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.

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.

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.

[Initial Management of Status Epilepticus].

Status epilepticus(SE)is defined as a prolonged seizure and is a common neurological emergency with high morbidity and mortality rates. As uncontrolled SE causes irreversible neurological damage, prompt diagnosis and treatment are required. If anti-seizure medications and benzodiazepines, which are initial treatments for SE, are not effective and SE deteriorates to refractory, anesthetic drugs are needed to suppress seizure activity under electroencephalogram(EEG)monitoring. Continuous EEG monitoring is useful not only for evaluating the control of SE but also for diagnosing non-convulsive SE(NCSE)and psychogenic non-epileptic seizures. New-onset refractory status epilepticus is defined as refractory SE in a patient without active epilepsy and without a clear acute or active structural, toxic, or metabolic cause. Because autoimmune encephalitis is the most frequently identified cause, immunotherapy can be attempted in addition to antiepileptic treatment within 2 weeks. Although NCSE is the major cause of unconsciousness, diagnosis is difficult because of uncertain clinical symptoms. Continuous EEG monitoring over 24 h is crucial for diagnosis, although arterial spin labeling-magnetic resonance imaging is alternatively useful. Finally, the building of a multidisciplinary cooperation system is required for prompt diagnosis and intensive treatment for controlling SE.

[A case of cryptogenic new-onset refractory status epilepticus (NORSE) in which cerebrospinal fluid IL-6 was elevated with increased seizure frequency early in the disease: a case report].

A 25-year-old male presented with clonic seizures three days following a fever. The patient developed status epilepticus and required mechanical ventilation and intravenous anesthesia. The patient's epileptic seizures persisted despite administering intravenous anesthesia and multiple anti-epileptic drugs. The clinical presentation in this case, without pre-existing relevant neurological disorder and an active structural, toxic, or metabolic cause in the acute phase, was compatible with new-onset refractory status epilepticus (NORSE). After immunotherapy, including intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin therapy, the epileptic discharge on electroencephalogram (EEG) decreased gradually, and mechanical ventilation was discontinued. Neversless the final outcome was poor. The patient's condition was finally diagnosed as cryptogenic NORSE. The IL-6 levels in the cerebrospinal fluid showed a significant increase between day 6 and 11 after onset, during which time there was a rapid escalation in seizure frequency on EEG. Considering this, IL-6 may be involved in the process of seizure exacerbation.

[Status epilepticus after brain tumor surgery]. / Epilepticheskii status posle udaleniya opukholei golovnogo mozga.

BACKGROUND: Status epilepticus (SE) is characterized by continuous course of clinical and/or electrographic epileptic seizures. There are little data on the course and outcomes of SE after resection of brain tumors. OBJECTIVE: To analyze clinical and electrographic manifestations of SE, its course and outcomes in short-term period after resection of brain tumors. MATERIAL AND METHODS: We analyzed medical records of 18 patients over 18 years old between 2012 and 2019. All patients underwent resection of brain tumor and developed SE after surgery. Clinical criteria were repeated epileptic seizures without interictal recovery of consciousness, stereotypical motor phenomena, impaired consciousness with continued epileptic activity according to video-EEG data. We analyzed EEG data, neurological status, CT and laboratory data. RESULTS: Metastases (33%) and meningiomas (16%) prevailed. Supratentorial tumors were observed in 61% of patients. Two patients had preoperative seizures. Non-convulsive SE was diagnosed in 62% of patients. SE was successfully treated in 77% of cases. Mortality rate in patients with SE was 44%. CONCLUSION: Early postoperative SE is rare after brain tumor surgery (about 0.09%). Nevertheless, this complication is associated with high mortality. Non-convulsive SE is common (62%) that should be considered in postoperative management.

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.

Epileptiform patterns predicting unfavorable outcome in postanoxic patients: A matter of time?

