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Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review



Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population.


This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017.


The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001).


SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors.


Epilepsy is a frequent symptom of patients with brain tumors, which are strong risk factors for seizures (relative risk = 40) [1] despite representing only 4% of all epilepsy etiologies [1,2,3]. In addition, greater than one-third of patients with brain tumors develop epilepsy [4, 5]. Seizures are the presenting clinical signs of tumors in 30–50% of patients, and an additional 10–30% exhibit epilepsy later in the disease course, often in association with neurosurgical procedures or disease progression [1, 4,5,6,7,8]. The prevalence of epilepsy varies greatly according to tumor type and location and appears to be inversely proportional to tumor grade, with reported frequencies approximating 100% in non-malignant dysembryoblastic neuroepithelial tumors, 29–49% in high-grade gliomas, 20–35% in metastases, and 10% in primary central nervous system (CNS) lymphomas [6, 9].

Status epilepticus (SE) is one of the most common neurological emergencies [10], which according to the latest definition proposed by the International League Against Epilepsy (ILAE), is a condition resulting from either the activation of abnormal mechanisms that prolong seizures or the failure of mechanisms that terminate seizure activity. SE can lead to cell damage, neuronal death, neuronal injury, or alteration of neuronal networks, depending on seizure type. Therefore, prompt seizure termination and prevention of recurrence is crucial in these cases [11,12,13].

The reported proportion of patients with SE that is attributable to brain tumors is 3–12% [10, 14]. However, limited information is available that specifically evaluates SE in this population [15]. Although seizures generally occur in low-grade malignancies and early disease stages, SE is more commonly found in high-grade tumors and later stages, suggesting a potentially distinct pathophysiological mechanism [9, 16]. A systematic review reported a higher short-term mortality in tumor-related SE cases compared to SE patients with other etiologies, although that study provided insufficient data to assess differences in treatment response, long-term mortality, or morbidity [15]. Two independent reviews indicated that tumor-associated SE (TASE) had a distinct clinical profile and stressed the need for prospective multi-center studies [9, 15].

The aim of this study was to use a large multi-center cohort to systematically describe the clinical characteristics, treatment, and short- and long-term outcomes of patients presenting with SE secondary to primary brain tumors and brain metastases.

Material and methods

Study design and setting

This retrospective, multicenter cohort study was conducted at the university hospitals of Frankfurt and Marburg between January 2011 and December 2017. Both hospitals offered a full range of neurological care services with expertise in epileptology, neurooncology, and intensive care medicine. Frankfurt University Hospital serves primarily an urban area[17], while its Marburg counterpart possesses a neurological department that services the city and surrounding rural areas, managing a population of more than 500,000. Due to its representative population structure, the area surrounding Marburg has been used for a population-based estimate of the incidence of SE in Germany [18].

This study included all adult patients (aged 18 or older) admitted to hospital due to non-anoxic SE with brain tumors or metastases. Only the first episode of SE during the study period was analyzed. Patient records were reviewed and data were collected using standardized study forms and ascertained by the study coordinator (AS) and one independent researcher at each site (SK, FR). The study was approved by local ethics committees and adhered to the STROBE guidelines [19].

Definition of SE

Following the latest definition and classification of SE published by the International League Against Epilepsy (ILAE) task force in 2015, all tonic–clonic seizures lasting > 5 min and focal seizures with impaired consciousness lasting > 10 min were considered SE events [11]. Refractory status epilepticus (RSE) is defined as recurrent seizure activity after two appropriately selected and dosed antiseizure medications (ASMs), which include a benzodiazepine. Super‐refractory status epilepticus (SRSE) is an SE that continues or recurs ≥ 24 h after the initiation of treatment with anesthetic drugs and includes cases in which seizure control is attained after induction of anesthesia but recurs once the anesthetic agent is tapered off [10, 20,21,22]. Nonconvulsive SE (NCSE) is defined according to the Salzburg criteria [23].

