# Burden of Status Epilepticus: prognosis and cost driving factors, insight from a nationwide retrospective cohort study of the French health insurance database

Quentin Calonge, François Le Gac, Mario Chavez, Adeline Degremont, Catherine Quantin, Florence Tubach, Sophie Tezenas Du Montcel, Vincent Navarro

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Quentin Calonge, François Le Gac, Mario Chavez, Adeline Degremont, Catherine Quantin, et al. Burden of Status Epilepticus: prognosis and cost driving factors, insight from a nationwide retrospective cohort study of the French health insurance database. Journal of Neurology, 2024, 10.1007/s00415-024-12589-6. hal-04701239

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**Burden of Status Epilepticus: prognosis and cost driving factors, insight from a nationwide retrospective cohort study of the French health insurance database.**

Quentin Calonge¹,²,³, François Le Gac¹, Mario Chavez¹, Adeline Degremont⁴, Catherine Quantin⁵,⁶, Florence Tubach⁷, Sophie Tezenas du Montcel⁸, Vincent Navarro¹,²,³

**Affiliations:**

¹Sorbonne Université, Paris Brain Institute – Institut du Cerveau, ICM, INSERM, CNRS, Pitié-Salpêtrière Hospital, Paris, France

²AP-HP, Epilepsy Unit, Pitié-Salpêtrière Hospital, DMU Neurosciences, Paris, France

³AP-HP, Center of Reference for Rare Epilepsies, ERN EpiCare, Pitié-Salpêtrière Hospital, Paris, France

⁴Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, CHU de Rennes, 35033 Rennes, France; Univ Rennes, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000, Rennes, France.

⁵Service de Biostatistiques et d'Information Médicale (DIM); CHU Dijon Bourgogne, INSERM, Université de Bourgogne, CIC 1432, Module Épidémiologie Clinique, F21000 Dijon, France

⁶Université Paris-Saclay, UVSQ, Inserm, CESP, 94807, Villejuif, France

⁷Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), F75013, Paris, France

⁸Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, CNRS, Inria, Inserm, AP HP, 75013 Paris, France

*Corresponding author
47-83 Boulevard de l'Hôpital, Paris 75013, France

Email: vincent.navarro@aphp.fr

Telephone: + 33 1 42 16 18 11

**Keywords:** Status Epilepticus; Epidemiology; Electronic health records; In-hospital mortality
Number of pages: 29

Number of words: 3578 (body of the manuscript)

Number of references: 44

Number of figures/tables: three tables and three figures

Supplementary materials: Supplementary Table 1, Supplementary Table 2, Supplementary Table 3, Supplementary Table 4, Supplementary Table 5, Supplementary Table 6, Supplementary Table 7,

**Statements and Declarations:**

V.N reports personal fees from UCB Pharma, EISAI, GW Pharma, and Angellini, outside the submitted work. F.T. is head of the Pharmacoepidemiology Center of the AP-HP and of the Clinical Research Unit of Pitié-Salpêtrière Hospitals; both these structures have received unrestricted research funding, grants, and consultancy fees from a large number of pharmaceutical companies that have contributed indiscriminately to the salaries of its employees; F.T. did not receive any personal remuneration from these companies. Other authors have no conflict of interest to disclose.
**Abstract**

**Background:** Status Epilepticus (SE) imposes a significant burden in terms of in-hospital mortality and costs, but the relationship between SE causes, patient comorbidities, mortality, and cost remains insufficiently understood. We determined the in-hospital mortality and cost-driving factors of SE using a large and comprehensive database.

**Methods:** We conducted a retrospective cohort study involving patients experiencing their first hospitalization with an ICD-10 code diagnosis of SE, spanning from January 1, 2015, to December 31, 2019, using the French health insurance database which covers 99% of population. Patient characteristics, SE causes, Intensive Care Unit (ICU) admissions, mechanical ventilation, discharge status, and health insurance costs were extracted for each hospitalization.

**Results:** We identified 52,487 patients hospitalized for a first SE. In-hospital mortality occurred in 11,464 patients (21.8%), with associated factors including age (Odds Ratio [OR], 10.3, 95% Confidence Interval [CI], 7.87 - 13.8 for ages over 80 compared to 10-19), acute causes (OR, 15.3, 95% CI, 13.9 - 16.8 for hypoxic cause), tumors (OR, 1.75, 95% CI, 1.63 - 1.8), comorbidities (OR, 3.00, 95% CI, 2.79 - 3.24 for 3 or more comorbidities compared to 0), and prolonged mechanical ventilation (OR, 2.61, 95% CI, 2.42 - 2.82). The median reimbursed cost for each SE hospitalization was 6517€ (3364 - 13,354), with cost factors mirroring those of in-hospital mortality.

**Conclusion:** Causes and co-morbidities are major determinants of mortality and hospital costs in status epilepticus, and factors associated with higher mortality are also often associated with higher costs. Further studies are needed to identify their long-term effects.

**Abbreviations**

SE, Status Epilepticus; EEG, Electroencephalogram; ICD-10, International Classification of Disease - 10th edition; SNDS, Système National des Données de Santé; PMSI, Programme de Médicalisation des Systèmes d'Information ; ATC, Anatomical Therapeutic Chemical ; LTD, Long-Term Disease ; ICU, Intensive Care Unit ; OR, Odds Ratio; CI, Confidence Interval; CR, Cost Ratio;
**Introduction**

Status epilepticus (SE), the most severe manifestation of epileptic seizure, poses a significant public health concern with an estimated overall incidence ranging from 9.9 to 41 per 100,000 person-years [1]. Mortality rates vary between 4.6% and 39% [2] and the cause of SE plays a crucial role in its prognosis [3,4]. While acute and hypoxic causes are consistently linked to poorer prognosis, limited studies have thoroughly investigated distinct subtypes of causes (vascular, traumatic, etc.). Moreover, the prognostic implications of some non-acute causes, such as neurodegenerative disease [5] or neurodevelopmental pathologies [6–8] remain largely unexplored despite their likely frequent involvement. Other prognostic factors, including age, clinical presentation (SE type, level of consciousness), history of epilepsy, electroencephalogram (EEG) characteristics, treatment modalities, complications, and comorbidities [9] are considered in various prognostic scores reported in the literature [10–14]. However, the impact of psychiatric comorbidities on SE prognosis remains elusive despite their prevalence among epileptic patients [15].

In the United States, the direct costs of SE could amount to as much as $4 billion annually [16]. Data on SE-related costs in France are lacking. However, existing European studies suggest that both the severity of SE and acute causes are associated with higher direct costs [17,18].

Medico-administrative databases offer a valuable opportunity to investigate diseases like SE and describe factors associated with mortality or costs. Recent studies have utilized such databases to explore SE epidemiology, focusing on hospitalizations with the International Classification of Disease – 10th edition (ICD-10) G41, SE-related code [19–22]. However, these studies have limitations such as incomplete population coverage or lack of in-depth historical data for each patient and not exploring all causes and comorbidities.

Leveraging the French health insurance database called the “Système National des Données de Santé (SNDS)”, which encompasses individual, comprehensive, and linkable but anony-
mous data on healthcare use for approximately 99% of the French population [23], we aimed to describe all first hospitalizations for SE that occurred between 2015 and 2019 in France and to identify the main risk factors for in-hospital mortality and the drivers of healthcare direct-costs associated with SE.

# Materials & methods

## Study design and data sources

We conducted a retrospective cohort study utilizing data from the SNDS. It aggregates information from the following sources:

- (a) The Programme de Médicalisation des Systèmes d'Information (PMSI), which includes discharge summaries for all inpatient admissions to hospitals in France. Diagnosis identified during the hospital stay are coded according to the ICD-10 classification and procedures are coded according to the Common Classification of Medical Procedures (CCAM)

- (b) The reimbursement data for out-of-hospital care, including drugs coded based on the Anatomical Therapeutic Chemical (ATC).

- (c) The codes for long-term disease (LTD) that grant patients coverage without coinsurance under the French national health insurance.

The study adhered to the guidelines outlined in the REporting of studies Conducted using Observational Routinely-collected Data (RECORD).

## Standard protocol approvals, registrations and patient consents

Given the permanent regulatory access granted to the “Assistance Publique des Hôpitaux de Paris, AP-HP,” specific authorization from the French data protection authority (CNIL) was
not required for this study. The SNDS operates as a strictly anonymous database, eliminating
the need for informed consent.

Population

We included all patients hospitalized between January 1, 2015, and December 31, 2019, with an ICD-10 status epilepticus (G41) code either as the main or associated diagnosis. ICD-10 hospitalization codes demonstrate good specificity in identifying patients with epilepsy [24]. We excluded patients with same-sex twins (due to indistinguishability in the PMSI), those lacking outpatient care records (necessary for identifying causes and comorbidities), outpatient encounters, and stays without health insurance reimbursement. Instances of stays within two different hospitals separated by one day or less were considered single stays. The start and end dates were defined based on the first and second stays, respectively [25]. Transfers to rehabilitation were identified if entry into rehabilitation occurred within 7 days before or after discharge from the hospital. Patients already hospitalized for SE between January 1, 2010, and December 31, 2014, were excluded, and only the first hospitalization for SE was retained.

Covariates

For each patient, we extracted age, sex, occurrence of an Intensive Care Unit (ICU) stays, and duration of mechanical ventilation. Pre-existing epilepsy was determined if the patient had prior hospitalization with an epilepsy related-code (G40), received at least one anti-epileptic treatment (refer to the list of ATC codes in Supplementary Table 1) up to five years before the stay for SE, or had an LTD code for epilepsy prior to SE.

We aimed to differentiate potential causes of SE by categorizing them into three groups: (i) acute causes (vascular, infectious/inflammatory, traumatic, toxic, metabolic, alcoholic, hypoxic), (ii) remote causes (vascular, infectious/inflammatory, traumatic, hypoxic), and (iii) progressive causes (tumors, neurodevelopmental disease, neurodegenerative disease, metabolic disease), utilizing the diagnostic codes of the ICD-10 classification (Supplementary Table 2).
The presence of toxic or metabolic causes was assessed solely during the hospital stay for SE.

For other causes (including remote and progressive causes), we examined both the hospital stay and all the patient's hospitalizations up to 5 years before SE. Additionally, we checked for the presence of an LTD condition before SE for each patient.

We differentiated acute and remote vascular/traumatic/infectious-inflammatory/hypoxic causes, as follows:

- If an "acute" code was identified during the SE stay, the patient had no previous hospitalization with an "acute" or "remote" code and had no active "acute/remote" LTD code before the SE stay, the cause was labeled as "acute".

