Premature Mortality and Causes of Death Among People With Epilepsy: A Nationwide Population-Based Incident Cohort Study.

BACKGROUND AND OBJECTIVES: People with epilepsy (PWE) are at risk of premature death with considerable variability according to the study population. We aimed to estimate the risk and causes of death in PWE according to age, disease severity, disease course, comorbidities, and socioeconomic status in Korea. METHODS: We conducted a nationwide population-based retrospective cohort study using the National Health Insurance database linked with the national death register. Newly treated PWE from 2008 to 2016 who were identified by antiseizure medication (ASM) prescriptions and diagnostic codes for epilepsy/seizure were included and observed until 2017. We assessed all-cause and cause-specific crude mortality rates and standardized mortality ratios (SMRs). RESULTS: Among 138,998 PWE, 20,095 deaths were identified, and the mean follow-up period was 4.79 years. The SMR was 2.25 in the overall group of PWE, with a higher value in the younger age group at diagnosis and a shorter time interval after diagnosis. The SMR in the monotherapy group was 1.56, while that in the group with 4 or more ASMs was 4.93. PWE without any comorbidities had an SMR of 1.61. PWE who were rural residents had a higher SMR than those who were urban residents (2.47 vs 2.03, respectively). The causes of death among PWE were cerebrovascular disease (18.9%, SMR 4.50), malignant neoplasms outside the CNS (15.7%, SMR 1.37), malignant neoplasms of the CNS (6.7%, SMR 46.95), pneumonia (6.0%, SMR 2.08), and external causes (7.2%, SMR 2.17), including suicide (2.6%, SMR 2.07). Epilepsy itself and status epilepticus accounted for 1.9% of the overall death. The excess mortality associated with pneumonia and external causes was persistently high, whereas the excess mortality associated with malignancy and cerebrovascular diseases tended to decrease with increasing time since diagnosis. DISCUSSION: This study showed excess mortality in PWE, even in those without comorbidities and those receiving monotherapy. Regional disparities and sustained risks of deaths from external causes over 10 years imply potential points of intervention. In addition to active control of seizures, education about injury prevention, monitoring for suicidal ideation, and efforts to improve accessibility to epilepsy care are all required to reduce mortality.

Sleep and Circadian Rhythm in Relation to COVID-19 and COVID-19 Vaccination-National Sleep Survey of South Korea 2022.

BACKGROUND: Currently, information on sleep and circadian patterns in relation to COVID-19 or vaccination remains limited. We aimed to investigate sleep and circadian patterns according to history of COVID-19 and COVID-19 vaccination side effects. METHODS: We used data from the National Sleep Survey of South Korea 2022, a nationwide cross-sectional population-based survey regarding sleep-wake behaviors and sleep problems among Korean adults. Analysis of covariance (ANCOVA) and logistic regression analyses were performed to explore the different sleep and circadian patterns according to the history of COVID-19 or self-reported side effects of the COVID-19 vaccination. RESULTS: The ANCOVA showed that individuals with a history of COVID-19 presented a later chronotype than individuals without a history of COVID-19. Individuals who had experienced vaccine-related side effects had a shorter sleep duration, poorer sleep efficiency, and worse insomnia severity. Multivariable logistic regression analysis showed a later chronotype related to COVID-19. A short sleep duration, poorer sleep efficiency, and worse insomnia severity were associated with self-reported side effects of the COVID-19 vaccination. CONCLUSIONS: Individuals who recovered from COVID-19 had a later chronotype than those without a history of COVID-19. Individuals who had experienced vaccine-related side effects presented with poorer sleep than those without side effects.