Definition of measures

The patients were divided into four subgroups based on tumor category: adult-type diffuse gliomas, including glioblastomas and other CNS WHO Grade 2–4 gliomas; intracranial extradural tumors, including meningiomas and other benign extradural tumors; metastatic entities, including solid metastases and leptomeningeal metastatic diseases; and other tumors, such as CNS lymphomas. The latter group was not included in the analysis at the subgroup level due to the small number and heterogeneity of the cases. In addition, patients were separated into two groups based on the presence of progression signs. Those who displayed the neuroradiological criteria for tumor growth, tumor recurrence, increased perifocal edema, or imaging changes (i.e., pseudoprogression) due to radiation therapy and/or systemic chemotherapy were classified into the group with tumor progression signs.

Data regarding patient and SE characteristics, as well as the treatment during the SE, tumor treatment prior to the SE, and patient outcomes, were collected. Comorbidities of the patients were scored using the Charlson Comorbidity Index (CCI) [24]. The functional status of the patients was determined using a modified Rankin scale (mRS) at admission and discharge (0–2 = good functional status, 3–5 = poor functional status, 6 = deceased) [25]. SE severity was evaluated using the SE severity score (STESS) [26] and the level of refractoriness (non-refractory = NRSE, refractory = RSE, super-refractory = SRSE). The short-term outcomes of the patients were defined using mortality, functional status (mRS), and destination at hospital discharge, while long-term outcomes were considered as mortality within one-year post-discharge.


Statistical analyses were performed using IBM SPSS Statistics Version 28.0. Descriptive data are presented as minimum, maximum, median, mean ± standard deviation (SD), range, and percentage values. Univariable comparisons of proportions were calculated using Pearson's chi-squared test. The Mann–Whitney U test was applied for comparisons of variables of ordinal or non-normally distributed data. Long-term outcomes were depicted using Kaplan–Meier survival curves, and the log-rank test was performed for comparisons between the subgroups. Two-sided p-values of less than 0.05 were considered to be significant in all statistical analyses.


During the study period, 208 patients presenting with SE due to a brain tumor or metastasis were identified. The mean age was 61.5 ± 14.7 years (median 63 years; range 23–89 years) and 106 patients (51%) were male. Adult-type diffuse gliomas formed the largest subgroup with 116 (55.8%) patients, with glioblastoma as the most common tumor type (n = 85, 40.9%), followed by intracranial extradural tumors (30 cases, 14.4%) and metastatic entities (53 cases, 25.5%). Details regarding tumor entities are presented in Table 1, and localization data are listed in Additional file 1: Table S1. At admission, 128 (61.5%) patients presented with the neuroradiological criteria for tumor progression, while the remaining 80 (38.5%) had no signs of progression in the imaging.

Table 1 Primary brain tumor and brain metastasis characteristics of patients presenting with SE (n = 208)

Clinical characteristics of the SE patients

Table 2 shows the patient characteristics, SE characteristics, and patient outcomes for all individuals, as well as the univariate subgroup analysis according to tumor category and tumor progression signs at admission.

Table 2 Patient characteristics, status epilepticus characteristics, and outcomes stratified by tumor categories and tumor progression signs

Patient characteristics

Patients with intracranial extradural tumors were significantly older than those in other tumor categories. The sex distribution showed higher proportions of female patients with intracranial extradural tumors (n = 23, 76.6%) and male patients with adult-type diffuse gliomas (n = 72, 62%). High comorbidity loads (CCI ≥ 6), were detected in 63 (30.3%) patients, most of whom had metastatic entities (n = 53, 84.1%), whereas patients in the other tumor subgroups generally had significantly lower CCI scores (2–5). The majority of patients (n = 127, 61.1%) had a previous history of seizures, and this finding was more pronounced among patients with no signs of tumor progression (n = 58, 72.5%) or adult-type diffuse gliomas (n = 83, 71.6%) at admission. In contrast, SE was often the first epileptic manifestation in patients with metastatic entities compared with those in other categories. The mRS before the SE showed no significant differences between the subgroups.

