represents critical care transports that have been avoided.

Nonconvulsive Status Epilepticus: Clinical Findings, EEG Features, and Prognosis in a Developing Country, Mexico.

PURPOSE: There is a lack of clinical and epidemiological knowledge about nonconvulsive status epilepticus (NCSE) in developing countries including Mexico, which has the highest prevalence of epilepsy in the Americas. Our aim was to describe the clinical findings, EEG features, and outcomes of NCSE in a tertiary center in Mexico. METHODS: We conducted a retrospective case series study (2010-2020) including patients (≥15 years old) with NCSE according to the modified Salzburg NCSE criteria 2015 with at least 6 months of follow-up. We extracted the clinical data (age, sex, history of epilepsy, antiseizure medications, clinical manifestations, triggers, and etiology), EEG patterns of NCSE, and outcome. Descriptive statistics and multinomial logistic regression were used. RESULTS: One hundred thirty-four patients were analyzed; 74 (54.8%) women, the total mean age was 39.5 (15-85) years, and 71% had a history of epilepsy. Altered state of consciousness was found in 82% (including 27.7% in coma). A generalized NCSE pattern was the most common (32.1%). The NCSE etiology was mainly idiopathic (56%), and previous uncontrolled epilepsy was the trigger in 48% of patients. The clinical outcome was remission with clinical improvement in 54.5%. Multinomial logistic regression showed that the patient's age (P = 0.04), absence of comorbidities (P = 0.04), history of perinatal hypoxia (P = 0.04), absence of clinical manifestations (P = 0.01), and coma (P = 0.03) were negatively correlated with the outcome and only the absence of generalized slowing in the EEG (P = 0.001) had a significant positive effect on the prognosis. CONCLUSIONS: Age, history of perinatal hypoxia, coma, and focal ictal EEG pattern influence negatively the prognosis of NCSE.

Hospital variation of outcomes in status epilepticus.

OBJECTIVE: Understanding factors driving variation in status epilepticus outcomes would be critical to improve care. We evaluated the degree to which patient and hospital characteristics explained hospital-to-hospital variability in intubation and postacute outcomes. METHODS: This was a retrospective cohort study of Medicare beneficiaries admitted with status epilepticus between 2009 and 2019. Outcomes included intubation, discharge to a facility, and 30- and 90-day readmissions and mortality. Multilevel models calculated percent variation in each outcome due to hospital-to-hospital differences. RESULTS: We included 29 150 beneficiaries. The median age was 68 years (interquartile range [IQR] = 57-78), and 18 084 (62%) were eligible for Medicare due to disability. The median (IQR) percentages of each outcome across hospitals were: 30-day mortality 25% (0%-38%), any 30-day readmission 14% (0%-25%), 30-day status epilepticus readmission 0% (0%-3%), 30-day facility stay 40% (25%-53%), and intubation 46% (20%-61%). However, after accounting for many hospitals with small sample size, hospital-to-hospital differences accounted for 2%-6% of variation in all unadjusted outcomes, and approximately 1%-5% (maximally 8% for 30-day readmission for status epilepticus) after adjusting for patient, hospitalization, and/or hospital characteristics. Although many characteristics significantly predicted outcomes, the largest effect size was cardiac arrest predicting death (odds ratio = 10.1, 95% confidence interval = 8.8-11.7), whereas hospital characteristics (e.g., staffing, accreditation, volume, setting, services) all had lesser effects. SIGNIFICANCE: Hospital-to-hospital variation explained little variation in studied outcomes. Rather, certain patient characteristics (e.g., cardiac arrest) had greater effects. Interventions to improve outcomes after status epilepticus may be better focused on individual or prehospital factors, rather than at the inpatient systems level.

Dural arteriovenous fistula presenting with recurrent focal status epilepticus and lateralised periodic epileptiform discharges.

