Status Epilepticus Identification and Treatment Among Emergency Medical Services Agencies.

This cross-sectional study examines the association between unidentified status epilepticus and prehospital benzodiazepine treatment.

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.

Identifying risk for status epilepticus with the ADAN scale: a prospective multicenter validation study. / Escala ADAN para la identificación del estado epiléptico: estudio de validación prospectivo y multicéntrico.

OBJECTIVES: Status epilepticus (SE) is a serious event associated with high mortality. This study aims to validate the recently developed ADAN (Abnormal speech, ocular Deviation, Automatisms, and Number of motor epileptic seizures) scale for detecting high risk for SE. MATERIAL AND METHODS: Prospective, multicenter, observational study in adults with suspected epileptic seizures. Consecutive recruitment took place over a 27-month period in 4 hospital emergency departments (EDs). The main endpoint was the proportion of patients with criteria for SE based on the collection and analysis of clinical characteristics and the ADAN scale criteria on arrival at the ED. RESULTS: Of the 527 patients recruited, 203 (38.5%) fulfilled the criteria that predicted SE. Multiple regression analysis demonstrated that the 4 ADAN criteria were the only variables independently associated with a final diagnosis of SE (P .001). The predictive power of the scale was 90.9% (95% CI, 88.4%-93.4%) for a final SE diagnosis. We established 3 risk groups based on ADAN scores: low (score, 0-1: 8.7%), moderate (2, 46.6%), and high (> 2, 92.6%). A cut point of more than 1 had a sensitivity of 88.2% for predicting SE, specificity of 77.8%, positive predictive value of 71.3%, and negative predictive value of 91.3%. CONCLUSION: The ADAN scale is a prospectively validated, simple clinical tool for identifying patients in the ED who are at high risk for SE.

OBJETIVO: El estado epiléptico (EE) es una enfermedad grave con elevada mortalidad. Este estudio tiene como objetivo validar la escala ADAN, propuesta recientemente para identificar pacientes con alto riesgo de desarrollar un EE. METODO: Se realizó un estudio prospectivo, multicéntrico y observacional que incluyó a pacientes adultos con sospecha de crisis epilépticas. Se llevó a cabo un reclutamiento consecutivo durante 27 meses en los servicios de urgencias (SU) de cuatro hospitales. La variable principal fue la proporción de pacientes que cumplían criterios para EE. Se han recopilado y analizado las características clínicas y la puntuación en la escala ADAN a su llegada al SU. RESULTADOS: Se reclutaron 527 pacientes, de los cuales 203 (38,5%) cumplieron criterios de EE. En el análisis de regresión múltiple, se demostró que el habla anormal, la desviación ocular, los automatismos y el número de crisis epilépticas motoras fueron las únicas variables independientemente asociadas con un diagnóstico final de EE (p 0,001). La capacidad predictiva de la escala fue del 90,9% (intervalo de confianza del 95%, 88,4-93,4) para identificar el EE como diagnóstico final. Se establecieron tres grupos de riesgo: bajo (0 1 puntos: 8,7%), moderado (2: 46,6%) y alto (> 2: 92,6%). Una puntuación de corte > 1 punto proporcionó una sensibilidad del 88,2%, especificidad del 77,8%, valor predictivo positivo del 71,3% y valor predictivo negativo del 91,3% para predecir el EE. CONCLUSIONES: La escala ADAN es una herramienta clínica simple y validada de manera prospectiva para identificar, en los SU, a los pacientes con elevado riesgo de EE.

Periodic discharges and status epilepticus: A critical reappraisal.