Mortality, Disability, and Prognostic Factors of Status Epilepticus: A Nationwide Population-Based Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: The outcome of status epilepticus (SE) largely varies depending on clinical characteristics. Risk stratification is necessary for tailoring the aggressiveness of treatment and predicting outcomes of individual patients with SE. In this study, we assessed differences in mortality, neurologic disability, and prognostic factors associated with SE across sociodemographic and clinical characteristics. METHODS: We conducted a nationwide population-based retrospective cohort study using the National Health Insurance Service (NHIS) database linked with the national death and disability registries. SE was identified from admission or emergency department visits using a diagnostic code of G41 from the International Classification of Diseases, 10th Revision. Individuals with new-onset SE that occurred from January 1, 2010, to December 31, 2018, were included. Active epilepsy, refractoriness of SE, potential etiology, and comorbidities were ascertained by diagnostic codes and/or prescription records from the NHIS database as potential prognostic factors. Outcomes included 30-day and 1-year mortality and neurologic disabilities after SE. Prognostic factors for mortality were assessed by the Cox regression hazard model. We performed a subgroup analysis according to age: pediatric SE (age <20 years) and adult SE (age ≥20 years). RESULTS: A total of 33,814 patients with new-onset SE were included (6,818 children/adolescents and 26,996 adults). The 30-day mortality was 8.5% (1.8% in pediatric SE and 10.2% in adult SE), and the 1-year mortality was 25.1% (4.6% in pediatric SE and 30.3% in adult SE). Overall, 10.7% of patients newly acquired neurologic disabilities after SE, with the highest incidence in children aged 5-9 years (21.3%). Intractable epilepsy developed in 0.8% of entire SE. Old age, presence of acute etiology, and refractoriness were poor prognostic factors for mortality in both pediatric and adult SE. Male sex, low economic status, no active epilepsy, and comorbidities were additional factors for a poor prognosis in adults. DISCUSSION: New-onset SE was associated with substantial mortality and disability. Although SE-related mortality was higher in adults, disabilities developed more commonly in children and adolescents. The major determinants of mortality differed between pediatric and adult SE.

Trends in Prescribing of Antiseizure Medications in South Korea: Real-World Evidence for Treated Patients With Epilepsy.

BACKGROUND AND PURPOSE: We investigated the trends in the prescribing of antiseizure medication (ASM) over a 9-year period, and provide real-world data regarding ASM prescriptions of patients with epilepsy in South Korea. METHODS: This study used data in the Korean National Health Information Database for the period from 2009 to 2017. We included 18 oral ASMs, which were classified into older and newer ASMs based on them first becoming available on the market before or after 1991, respectively. The annual trends in ASM prescriptions were plotted over the 9-year study period, and changes in these trends were evaluated as average annual percentage changes (AAPCs) using Poisson regression. Age- and sex-stratified analyses were also conducted. RESULTS: Overall, the proportion of prescriptions involving polytherapy with three or more ASMs increased from 10.08% in 2009 to 10.99% in 2017 (AAPC=0.9%, p<0.001) over the 9-year study period. Among monotherapies, although valproate (VPA) was the most frequently prescribed ASM, the prescription rate of levetiracetam (LEV) steadily increased regardless of age and sex over the study period. The monotherapy prescription trends differed depending on age and sex. In the five most frequently used ASM combination regimens, the prescription rates of VPA/LEV, LEV/oxcarbazepine, and LEV/lamotrigine regimens showed increasing tendencies. In contrast, prescription rates for all combined regimens of older ASMs declined over time in all age groups. CONCLUSIONS: This is the first epidemiological study of the changes in prescription trends for ASM in South Korea based on nationwide data from 2009 to 2017. We found progressive increases in the use of newer ASMs for both monotherapy and duotherapy, and for polytherapy with three or more ASMs over the 9-year study period.

Survey on Antiepileptic Drug Therapy in Patients with Drug Resistant Epilepsy.