- In other cases, if a "remote" code was found during the stay for SE, or if the patient had been previously hospitalized, or if the patient had an active LTD with an "acute/remote" code before hospitalization for SE, the cause was labeled as "remote".

If a patient had a history of epilepsy with no other identified potential cause for the episode of SE, the cause was categorized as "epilepsy without other causes". For each patient, we calculated the number of potentially involved causes in SE, distinguishing patients with zero, one, two, three, and four or more causes.

The variable "number of comorbidities" was defined as the presence of comorbidities associated with mortality, included in the Charlson score [26] up to 5 years before the stay for SE but not during the hospital stay, using hospitalization and LTD ICD-10 codes. The list of all the comorbidities thus defined and the ICD-10 codes used to identify them can be found in Supplementary Table 2. We then classified, for each patient, the presence of no comorbidity, one or two comorbidities, or three or more comorbidities.

Psychiatric comorbidity was defined based on either an ICD-10 diagnostic code related to psychiatric disease or at least three deliveries of psychiatric drugs over one year up to five
years prior to the stay for SE, or in the case of an active LTD with a code related to psychiatric disease. Detailed ICD-10 and ATC codes used are available in Supplementary Table 1.

All the ICD-10 codes were selected based on previously published studies [19] and by looking at all the diagnostic codes if they were present in at least 100 hospitalizations over the 5 years. All codes were reviewed by a neurologist and a physician specializing in medical information (Q.C, S.TM).

## Outcome

The primary outcome was in-hospital mortality, obtained from the PMSI and accessible for each hospitalization. The secondary outcome was costs reimbursed by health insurance, collected from PMSI for public hospitalization using the amount calculated by the “Agence Technique de l’Information sur l’Hospitalisation” (ATIH) according to the “Diagnoses Relatées Group” (DRH) or Groupe Homogène de Malades (GHM) and using DRG/GHM and fees reimbursed during the period of hospitalization for private hospitalization.

## Statistical Analysis

Descriptive statistics were calculated for patients characteristics of the whole cohort and for each subgroup of interest (age group < 18, 18 – 64 and more than 64, patients without an acute hypoxic cause of SE). Variables were presented as counts and percentage or median and inter-quartile range. Proportions were compared between age groups using Chi-square fit test. Crude mean incidence rate per 100,000 persons was calculated by dividing the total number of cases from 2015 to 2019 by the total population of France from 2015 to 2019 using mid-year population estimates obtained using the data provided by the Institut National de la Statistique et des Etudes Economiques (INSEE).
## In-hospital mortality

Univariable logistic regression analysis was performed to explore the association between each variable and in-hospital mortality. Subsequently, multivariable logistic regression analysis was performed, excluding the “number of causes” variable as redundant with the inclusion of all causes variables. The reference classes were “10-29” for age groups, 0 for the number of comorbidities, and 1 for the number of possible causes.

## Subgroup analysis for in-hospital mortality

The same approach was applied in the following subgroups: ages <18, between 18 and 64, and >64 to look for factors associated with in-hospital mortality specific to pediatric, adult or older ages., and after excluding patients with an acute hypoxic cause of SE.

## Cost of hospitalization

Simple linear regression analysis was performed to explore the association between each variable and the log of cost of hospitalization, considering the right-skewed deviation of the cost distribution. Multivariable linear regression analysis was then performed using the same variables as in the multivariable logistic regression analysis for in-hospital mortality.

Statistical significance was set at p < 0.05. All analyses were performed using R V4.1.2.

## Data availability

Permanent access to the French health care database is automatically granted to certain government agencies, public institutions, and public service authorities (French decree No.2016-1871 of December 26, 2016, on the processing of personal data called National Health Data System and French law). Temporary access for studies and research is possible on request from the National Health Data Institute (Institut National des Données de Santé); https://www.health-data-hub.fr/page/faq-english)
# Results

## Study population and characteristics

A total of 69,926 hospitalizations were identified with a G41 code as the main or associated diagnosis in France between January 1, 2015, and December 31, 2019. Of these, 52,487 patients undergoing their initial hospitalization for SE were included in the analysis (Figure 1), which correspond to a crude mean incidence rate of 15,7 / 100,000 persons (95% CI: 15,6 – 15,8). Among these patients, 23,984 were females (45.7%), with a median age of 62 years ([IQR], 42 – 77, Table 1). A history of epilepsy was present in 21,113 (40.2%) patients. At least one acute cause was present in 27,157 (51.7%) patients, remote cause in 16,910 (32.2%) patients, and progressive cause in 20,448 (39.0%) patients. Acute causes were less frequent in the <18 age group (2,162 patients, 28.8%) than in the >64 group (12,496 patients, 52.4%, p < .001, Appendix 4). Certain causes were over-represented in specific age groups, such as toxic causes in the 18-64 age group (18.9%, Figure 2.A), remote hypoxic causes in the <18 age group (11.6%, Figure 2.B), neurodevelopmental causes in the <18 (30.7%, Figure 2.C), and neurodegenerative causes in the >64 (30.0%, Figure 2.C). Detailed characteristics of patients according to age group are presented in Supplementary Table 1. There was more than one possible cause in 24,753 (47.2%) patients, and no cause was found in 4,752 (9.1%) patients. No comorbidity was found in 20,962 (40.0%) patients, one or two comorbidities in 19,508 (37.2%) patients, and three or more comorbidities in 11,994 (22.9%) patients. Psychiatric comorbidities were present in 17,567 (33.5%) patients. A stay in ICU occurred in 31,362 (59.8%) patients, with mechanical ventilation in 18,728 (35.7%) patients, lasting more than 2 days in 13,097 (25.0%) patients.

Patients with a first SE had an in-hospital mortality rate of 21.8%. The in hospital-mortality rate was highest in the >64 age group (31.8%) and lowest in the <18 age group (5.2%) (Supplementary Table 3) and was 18.2% after exclusion of acute hypoxic causes (Supplementary
Table 4). Detailed results for in-hospital mortality rate according to each variable are present-
ed in Supplementary Table 5.

Factors associated with mortality

In-hospital mortality demonstrated an association with the oldest age group compared with the reference age group of 10-19 (OR 10.3, 95% CI 7.87 – 13.8 for the age group 80 and more, Figure 3.A)

A history of epilepsy reduced the probability of in-hospital mortality (OR: 0.58 CI: 0.55 – 0.61). Acute vascular (OR 1.60, 95% CI 1.49 – 1.72), traumatic (OR 1.21, 95% CI: 1.09 – 1.33), inflammatory (OR 1.31, 95% CI 1.18 – 1.46) and hypoxic (OR 15.3, 95% CI 13.9 – 16.8) causes increased the probability of in-hospital mortality. Among remote causes, only remote hypoxia (OR: 1.79, 95% CI: 1.44 – 2.20) was associated with higher in-hospital mortality. Within progressive causes, only the presence of a brain tumor was associated with an increased risk of in-hospital mortality (OR: 1.76, 95% CI: 1.63 – 1.88, Figure 3.C). The presence of one or two comorbidities (OR: 1.73, 95% CI: 1.62 – 1.85) and especially 3+ comorbidities (OR: 3.01, 95% CI: 2.79 – 3.24) was associated with an increase in in-hospital mortality, Figure 3.B). Invasive ventilation for more than 2 days was associated with an increased risk of in-hospital mortality (OR: 2.61 95% CI: 2.42 – 2.82, Table 2).

Factors associated with mortality in subgroups

The subgroup analysis after exclusion of acute hypoxic causes found similar factors associat-
ed with in-hospital mortality, except for age under 1 year, which was associated with an in-
creased likelihood of in-hospital death (OR: 2.20, 95% CI: 1.54 - 3.20), and for neurodevel-
opmental causes, which were associated with a slight increase of in-hospital mortality (OR:
1.18, 95% CI: 1.04 - 1.33, Table 2). Subgroup analysis based on age demonstrated a strong
association between in-hospital mortality and the number of comorbidities (OR 19.4, 95% CI
7.58 – 47.5 for 3 and more comorbidities) and mechanic ventilation (OR 15.9, 95% CI 10.8 – 24.0 for more than 2 days) in the <18 age group. The presence of a metabolic disease increased in-hospital mortality in the <18 age group (OR 1.84, 95% CI 1.15 – 2.89). In the older age groups, the strongest association with in-hospital-mortality concerned acute hypoxic cause (OR 20.6, 95% CI 17.9 – 23.7 and OR 12.8, 95% CI 11.0 – 15.0 in the 18-64 and >64 groups respectively, Supplementary Table 6).

## Cost Analysis

The median costs reimbursed for each hospitalization were 6,517€ (IQR, 3,364 – 13,354), totaling 609,816,650€ over 5 years, (in dollars: $6,937, IQR, 3,581 – 14,214, totaling $649,076,646). Details of hospitalization costs for each variable are presented in Supplementary Table 7.

Compared with the reference age group of 10-19, an age of less than one year was associated with a higher cost of hospitalization (Cost Ratio, CR: 1.48, 95% CI: 1.40 – 1.56) as with an age group higher than 20-29 (CR: 1.10, 95% CI 1.05 – 1.15 for 30-39, Figure 3.A). All the acute causes were associated with a higher cost except for alcoholic causes (CR: 0.96, 95% CI: 0.94 - 0.98, Table 3). The remote inflammatory cause was associated with a higher cost (CR: 1.22, 95% IC 1.17 – 1.26). All progressive causes were associated with a higher cost, particularly tumors (CR: 1.32, 95% CI: 1.29 – 1.35, Figure 3.C). Comorbidities were associated with higher hospitalization costs (CR: 1.17, 95% CI: 1.15-1.19 for 1-2 comorbidities, CR: 1.24, 95% CI: 1.21 – 1.27 for 3 or more comorbidities, Figure 3.B).

## Discussion

Our study provides a comprehensive analysis of the hospitalizations using a large, comprehensive database with significant historical depth, shedding light on risk factors for in-hospital
mortality and hospital cost drivers. We found an overall in-hospital mortality of 21.8%, ranging from 5.2% for the youngest (<18) to 31.8% for the oldest (> 64), in line with previously published studies [19,27] and a significant direct cost over the 5 years totaling 609,816,650€.

Etiology is a major prognostic factor in SE, as reflected in our study and consistent with previous studies [28]. Acute causes, particularly hypoxic causes (OR: 15.3, 95% CI 13.9 – 16.8) were strongly associated with increased mortality, corroborating established evidence [4,29].

Toxic causes are rarely specifically investigated in epidemiological studies of SE, and our study finds that they are both frequent (particularly in the 18 - 64 age group) but not associated with increased in-hospital mortality, like alcoholic causes, for which the absence of increased mortality has been reported in another study [30].