SE characteristics

A favorable STESS score of 0–3 points was present in 176 (84.6%) patients at admission, and this fraction was significantly lower in intracranial extradural tumor patients (n = 18, 60%), who tended to exhibit lower proportions of NRSE cases (n = 10, 33.3% vs. all patients n = 95, 45.7%) and higher proportions of SRSE cases (n = 5, 16.7% vs. all patients n = 19, 9.1%). Tumor progression signs (n = 128, 61.5%) were common in patients with metastatic entities (n = 41, 77.4%) and less prevalent in those with intracranial extradural tumors (n = 9, 30%). Brain tumors were newly diagnosed at SE admission in 57 patients (27.4%) and more frequently in patients with metastatic entities (n = 23, 43.3%) and tumors with radiological progression (n = 53, 41.4%) than those with adult-type diffuse gliomas (n = 22, 19%) and tumors without radiological progression (n = 4, 5%). The time between tumor diagnosis and SE averaged 2.3 ± 4.4 years (median 0.5, range 0–24.5 years), with the shortest time interval occurring for the metastatic entities (mean 0.6 ± 0.9, median 0.2, range 0–4.5 years) and the longest for the intracranial extradural tumor group (mean 5.3 ± 7.1, median 2.1, range 0–21.2 years).


On admission, 61 (29.3%) patients were receiving ongoing tumor-specific therapy and 53 (25.5%) experienced the SE within six months of completing radiation therapy. Patients with adult-type diffuse gliomas had significantly more ongoing treatment (n = 44, 37.9%) and radiation therapy in the six-month period (n = 43, 37.1%) than those in the other groups; details are presented in Table 3. None of the patients with intracranial extradural tumors had ongoing therapy or radiation therapy close to the time of the SE event.

Table 3 Hospital treatment, medication used for SE treatment, and tumor treatments prior to and during SE, stratified by tumor categories and tumor progression signs

At admission, 64 (30.8%) patients were on dexamethasone, and this number increased to 101 (48.6%) at discharge. Patients with intracranial extradural tumors showed the lowest level of dexamethasone therapy (admission n = 2, 6.7%, discharge n = 3, 10%). In addition, patients without progression signs were more often receiving dexamethasone therapy at the time of admission (n = 27, 33.8%) than patients with progression signs (n = 37, 28.9%), but as expected, the increase in usage was more clear among patients with progression signs at discharge (with n = 71, 55.5% vs. without n = 30, 37.5%).

Prior to SE onset, 126 (60.6%) patients used an average of 1.6 ± 0.8 (median 1, range 1–5) ASMs, with the greatest usage by patients with adult-type diffuse gliomas (n = 84, 72.4%) compared to the other two tumor categories. During the SE period, the average number of treatment steps with an ASM was 3.6 ± 2.2 (median 3, range 1–10), and patients were discharged with an increased mean number of ASMs (2.2 ± 1.1, median 2, range 1–5, p < 0.001); a detailed description of the treatment steps is presented in Additional file 1: Table S2.

The mean length of stay (LOS) in hospital was 14.8 ± 11.5 days (median 12, range 1–57 days). Of all patients, 171 (82.2%) were admitted to the intensive care unit (ICU) or intermediate care (IMC) department and 44 (21.2%) required mechanical ventilation. The mean LOS in the ICU/IMC was 8.9 ± 9.8 days (median 5, range 1–46), while patients with intracranial extradural tumors had hospital (17.3 ± 11.7, median 15, range 3–45 days) and ICU/IMC (12.2 ± 8.8, median 11, range 1–31 days) stays that were significantly longer and required mechanical ventilation more often than patients from both other tumor categories. Treatments or administered therapies were limited during the SE event in 36 (17.3%) patients, with less limitations for those with intracranial extradural tumors (n = 2, 6.7%); however, significantly reduced levels of therapy were noted in patients with signs of tumor progression (n = 29, 22.7%). The detailed information on inpatient stay, medications, and tumor treatments of the SE patients is presented in Table 3.