OBJECTIVE: Periodic Discharges (PDs) in Status Epilepticus (SE) are historically related to negative outcome, and the Epidemiology-based Mortality Score in SE (EMSE) identifies PDs as an EEG feature associated with unfavorable prognosis. However, supportive evidence is conflicting. This study aims to evaluate the prognostic significance of interictal PDs during and following SE. METHODS: All 2020-2023 non-hypoxic-ischemic SE patients with available EEG during SE were retrospectively assessed. Interictal PDs during SE (SE-PDs) and PDs occurring 24-72 h after SE resolution (post-SE-PDs) were examined. In-hospital death was defined as the primary outcome. RESULTS: 189 SE patients were finally included. SE-PDs were not related to outcome, while post-SE-PDs were related to poor prognosis confirmed after multiple regression analysis. EMSE global AUC was 0.751 (95%CI:0.680-0.823) and for EMSE-64 cutoff sensitivity was 0.85, specificity 0.52, accuracy 63%. We recalculated EMSE score including only post-SE-PDs. Modified EMSE (mEMSE) global AUC was 0.803 (95%CI:0.734-0.872) and for mEMSE-64 cutoff sensitivity was 0.84, specificity 0.68, accuracy 73%. CONCLUSION: Interictal PDs during SE were not related to outcome whereas PDs persisting or appearing > 24 h after SE resolution were strongly associated to unfavorable prognosis. EMSE performed well in our cohort but considering only post-SE-PDs raised specificity and accuracy for mEMSE64 cutoff. SIGNIFICANCE: This study supports the utility of differentiating between interictal PDs during and after SE for prognostic assessment.

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.

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.

[Long-term follow-up of adult patients with serial and status course of epileptic seizures]. / Dolgosrochnyi katamnez vzroslykh patsientov s epilepsiei s epilepticheskim statusom ili seriinymi pristupami.

OBJECTIVE: To study the follow-up of adult patients with status epilepticus or a history of serial seizures, assessing the likelihood of achieving long-term remission and identifying predictors of treatment effectiveness. MATERIAL AND METHODS: The study included 280 patients divided into 137 patients with epilepsy with a series of seizures or a history of status epilepticus (group 1) and 143 patients, who had not previously received therapy and did not have a series of seizures or a history of status epilepticus (group 2). A clinical and neurological examination, analysis of medical documentation data, electroencephalography, and MRI were performed. RESULTS: After correction of therapy, remission in patients in group 1 was achieved in 21.9%, improvement in 30%, no effect was observed in 48.1%; in group 2 the indicators were 51%, 28.7%, 20.3%, respectively. The onset of epilepsy in childhood, frequent seizures, and regional epileptiform activity were associated with the lack of treatment effect. CONCLUSION: The results confirm the main role of the clinical examination in determining the prognosis of epilepsy in a particular patient. Currently available instrumental techniques have limited predictive value.

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

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

Dynamic "spiked helmet sign": Further evidence for prolonged QT.

A 69-year-old woman was admitted after a cardiac arrest. She developed status epilepticus and was later found to have variable morphologies of a "spiked helmet sign" (SHS) on ECGs in the setting of prolonged QT interval, raising the question of whether this sign is a manifestation of QT prolongation.

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.

Evaluation of prognostic scores for status epilepticus in the neurology ICU: A retrospective study.

OBJECTIVE: Status epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU. METHODS: Neurology ICU patients with SE requiring continuous electroencephalography (cEEG) monitoring over a 10 year period were included. The STESS, EMSE-EACE and END-IT scores were applied retrospectively. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory value of the scores for inpatient mortality and functional decline, as measured by increase in the modified Rankin Scale (mRS) on discharge. RESULTS: Eighty-five patients were included in the study, of which 71 (83.5%) had refractory SE. Inpatient mortality was 36.5%. Sixty - seven (78.8%) of patients suffered functional decline, with a median mRS of 5 upon hospital discharge. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with inpatient mortality were 0.723 (95% CI 0.613-0.833), 0.722 (95% CI 0.609-0.834) and 0.560 (95% CI 0.436-0.684) respectively. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with functional decline were 0.604 (95% CI 0.468-0.741), 0.596 (95% CI 0.439-0.754) and 0.477 (95% CI 0.331-0.623). SIGNIFICANCE: SE was associated with high mortality and morbidity in this cohort of neurology ICU patients requiring cEEG monitoring. The STESS and EMSE-EACE scores had acceptable AUCs for prediction of inpatient mortality. However, the STESS, EMSE-EACE and END-IT were poorly-correlated with discharge functional outcomes. Further refinements of the scores may be necessary among neurology ICU patients for predicting discharge functional outcomes.