Our study describes more precisely the progressive causes, notably neurodevelopmental and neurodegenerative diseases. Using ICD-10 codes, which showed good performances [31] to identify neurodevelopmental disorders, we found them to significantly account for SE patients (9.8%), particularly in patients under age 18 (30.7%). However, our study revealed that the presence of a neurodevelopmental disorder did not increase in-hospital mortality in the case of a first SE. The link between neurodegenerative disease and epilepsy is known [5,32,33], but their frequency and impact on status epilepticus is unclear.

Our study show that they are frequent, particularly in older subjects (30% of patients older than 64 years) but that their presence was not associated with an increased risk of in-hospital mortality. A history of epilepsy was prevalent among SE patients (40.2%) and associated with a more favorable prognosis, in line with previous reports [12,34]. Psychiatric diseases are common in epileptic patients, depression may affect up to 50-55% of epilepsy patients requiring hospitalization [15], and up to 6% of epilepsy patients may also suffer from psychosis [35] but little is known about the frequency and impact on prognosis of psychiatric disease in SE. Interestingly, our study found that psychiatric comorbidities were common even in non-
epileptic patients prior to their first SE, but their presence did not increase the risk of in-hospital mortality.

ICU admission was common (59.8%) and associated with reduced in-hospital mortality. Admission to intensive care depends on many factors, such as the severity of the pathology, age, and number of comorbidities [36]. Non-admission of a patient to the ICU could be related to a poorer general condition difficult to identify by ICD-10 diagnostic codes, explaining why ICU admission was associated with lower mortality after taking confounding factors into account.

We previously reported that a significant proportion (11%) of patients intubated for generalized SE and admitted in ICU did not fulfill the criteria for SE at the time of initial management [37]. On the other hand, prolonged —more than 2 days— invasive ventilation was associated in our study with increased mortality. This could reflect a refractory SE [21], or complications. A similar association was reported in patients with continuation of mechanical ventilation after the end of SE, even after considering confounding factors [38].

Only a few studies explored the cost of SE and associated factors, showing that more severe SE or those linked to acute causes are associated with higher costs [17,18,27]. We noticed that most factors associated with in-hospital mortality were also associated with higher costs: extreme ages, acute causes, brain tumors, number of comorbidities, and prolonged invasive ventilation. Several etiologies—neurodevelopmental, neurodegenerative, and metabolic diseases—, not associated with higher in-hospital mortality, increased the cost of SE stay. A history of epilepsy before the first SE, which was already associated with lower in-hospital mortality, was also associated with lower direct costs.

Our study faces several limitations, primarily stemming from the lack of detailed clinical information, such as the specific type of SE (focal or generalized). While some studies showed good performance of G41 and G40 hospitalization codes in identifying epileptic patients [24], there is neither a specific study on the performance of the G41 code for targeting hospitaliza-
tions for SE, nor a study to measure the performance of code G41.0 to target generalized SE
and G41.2 to target focal SE, whose prognosis is very different. Nevertheless, the perfor-
mance of the G41 code for identifying SE in the French health insurance database should be
good, because among validation studies of algorithms using French health insurance data on
acute hemorrhages [39], viral hepatitis [40], and chronic kidney disease [41], the ICD-10
codes consistently showed high levels of specificity and negative predictive value (> 90%).
Moreover, another study suggested that the positive predictive value of the G41 code could be
high, especially for the G410 and G412 codes, even if it may be lower for other codes includ-
ing G419 [42]. Finally, the G41 code is associated in France with hospital stay reimburse-
ment, providing a financial incentive to accurate coding, which also suggests that this code
should have a good sensitivity. Nevertheless, we have chosen to include all the G41 codes in
our analysis to align with prior epidemiological studies of SE [19–21,43,44]. Another limita-
tion arises from the coding system, which does not allow to distinguish whether certain varia-
bles described as “potential” causes are the real cause of the SE, or a complication linked to it,
as in the case of metabolic disorders. Furthermore, our study was unable to identify patients
who succumbed to SE before hospital admission or those who did not seek hospitalization
following SE episodes. Additionally, we did not account for costs unrelated to hospitalization
associated with SE (such as the cost of anti-epileptic treatments or neurological consulta-
tions), which likely surpass direct costs and represent a significant economic burden.

Conclusion

Our study extends the analysis of the different causes of SE in a large population and shows
that the causes of SE are major factors involved in in-hospital mortality and direct cost. Post-
anoxic SE is associated with the worst prognosis, followed by tumors and then by acute vas-
cular lesions. Neurodegenerative and neurodevelopmental causes, which were rarely assessed
in previous studies, were frequent and associated with an increase in hospitalization costs, but
not with in-hospital mortality. Psychiatric comorbidities were also frequent but did not have a
significant impact on hospitalization costs or in-hospital mortality. Further investigations are
warranted to explore the long-term prognosis associated with diverse SE causes.
## Acknowledgments

This work was supported by Agence nationale de la recherche, 'Investissements d'avenir' program ANR-10-IAIHU-06 Fondation Assistance Publique-Hôpitaux de Paris (EPIRES, Marie Laure PLV Merchandising).

We thank Aurélie Hanin for critical reading of the manuscript, and Octave Guinebretiere for his help with the figures.

## Author contributions

Conceptualization: Quentin Calonge, Vincent Navarro

Methodology: all authors

Acquisition and analysis of data: all authors

Drafting a significant portion of the manuscript or figures: Quentin Calonge, Vincent Navarro

All authors read and approved the final manuscript.
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<figure><img src="image_3.png" /><figcaption>Figure 1: Flow-chart of hospital stays for status epilepticus during the study period.</figcaption></figure>
<table><caption>Table 1: Demographic and clinical characteristics of patients.</caption><thead><tr><th>Clinical variable</th><th>All (n = 52,487)</th></tr></thead><tbody><tr><td>Sex (female)</td><td>23,984 (45.7%)</td></tr><tr><td>Age</td><td>62 (42 - 77)</td></tr><tr><td>Age groups</td><td></td></tr><tr><td>&lt;1</td><td>1,831 (3.5%)</td></tr><tr><td>1-4</td><td>2,816 (5.4%)</td></tr><tr><td>5-9</td><td>1,402 (2.7%)</td></tr><tr><td>10-19</td><td>1,840 (3.5%)</td></tr><tr><td>20-29</td><td>2,074 (4.0%)</td></tr><tr><td>30-39</td><td>2,577 (4.9%)</td></tr><tr><td>40-49</td><td>4,335 (8.3%)</td></tr><tr><td>50-59</td><td>7,216 (13.7%)</td></tr><tr><td>60-69</td><td>9,406 (17.9%)</td></tr><tr><td>70-79</td><td>8,314 (15.8%)</td></tr><tr><td>≥80</td><td>10,676 (20.3%)</td></tr><tr><td>History of epilepsy</td><td>21,113 (40.2%)</td></tr><tr><td>Causes</td><td></td></tr><tr><td>Acute<sup>a</sup></td><td>27,157 (51.7%)</td></tr><tr><td>Vascular</td><td>5,420 (10.3%)</td></tr><tr><td>Traumatic</td><td>2,645 (5.0%)</td></tr><tr><td>Infectious / Inflammatory</td><td>2,636 (5.0%)</td></tr><tr><td>Hypoxic</td><td>3,416 (6.5%)</td></tr><tr><td>Metabolic disorder</td><td>13,401 (25.5%)</td></tr><tr><td>Alcohol</td><td>7,335 (14.0%)</td></tr><tr><td>Toxic</td><td>5,610 (10.7%)</td></tr><tr><td>Remote<sup>b</sup></td><td>16,910 (32.2%)</td></tr><tr><td>Vascular</td><td>12,008 (22.9%)</td></tr><tr><td>Traumatic</td><td>4,975 (8.9%)</td></tr><tr><td>Infectious / inflammatory</td><td>1,697 (3.2%)</td></tr><tr><td>Hypoxic</td><td>1,190 (2.3%)</td></tr><tr><td>Progressive<sup>c</sup></td><td>20,448 (39.0%)</td></tr><tr><td>Neurodegenerative disease</td><td>8,498 (16.2%)</td></tr><tr><td>Tumor</td><td>6,567 (12.5%)</td></tr><tr><td>Neurodevelopmental disease</td><td>5,123 (9.8%)</td></tr><tr><td>Metabolic disease</td><td>2,117 (4.0%)</td></tr><tr><td></td><td>3,296 (6.3%)</td></tr><tr><td>Number of possible causes</td><td></td></tr><tr><td>0</td><td>4,752 (9.1%)</td></tr><tr><td>1</td><td>29,982 (43.8%)</td></tr><tr><td>2</td><td>15,134 (28.8%)</td></tr><tr><td>3</td><td>6,840 (13.0%)</td></tr><tr><td>4+</td><td>2,779 (5.3%)</td></tr></tbody></table>
<table><caption>Table 1: Demographic and clinical characteristics of patients (continued)</caption><thead><tr><th></th><th></th></tr></thead><tbody><tr><td>Number of comorbidities</td><td></td></tr><tr><td>0</td><td>20,962 (40.0%)</td></tr><tr><td>1-2</td><td>19,508 (37.2%)</td></tr><tr><td>3+</td><td>11,994 (22.9%)</td></tr><tr><td>Psychiatric comorbidity</td><td>17,567 (33.5%)</td></tr><tr><td>Intensive Care Unit</td><td>31,362 (59.8%)</td></tr><tr><td>Mechanical ventilation</td><td></td></tr><tr><td>0 day</td><td>18,728 (35.7%)</td></tr><tr><td>1-2 days</td><td>5,631 (10.7%)</td></tr><tr><td>&gt; 2 days</td><td>13,097 (25.0%)</td></tr><tr><td>Transfert to rehabilitation</td><td>8,421 (16.0%)</td></tr><tr><td>In-hospital death</td><td>11,464 (21.8%)</td></tr></tbody></table>

<footnote>aAt least one of the acute causes was present during the stay for SE</footnote>

<footnote>bAt least one of the remote causes was present during the stay for SE</footnote>