BACKGROUND AND PURPOSE: Individualized anti-epileptic drug (AED) selection in patient with epilepsy is crucial. However, there is no unified opinion in treating patients with drug resistant epilepsy (DRE). This survey aimed to make a consolidate consensus with epileptologists' perspectives of the treatment for Korean DRE patients by survey responses. METHODS: The survey was conducted with Korean epilepsy experts who have experience prescribing AEDs via e-mail. Survey questionnaires consisted of six items regarding prescription patterns and practical questions in treating patients with DRE in Korea. The research period was from February 2021 to March 2021. RESULTS: The survey response rate was 83.3% (90/108). Most (77.8%) of the responders are neurologists. The proportion of patients whose seizures were not controlled by the second AED was 26.9%. The proportion of patients who had taken five or more AEDs is 13.9%, and those who are currently taking five or more AEDs are 7.3%, of which 54.5% and 37.9% reported positive effects on additional AED, respectively. The majority (91.1%) of respondents answered that the mechanism of action was the top priority factor when adding AED. Regarding data priority, responders considered that expert opinion should have the top priority, followed by clinical experiences, reimbursement guidelines and clinical evidence. Responders gave 64.9 points (range from 0 to 100) about overall satisfaction on reimbursement system of Health Insurance Review and Assessment Service for AED. CONCLUSIONS: This study on AED therapy for DRE patients is the first nationwide trial in Korean epilepsy experts. In five drug failure, the top priorities on AED selection are mechanism of action and expert opinion. These findings might help to achieve consensus and recognize the insight on optimal therapy of AED in DRE.

Increasing Trends in the Incidence and Prevalence of Epilepsy in Korea.

BACKGROUND AND PURPOSE: There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009-2017. METHODS: This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). RESULTS: The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). CONCLUSIONS: There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.

Real-world prescribing trends of valproate in women with epilepsy in Korea.

Avoiding valproate is recommended in women of childbearing age due to possible teratogenicity and infertility. We aimed to examine the recent trend of valproate prescriptions in Korea to review the adequacy of anticonvulsant prescriptions in women with epilepsy (WWE). Oral valproate utilization was assessed using nationwide and unselected data from the Korean National Health Insurance Service from 2009 to 2017. The temporal trends of the proportions of valproate prescriptions were analyzed using the Poisson regression model and expressed as average annual percentage change (AAPC). Among the WWE of childbearing age, valproate was prescribed in 37.0% overall and 29.4% as initial prescription in 2017. The proportion of valproate utilization showed a decreasing trend in overall prescription (AAPC = -1.10%) and initial prescription (AAPC = -2.63%). However, the proportion was static over time in the initial monotherapy group (AAPC = -0. 53%), while it was significantly decreasing in the initial polytherapy group (AAPC = -8.25%). A noticeable proportion of WWE was still being prescribed valproate in Korea. In particular, the use of valproate for initial monotherapy has not decreased over the past nine years. This result calls not only for reinforcement of education regarding anticonvulsant selection but also for monitoring the actual prescription.

Cefepime-Induced Encephalopathy in a Tertiary Medical Center in Korea.

BACKGROUND AND PURPOSE: Cefepime is a widely used fourth-generation cephalosporin. It is commonly used as a first-line antibiotic to treat various infectious diseases such as hospital-acquired pneumonia, urinary tract infections, and bacterial meningitis. The primary outcome of this study was the development of cefepime-induced encephalopathy (CIE) at a tertiary medical center in Korea. We also aimed to describe the clinical features of CIE. METHODS: We enrolled 1,793 consecutive patients treated with cefepime. The CIE group included 44 patients who experienced altered consciousness after receiving cefepime without any other obvious cause and showed full recovery after stopping cefepime. This study collected demographic data, laboratory findings, and clinical data including the cause of infection, duration for onset of altered consciousness, duration of cefepime treatment, dosage of cefepime, duration of recovering consciousness after stopping cefepime, sequelae after encephalopathy, and electroencephalography data. RESULTS: Forty-four (2.5%) patients were included in the CIE group. The age was significantly higher in the CIE group than in the control group (71.2±10.8 years vs. 64.7±16.1 years, mean±standard deviation; p=0.007), and females constituted a significantly large proportion in the CIE group (27 of 44, 61.4%). The CIE group had higher blood urea nitrogen (34.7±22.6 mg/dL vs. 23.0±17.5 mg/dL, p<0.001) and creatinine (2.2±2.5 mg/dL vs. 1.1±1.3 mg/dL, p<0.001), and lower estimated glomerular filtration rate (eGFR) (56.3±46.0 mL/min/1.73 mm² vs. 98.8±66.3 mL/min/1.73 mm², p<0.001). Multivariate analysis showed that only eGFR was significantly related to CIE. CONCLUSIONS: The incidence of CIE was 2.5% in this study. It is essential to consider the possibility of CIE occurring, especially in patients with lower values of eGFR and dialysis.