OBJECTIVE: Historically, epileptiform malignant EEG patterns (EMPs) have been considered to anticipate an unfavorable outcome, but an increasing amount of evidence suggests that they are not always or invariably associated with poor prognosis. We evaluated the prognostic significance of an EMP onset in two different timeframes in comatose patients after cardiac arrest (CA): early-EMPs and late-EMPs, respectively. METHODS: We included all comatose post-CA survivors admitted to our intensive care unit (ICU) between 2016 and 2018 who underwent at least two 30-minute EEGs, collected at T0 (12-36 h after CA) and T1 (36-72 h after CA). All EEGs recordings were re-analyzed following the 2021 ACNS terminology by two senior EEG specialists, blinded to outcome. Malignant EEGs with abundant sporadic spikes/sharp waves, rhythmic and periodic patterns, or electrographic seizure/status epilepticus, were included in the EMP definition. The primary outcome was the cerebral performance category (CPC) score at 6 months, dichotomized as good (CPC 1-2) or poor (CPC 3-5) outcome. RESULTS: A total of 58 patients and 116 EEG recording were included in the study. Poor outcome was seen in 28 (48%) patients. In contrast to late-EMPs, early-EMPs were associated with a poor outcome (p = 0.037), persisting after multiple regression analysis. Moreover, a multivariate binomial model coupling the timing of EMP onset with other EEG predictors such as T1 reactivity and T1 normal voltage background can predict outcome in the presence of an otherwise non-specific malignant EEG pattern with quite high specificity (82%) and moderate sensitivity (77%). CONCLUSIONS: The prognostic significance of EMPs seems strongly time-dependent and only their early-onset may be associated with an unfavorable outcome. The time of onset of EMP combined with other EEG features could aid in defining prognosis in patients with intermediate EEG patterns.

Neuropathology of New-Onset Refractory Status Epilepticus (NORSE).

New-Onset Refractory Status Epilepticus (NORSE), including its subtype with a preceding febrile illness known as FIRES (Febrile Infection-Related Epilepsy Syndrome), is one of the most severe forms of status epilepticus. Despite an extensive workup (clinical evaluation, EEG, imaging, biological tests), the majority of NORSE cases remain unexplained (i.e., "cryptogenic NORSE"). Understanding the pathophysiological mechanisms underlying cryptogenic NORSE and the related long-term consequences is crucial to improve patient management and preventing secondary neuronal injury and drug-resistant post-NORSE epilepsy. Previously, neuropathological evaluations conducted on biopsies or autopsies have been found helpful for identifying the etiologies of some cases that were previously of unknown cause. Here, we summarize the findings of studies reporting neuropathology findings in patients with NORSE, including FIRES. We identified 64 cryptogenic cases and 66 neuropathology tissue samples, including 37 biopsies, 18 autopsies, and seven epilepsy surgeries (the type of tissue sample was not detailed for 4 cases). We describe the main neuropathology findings and place a particular emphasis on cases for which neuropathology findings helped establish a diagnosis or elucidate the pathophysiology of cryptogenic NORSE, or on described cases in which neuropathology findings supported the selection of specific treatments for patients with NORSE.

Manejo del estado epiléptico en niños: encuesta en hospitales pediátricos de la Ciudad Autónoma de Buenos Aires / Management of status epilepticus in childhood: a survey conducted at pediatric hospitals in the City of Buenos Aires

Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.

Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous access is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.

Status Epilepticus in Older Adults: Diagnostic and Treatment Considerations.

Status epilepticus (SE) is one of the leading life-threatening neurological emergencies in the elderly population, with significant morbidity and mortality. SE presents unique diagnostic and therapeutic challenges in the older population given overlap with other causes of encephalopathy, complicating diagnosis, and the common occurrence of multiple comorbid diseases complicates treatment. First-line therapy involves the use of rescue benzodiazepine in the form of intravenous lorazepam or diazepam, intramuscular or intranasal midazolam and rectal diazepam. Second-line therapies include parenteral levetiracetam, fosphenytoin, valproate and lacosamide, and underlying comorbidities guide the choice of appropriate medication, while third-line therapies may be influenced by the patient's code status as well as the cause and type of SE. The standard of care for convulsive SE is treatment with an intravenous anesthetic, including midazolam, propofol, ketamine and pentobarbital. There is currently limited evidence guiding appropriate therapy in patients failing third-line therapies. Adjunctive strategies may include immunomodulatory treatments, non-pharmacological strategies such as ketogenic diet, neuromodulation therapies and surgery in select cases. Surrogate decision makers should be updated early and often in refractory episodes of SE and informed of the high morbidity and mortality associated with the disease as well as the high probability of subsequent epilepsy among survivors.