<footnote>cAt least one of the progressive causes was present during the stay for SE</footnote>
<figure><img src="image_4.png" /><figcaption>**Figure 2:** Proportion of patients with cause of SE according to age groups for each acute (A), remote (B) or progressive cause including epilepsy without other cause (C). In the acute causes part, Metabolic indicates "Metabolic disorder", in the progressive causes part, Metabolic indicates "Metabolic disease".</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>**Figure 3: Factors associated with in-hospital mortality and direct costs for SE :** For mortality, each point represents the adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) from multiple logistic regression. For cost, each point represents the adjusted Cost Ratio indicating augmentation of direct cost if the variable was associated with a ratio more than one and less than one otherwise, with 95% CI from multiple linear regression. Variables are grouped according to demographics (A), comorbidities and characteristics of hospital stays (B), and causes (C).</figcaption></figure>
<table><caption>**Table 2: factors associated with mortality in all stays for SE.** Abbreviations: OR Univariable: odd ratio with 95% confidence interval found using logistic regression. OR multivariable: odd ratio with 95% confidence interval found using logistic regression model. Ref: Reference class. *Only significant change after exclusion of acute hypoxic causes</caption><thead><tr><th>Clinical variable</th><th>All SE<br>OR univariable<br>(CI 95)</th><th>All SE<br>OR multivariable<br>(CI 95)</th><th>Exclusion of acute<br>hypoxic cause<br>OR univariable<br>(CI 95)</th><th>Exclusion of acute<br>hypoxic cause<br>OR multivariable<br>(CI 95)</th></tr></thead><tbody><tr><td>Sex (Reference: female)</td><td>0.94 (0.90 – 0.98)</td><td>1.03 (0.98 – 1.09)</td><td>0.85 (0.81 – 0.89)</td><td>1.02 (0.97 – 1.08)</td></tr><tr><td><strong>Age groups</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;1</td><td>3.96 (2.98 – 5.33)</td><td>1.31 (0.96 – 1.81)</td><td>2.98 (2.11 – 4.28))</td><td><strong>2.20 (1.54 – 3.20)*</strong></td></tr><tr><td>1-4</td><td>0.89 (0.64 – 1.25)</td><td>0.79 (0.56 – 1.14)</td><td>0.80 (0.54 – 1.19)</td><td>0.76 (0.51 – 1.15)</td></tr><tr><td>5-9</td><td>0.76 (0.49 – 1.14)</td><td>0.77 (0.50 – 1.19)</td><td>0.72 (0.44 – 1.17)</td><td>0.75 (0.45 – 1.22)</td></tr><tr><td>10 - 19</td><td>Ref</td><td>Ref</td><td>Ref</td><td>Ref</td></tr><tr><td>20 - 29</td><td>2.25 (1.67 – 3.07)</td><td>1.81 (1.31 – 2.52)</td><td>1.71 (1.18 – 2.48)</td><td>1.71 (1.18 – 2.51)</td></tr><tr><td>30 – 39</td><td>3.31 (2.52 – 4.44)</td><td>2.29 (1.70 – 3.13)</td><td>2.65 (1.91 – 3.76)</td><td>2.26 (1.62 – 3.23)</td></tr><tr><td>40 – 49</td><td>4.91 (3.79 – 6.48)</td><td>3.09 (2.33 – 4.15)</td><td>4.32 (3.19 – 5.98))</td><td>3.16 (2.32 – 4.41)</td></tr><tr><td>50 – 59</td><td>6.63 (5.16 – 8.68)</td><td>3.75 (2.86 – 5.01)</td><td>6.30 (4.71 – 8.66)</td><td>(3.95 (2.92 – 5.47)</td></tr><tr><td>60 – 69</td><td>9.44 (7.37 – 12.3)</td><td>4.68 (3.57 – 6.23)</td><td>9.76 (7.32 – 13.4)</td><td>5.05 (2.92 – 5.47)</td></tr><tr><td>70 – 79</td><td>11.6 (9.02 – 15.1)</td><td>5.96 (4.57 – 7.92)</td><td>12.7 (9.49 – 17.3)</td><td>6.27 (4.65 – 8.66)</td></tr><tr><td>≥ 80</td><td>16.7 (13.1 – 21.8)</td><td>10.3 (7.87 – 13.8)</td><td>20.7 (15.5 – 28.3)</td><td>11.0 (8.18 – 15.2)</td></tr><tr><td><strong>History of epilepsy</strong></td><td>0.29 (0.28 – 0.30)</td><td>0.58 (0.55 – 0.61)</td><td>0.33 (0.32 – 0.35)</td><td>0.58 (0.55 – 0.62)</td></tr><tr><td><strong>Causes</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Acute</td><td></td><td></td><td></td><td></td></tr><tr><td>Vascular</td><td>2.58 (2.43 – 2.74)</td><td>1.60 (1.49 – 1.72)</td><td>3.04 (2.86 – 3.24)</td><td>1.74 (1.62 – 1.88)</td></tr><tr><td>Traumatic</td><td>1.60 (1.46 – 1.74)</td><td>1.21 (1.09 – 1.33)</td><td>1.82 (1.66 – 1.99)</td><td>1.28 (1.15 – 1.42)</td></tr><tr><td>Infectious / Inflammatory</td><td>1.42 (1.29 – 1.55)</td><td>1.31 (1.18 – 1.46)</td><td>1.58 (1.44 – 1.74)</td><td>1.37 (1.23 – 1.53)</td></tr><tr><td>Hypoxic</td><td>15.3 (14.2 – 16.5)</td><td>15.3 (13.9 – 16.8)</td><td>NA</td><td>NA</td></tr><tr><td>Metabolic disorder</td><td>1.70 (1.63 – 1.77)</td><td>1.14 (1.08 – 1.20)</td><td>1.66 (1.58 – 1.74)</td><td>1.18 (1.11 – 1.25)</td></tr><tr><td>Alcohol</td><td>0.73 (0.69 – 0.78)</td><td>0.80 (0.74 – 0.87)</td><td>0.68 (0.64 – 0.73)</td><td>0.80 (0.74 – 0.88)</td></tr><tr><td>Toxic</td><td>0.70 (0.66 – 0.76)</td><td>0.68 (0.62 – 0.74)</td><td>0.59 (0.55 – 0.65)</td><td>0.69 (0.63 – 0.76)</td></tr><tr><td>Remote</td><td></td><td></td><td></td><td></td></tr><tr><td>Vascular</td><td>0.97 (0.93 – 1.02)</td><td>0.69 (0.65 – 0.74)</td><td>1.15 (1.10 – 1.21)</td><td>0.71 (0.67 – 0.76)</td></tr><tr><td>Traumatic</td><td>0.65 (0.60 – 0.69)</td><td>0.86 (0.79 – 0.94)</td><td>0.69 (0.64 – 0.74)</td><td>0.85 (0.78 – 0.93)</td></tr><tr><td>Infectious / inflammatory</td><td>0.48 (0.43 – 0.54)</td><td>0.80 (0.68 – 0.93)</td><td>0.53 (0.47 – 0.60)</td><td>0.81 (0.69 – 0.95)</td></tr><tr><td>Hypoxic</td><td>0.39 (0.33 – 0.46)</td><td>1.79 (1.44 – 2.20)</td><td>0.49 (0.42 – 0.57)</td><td>1.68 (1.35 – 2.07)</td></tr><tr><td>Progressive</td><td></td><td></td><td></td><td></td></tr><tr><td>Neurodegenerative disease</td><td>1.45 (1.38 – 1.52)</td><td>0.86 (0.81 – 0.92)</td><td>1.72 (1.63 – 1.81)</td><td>0.86 (0.81 – 0.92)</td></tr><tr><td>Tumor</td><td>1.65 (1.56 – 1.74)</td><td>1.76 (1.63 – 1.88)</td><td>2.05 (1.94 – 2.17)</td><td>1.83 (1.70 – 1.96)</td></tr><tr><td>Neurodevelopmental disease</td><td>0.24 (0.22 – 0.26)</td><td>1.06 (0.94 – 1.20)</td><td>0.24 (0.22 – 0.26)</td><td><strong>1.18 (1.04 – 1.33)*</strong></td></tr><tr><td>Metabolic disease</td><td>0.94 (0.86 – 1.03)</td><td>1.01 (0.89 – 1.13)</td><td>0.99 (0.89 – 1.09)</td><td>0.98 (0.87 – 1.11)</td></tr><tr><td>Epilepsy without other cause</td><td>0.12 (0.10 – 0.15)</td><td>0.45 (0.37 – 0.55)</td><td>0.15 (0.13 – 0.18)</td><td>0.49 (0.40 – 0.59)</td></tr></tbody></table>
<caption>Table 2: factors associated with mortality in all stays for SE (continued). Abbreviations:</caption>

OR Univariable: odd ratio with 95% confidence interval found using logistic regression. OR multivariable: odd ratio with 95% confidence interval found using logistic regression model.
Ref: Reference class. *Only significant change after exclusion of acute hypoxic causes