A case of NMDAR encephalitis treated in the third trimester - novel arterial spin labeling findings and a review of literature.

Diagnosis and treatment of anti-NMDAR encephalitis during pregnancy are challenging. We report a case of anti-NMDAR encephalitis in a 28-year-old, 24 weeks pregnant woman. Her brain magnetic resonance imaging was normal, but arterial spin labeling (ASL) showed increased cerebral blood flow in the right insula and temporal area. She was successfully treated with emergent cesarean section and immunotherapies including intravenous immunoglobulin, steroids, and rituximab. The newborn was healthy and she recovered fully. Early suspicion and proper management is important in treatment of anti-NMDAR encephalitis during pregnancy. ASL can help diagnosing anti-NMDAR encephalitis during pregnancy.

Comparative Study of the Effect of 5,6-Dihydroergosterol and 3-epi-5,6-dihydroergosterol on Chemokine Expression in Human Keratinocytes.

5,6-Dihydroergosterol-glucose is an organic synthetic derivative of spinasterol-glucose, which has potent anti-inflammatory activity. We previously synthesized alpha and beta anomers of DHE-glycosides and compared their inhibitory activity on CCL17 and CCL22 mRNA expression induced by TNF-α/IFN-γ in activated HaCaTs. Recently, we synthesized a new type of DHE-glycosides, 3-epi-5,6-dihydroergosterol(3-epi-DHE)-glycosides, and compared its inhibitory activity on mRNA expression levels of CCL17 and CCL22 in TNF-α/IFN-γ-induced HaCaT. DHE-Xly did not affect TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression in HaCaTs, however, 3-epi-DHE-Xly strongly inhibited TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression levels in human keratinocytes. These results provide important clues for development of chronic dermatitis treatment via inhibition of chemokine expression using DHE derivatives.

Effect of Group-Task-Oriented Training on Gross and Fine Motor Function, and Activities of Daily Living in Children with Spastic Cerebral Palsy.

Aims: To determine the effects of group-task-oriented training (group-TOT) on gross and fine motor function, activities of daily living (ADL) and social function of children with spastic cerebral palsy (CP).Methods: Eighteen children with spastic CP (4-7.5 years, gross motor function classification system level I-III) were randomly assigned to the Group-TOT (9 children received group-TOT for 1 hour, twice a week for 8 weeks) or the comparison group (9 children received individualized traditional physical and occupational therapy). The Gross Motor Function Measure (GMFM)-88, the Bruininks-Oseretsky Test of Motor Proficiency 2nd edition (BOT-2), and the Pediatric Evaluation of Disability Inventory (PEDI) were administered before and after the intervention, and in the Group-TOT, 16 weeks after the intervention.Results: Children in the Group-TOT showed significant improvements in the GMFM-88 standing and walking/running/jumping subscales, the BOT-2 manual dexterity subscale, and the PEDI social function subscale (p < 0.05); changes were maintained 16 weeks after the intervention ended. In contrast, the comparison group improved in only the BOT-2 fine motor integration subscale (p < 0.05).Conclusions: The findings provide evidence of effectiveness of group-TOT in improving gross and fine motor function, and social function in children with CP.

Suicidality and its risk factors in tension-type headache patients: A multicenter case-control study.