In total, 61 (29.4%) patients were discharged with good functional status (mRS 0–2), 111 (53.3%) had poor functional status (mRS 3–5), and 36 (17.3%) patients were deceased. The functional status at discharge did not differ significantly between the tumor categories; however, a clear difference was observed depending on the presence of the radiological criteria of tumor progression, with only 28 (21.9%) of the patients with progression presenting with good functional outcomes compared to 33 (41.3%) of those without progression. A clear shift to a poorer functional status at discharge compared to that at admission was significant for all patients (p < 0.001) and all subgroups (tumor category, progression signs, and refractoriness; all p-values < 0.001). The mRS distribution of the subgroups is shown in Fig. 1. The mortality at discharge was higher among patients with metastatic entities (n = 14, 26.4%) than those with adult-type diffuse gliomas, and higher among patients with progression signs (n = 32, 25%) than those without (n = 4, 5%) these signs.

Fig. 1
figure 1

Functional status of all patients measured by modified Rankin Scale before and after SE (A) stratified by tumor progression signs (B), tumor category (C), and SE refractoriness (D)

The long-term patient survival at one year is depicted using Kaplan–Meier curves in Fig. 2. Survival among patients with intracranial extradural tumors was higher than that for patients with adult-type diffuse gliomas (log-rank p-value 0.002) and metastatic entities (log-rank p-value < 0.001) (Fig. 2a). There was no difference between the results for the latter two groups (log-rank p-value 0.059). Figure 2b shows the survival of patients with meningiomas, glioblastomas, and solid metastases. Patients with signs of tumor progression had significantly poorer survival rates than those without signs of progression (log-rank p-value < 0.001) (Fig. 2c). Refractoriness is depicted in Fig. 2d, whereby patients with NRSE showed better survival rates than patients with RSE (SRSE not included, log-rank p-value 0.020), while no statistical difference was identified between NRSE and SRSE patients (log-rank p-value 0.512) or between RSE and SRSE patients (log-rank p-value 0.066). There was no difference between those with a previous history of epilepsy or SE compared to those with new-onset SE (log-rank p-value 0.456, Kaplan-Meier curves not shown).

Fig. 2
figure 2

Long-term outcomes depicted by Kaplan-Maier curves stratified by tumor category (A, B), tumor progression signs (C), and SE refractoriness (D)


This retrospective, multicenter study described the clinical characteristics, treatment, and outcomes of 208 SE patients with brain tumors and metastases using the largest identified cohort published to date. The results indicated that the SE event caused a clear decline in the functional status (mRS) of the patients, which was independent of tumor type, radiological progression, and SE refractory level. Less than half of the patients survived for a year after the SE event, and considerable mortality was observed among the patients with nonmalignant intracranial extradural tumors. The SRSE cases presented better survival rates than those of the less refractory cases at one year after SE. The definition of SRSE requires anesthesia and only patients with a better outcome are likely to be considered for anesthesia. In principle, refractoriness could also be defined according to the duration of SE and number of therapies; this is currently being discussed and researched [27,28,29,30,31].

The existing literature regarding SE in patients with brain tumors is scarce [9, 15], despite brain tumors presenting a high risk for the development of SE and accounting for approximately 10% of all SE cases [10, 32]. A limited number of studies have focused on this specific patient group, and the majority of these were retrospective, involved only a single center, and consisted of small patient cohorts. Our literature review identified seven original studies [14, 16, 33,34,35,36,37] and two reviews [9, 15], the details of which are presented in Table 4. These studies indicated that SE patients with brain tumors averaged 55–68 years of age and mainly included males. The data from the present cohort were concordant with those of the previous studies, although the sex distribution differed significantly between tumor categories, as patients with adult-type diffuse gliomas were more likely to be male, while those from other groups were more often female. In addition, patients with intracranial extradural tumors were significantly older than the patients from the other groups.