<table><thead><tr><th>Clinical variable</th><th>All SE<br>OR Univariable<br>(CI 95)</th><th>All SE<br>OR Multivariable<br>(CI 95)</th><th>Exclusion of acute<br>hypoxic cause<br>OR univariable<br>(CI 95)</th><th>Exclusion of acute<br>hypoxic cause<br>OR multivariable<br>(CI 95)</th></tr></thead><tbody><tr><td><strong>Number of possible causes</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>0</td><td>0.91 (0.84 – 0.99)</td><td></td><td>1.10 (1.00 – 1.20)</td><td></td></tr><tr><td>1</td><td>Ref</td><td></td><td>Ref</td><td></td></tr><tr><td>2</td><td>1.51 (1.44 – 1.58)</td><td></td><td>1.44 (1.37 – 1.51)</td><td></td></tr><tr><td>3</td><td>1.56 (1.47 – 1.65)</td><td></td><td>1.39 (1.30 – 1.49)</td><td></td></tr><tr><td>4+</td><td>1.41 (1.29 – 1.53)</td><td></td><td>1.18 (1.07 – 1.30)</td><td></td></tr><tr><td><strong>Number of comorbidities</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>0</td><td>Ref</td><td>Ref</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2</td><td>1.82 (1.73 – 1.91)</td><td>1.73 (1.62 – 1.85)</td><td>2.51 (2.37 – 2.67)</td><td>1.90 (1.77 – 2.04)</td></tr><tr><td>3+</td><td>3.12 (2.96 – 3.29)</td><td>3.01 (2.79 – 3.24)</td><td>4.52 (4.25 – 4.80)</td><td>3.29 (3.04 – 3.56)</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>1.15 (1.10 – 1.19)</td><td>1.00 (0.95 – 1.05)</td><td>1.21 (1.15 – 1.26)</td><td>0.99 (0.94 – 1.05)</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>1.04 (1.00 – 1.08)</td><td>0.60 (0.56 – 0.65)</td><td>0.72 (0.69 – 0.76)</td><td>0.61 (0.56 – 0.65)</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>0</td><td>Ref</td><td>Ref</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2 days</td><td>0.74 (0.68 – 0.80)</td><td>1.05 (0.94 – 1.16)</td><td>0.49 (0.45 – 0.54)</td><td>0.93 (0.82 – 1.04)</td></tr><tr><td>&gt; 2 days</td><td>2.56 (2.44 – 2.68)</td><td>2.61 (2.42 – 2.82)</td><td>1.65 (1.56 – 1.74)</td><td>2.59 (2.39 – 2.80)</td></tr></tbody></table>
<table><caption>**Table 3: Factors associated with hospital cost in all stays for SE.** Results are presented as cost ratios, on the multiplicative scale, with values greater than 1 indicating higher costs. Abbreviations: Univariable: cost ratios with 95% confidence interval found using linear regression. Multivariable: cost ratios with 95% confidence interval found using linear regression model. Ref: Reference class</caption><thead><tr><th>Clinical variable</th><th>Univariable (CI 95)</th><th>Multivariable (CI 95)</th></tr></thead><tbody><tr><td>Sex (Reference: female)</td><td>1.12 (1.10 - 1.14)</td><td>0.97 (0.96 - 0.99)</td></tr><tr><td><strong>Age groups</strong></td><td></td><td></td></tr><tr><td>&lt;1</td><td>2.22 (2.07 - 2.38)</td><td>1.48 (1.40 - 1.56)</td></tr><tr><td>1-4</td><td>0.86 (0.81 - 0.92)</td><td>0.92 (0.87 - 0.96)</td></tr><tr><td>5-9</td><td>0.80 (0.84 - 0.86)</td><td>0.86 (0.81 - 0.91)</td></tr><tr><td>10 - 19</td><td>Ref</td><td>Ref</td></tr><tr><td>20 - 29</td><td>1.19 (1.12 - 1.27)</td><td>1.02 (0.97 - 1.07)</td></tr><tr><td>30 - 39</td><td>1.41 (1.33 - 1.51)</td><td>1.10 (1.05 - 1.15)</td></tr><tr><td>40 - 49</td><td>1.66 (1.57 - 1.76)</td><td>1.18 (1.13 - 1.24)</td></tr><tr><td>50 - 59</td><td>1.87 (1.77 - 1.97)</td><td>1.28 (1.23 - 1.34)</td></tr><tr><td>60 - 69</td><td>2.11 (2.00 - 2.22)</td><td>1.39 (1.33 - 1.45)</td></tr><tr><td>70 - 79</td><td>2.03 (1.93 - 2.14)</td><td>1.43 (1.37 - 1.49)</td></tr><tr><td>≥ 80</td><td>1.44 (1.37 - 1.52)</td><td>1.40 (1.34 - 1.46)</td></tr><tr><td><strong>History of epilepsy</strong></td><td>0.55 (0.54 - 0.56)</td><td>0.85 (0.83 - 0.86)</td></tr><tr><td><strong>Causes</strong></td><td></td><td></td></tr><tr><td>Acute</td><td></td><td></td></tr><tr><td>Vascular</td><td>2.33 (2.26 - 2.40)</td><td>1.51 (1.48 - 1.55)</td></tr><tr><td>Traumatic</td><td>1.93 (1.85 - 2.01)</td><td>1.27 (1.23 - 1.32)</td></tr><tr><td>Infectious / Inflammatory</td><td>2.98 (2.86 - 3.10)</td><td>1.79 (1.73 - 1.85)</td></tr><tr><td>Hypoxic</td><td>2.60 (2.50 - 2.69)</td><td>1.10 (1.07 - 1.13)</td></tr><tr><td>Metabolic disorder</td><td>1.86 (1.82 - 1.89)</td><td>1.24 (1.22 - 1.26)</td></tr><tr><td>Alcohol</td><td>1.26 (1.24 - 1.30)</td><td>0.96 (0.94 - 0.98)</td></tr><tr><td>Toxic</td><td>1.42 (1.38 - 1.46)</td><td>1.12 (1.09 - 1.14)</td></tr><tr><td>Remote</td><td></td><td></td></tr><tr><td>Vascular</td><td>0.99 (0.97 - 1.01)</td><td>1.03 (1.01 - 1.05)</td></tr><tr><td>Traumatic</td><td>0.89 (0.86 - 0.91)</td><td>1.00 (0.97 - 1.02)</td></tr><tr><td>Infectious / inflammatory</td><td>1.00 (0.96 - 1.04)</td><td>1.22 (1.17 - 1.26)</td></tr><tr><td>Hypoxic</td><td>0.79 (0.75 - 0.83)</td><td>1.05 (1.00 - 1.11)</td></tr><tr><td>Progressive</td><td></td><td></td></tr><tr><td>Neurodegenerative disease</td><td>0.92 (0.90 - 0.95)</td><td>1.03 (1.01 - 1.05)</td></tr><tr><td>Tumor</td><td>1.27 (1.24 - 1.30)</td><td>1.32 (1.29 - 1.35)</td></tr><tr><td>Neurodevelopmental disease</td><td>0.62 (0.61 - 0.64)</td><td>1.08 (1.06 - 1.11)</td></tr><tr><td>Metabolic disease</td><td>1.14 (1.10 - 1.19)</td><td>1.11 (1.07 - 1.15)</td></tr><tr><td>Epilepsy without other cause</td><td>0.46 (0.45 - 0.48)</td><td>0.85 (0.82 - 0.88)</td></tr><tr><td><strong>Number of possible causes</strong></td><td></td><td></td></tr><tr><td>0</td><td>0.86 (0.83 - 0.89)</td><td></td></tr><tr><td>1</td><td>Ref</td><td></td></tr><tr><td>2</td><td>1.38 (1.36 - 1.41)</td><td></td></tr><tr><td>3</td><td>1.66 (1.62 - 1.70)</td><td></td></tr><tr><td>4+</td><td>1.87 (1.81 - 1.94)</td><td></td></tr></tbody></table>
<table><caption>**Table 3: Factors associated with hospital cost in all stays for SE (continued).** Results are presented as cost ratios, on the multiplicative scale, with values greater than 1 indicating higher costs. Abbreviations: Univariable: cost ratios with 95% confidence interval found using linear regression. Multivariable: cost ratios with 95% confidence interval found using linear regression model. Ref: Reference class</caption><thead><tr><th>Clinical variable</th><th>Univariable (CI 95)</th><th>Multivariable (CI 95)</th></tr></thead><tbody><tr><td><strong>Number of comorbidities</strong></td><td></td><td></td></tr><tr><td>0</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2</td><td>1.18 (1.16 - 1.20)</td><td>1.17 (1.15 - 1.19)</td></tr><tr><td>3+</td><td>1.31 (1.28 - 1.33)</td><td>1.24 (1.21 - 1.27)</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>0.99 (0.98 - 1.01)</td><td>0.98 (0.96 - 0.99)</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>2.64 (2.60 - 2.68)</td><td>1.63 (1.60 - 1.66)</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td><td></td></tr><tr><td>0 day</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2 days</td><td>1.69 (1.65 - 1.73)</td><td>1.23(1.20 - 1.26)</td></tr><tr><td>&gt; 2 days</td><td>4.43 (4.35 - 4.51)</td><td>2.72 (2.66 - 2.78)</td></tr></tbody></table>
<table><caption>**Supplementary table 1:** Combination of codes (ICD-10 and ATC) used to detect epilepsy or psychiatric disease</caption><tr><td>Epilepsy</td><td>G40</td></tr><tr><td>ICD-10 code</td><td></td></tr><tr><td>ATC codes</td><td>N03AX14, N03AX09, N03AX18, N03AF01, N03AG01 (Exclusion of Depakote CIP codes), N03AF02, N03AX11, N03AG06, N03AG04, N03AX15, N03AF04, N03AX22, N03AF03, N03AX23, N03AD01, N03AA02, N03AB02, N03AC02, N03AX17, N03AX10</td></tr><tr><td>Psychiatric disease</td><td></td></tr><tr><td>ICD-10 codes</td><td>F20, F21, F22, F23, F24, F25, F28, F29, F30, F31, F32, F33, F34, F38, F39</td></tr><tr><td>ATC codes</td><td>N05A (excluding N05AL06 and CIP 3400932896332) N06A (excluding N06AX12 and CIP 340093338022) N03AG02</td></tr></table>