BACKGROUND: Dural arteriovenous fistulae (dAVF) are relatively infrequently encountered, and status epilepticus (SE) and lateralised periodic discharges (LPDs) on electroencephalography (EEG) have only rarely been associated with these arteriovenous malformations. METHODS: We present a patient with recurrent presentations with focal SE, aphasia and other focal deficits of cortical function and ictal and peri-ictal LPDs on serial EEG, who was shown to have a left hemispheric dAVF associated with left transverse and sigmoid sinus thrombosis. Seizures proved refractory to four anti-seizure medications but became more amenable to control after successful embolisation of the dAVF, with subsequent resolution of the focal cortical deficits. We discuss the co-occurrence of SE and LPDs with dAVF and review previously reported cases with this rare association. CONCLUSIONS: Our report supports a causative relationship between dAVF and focal SE, manifesting as ictal LPDs on EEG, and highlights the importance of active dAVF management in achieving seizure control. The relatively good patient outcome contrasts to the few similar case reports. Whilst rare, it is important to consider dAVF as a potentially treatable condition underlying new-onset seizures, including SE.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Patient-reported outcomes in adults after status epilepticus: A systematic review.

Impairments after status epilepticus have generally been assessed by physicians, using generic scales. Patient-reported outcomes (PROs) directly reflect each patient's experience and are therefore recommended to improve patient-centered care. The objective of this systematic review was to compile the available information on patient-reported outcomes of adults after status epilepticus. We used Medical Subject Headings terms to search PubMed, Embase, and the Cochrane Library from database inception to February 2023. We excluded reviews, case reports, abstract-only reports, editorials, and publications in languages other than English or French. Studies reporting PROs in adults after SE were eligible. Bias in included studies was assessed using the Newcastle-Ottawa Scale (NOS). Given the heterogeneity in assessment tools and outcomes, most of the results are presented separately for each included study. Only three studies met our criteria. All used an observational cohort design. Two were retrospective and one prospective. Of the 141 patients (76 males and 65 females, mean age 43-63 years), 105 (74.4 %) had a history of epilepsy before status epilepticus. The studies used four epilepsy-specific and five generic tools to assess five patient-reported outcomes: quality of life (n = 141), mental health (depression, n = 81, or anxiety, n = 49), physical health including fatigue (n = 130), return to work (n = 49), and side effects of antiepileptic drugs (n = 81). A single study (n = 81) was of good methodological quality. Health-related quality of life (HRQOL) and mental health were the most extensively studied outcomes, and both were impaired. HRQOL scores ranged from 41.7 ±â€¯11.5 to 48.3 ±â€¯24.5. The prevalence of depression and anxiety varied from 30 % to 36 %, and from 22 % to 62 %, respectively. However, data were not collected before the status epilepticus episode, and the possible impact of this last on the outcomes cannot therefore be assessed. Information on PROs of adults after status epilepticus is extremely scant. Patient-reported outcomes should be collected more widely in adults after status epilepticus.

Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

Risk model of seizure cluster or status epilepticus and intervention in the emergency department.

OBJECTIVES: To identify possible predictors of seizure cluster or status epilepticus (SE) and to evaluate whether these patients receive greater interventions in emergency departments. METHODOLOGY: We conducted a secondary analysis of the ACESUR Registry, a multipurpose, observational, prospective, multicentre registry of adult patients with seizures from 18 emergency departments. Clinical and care-related variables were collected. We identified risk factors and risk models for seizure cluster or SE and assessed the effect of interventions by prehospital emergency services and the hospital emergency department. RESULTS: We identified a total of 186 (28%) patients from the ACESUR registry with seizure cluster (126 [19%]) or SE (60 [9%]); the remaining 478 patients (72%) had isolated seizures. The risk model for seizure cluster or SE in the emergency department included Charlson Comorbidity Index scores ≥ 3 (OR: 1.60; 95% CI, 1.05-2.46; P=.030), ≥ 2 habitual antiepileptic drugs (OR: 2.29; 95% CI, 1.49-3.51; P<.001), and focal seizures (OR: 1.56; 95% CI, 1.05-2.32; P=.027). The area under the curve of the model was 0.735 (95% CI, 0.693-0.777; P=.021). Patients with seizure cluster and SE received more aggressive interventions both by prehospital emergency services (OR: 2.89; 95% CI, 1.91-4.36; P<.001) and at the emergency department (OR: 4.41; 95% CI, 2.69-7.22; P<.001). CONCLUSIONS: This risk model may be of prognostic value in identifying adult patients at risk of presenting seizure cluster or SE in the emergency department. In our sample, these patients received more aggressive treatment than adult patients with isolated seizures before arriving at hospital, and even more so in the emergency department.

Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model.

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. RESULTS: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 µA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. SIGNIFICANCE: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. PLAIN LANGUAGE SUMMARY: In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure-like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy.