Table 4 Summary of published studies on status epilepticus cases caused by brain tumors and metastases

Adult-type diffuse gliomas and intracranial extradural tumors accounted for the vast majority of primary brain tumors in this study (70.2%), while 29.9% of the patients had metastatic entities or other tumors. The proportion of adult-type diffuse gliomas (55.8%) was comparable with the results of previously reported SE cohorts that indicated 41.5–65.7% for malignant brain tumors or gliomas (high-grade and low-grade gliomas) [18, 34, 37]. Similarly, the intracranial extradural tumor (14.4%) and metastatic entity (25.5%) percentages corroborated those of previous studies, which reported 14.3–25% of benign brain tumors/meningiomas and 26.8%–34.4% of metastatic tumors [16, 34, 37]. These findings were expected, as a higher frequency of seizures and SE events occurs among patients with primary brain tumors compared to those with metastasis [5, 16] and a higher risk of SE is associated with increasing WHO grades [9, 14, 36, 38].

Arik et al. conducted a systematic review that considered SE outcomes and found that SE events caused by brain tumors have higher in-hospital mortalities than non-anoxic SE caused by other factors (17.2% vs. 6%) [15]. Goonawardena et al. compared tumor-associated SE (TASE) to SE in the general population and tumor-associated epilepsy (TAE) in a systematic review and found that the 30-day mortality of TASE ranged between 12 and 50%, which was similar to or higher than the mortality percentage of the general population [9]. In the present cohort, the overall mortality at discharge (17.3%) and at 30 days (24%) was comparable to the 30 days mortality range estimated by Goonawardena et al. [9] and the 17.1% in-hospital mortality identified in a prospective cohort of 82 patients published by Vilaseca-Jolonch et al. [34]

Our data showed that the highest in-hospital mortality rate occurred among patients with metastatic entities (26.4%) and that this value was significantly higher than that of patients with adult-type diffuse gliomas. Higher short-term mortalities and poorer outcomes in patients with brain metastases compared those with to primary brain tumors are consistent with the current literature [16, 34, 37]. High-grade gliomas have shown greater 30-day mortality rates (20%) than low-grade gliomas with no mortality [36]. In our cohort, patients with adult-type diffuse gliomas had an in-hospital mortality rate of 13%; however, a clear increase in mortality (up to 70%) was noticed during the first year after discharge. In particular, the survival of glioblastoma patients was similar to that of metastatic entity patients at one year and distinctively lower than that of patients with other types of glioma or meningioma. In this regard, the long-term mortality of TASE has been related to the natural prognosis of tumor types [14].

Radiological progression was present in the majority of SE patients in the cohort (61%). Previous literature regarding the occurrence of SE concomitant with progression is inconsistent, as no difference was observed between patients with stable tumors and those with tumor progression in terms of the occurrence of SE in the study by Knudsen-Baas et al. [36], although the occurrence of TASE has been associated with tumor progression [9]. Progressing brain lesions and tumor recurrences are associated with a risk of mortality within 2 months of the SE [37]. Similarly, tumor progression at the onset of SE has been associated with long-term mortality, with up to 73.3% of the patients dying due to tumor progression during the median 10.5-month follow-up period [34]. These associations were confirmed in our cohort. Radiological signs of CNS-related tumor progression at admission were most prevalent in patients with metastatic entities and least evident in those with intracranial extradural tumors, which could partly explain the poor outcomes of the former group. Dexamethasone use at admission was more frequent among patients without signs of progression but naturally increased among patients showing signs of progression, which accounts for the significant difference between the groups.

Giovannini et al. identified no increases in mortality or morbidity after a TASE episode among glioma patients [14]. Another study reported that 30% of patients acquired new neurological deficits after glioma-associated SE; however, this finding was suggested to be related to tumor progression as an etiology of SE [36]. Our study showed a statistically significant decline in the functional status of all patients during the SE treatment period. SRSE showed the largest overall decline, which is in line with the results of other studies [39]. In addition, patients with intracranial extradural tumors experienced a clear decline in functional status. The pre-SE functional status did not differ between the subgroups; however, the status at discharge was significantly poorer in patients with signs of tumor progression compared to those without progression signs.