<table><caption>**Supplementary Table 2:** ICD-10 codes used to identify potential causes of SE and comorbidities of patient</caption><thead><tr><th colspan="2">Potential causes of SE</th></tr></thead><tbody><tr><td>Vascular : acute</td><td>G08, I60:I64, I673:I678, I68, O225, O873, P52</td></tr><tr><td>Vascular : remote</td><td>I69, Z8670</td></tr><tr><td>Traumatic Brain Injury : acute</td><td>F072, S020, S021, S023, S027, S028, S029, S06, S071</td></tr><tr><td>Traumatic Brain Injury : remote</td><td>T902, T905</td></tr><tr><td>Infectious / Inflammatory : acute</td><td>B003, B004, B010, B011, B020, B021, B050, B051, B060, B220, B261, B262, B375, B384, B431, B451, B461, B500, B574, B582, B602, B690, F021, F024, G00:G03, G040, G042, G048, G049, G05, G060, G062, G07, G131, G35</td></tr><tr><td>Infectious / Inflammatory : remote</td><td>B900, B941, G09</td></tr><tr><td>Neurodevelopmental disease</td><td>F70, F71, F72, F73, F78, F79, F80, F81, F82, F83, F84 Q00, Q02, Q03, Q04, Q283, Q85, Q90, Q91, Q92, Q93, Q99</td></tr><tr><td>Toxic</td><td>F11, F12, F13, F14, F15, F16, F17, F18, F19, G92, T36, T37, T38, T39, T40, T41, T42, T43, T44, T45, T46, T47, T48, T49, T50, T52, T53, T54, T55, T56, T57, T58, T59, T60, T61, T62, T63, T64, T65</td></tr><tr><td>Alcohol</td><td>E512, F10, G312, K70, T51, X45, X65, Y15, Y90, Y91</td></tr><tr><td>Metabolic disorder</td><td>E15, E160, E161, E162, E834, E835, E87, P703, P704, P710, P711, P712, P74</td></tr><tr><td>Metabolic disease</td><td>E70, E71, E72, E74, E75, E76, E77, E79, E80, E830, E833</td></tr><tr><td>Brain tumor :</td><td>C700, C709, C71, C722, C723, C724, C725, C728, C729, D32, D33, D420, D429, D430, D431, D432, D433, D439, C793, C799</td></tr><tr><td>Hypoxic</td><td>G931, I46, P20, P21, P910, P916</td></tr><tr><td>Neurodegenerative disease</td><td>F00:F03, F051, G10:G12, G20, G23, G30, G310, G318, G912</td></tr><tr><td>Metastatic solid tumor</td><td>C77:C80</td></tr><tr><td>AIDS / HIV</td><td>B20:B22, B24</td></tr></tbody></table>
<table><caption>**Supplementary Table 2 (continued):** ICD-10 codes used to identify potential causes of SE and comorbidities of patient</caption><thead><tr><th></th><th>Comorbidities</th></tr></thead><tbody><tr><td>Myocardial infarction</td><td>I21, I22, I252</td></tr><tr><td>Congestive heart failure</td><td>I099, I110, I130, I132, I255, I420, I425, I426, I427, I428, I429, I43, I50, P290</td></tr><tr><td>Peripheral vascular disease</td><td>I70, I71, I731, I738, I739, I771, I790, I792, K551, K558, K559, Z958, Z959</td></tr><tr><td>Cerebrovascular disease</td><td>G45, G46, H340, I60, I61, I62, I63, I64, I65, I66, I67, I68, I69</td></tr><tr><td>Dementia</td><td>F00, F01, F02, F03, F051, G30, G311</td></tr><tr><td>Chronic pulmonary disease</td><td>I278, I279, J40:J47, J60:J67, J684, J701, J703</td></tr><tr><td>Rheumatic disease</td><td>M05, M06, M315, M32:M34, M351, M353, M360</td></tr><tr><td>Peptic ulcer disease</td><td>K25:K28</td></tr><tr><td>Mild liver disease</td><td>B18, K700, K701, K702, K703, K709, K713, K714, K715, K73, K74, K760, K762:K764, K768, K769, Z944</td></tr><tr><td>Moderate or severe liver disease</td><td>K704, K711, K721, K729, K765:K767, I850, I859, I864, I982</td></tr><tr><td>Diabetes without complication</td><td>E100, E101, E106, E108:E111, E116, E118:E121, E126, E128:E131, E136, E138:E141, E146, E148, E149</td></tr><tr><td>Diabetes with complication</td><td>E102:E105, E107, E112:E115, E117, E122:E125, E127, E132:E135, E137, E142:E145, E147</td></tr><tr><td>Hemiplegia or paraplegia</td><td>G041, G114, G801, G802, G81, G82, G830:G834, G839</td></tr><tr><td>Renal disease</td><td>N032:N037, N052:N057, N18, N19, Z490:Z492, Z940, Z992</td></tr><tr><td>Malignancy</td><td>C00:C26, C30:C34, C37:C41, C43, C45:C58, C60:C76, C81:C85, C88, C90:C97</td></tr><tr><td>Metastatic solid tumor</td><td>C77:C80</td></tr><tr><td>AIDS / HIV</td><td>B20:B22, B24</td></tr></tbody></table>
<table><caption>Supplementary Table 3: Demographic and clinical characteristics of patients with SE, by age group.</caption><thead><tr><th>Clinical variable</th><th>&lt;18<br>(n = 7,510)</th><th>18-64<br>(n = 21,130)</th><th>65+<br>(n = 23,847)</th><th>P value</th></tr></thead><tbody><tr><td>Sex (Female)</td><td>3,455 (46.0%)</td><td>8,084 (38.3%)</td><td>12,445 (52.2%)</td><td>&lt;.001</td></tr><tr><td>History of epilepsy</td><td>2,841 (37.8%)</td><td>10,470 (49.6%)</td><td>7,802 (32.7%)</td><td>&lt;.001</td></tr><tr><td><strong>Causes</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Acute<sup>a</sup></td><td>2,162 (28.8%)</td><td>12,499 (59.2%)</td><td>12,496 (52.4%)</td><td>&lt;.001</td></tr><tr><td>Vascular</td><td>377 (5.0%)</td><td>1,803 (8.5%)</td><td>3,240 (13.6%)</td><td>&lt;.001</td></tr><tr><td>Traumatic</td><td>347 (4.6%)</td><td>961 (4.5%)</td><td>1,337 (5.6%)</td><td>&lt;.001</td></tr><tr><td>Infectious / Inflammatory</td><td>608 (8.1%)</td><td>1,086 (5.1%)</td><td>942 (4.0%)</td><td>&lt;.001</td></tr><tr><td>Hypoxic</td><td>402 (5.4%)</td><td>1,586 (7.5%)</td><td>1,428 (6.0%)</td><td>&lt;.001</td></tr><tr><td>Metabolic disorder</td><td>1,019 (13.6%)</td><td>5,520 (26.1%)</td><td>6,862 (28.8%)</td><td>&lt;.001</td></tr><tr><td>Alcohol</td><td>5 (0.01%)</td><td>5,203 (24.6%)</td><td>2,127 (8.9%)</td><td>&lt;.001</td></tr><tr><td>Toxic</td><td>174 (2.3%)</td><td>4,003 (18.9%)</td><td>1,433 (6.0%)</td><td>&lt;.001</td></tr><tr><td>Remote<sup>b</sup></td><td>1,424 (19.0%)</td><td>5,995 (28.4%)</td><td>9,491 (39.8%)</td><td>&lt;.001</td></tr><tr><td>Vascular</td><td>357 (4.8%)</td><td>3,625 (17.2%)</td><td>8,026 (33.7%)</td><td>&lt;.001</td></tr><tr><td>Traumatic</td><td>195 (2.6%)</td><td>2,300 (10.9%)</td><td>2,180 (9.1%)</td><td>&lt;.001</td></tr><tr><td>Infectious / inflammatory</td><td>211 (2.8%)</td><td>1,007 (4.8%)</td><td>479 (2.0%)</td><td>&lt;.001</td></tr><tr><td>Hypoxic</td><td>874 (11.6%)</td><td>170 (0.8%)</td><td>146 (0.6%)</td><td>&lt;.001</td></tr><tr><td>Progressive<sup>c</sup></td><td>2,665 (35.5%)</td><td>7,032 (33.3%)</td><td>10,751 (45.1%)</td><td>&lt;.001</td></tr><tr><td>Neurodegenerative disease</td><td>131 (1.7%)</td><td>1,213 (5.7%)</td><td>7,154 (30.0%)</td><td>&lt;.001</td></tr><tr><td>Tumor</td><td>243 (3.2%)</td><td>3,314 (15.7%)</td><td>3,010 (12.6%)</td><td>&lt;.001</td></tr><tr><td>Neurodeveloppmental disease</td><td>2,308 (30.7%)</td><td>2,358 (11.2%)</td><td>457 (1.9%)</td><td>&lt;.001</td></tr><tr><td>Metabolic disease</td><td>306 (4.1%)</td><td>830 (3.9%)</td><td>981 (4.1%)</td><td>0.6</td></tr><tr><td>Epilepsy without other cause</td><td>799 (10.6%)</td><td>1,749 (8.3%)</td><td>748 (3.1%)</td><td>&lt;.001</td></tr><tr><td><strong>Number of possible causes</strong></td><td></td><td></td><td></td><td>&lt;.001</td></tr><tr><td>0</td><td>1,828 (24.3%)</td><td>1,179 (5.6%)</td><td>1,745 (7.3%)</td><td></td></tr><tr><td>1</td><td>3,723 (49.6%)</td><td>9,557 (45.2%)</td><td>9,702 (40.7%)</td><td></td></tr><tr><td>2</td><td>1,394 (18.6%)</td><td>5,953 (28.2%)</td><td>7,787 (32.7%)</td><td></td></tr><tr><td>3</td><td>443 (5.9%)</td><td>2,942 (13.9%)</td><td>3,455 (14.5%)</td><td></td></tr><tr><td>4+</td><td>122 (1.6%)</td><td>1,499 (7.1%)</td><td>1,158 (4.9%)</td><td></td></tr><tr><td><strong>Number of comorbidities</strong></td><td></td><td></td><td></td><td>&lt;.001</td></tr><tr><td>0</td><td>6,360 (84.7%)</td><td>9,769 (46.2%)</td><td>4,833 (20.3%)</td><td></td></tr><tr><td>0<br>1-2</td><td>1,087 (14.5%)</td><td>7,909 (37.4%)</td><td>10,512 (44.1%)</td><td></td></tr><tr><td>3+</td><td>63 (0.8%)</td><td>3,446 (16.3%)</td><td>8,485 (35.6%)</td><td></td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>230 (3.1%)</td><td>7,820 (37.0%)</td><td>9,517 (39.9%)</td><td>&lt;.001</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>5,142 (68.5%)</td><td>14,783 (70.0%)</td><td>11,423 (48.0%)</td><td>&lt;.001</td></tr></tbody></table>
<table><caption>Supplementary Table 3: Demographic and clinical characteristics of patients with SE, by age group (continued).</caption><thead><tr><th>Clinical variable</th><th>&lt;18<br>(n = 7,510)</th><th>18-64<br>(n = 21,130)</th><th>65+<br>(n = 23,847)</th><th>P value</th></tr></thead><tbody><tr><td><strong>Mechanical ventilation</strong></td><td></td><td></td><td></td><td>&lt;.001</td></tr><tr><td>0 day</td><td>5,643 (75.1%)</td><td>11,388 (53.9%)</td><td>16,728 (70.1%)</td><td></td></tr><tr><td>1-2 days</td><td>768 (10.2%)</td><td>3,091 (14.6%)</td><td>1,772 (7.4%)</td><td></td></tr><tr><td>&gt; 2 days</td><td>1,099 (14.6%)</td><td>6,651 (31.5%)</td><td>5,347 (22.4%)</td><td></td></tr><tr><td><strong>Transfert to rehabilitation</strong></td><td>297 (4.0%)</td><td>2,856 (13.5%)</td><td>5,268 (22.1%)</td><td>&lt;.001</td></tr><tr><td><strong>In-hospital death</strong></td><td>390 (5.2%)</td><td>3,502 (16.6%)</td><td>7,572 (31.8%)</td><td>&lt;.001</td></tr></tbody></table>