Bridging the Gap: Tailoring an Approach to Treatment in Febrile Infection-Related Epilepsy Syndrome.

Cytokine profiling before immunotherapy is increasingly prevalent in febrile infection-related epilepsy syndrome (FIRES). In this case, an 18-year-old man presented with first-onset seizure after a nonspecific febrile illness. He developed super-refractory status epilepticus requiring multiple antiseizure medications and general anesthetic infusions. He was treated with pulsed methylprednisolone and plasma exchange and started on ketogenic diet. Contrast-enhanced MRI brain revealed postictal changes. EEG findings showed multifocal ictal runs and generalized periodic epileptiform discharges. CSF analysis, autoantibody testing, and malignancy screening were unremarkable. Genetic testing revealed variants of uncertain significance in the CNKSR2 and OPN1LW genes. Initial serum and CSF cytokine analyses performed on days 6 and 21 revealed that interleukin (IL)-6, IL-1RA, monocyte chemoattractant protein-1, macrophage inflammatory protein 1ß, and interferon γ were elevated predominantly in the CNS, a profile consistent with cytokine release syndrome. Tofacitinib was initially trialed on day 30 of admission. There was no clinical improvement, and IL-6 continued to rise. Tocilizumab was given on day 51 with significant clinical and electrographic response. Anakinra was subsequently trialed from days 99 to 103 because clinical ictal activity re-emerged on weaning anesthetics but stopped because of poor response. Serial cytokine profiles showed improvement after 7 doses of tocilizumab. There was corresponding improved seizure control. This case illustrates how personalized immunomonitoring may be helpful in cases of FIRES, where proinflammatory cytokines are postulated to act in epileptogenesis. There is an emerging role for cytokine profiling and close collaboration with immunologists for the treatment of FIRES. The use of tocilizumab may be considered in patients with FIRES with upregulated IL-6.

[Elderly Onset Epilepsy and Post-Stroke Epilepsy].

It has been reported that the incidence of epilepsy in individuals over the age of 75 years is similar to or higher than one year, suggesting that epilepsy is an important clinical condition in older people. The aging rate in Japan, which reached 27.3% in 2017, makes this an issue of increasing concern. Diagnosis begins with the collection of medical history and knowledge of seizure semiology. In the elderly, most seizures are of extratemporal origin with various seizure semiologies. Difficulties in diagnosis lie in the influence of the autonomic nervous system and nonconvulsive status epilepticus(NCSE). It is necessary to suspect "epilepsy" for any sudden-onset episodes of atypical symptoms and unusual behaviors. NCSE can be diagnosed by recording EEG for more than 6 hours. The narrow therapeutic window and pharmacokinetics complicated by aging make treatment much more difficult with anti-seizure medication(ASM). Comorbidities and drug interactions should also be considered. Stroke is the most common etiology of geriatric epilepsy. Despite several clinical reports on the risk factors of post-stroke epilepsy(PSE)on the preventive administration of enzyme-inducing ASM, a treatment protocol has not yet been established. Prophylactic administration is not recommended; however, ASM is often administered in the acute phase. Therefore, some guidelines for non-enzyme-inducing ASM are required for efficient control of PSE.

[Status Epilepticus: Convulsive and Nonconvulsive].

Status epilepticus(SE)is common, particularly among neurological emergency physicians. SE includes convulsive SE(CSE)and nonconvulsive SE(NCSE). Recently, the number of elderly patients with status epilepticus has increased. Most patients were diagnosed with NCSE. Prolonged SE often impairs neuronal function and is sometimes life threatening. Prompt diagnosis of SE and treatment initiation are essential for good outcomes. However, an accurate diagnosis of NCSE is difficult because the clinical symptoms of NCSE may vary, and electroencephalography may show various characteristics. Recent advances in the diagnosis and treatment of SE have been reported, particularly with regard to electroencephalography(EEG)and newly available drugs.

High end-of-life incidence of seizures and status epilepticus in patients with primary and secondary brain tumors.