EEG and acute confusional state at the emergency department.

OBJECTIVES: Acute confusional state (ACS) is a common cause of admission to the emergency department (ED). It can be related to numerous etiologies. Electroencephalography (EEG) can show specific abnormalities in cases of non-convulsive status epilepticus (NCSE), or metabolic or toxic encephalopathy. However, up to 80% of patients with a final diagnosis of NCSE have an ACS initially attributed to another cause. The exact place of EEG in the diagnostic work-up remains unclear. METHODS: Data of consecutive patients admitted to the ED for an ACS in a two-year period and who were referred for an EEG were collected. The initial working diagnosis was based on medical history, clinical, biological and imaging investigations allowing classification into four diagnostic categories. Comparison to the final diagnosis was performed after EEG recordings (and sometimes additional tests) were performed, which allowed the reclassification of some patients from one category to another. RESULTS: Seventy-five patients (mean age: 71.1 years) were included with the following suspected diagnoses: seizures for 8 (11%), encephalopathy for 14 (19%), other cause for 34 (45%) and unknown for 19 (25%). EEG was recorded after a mean of 1.5 days after symptom onset, and resulted in the reclassification of patients as follows: seizure for 15 (20%), encephalopathy for 15 (20%), other cause for 29 (39%) and unknown cause for 16 (21%). Moreover, ongoing epileptic activity (NCSE or seizure) and interictal epileptiform activity were found in eight (11%) patients initially diagnosed in another category. DISCUSSION: In our cohort, EEG was a key examination in the management strategy of ACS in 11% of patients admitted to the ED. It resulted in a diagnosis of epilepsy in these patients admitted with unusual confounding presentations.

Neonatal seizures during extra corporeal membrane oxygenation support.

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1-20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1-7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4-103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8-41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7-52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97-20.5, p = 0.002)Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only.

Cerebral malaria presenting as nonconvulsive status epilepticus: a case report.

BACKGROUND: Malaria is an infectious malady caused by Plasmodium parasites, cerebral malaria standing out as one of its most severe complications. Clinical manifestation include elevated body temperature, loss of consciousness, and seizures. However, reports of cerebral malaria presenting as nonconvulsive status epilepticus are extremely rare. The case presented involves psychiatric symptoms, with the electroencephalogram indicated nonconvulsive status epilepticus associated with cerebral malaria. CASE PRESENTATION: A 53-year-old male, was urgently admitted, due to confusion and abnormal behaviour for 10 h. The patient returned to China after developing a fever while working in Tanzania two months ago. The blood smear revealed Plasmodium vivax and Plasmodium falciparum, and he was diagnosed with malaria. He recovered following anti-malarial treatment. After admission, the patient was confused, unable to communicate normally, and unwilling to cooperate with the physical examination. Plasmodium was not found in the blood smear, but the DNA sequence of P. falciparum was discovered using metagenomic next-generation sequencing of cerebrospinal fluid. Brain MRI revealed no significant abnormalities. Continuous electroencephalogram monitoring revealed that the patient had non-convulsive status epilepticus, which was treated with diazepam and levetiracetam. The patient had normal consciousness and behaviour. He received anti-malarial treatment for two weeks and fully recovered. CONCLUSIONS: This case demonstrates that nonconvulsive status epilepticus can be a manifestation of cerebral malaria. It is imperative for attending physicians to heighten vigilance when encountering patients with a history of travel to malaria-endemic regions or a prior malaria infection, especially in the presence of unusual clinical presentations.

Status epilepticus: what's new for the intensivist.

PURPOSE OF REVIEW: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. RECENT FINDINGS: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. SUMMARY: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.

Novel NARS2 variants in a patient with early-onset status epilepticus: case study and literature review.

BACKGROUND: NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy. CASE PRESENTATION: Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later. CONCLUSION: We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.