This study evaluated suicidality and its risk factors in patients with tension-type headache (TTH). We recruited new patients with TTH who visited general hospitals. We recorded their clinical characteristics and conducted the Headache Impact Test-6 (HIT-6) and the Insomnia Severity Index (ISI) for assessment. We also interviewed the patients to identify major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidality with the Mini International Neuropsychiatric Interview-Plus Version 5.0.0 (MINI). The frequency of suicidality was compared between TTH patients and healthy controls. Major risk factors for suicidality were also determined. A total of 332 TTH patients with the same number of healthy controls were recruited from five general hospitals. Suicidality was observed in 82 (24.7%) TTH patients. The frequency of suicidality was significantly higher in patients with TTH than in the controls. Furthermore, the frequency of suicidality was higher in patients with chronic TTH (CTTH) than in the controls. The major risk factors for suicidality were MDD, GAD, a low education level, insomnia, chronicity of TTH, and pericranial tenderness. Suicidal ideation or attempt seems to be a common feature in TTH. Therefore, it is important to identify risk factors related to suicidality in TTH patients, which may help reduce suicidality.

The first night effect during polysomnography, and patients' estimates of sleep quality.

We surveyed patients the next morning after in-laboratory polysomnography (PSG) to compare the first night effect (FNE) and reverse first night effect (RFNE) in different sleep disorders. A questionnaire was given to 852 patients with insomnia (n = 171), restless legs syndrome (n = 186), obstructive sleep apnea (n = 369), simple snoring (n = 54), REM sleep behavior disorder (n = 39), and hypersomnia (n = 33). FNE was seen in 48.9%, 30.5% slept as usual, and 20.6% had RFNE. The highest incidences of FNE were seen in OSA, simple snoring, hypersomnia, and in men. We propose to use these findings as a reference when interpreting nocturnal in-laboratory PSG results.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Surgical Prognostic Value of Epileptic Aura Based on History and Electrical Stimulation.

BACKGROUND AND PURPOSE: We attempted to evaluate the surgical prognostic value of various types of aura in conjunction with the results of other presurgical evaluations in patients with an intracranial ictal onset zone confirmed by invasive studies and focal resection. We also attempted to determine how often the habitual auras could be elicited and to demonstrate the prognostic value of these stimulation-induced auras (SIAs). METHODS: We reviewed retrospectively the records of patients who had undergone intracranial electroencephalography evaluation and focal resective surgery for intractable partial epilepsy between 1995 and 2009. We identified the localizing value and prognostic value of the patients' auras. We correlated the resection of the area with SIA and surgical outcome. RESULTS: Aura was reported in 225 out of 300 patients. Patients with medial temporal lobe epilepsy (TLE) or occipital lobe epilepsy had a higher chance of having aura. The presence of aura, medial TLE, hippocampal sclerosis on pathology, focal lesions on magnetic resonance imaging (MRI), and ipsilateral abnormality on fluorodeoxyglucose-positron emission tomography were significantly correlated with seizure-free outcome. The presence of auditory aura, parietal lobe epilepsy, multifocal epilepsy, and dual pathology was associated with poor outcomes. Multivariate analysis revealed that auditory aura, multifocal epilepsy, hippocampal sclerosis, and lesion on MRI were prognostic factors for intractable partial epilepsy. SIA was observed in 29 out of the 134 patients who had habitual aura on history. The degree of complete resection of the area with SIA was not related to seizure-free outcome. CONCLUSIONS: The presence of aura favors good surgical outcome and certain types of aura, such as auditory aura, have poor prognostic value. SIA, which was encountered in 21.6% of patients, was not related to seizure-free outcome.

Development and Validation of Predictive Model for Salmonella Growth in Unpasteurized Liquid Eggs.