PURPOSE: Seizures pose a significant burden in patients with primary and secondary brain tumors during the end-of-life period. A wide range of 6 to 56% of clinically observed epileptic seizures at the end of life has been reported. We aimed to analyse the incidence of epileptic seizures at the end of life in brain tumor patients more accurately using not only clinical but also electrophysiological findings. METHODS: This retrospective, single center study included brain tumor patients who died during the stay on the ward or within 7 days after discharge between 01/2015 and 08/2020. Clinical observation of seizures derived from the original medical records and EEG findings (within 45 days prior to death) were analyzed to determine the incidence of seizures in that period. RESULTS: Of the 68 eligible patients, 50 patients (73.5%) suffered from seizures within 45 days prior to death, of which n = 24 had a status epilepticus. The diagnosis of seizures/ status epilepticus was determined either by the presentation of clinical signs in 45 patients and if not, by the detection of a (possible) non-convulsive status epilepticus in the EEG of five patients. CONCLUSION: In the presence of neurologically trained staff and with the frequent use of routine EEG, we were able to identify seizures and to distinguish status epilepticus from encephalopathy/ hypoactive delirium. We detected a higher incidence of seizures and status epilepticus at the end of life in neurooncological patients than previously reported.

The clinical analysis of new-onset status epilepticus.

OBJECTIVE: To investigate and analyze the etiology and prognosis of patients with new-onset status epilepticus (NOSE). METHODS: We conducted a retrospective analysis of all adult patients (≧16 years old) who were admitted to Sichuan Provincial People's Hospital between January 2018 and December 2020 with status epilepticus (SE) and no prior epilepsy history. RESULTS: We collected data from 85 patients, aged from 16 to 90 years, of whom 49 were male and 36 were female. Fifty-five of these cases (64.7%) were younger than 60 years of age. Acute symptomatic SE was mostly seen in the NOSE (53.9%), followed by unknown SE (25.9%), progressive SE (11.8%), and remote SE (9.4%). The differences in the etiology of NOSE between age groups were statistically significant (P < .05). For the young, the main etiology remained unknown (36.3%), followed by autoimmune-related SE (16.4%); in the elderly, the primary etiology was central nervous system (CNS) infection (23.3%), followed by cerebrovascular disease (20%), and intracranial tumors (20%). Normal imaging was mostly seen in young people with NOSE (P < .001). Regarding outcome parameters and risk factors in patients with NOSE, adverse outcome was associated with age (OR = 3.5, 95% CI = 0.108-0.758, P = .012), co-infection (OR = 4.5, 95% CI = 0.083-0.599, P = .003), and tracheal intubation (OR = 6.318, 95% CI = 0.060-0.204, P = .011). SIGNIFICANCE: In our cohort, intracranial tumors, CNS infections, and cerebrovascular disease were the predominant causes of NOSE in the elderly, while autoimmune encephalitis was the largest recognized cause of NOSE in young patients. In addition, imaging varies with age. According to the data, preventing infections may enhance patient prognosis because greater infection rates are connected with less favorable results. Meanwhile, age and mechanical ventilation are related to the prognosis of NOSE.

Long-term outcome of convulsive status epilepticus: a 10-year follow-up

Objective: This study aimed to determine the mortality, causes of death and factors affecting the outcome of convulsive status epilepticus (CSE) at 10 years. Method: This retrospective study consisted of 62 consecutive adult patients diagnosed with CSE at the Helsinki University Hospital (HUS) emergency department during 2002-2003. Patients were followed for up to 10 years or up to the time of death. Data on patient demographics, CSE characteristics, treatment, complications, and outcome from the time of CSE were collected. The Official Statistics of Finland provided the information on mortality and causes of death. Survival analysis was conducted using Cox proportional hazards regression analysis. Results: In-hospital mortality was 8.1%, and mortality was 25.8% at one year, 51.6% at five years and 64.5% at 10 years. Estimated standardized mortality ratio (SMR) was 5.3 and the deceased patients lost 20.9 potential years of life, on average. The leading causes of death were disorders of the brain or the circulatory system, epilepsy-related conditions or intracranial tumours. The univariable survival analysis demonstrated that age ≥65 (HR=2.8, p=0.001), Charlson Comorbidity Index (CCI)>0 (CCI=1-3: HR=3.0, p=0.009; CCI>3: HR=8.4, p<0.001), Status Epilepticus Severity Score (STESS)>4 (HR=5.3, p<0.001) and Epidemiology-Based Mortality Score (EMSE-EAC)>15 (HR=2.2, p=0.036) were risk factors and a Glasgow outcome scale (GOS) of 5 at discharge (HR=0.14, p=0.025) was a protective factor for survival. The multivariable analysis established STESS>4 (HR=5.0, p=0.002) and CCI>0 (CCI=1-3: HR=2.9, p=0.015;CCI>3: HR=6.3, p=0.006) as independent risk factors and GOS>3 (time-dependent) (GOS=4: HR=0.33, p=0.048;GOS=5: HR=0.13, p=0.019) as a protective factor for survival. Significance: The rate of long-term mortality and number of potential years of life lost were high. Factors demonstrative of the overall situation of the patients, such as comorbidities, functional state after CSE and age, were significant predictors for long-term outcome.