<sup>b</sup>At least one of the acute causes was present during the stay for SE

<sup>c</sup>At least one of the remote causes was present during the stay for SE

<sup>d</sup>At least one of the progressive causes was present during the stay for SE
<table><caption>Table 4: Demographic and clinical characteristics of patients with SE, after exclusion of acute hypoxic causes.</caption><thead><tr><th>Clinical Variable</th><th>All (n = 49,071)</th></tr></thead><tbody><tr><td>Sex (female)</td><td>22,805 (46.5%)</td></tr><tr><td>Age</td><td>62 (41 - 77)</td></tr><tr><td>Age groups</td><td></td></tr><tr><td>&lt;1</td><td>1,540 (3.1%)</td></tr><tr><td>1-4</td><td>2,757 (5.6%)</td></tr><tr><td>5-9</td><td>1,377 (2.8%)</td></tr><tr><td>10-19</td><td>1,805 (3.7%)</td></tr><tr><td>20-29</td><td>1,963 (4.0%)</td></tr><tr><td>30-39</td><td>2,407 (4.9%)</td></tr><tr><td>40-49</td><td>4,004 (8.2%)</td></tr><tr><td>50-59</td><td>6,650 (13.6%)</td></tr><tr><td>60-69</td><td>8,623 (17.6%)</td></tr><tr><td>70-79</td><td>7,731 (15.8%)</td></tr><tr><td>≥80</td><td>10,214 (20.8%)</td></tr><tr><td>History of epilepsy</td><td>20,524 (41.8%)</td></tr><tr><td>Causes</td><td></td></tr><tr><td>Acute<sup>a</sup></td><td>23,741 (48.4%)</td></tr><tr><td>Vascular</td><td>5,087 (10.4%)</td></tr><tr><td>Traumatic</td><td>2,495 (5.1%)</td></tr><tr><td>Infectious / Inflammatory</td><td>2,514 (5.1%)</td></tr><tr><td>Metabolic disorder</td><td>12,148 (24.8%)</td></tr><tr><td>Alcohol</td><td>6,855 (14.0%)</td></tr><tr><td>Toxic</td><td>5,132 (10.5%)</td></tr><tr><td>Remote<sup>b</sup></td><td>16,372 (33.4%)</td></tr><tr><td>Vascular</td><td>11,633 (23.7%)</td></tr><tr><td>Traumatic</td><td>4,497 (9.2%)</td></tr><tr><td>Infectious / inflammatory</td><td>1,658 (3.4%)</td></tr><tr><td>Hypoxic</td><td>1,190 (2.4%)</td></tr><tr><td>Progressive<sup>c</sup></td><td>19,780 (40.3%)</td></tr><tr><td>Neurodegenerative disease</td><td>8,214 (16.7%)</td></tr><tr><td>Tumor</td><td>6,430 (13.1%)</td></tr><tr><td>Neurodevelopmental disease</td><td>4,928 (10.0%)</td></tr><tr><td>Metabolic disease</td><td>2,004 (4.1%)</td></tr><tr><td>Epilepsy without other cause</td><td>3,296 (6.7%)</td></tr><tr><td>Number of possible causes</td><td></td></tr><tr><td>0</td><td>4,752 (9.7%)</td></tr><tr><td>1</td><td>22,005 (44.8%)</td></tr><tr><td>2</td><td>13,859 (28.2%)</td></tr><tr><td>3</td><td>6,071 (12.4%)</td></tr><tr><td>4+</td><td>2,384 (4.9%)</td></tr></tbody></table>
<table><caption>Supplementary Table 4: Demographic and clinical characteristics of patients with SE, after exclusion of acute hypoxic causes (continued).</caption><thead><tr><th>Clinical Variable</th><th>All (n = 49,071)</th></tr></thead><tbody><tr><td><strong>Number of comorbidities</strong></td><td></td></tr><tr><td>0</td><td>19,283 (39.3%)</td></tr><tr><td>1-2</td><td>18,428 (37.6%)</td></tr><tr><td>3+</td><td>11,337 (23.1%)</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>16,539 (33.7%)</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>28,147 (57.4%)</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td></tr><tr><td>0 day</td><td>33,306 (67.9%)</td></tr><tr><td>1-2 days</td><td>5,247 (10.7%)</td></tr><tr><td>&gt; 2 days</td><td>10,518 (21.4%)</td></tr><tr><td><strong>Transfert to rehabilitation</strong></td><td>8,102 (16.5%)</td></tr><tr><td><strong>In-hospital death</strong></td><td>8,934 (18.2%)</td></tr></tbody></table>

<footnote>aAt least one of the acute causes was present during the stay for SE</footnote>

<footnote>bAt least one of the remote causes was present during the stay for SE</footnote>

<footnote>cAt least one of the progressive causes was present during the stay for SE</footnote>
<table><caption>Table 5: In-hospital mortality rate according to the presence of each variable.</caption><thead><tr><th></th><th>In-Hospital mortality rate</th></tr></thead><tbody><tr><td><strong>Sexe</strong></td><td></td></tr><tr><td>Female</td><td>22.1%</td></tr><tr><td>Male</td><td>21.6%</td></tr><tr><td>&lt;1</td><td>12.1%</td></tr><tr><td>1-4</td><td>3.2%</td></tr><tr><td>5-9</td><td>2.6%</td></tr><tr><td>10-19</td><td>3.4%</td></tr><tr><td>20-29</td><td>7.3%</td></tr><tr><td>30-39</td><td>10.4%</td></tr><tr><td>40-49</td><td>14.6%</td></tr><tr><td>50-59</td><td>18.8%</td></tr><tr><td>60-69</td><td>24.8%</td></tr><tr><td>70-79</td><td>28.7%</td></tr><tr><td>≥80</td><td>36.8%</td></tr><tr><td><strong>History of epilepsy</strong></td><td>13.0%</td></tr><tr><td><strong>Causes</strong></td><td></td></tr><tr><td>Acute<sup>a</sup></td><td>28.0%</td></tr><tr><td>Vascular</td><td>34.8%</td></tr><tr><td>Traumatic</td><td>26.9%</td></tr><tr><td>Infectious / Inflammatory</td><td>24.1%</td></tr><tr><td>Hypoxic</td><td>74.1%</td></tr><tr><td>Metabolic disorder</td><td>27.4%</td></tr><tr><td>Alcohol</td><td>17.6%</td></tr><tr><td>Toxic</td><td>16.7%</td></tr><tr><td>Remote<sup>b</sup></td><td>19.7%</td></tr><tr><td>Vascular</td><td>21.8%</td></tr><tr><td>Traumatic</td><td>17.9%</td></tr><tr><td>Infectious / inflammatory</td><td>13.4%</td></tr><tr><td>Hypoxic</td><td>11.4%</td></tr><tr><td>Progressive<sup>c</sup></td><td>23.2%</td></tr><tr><td>Neurodegenerative disease</td><td>27.6%</td></tr><tr><td>Tumor</td><td>28.3%</td></tr><tr><td>Neurodevelopmental disease</td><td>8.7%</td></tr><tr><td>Metabolic disease</td><td>23.5%</td></tr><tr><td>Epilepsy without other cause</td><td>3.5%</td></tr><tr><td><strong>Number of possible causes</strong></td><td></td></tr><tr><td>0</td><td>14.2%</td></tr><tr><td>1</td><td>18.8%</td></tr><tr><td>2</td><td>25.8%</td></tr><tr><td>3</td><td>26.8%</td></tr><tr><td>4+</td><td>26.0%</td></tr></tbody></table>
<table><caption>Supplementary Table 5: In-hospital mortality rate according to the presence of each variable (continued).</caption><thead><tr><th></th><th>In-Hospital mortality rate</th></tr></thead><tbody><tr><td><strong>Number of comorbidities</strong></td><td></td></tr><tr><td>0</td><td>13.5%</td></tr><tr><td>1-2</td><td>23.5%</td></tr><tr><td>3+</td><td>33.7%</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>23.6%</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>21.8%</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td></tr><tr><td>0 day</td><td>17.8%</td></tr><tr><td>1-2 days</td><td>13.8%</td></tr><tr><td>&gt; 2 days</td><td>35.7%</td></tr></tbody></table>

<footnote>aAt least one of the acute causes was present during the stay for SE</footnote>

<footnote>bAt least one of the remote causes was present during the stay for SE</footnote>