Liquid egg products can be contaminated with Salmonella spp. during processing. A predictive model for the growth of Salmonella spp. in unpasteurized liquid eggs was developed and validated. Liquid whole egg, liquid yolk, and liquid egg white samples were prepared and inoculated with Salmonella mixture (approximately 3 Log CFU/mL) containing five serovars (S. Bareilly, S. Richmond, S. Typhimurium monophasic, S. Enteritidis, and S. Gallinarum). Salmonella growth data at isothermal temperatures (5, 10, 15, 20, 25, 30, 35, and 40°C) was collected by 960 h. The population of Salmonella in liquid whole egg and egg yolk increased at above 10°C, while Salmonella in egg white did not proliferate at all temperature. These results demonstrate that there is a difference in the growth of Salmonella depending on the types of liquid eggs (egg yolk, egg white, liquid whole egg) and storage temperature. To fit the growth data of Salmonella in liquid whole egg and egg yolk, Baranyi model was used as the primary model and the maximum growth rate and lag phase duration for each temperature were determined. A secondary model was developed with maximum growth rate as a function of temperature. The model performance measures, bias factor (B f , 0.96-0.99) and r2 (0.96-0.99) indicated good fit for both primary and secondary models. In conclusion, it is thought that the growth model can be used usefully to predict Salmonella spp. growth in various types of unpasteurized liquid eggs when those are exposed to various temperature and time conditions during the processing.

Comorbid Insomnia With Obstructive Sleep Apnea: Clinical Characteristics and Risk Factors.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and chronic insomnia are two common sleep disorders and both are considered independent risk factors for heart disease. The aim of this study was to investigate the prevalence of comorbid insomnia with OSA and to compare its clinical characteristics with those of OSA without insomnia. METHODS: Patients who visited two tertiary university hospital sleep centers were screened. Those with a diagnosis of OSA using polysomnography were divided into two groups based on their scores on the Korean version of the Insomnia Severity Index (ISI-K): OSA with insomnia (OSA+I) (ISI-K score ≥ 15) and OSA without insomnia (OSA-I) (ISI-K score < 15). Subjective symptoms were evaluated using sleep questionnaires including ISI-K. Demographic and clinical characteristics of OSA+I and OSA-I were compared. RESULTS: Out of 476 patients with OSA, 139 (29.2%) had significant insomnia. Patients in the OSA+I group had a higher percentage of females (35.3% versus 19.6%, P < .001) and have higher rates of heart disease (19.4% versus 8.6%, P < .001). OSA+I group showed lower quality of life, lower quality of sleep, higher sleep propensity, and higher depression as measured by the Korean versions of the Short-Form 36-Item Health Survey, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Beck Depression Inventory, respectively. There were no significant differences in adherence to continuous positive airway pressure between the groups. CONCLUSIONS: There is a high prevalence of comorbid insomnia with OSA (29.2%), consistent with previous findings in Western studies. Comorbid insomnia with OSA may constitute a cumulative risk factor for cardiovascular disease. These findings warrant further investigation into the mechanisms involved in its pathogenesis and devising more efficient treatments.

Clinical characterization of unknown/cryptogenic status epilepticus suspected as encephalitis: A multicenter cohort study.

Autoimmune and unknown/cryptogenic encephalitis have been increasingly noted in the inflammatory etiology of new-onset status epilepticus (SE). We aimed to investigate clinical characteristics and the potential role of immunotherapy in encephalitis-related adult SE through our multicenter prospective SE registry. Among the 274 patients with SE, 35 (12.8%) patients demonstrated an inflammatory etiology and 19 out of 35 (54.3%) patients demonstrated unknown/cryptogenic cause. Patients with autoimmune and unknown/cryptogenic encephalitis shared similar clinical features. In unknown/cryptogenic encephalitis, the proportion of favorable outcomes (mRS 0-3) showed a different propensity at 3-6months after discharge between patients receiving active immunotherapy and not receiving any immunotherapy, although it was not statistically significant (at admission 28.6% vs 20%, p=0.603; at discharge 57.1% vs 60%, p=0.570; at 3-6months after discharge 90% vs 60%, p=0.214 in patients treated with active immunotherapy or without immunotherapy, respectively). Extensive autoantibody screening should be carried out and empirical immunotherapy may be potentially helpful even in patients without antibodies, although longer term and multi-national studies may be necessary to make a stronger recommendation.