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.

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.

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.

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.

Diagnosis of Lennox-Gastaut syndrome and strategies for early recognition.

INTRODUCTION: Lennox Gastaut syndrome (LGS) as an electroclinical diagnosis has been utilized as a clinical entity for more than 70 years. However, with the recognition of other distinct electroclinical epilepsy syndromes, no consistent single etiology, and the variability of criteria used in clinical trials, the clinical utility of such a diagnosis has been questioned. Recently, the International League Against Epilepsy for the first time defined diagnostic criteria for epilepsy syndromes, thereby allowing consistent language and inclusion criteria to be utilized. AREAS COVERED: Recent diagnostic criteria for syndrome diagnosis are explored as defined by the International League Against Epilepsy, with further literature reviewed to highlight relevant features, and differential diagnosis explored. EXPERT OPINION: Developmental and Epileptic Encephalopathy (DEE) is an overall term that may be descriptive of many different epilepsies, most of early onset, whether electroclinically or etiologically defined, of which LGS is one. Although we have moved forward in defining an increasing number of etiologically specific syndromes, this to date remains a minority of the DEEs. Although there is progress with precision medicine targeted at specific causes, the term LGS still remains useful as a diagnosis in defining treatment options, as well as overall prognosis.

Correlation between serum galanin and neuron-specific enolase levels with EEG abnormalities in pediatric convulsive status epilepticus and the efficacy of triple drug therapy.

OBJECTIVE: This study aimed to investigate the association between serum galanin (GAL) and neuron-specific enolase (NSE) levels in children with convulsive status epilepticus (CSE) and their relationship with abnormal electroencephalogram (EEG) patterns. Additionally, the study assessed the effectiveness of a combination therapy involving midazolam, diazepam, and phenobarbital in treating CSE. PATIENTS AND METHODS: The research involved 100 children diagnosed with CSE and included a control group of 50 healthy children. Serum GAL and NSE levels were measured, and EEGs were analyzed for abnormalities in the CSE group. Comparisons were made between the healthy control group and the CSE group, particularly within the first 24 hours after persistent seizures. The severity of EEG abnormalities was correlated with GAL and NSE levels. The treatment consisted of an observation group that received the triple therapy of midazolam, diazepam, and phenobarbital, while a control group received diazepam and phenobarbital. Clinical efficacy, symptom improvement, Status Epilepticus Severity Score (STESS), and adverse reactions were evaluated. RESULTS: The results indicated elevated levels of GAL and NSE in the CSE group, with higher levels noted within 24 hours after persistent seizures. Furthermore, a positive correlation was observed between the severity of EEG abnormalities and GAL and NSE levels. The group receiving the triple therapy demonstrated superior efficacy, faster resolution of seizures and fever, reduced STESS scores, and fewer adverse reactions than the control group. In conclusion, this study highlights the positive correlation between serum GAL and NSE levels and the severity of EEG abnormalities in pediatric CSE. The triple therapy approach is effective in treating CSE, leading to improved clinical symptoms, reduced brain damage, and enhanced safety. CONCLUSIONS: The study concludes that serum GAL and NSE levels in children with convulsive status epilepticus are positively correlated with the degree of EEG abnormalities. The combination therapy involving midazolam, diazepam, and phenobarbital is effective in treating children with convulsive status epilepticus, significantly improving clinical symptoms, reducing brain damage, and ensuring safety.

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.

Impact of frailty, biomarkers and basic biochemical parameters on outcomes of comatose patients in status epilepticus: a single-center prospective pilot study.

BACKGROUND: Status epilepticus (SE) is a severe acute condition in neurocritical care with high mortality. Searching for risk factors affecting the prognosis in SE remains a significant issue. The primary study's aim was to test the predictive values of the Clinical Frailty Scale (CFS) and the Modified 11-item Frailty Index (mFI-11), the biomarkers and basic biochemical parameters collected at ICU on the Glasgow Outcome Scale (GOS) assessed at hospital discharge (hosp), and three months later (3 M), in comatose patients with SE. The secondary aim was to focus on the association between the patient's state at admission and the duration of mechanical ventilation, the ICU, and hospital stay. METHODS: In two years single-centre prospective pilot study enrolling 30 adult neurocritical care patients with SE classified as Convulsive SE, A.1 category according to the International League Against Epilepsy (ILAE) Task Force without an-/hypoxic encephalopathy, we evaluated predictive powers of CFS, mFI-11, admission Status Epilepticus Severity Score (STESS), serum protein S100, serum Troponin T and basic biochemical parameters on prognosticating GOS using univariate linear regression, logistic regression and Receiver Operating Characteristic (ROC) analysis. RESULTS: Our study included 60% males, with a mean age of 57 ± 16 years (44-68) and a mean BMI of 27 ± 5.6. We found CFS, mFI-11, STESS, and age statistically associated with GOS at hospital discharge and three months later. Among the biomarkers, serum troponin T level affected GOS hosp (p = 0.027). Serum C-reactive protein significance in prognosticating GOS was found by logistic regression (hosp p = 0.008; 3 M p = 0.004), and serum calcium by linear regression (hosp p = 0.028; 3 M p = 0.015). In relation to secondary outcomes, we found associations between the length of hospital stay and each of the following: age (p = 0.03), STESS (p = 0.009), and serum troponin T (p = 0.029) parameters. CONCLUSIONS: This pilot study found promising predictive powers of two frailty scores, namely CFS and mFI-11, which were comparable to age and STESS predictors regarding the GOS at hospital discharge and three months later in ICU patients with SE. Among biomarkers and biochemical parameters, only serum troponin T level affected GOS at hospital discharge.

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Electroencephalography in encephalopathy and encephalitis.