Encephalitis with status epilepticus and stroke as complications of non-severe COVID-19 in a young female patient: a case report.

BACKGROUND: Neurological manifestations of COVID-19 are thought to be associated with the disease severity of COVID-19 and poor clinical outcomes. Dysregulated immune responses are considered to be mediating such complications. Our case illustrates multiple critical neurological complications simultaneously developed in a patient with non-severe COVID-19 and successful recovery with a multifaceted therapeutic approach. The cerebrospinal fluid (CSF) interleukin-6 (IL-6) level was temporally correlated with the clinical severity of the status epilepticus in our patient, suggesting a causal relationship. CASE PRESENTATION: A previously healthy 20-year-old female patient presented with a first-onset seizure. Concomitant non-severe COVID-19 pneumonia was diagnosed. CSF study showed lymphocytic pleocytosis with elevated IL-6 levels in CSF. During hospitalization under the diagnosis of autoimmune encephalitis, status epilepticus developed, and the seizure frequency was temporally correlated with the CSF IL-6 level. Furthermore, a new embolic stroke developed without a significant cardioembolic source. Contrary to the exacerbated COVID-19-associated neurological complications, COVID-19 pneumonia was cleared entirely. After treatment with antiseizure medications, antithrombotics, antiviral agents, and immunotherapy, the patient was discharged with near-complete recovery. CONCLUSION: Active serological, and radiological evaluation can be helpful even in non-severe COVID-19, and multidimensional treatment strategies, including immunotherapy, can successfully reverse the neurological complication.

Development and Validation of a Nomogram Based on the Epidemiology-Based Mortality Score in Status Epilepticus (EMSE) Parameters to Predict 30-day Mortality in Status Epilepticus.

BACKGROUND: To develop a nomogram using the parameters of the Epidemiology-Based Mortality Score in Status Epilepticus (EMSE) and to evaluate its accuracy compared with the EMSE alone in the prediction of 30-day mortality in patients with status epilepticus (SE). METHODS: We included a cohort of patients with SE aged ≥ 21 years admitted from 2013 to 2021. Regression coefficients from the multivariable logistic regression model were used to generate a nomogram predicting the risk of 30-day mortality. Discrimination of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUCROC) with 95% confidence interval. Internal validation was performed by bootstrap resampling. RESULTS: Among 698 patients with SE, the 30-day mortality rate was 28.9% (202 of 698). On the multivariable analysis, all EMSE parameters (except for the comorbidity group including metastatic solid tumor or AIDS) were associated with a significantly higher risk of 30-day mortality and were included in the nomogram. The discriminatory capability of the nomogram with bootstrap resampling (5000 resamples) had an AUCROC of 0.830 (95% confidence interval 0.798-0.862). Conversely, the AUCROC of the EMSE was 0.777 (95% confidence interval 0.742-0.813). Thus, the probability that a patient who died within 30 days from SE had a higher score than a patient who survived was 83%, indicating good discriminatory power of the nomogram. Conversely, the risk predicted using the EMSE alone was 77%. The nomogram was well calibrated. CONCLUSIONS: A nomogram based on EMSE parameters appears superior to the EMSE in predicting the risk of 30-day mortality after SE. The discrimination and calibration of the nomogram shows a better predictive accuracy than the EMSE alone.