<footnote>cAt least one of the progressive causes was present during the stay for SE</footnote>
<table><caption>Supplementary Table 6: factors associated with mortality for SE for each age group using logistic regression model. Abbreviations: Ref: Reference class</caption><thead><tr><th>Clinical variable</th><th>&lt;18<br>OR multivariable (CI 95)</th><th>18-64<br>OR multivariable (CI 95)</th><th>65+<br>OR multivariable (CI 95)</th></tr></thead><tbody><tr><td>Sex (Female)</td><td>0.94 (0.73 – 1.20)</td><td>1.08 (0.98 – 1.18)</td><td>0.98 (0.92 – 1.04)</td></tr><tr><td>History of epilepsy</td><td>0.50 (0.32 – 0.76)</td><td>0.54 (0.48 – 0.59)</td><td>0.57 (0.53 – 0.61)</td></tr><tr><td><strong>Causes</strong></td><td></td><td></td><td></td></tr><tr><td>Acute</td><td></td><td></td><td></td></tr><tr><td>Vascular</td><td>1.63 (1.16 – 2.27)</td><td>2.03 (1.78 – 2.32)</td><td>1.49 (1.37 – 1.62)</td></tr><tr><td>Traumatic</td><td>0.81 (0.53 – 1.21)</td><td>0.82 (0.66 – 1.01)</td><td>1.45 (1.29 – 1.64)</td></tr><tr><td>Infectious / Inflammatory</td><td>0.80 (0.56 – 1.14)</td><td>1.19 (0.99 – 1.42)</td><td>1.31 (1.14 – 1.52)</td></tr><tr><td>Hypoxic</td><td>6.70 (4.96 – 9.08)</td><td>20.6 (17.9 – 23.7)</td><td>12.8 (11.0 – 15.0)</td></tr><tr><td>Metabolic disorder</td><td>1.83 (1.41 – 2.37)</td><td>1.13 (1.02 – 1.24)</td><td>1.10 (1.03 – 1.18)</td></tr><tr><td>Alcohol</td><td>NA</td><td>0.96 (0.86 – 1.07)</td><td>0.64 (0.57 – 0.72)</td></tr><tr><td>Toxic</td><td>0.42 (0.21 – 0.76)</td><td>0.59 (0.52 – 0.67)</td><td>0.72 (0.63 – 0.83)</td></tr><tr><td><strong>Remote</strong></td><td></td><td></td><td></td></tr><tr><td>Vascular</td><td>0.40 (0.19 – 0.77)</td><td>0.64 (0.56 – 0.73)</td><td>0.73 (0.68 – 0.78)</td></tr><tr><td>Traumatic</td><td>0.16 (0.02 – 0.56)</td><td>0.74 (0.63 – 0.87)</td><td>0.96 (0.86 – 1.07)</td></tr><tr><td>Infectious / inflammatory</td><td>0.38 (0.14 – 0.87)</td><td>0.75 (0.60 – 0.93)</td><td>0.76 (0.60 – 0.95)</td></tr><tr><td>Hypoxic</td><td>1.79 (1.22 – 2.59)</td><td>1.92 (1.26 – 2.84)</td><td>1.53 (1.07 – 2.15)</td></tr><tr><td><strong>Progressive</strong></td><td></td><td></td><td></td></tr><tr><td>Neurodegenerative disease</td><td>2.17 (0.96 – 4.56)</td><td>1.00 (0.83 – 1.20)</td><td>0.93 (0.86 – 0.99)</td></tr><tr><td>Tumor</td><td>2.41 (1.38 – 4.09)</td><td>2.42 (2.15 – 2.72)</td><td>1.23 (1.12 – 1.35)</td></tr><tr><td>Neurodeveloppmental disease</td><td>0.79 (0.55 – 1.11)</td><td>1.17 (0.99 – 1.37)</td><td>0.91 (0.72 – 1.15)</td></tr><tr><td>Metabolic disease</td><td>1.84 (1.15 – 2.89)</td><td>1.12 (0.91 – 1.37)</td><td>0.87 (0.75 – 1.01)</td></tr><tr><td>Epilepsy without other cause</td><td>0.17 (0.01 – 0.83)</td><td>0.30 (0.20 – 0.44)</td><td>0.56 (0.44 – 0.71)</td></tr><tr><td><strong>Number of comorbidities</strong></td><td></td><td></td><td></td></tr><tr><td>0</td><td>Ref</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2</td><td>2.28 (1.57 – 3.30)</td><td>2.15 (1.93 – 2.40)</td><td>1.51 (1.39 – 1.64)</td></tr><tr><td>3+</td><td>19.4 (7.58 – 47.5)</td><td>4.39 (3.85 – 5.01)</td><td>2.50 (2.28 – 2.74)</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>2.25 (1.00 – 4.63)</td><td>0.93 (0.85 – 1.02)</td><td>1.02 (0.96 – 1.08)</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>1.27 (0.71 – 2.)</td><td>0.44 (0.38 – 0.51)</td><td>0.66 (0.60 – 0.72)</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td><td></td><td></td></tr><tr><td>0 day</td><td>Ref</td><td>Ref</td><td>Ref</td></tr><tr><td>1-2 days</td><td>7.06 (4.59 – 11.0)</td><td>1.34 (1.12 – 1.59)</td><td>0.71 (0.61 – 0.82)</td></tr><tr><td>&gt; 2 days</td><td>15.9 (10.8 – 24.0)</td><td>3.49 (3.05 – 4.02)</td><td>1.79 (1.62 – 1.97)</td></tr></tbody></table>
<table><caption>Supplementary Table 7: Costs of hospitalization for status epilepticus presented as mean (standard deviation), median (inter-quartile range) and total costs according to the presence of each of the variables studied.</caption><thead><tr><th></th><th>Mean (sd)</th><th>Median (IQR)</th><th>Total cost</th></tr></thead><tbody><tr><td><strong>Total</strong></td><td>11,618 (18,124)</td><td>6,517 (3,364 – 13,354)</td><td>609,816,650</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td></tr><tr><td>Female</td><td>10,800 (17,835)</td><td>6,088 (3,279 – 11,910)</td><td>259,015,270</td></tr><tr><td>Male</td><td>12,308 (18,335)</td><td>7,074 (3,511 – 14,609)</td><td>350,801,379</td></tr><tr><td><strong>Age groups</strong></td><td></td><td></td><td></td></tr><tr><td>&lt;1</td><td>15,275 (20,084)</td><td>9,217 (3,947 – 19,946)</td><td>27,968,995</td></tr><tr><td>1 – 4</td><td>6,852 (18,340)</td><td>3,306 (1,656 – 6,130)</td><td>19,294,781</td></tr><tr><td>5-9</td><td>6,976 (16,318)</td><td>3,035 (1,480 – 6,121)</td><td>9,779,695</td></tr><tr><td>10 – 19</td><td>9,649 (23,960)</td><td>3,643 (1,584 – 9,420)</td><td>17,753,343</td></tr><tr><td>20 – 29</td><td>11,316 (24,787)</td><td>4,514 (2,069 – 10,859)</td><td>23,470,338</td></tr><tr><td>30 – 39</td><td>12,467 (24,818)</td><td>5,687 (2,460 – 13,357)</td><td>32,127,221</td></tr><tr><td>40 – 49</td><td>12,990 (21,766)</td><td>6,838 (3,002 – 14,619)</td><td>56,311,453</td></tr><tr><td>50 – 59</td><td>13,240 (18,521)</td><td>7,737 (3,780 – 15,770)</td><td>95,541,960</td></tr><tr><td>60 – 69</td><td>14,300 (19,717)</td><td>8,750 (4,282 – 16,860)</td><td>134,506,060</td></tr><tr><td>70 – 79</td><td>12,888 (15,663)</td><td>8,200 (4,264 – 15,858)</td><td>107,151,139</td></tr><tr><td>≥ 80</td><td>8,047 (7,921)</td><td>5,997 (3,841 – 9,416)</td><td>85,911,666</td></tr><tr><td><strong>History of epilepsy</strong></td><td>8,221 (11,574)</td><td>4,953 (2,501 – 9,558)</td><td>173,566,232</td></tr><tr><td><strong>Causes</strong></td><td></td><td></td><td></td></tr><tr><td>Acute<sup>a</sup></td><td>15,651 (21,985)</td><td>9,475 (5,018 – 18,380)</td><td>425,038,029</td></tr><tr><td>Vascular</td><td>19,191 (23,126)</td><td>12,094 (7,167 – 23,671)</td><td>104,013,211</td></tr><tr><td>Traumatic</td><td>17,346 (19,308)</td><td>12,174 (6,224 – 22,601)</td><td>45,879,586</td></tr><tr><td>Infectious / Inflammatory</td><td>26,767 (35,974)</td><td>17,203 (9,097 – 31,077)</td><td>70,557,890</td></tr><tr><td>Hypoxic</td><td>22,228 (26,646)</td><td>15,764 (6,224 – 22,601)</td><td>45,879,586</td></tr><tr><td>Metabolic disorder</td><td>16,583 (24,544)</td><td>9,488 (5,134 – 19,018)</td><td>222,235,176</td></tr><tr><td>Alcohol</td><td>13,735 (17,472)</td><td>8,608 (4,307 – 16,223)</td><td>100,743,386</td></tr><tr><td>Toxic</td><td>15,940 (23,255)</td><td>9,672 (4,802 – 18,875)</td><td>89,422,729</td></tr><tr><td>Remote<sup>b</sup></td><td>10,455 (16,064)</td><td>6,191 (3,594 – 11,770)</td><td>176,799,890</td></tr><tr><td>Vascular</td><td>10,298 (15,788)</td><td>6,221 (3,735 – 11,425)</td><td>123,661,064</td></tr><tr><td>Traumatic</td><td>10,161 (13,954)</td><td>6,146 (3,379 – 11,653)</td><td>47,504,951</td></tr><tr><td>Infectious / inflammatory</td><td>12,926 (20,877)</td><td>7,081 (3,821 – 15,174)</td><td>21,934,680</td></tr><tr><td>Hypoxic</td><td>8,563 (15,830)</td><td>4,991 (2,677 – 11,259)</td><td>11,894,284</td></tr><tr><td>Progressive<sup>c</sup></td><td>10,152 (15,539)</td><td>6,223 (3,636 – 11,550)</td><td>207,593,398</td></tr><tr><td>Neurodegenerative disease</td><td>8,677 (11,309)</td><td>5,975 (3,816 – 9,477)</td><td>73,740,123</td></tr><tr><td>Tumor</td><td>11,435 (12,681)</td><td>7,949 (4,253 – 14,406)</td><td>75,092,130</td></tr><tr><td>Neurodevelopmental disease</td><td>8,798 (18,425)</td><td>4,423 (2,202 – 9,515)</td><td>45,071,928</td></tr><tr><td>Metabolic disease</td><td>16,205 (25,468)</td><td>9,141 (4,469 – 18,327)</td><td>34,306,990</td></tr><tr><td>Epilepsy without other cause</td><td>4,602 (5,976)</td><td>2,836 (1,442 – 5,515)</td><td>15,167,788</td></tr></tbody></table>
<table><caption>Supplementary Table 7: Costs of hospitalization for status epilepticus presented as mean (standard deviation), median (inter-quartile range) and total costs according to the presence of each of the variables studied (continued).</caption><thead><tr><th></th><th>Mean (sd)</th><th>Median (IQR)</th><th>Total cost</th></tr></thead><tbody><tr><td><strong>Number of possible causes</strong></td><td></td><td></td><td></td></tr><tr><td>0</td><td>7,730 (14,904)</td><td>3,858 (2,051 – 7,671)</td><td>36,734,635</td></tr><tr><td>1</td><td>9,593 (15,572)</td><td>5,515 (2,659 – 10,857)</td><td>220,473,001</td></tr><tr><td>2</td><td>12,765 (18,035)</td><td>7,688 (4,072 – 14,972)</td><td>193,182,568</td></tr><tr><td>3</td><td>15,274 (19,655)</td><td>9,176 (4,873 – 18,365)</td><td>104,474,474</td></tr><tr><td>4+</td><td>19,774 (30,507)</td><td>11,640 (6,222 – 22,924)</td><td>54,951,972</td></tr><tr><td><strong>Number of comorbidities</strong></td><td></td><td></td><td></td></tr><tr><td>0</td><td>11,098 (17,930)</td><td>5,714 (2,601 – 13,068)</td><td>232,643,737</td></tr><tr><td>1-2</td><td>12,114 (19,619)</td><td>6,849 (3,800 – 13,625)</td><td>236,310,229</td></tr><tr><td>3+</td><td>11,724 (16,784)</td><td>7,097 (4,077 – 13,367)</td><td>140,612,605</td></tr><tr><td><strong>Psychiatric comorbidity</strong></td><td>10,492 (14,714)</td><td>6,309 (3,707 – 12,202)</td><td>184,312,163</td></tr><tr><td><strong>Intensive Care Unit</strong></td><td>15,994 (22,030)</td><td>10,107 (4,893 – 19,107)</td><td>501,588,402</td></tr><tr><td><strong>Mechanical ventilation</strong></td><td></td><td></td><td></td></tr><tr><td>0 day</td><td>6,370 (8,681)</td><td>4,451 (2,484 – 7,739)</td><td>215,039,750</td></tr><tr><td>1-2 days</td><td>10,273 (11,639)</td><td>7,330 (4,244 – 11,901)</td><td>57,849,730</td></tr><tr><td>&gt; 2 days</td><td>25,726 (28,162)</td><td>18,307 (11,797 – 29,884)</td><td>336,927,169</td></tr></tbody></table>

<footnote>aAt least one of the acute causes was present during the stay for SE</footnote>

<footnote>bAt least one of the remote causes was present during the stay for SE</footnote>

<footnote>cAt least one of the progressive causes was present during the stay for SE</footnote>