Prognostic value of Salzburg nonconvulsive status epilepticus criteria: The SACE score.

OBJECTIVE: This study was undertaken to investigate the association between the Salzburg nonconvulsive status epilepticus (NCSE) criteria and in-hospital outcome, to determine the predictive accuracy of the Status Epilepticus Severity Score (STESS), modified STESS (mSTESS), Epidemiology-Based Mortality Score in Status Epilepticus (EMSE), and END-IT (encephalitis, NCSE, diazepam resistance, imaging features, and tracheal intubation) in NCSE patients, and to develop a new prognostic score specifically designed for NCSE patients. METHODS: Clinical and electroencephalographic (EEG) data of adult patients treated for NCSE from 2020 to 2023 were retrospectively assessed. Age, sex, modified Rankin Scale at admission, comorbidities, history of seizures, etiology, status epilepticus type, and outcome were collected from the patients' digital charts. EEG data were assessed and categorized applying the Salzburg NCSE criteria. In-hospital death was defined as the primary outcome. RESULTS: A total of 116 NCSE patients were included. Multivariable logistic regression revealed that Salzburg NCSE criterion A2 (ictal morphological, spatial, and temporal evolution) was associated with in-hospital survival. The best STESS cutoff was ≥4 (sensitivity = .62, specificity = .69, accuracy = 67%). mSTESS ≥ 5 reached a sensitivity of .68, a specificity of .57, and an overall accuracy of 60%, EMSE ≥ 64 a sensitivity of .82, a specificity of .39, and an overall accuracy of 52%, and END-IT ≥ 3 a sensitivity of .65, a specificity of .44, and an overall accuracy of 50%. Through a hypothesis-generating approach, we developed the SACE score, which integrates EEG features (criterion A2) with patient age (with a 75-year cutoff), history of seizures, and level of consciousness. With a cutoff of ≥3, it had a sensitivity of .77, a specificity of .74, and an overall accuracy of 76%, performing better than other prognostic scores. SIGNIFICANCE: We developed a new user-friendly scoring system, the SACE score, which integrates EEG features with other established outcome-related variables assessable in early stages, to assist neurologists and neurointensivists in making more tailored prognostic decisions for NCSE patients.

Refractory status epilepticus arrested by vagus nerve stimulation.

A 54-year-old man developed altered mental state and generalised tonic-clonic seizures after 1 week of upper respiratory tract symptoms and diarrhoea, having been previously well. His MR scan of brain showed multifocal progressive T2 cortical signal changes. He was diagnosed with new-onset refractory status epilepticus (NORSE), initially treated as being secondary to autoimmune/paraneoplastic limbic encephalitis, although subsequent investigations were negative. His seizures and electrographic epileptiform activity continued despite escalating doses of antiseizure medications, immunosuppression with corticosteroids, immunoglobulins, plasma exchange and rituximab, and thereafter anaesthetic agents. A vagus nerve stimulator (VNS) was implanted 6 weeks after admission and its voltage rapidly increased over 4 days; his seizure activity resolved in the third week after VNS implantation. This case highlights the role of VNS in the early management of NORSE.

Evaluation and systematic review of guidance documents for status epilepticus.

Guidance documents play a pivotal role in shaping the management of status epilepticus (SE). However, the methodological quality of these documents remains uncertain. In this systematic review, we comprehensively searched 12 literature and guideline databases to assess the quality of clinical practice guidelines and consensus statements related to SE management using the AGREE II methodology. Additionally, we summarized the associated recommendations. We identified a total of 14 clinical practice guidelines and 11 consensus statements spanning the period from 1993 to 2022. The median score for clarity of presentation was 71.8% (ranging from 15.3% to 91.7%), indicating generally good clarity. However, the aspect of editorial independence received poor ratings, with a median score of 32.1% (ranging from 0% to 83.3%). Notably, the 2016 guideline published by the American Epilepsy Society in Epilepsy (AES) received the highest overall scores. Across these guidance documents, there was consistency in the definition and diagnosis of SE. However, significant variability was observed in therapeutic recommendations, particularly in terms of the timing for adding or changing medications. The methodological approaches used in most SE guidance documents require improvement, and the disparities in recommendations highlight existing gaps in evidence. Enhanced methodological rigor results in increased standardization of the guideline, consequently augmenting its reference value. Given the urgency of SE as an emergency condition, it is imperative that these documents also address relevant management strategies before admission.