Electroencephalography (EEG) is a useful adjunct to clinical neurological examination, particularly as it may detect subtle or subclinical disturbance of cerebral function and it allows monitoring of cerebral activity over time. Continuous EEG combined with quantitative analysis and machine learning may help identify changes in real time, before the emergence of clinical signs and response to interventions. EEG is rarely pathognomonic in encephalopathy/encephalitis but when interpreted correctly and within the clinical context, certain phenotypes may indicate a specific pathophysiology (eg, lateralised periodic discharges in HSV-1, generalised periodic discharges in sporadic Creutzfeldt-Jakob disease, and extreme delta brushes in anti-n-methyl-D-aspartate receptor autoimmune encephalitis). EEG is included in some specialist guidelines for disease assessment, monitoring and prognostication (ie, hepatic, cancer immunotherapy, viral, prion, autoimmune encephalitis and hypoxic ischaemic encephalopathy). EEG is invaluable for confirming or excluding non-convulsive seizures or status epilepticus, particularly in critically ill patients, and in understanding new concepts such as epileptic encephalopathy and the ictal-interictal continuum.

Prevalence of non-convulsive seizures and electroencephalographic abnormalities in critically ill patients-A retrospective observational study.

OBJECTIVE: Electroencephalographic (EEG) abnormalities especially non-convulsive status epilepticus (NCSE) have been found to be associated with worse outcomes in critically ill patients. We aimed to assess the prevalence of non-convulsive seizures and electroencephalographic abnormalities in critically ill patients. Furthermore, we aimed to investigate any association between the type of EEG abnormality and outcomes including ICU mortality and successful ICU discharge. METHODS: This was a cross-sectional observational study carried out among critically ill patients in a mixed medical-surgical ICU from January 1, 2018 to May 15, 2020. A total of 178 records of 30 min bedside EEG records were found. EEG findings were grouped as normal, non-convulsive seizures (NCS), non-convulsive status epilepticus (NCSE), and other abnormalities. Descriptive analytical tools were used to characterize the case details in terms of the type of EEG abnormalities. Chi square test was used to describe the EEG abnormalities in terms of mortality. The status epilepticus severity scores (STESS) were further calculated for records with NCSE. These data were then analyzed for any association between STESS and mortality for cases with NCSE. RESULTS: The prevalence of EEG abnormality in our cohort of all critically ill patients was found to be 7.3% (170/2234). Among the patients with altered sensorium in whom EEG was done, 42.9% had non-conclusive seizure activity with 25.2% in NCSE. Though the study was not adequately powered, there was a definite trend towards a lower proportion of successful ICU discharge rates seen among patients with higher STESS (>2) with only 33.3% being discharged for patients with a STESS of 6 versus 92.9% for those with STESS 3. SIGNIFICANCE: When combined with a strong clinical suspicion, even a 30-min bedside EEG can result in detection of EEG abnormalities including NCS and NCSE. Hence, EEG should be regularly included in the evaluation of critically ill patients with altered sensorium. PLAIN LANGUAGE SUMMARY: Electroencephalographic (EEG) abnormalities and seizures can have high prevalence in critically ill patients. These abnormalities notably, non-convulsive status epilepticus (NCSE) has been found to be associated with poor patient outcomes. This was a retrospective observational study analyzing 178 EEG records, from a mixed medical-surgical ICU. The indication for obtaining an EEG was based solely on the clinical suspicion of the treating physician. The study found a high prevalence of EEG abnormalities in 96.5% in whom it was obtained with 42.9% having any seizure activity and 28.8% having NCSE. The study was not powered for detection of association of the EEG abnormalities with clinical outcomes. However, a definite trend towards decreased chances of successful discharge from the ICU was seen. This study used strong clinical suspicion in patients with altered sensorium to obtain an EEG. High detection rates of EEG abnormalities were recorded in this study. Hence, combination of clinical judgement and EEG can improve detection of EEG abnormalities and NCSE.

Ictal EEG: Etiology and Mortality in Older Adults With Nonconvulsive Status Epilepticus.

Clinical-electroencephalogram (EEG), as well as etiological and prognostic data on subtypes of nonconvulsive status epilepticus (NCSE) are yet to be established. Objective: Evaluate the clinical semiology and EEG findings and prognostic data of older adults with NCSE. Methodology: Characterize the clinical-EEG and prognostic data in the subtypes of NCSE in older adults consecutively admitted to the emergency room of the Pontifícia Universidade Católica de Campinas (PUC-Campinas) University Hospital. Results: When evaluating 105 older adults with altered consciousness, it was possible to diagnose NCSE in 50 (47.6%) older adults, with a mean age of 72.8 ± 8.8 years. NCSE-coma occurred in 6 cases, with NCSE-without coma in 44 cases. The etiology was structural in 41(82%) cases, metabolic in 5 cases, and unknown etiology in 4 cases. Twelve cases had a history of epileptic seizures. On the EEG, epileptiform discharges (EDs > 2.5 Hz) were present in 34(68%) cases and rhythmic delta activity /lateralized periodic patterns occurred in 35(70%) cases. There was clinical improvement after the initial pharmacological treatment in 36 cases and, within 30 days, 18 cases died. The better prognosis was associated with a good response to initial pharmacological treatment (n = 14) and with EDs > 2.5 Hz on EEG (Fisher's exact test; 26 vs 8; P = .012). Conclusion: Focal NCSE with impaired consciousness was the most frequent subtype. The most frequent finding on the EEG was the recording of focal/regional seizures. A high number of cases showed initial clinical improvement, but mortality was high. The favorable prognosis was associated with initial clinical improvement and the presence of EDs > 2.5 Hz. There was no relationship between EEG patterns and the etiology and subtypes of NCSE in older adults.