Previous studies have reported tumor-associated SE refractoriness ranging from 12 to 57.9% [9, 14,15,16, 33,34,35,36,37]. Reviews have indicated that TASE tends to be more responsive than SE to first- and second-line ASMs in the general population, with refractoriness evident in only 12–18% of cases [9]. Furthermore, TASE appears to have a shorter duration than SE in the general population (153 min vs. 174 min) [15]. The present study showed a markedly high proportion of refractoriness (54.3%), which is comparable with the 52.5% refractoriness level found in another cohort study [34]. In addition, refractoriness was not related to tumor category or the signs of progression, which corroborates the results of a previous study [36]. Although SRSE has been associated with poor prognoses in SE patients, the SRSE cases identified here showed better outcomes than those of the less refractory cases at one year [29, 40, 41]. This result could be partly explained by the variation in SE treatment approaches based on the overall prognosis of the patients; thus, patients with better tumor prognoses might be offered more therapy options, such as intubation and anesthesia treatment, whereas patients with poorer overall prognoses are more likely to be administered ASM treatment without the use of anesthesia. This study showed that therapy limitations were more common in patients with signs of tumor progression.

The majority of patients in this study had a previous history of seizures (61.1%), whereas other cohorts showed slightly lower proportions (35–56.3%) [14, 16, 34,35,36]. This result was more prominent in patients with adult-type diffuse gliomas and those without progression signs. A new brain tumor diagnosis was made in every fourth patient at admission. The lowest percentage (15.8%, range 15.8–54%) of newly diagnosed tumors at SE onset reported in the literature occurred in a study focusing on SE in patients with brain metastasis, while our study determined that a new tumor was usually diagnosed in patients with metastatic entities or signs of progression. The overall time between tumor diagnoses and SE (2.3 years) was considerably longer than the 60 days to 4 months reported in other studies [14, 35]. The longest interval was found among patients with intracranial extradural tumors and the shortest was identified among those with metastatic entities and tumors with progression signs. Our findings confirm the overall supposition that SE occurs later in the disease course or prior to tumor progression [9, 42].

The median LOS in hospital (12 days) was comparable to that of TASE patients in another study (9 days) [34]. However, the LOS value was in the upper range of the reported median of 5–14 days among general SE patients [29, 41, 43, 44]. The present study is the first identified report that determined the ICU LOS in the patient group (median 5 days), which was revealed to be slightly higher than the LOS for general SE patients (3 days) [29]. Similar to the 22% reported by Marcuse, 21.2% of the patients required mechanical ventilation [37].

Finally, intracranial extradural tumors were the predominant tumors in all categories studied. The associated patients differed significantly from those with adult-type diffuse gliomas, as they presented more frequently with SRSE, required additional mechanical ventilation, and endured longer ICU stays. In addition, intracranial extradural tumor patients showed less frequent tumor progression signs than patients with other tumors and were administered less dexamethasone treatments than adult-type diffuse glioma patients. However, the decline in the functional status of these patients was clear during the SE and the mortality at one year reached 36.7%. The older age of these patients may partly explain the poor outcomes; however, the direct effect of SE and related treatments cannot be discounted.


This study is limited by its retrospective design. However, the multicenter approach covering a study period of over seven years and the considerable amount of material reviewed increase the reliability of the results.

Direct comparisons of the results with prior studies were compromised by the heterogeneity in study design and differences in tumor categorization. The recent increase in the biomolecular understanding of brain tumors has changed the field, but since this retrospective study aimed for a comprehensive cohort, gliomas were included that were diagnosed according to former WHO CNS tumor classification guidelines. Causes of death were not assessed; therefore, it was not possible to differentiate whether patients died as a direct consequence of SE, related complications, or withdrawal of care. Furthermore, we provided only descriptive data on different tumor therapies such as neurosurgery, radiation, and chemo- and immunotherapies, and further studies with each tumor entity are required to determine the correlations among different therapies and their benefits or risks related to seizure and SE occurrence [45]. In addition, future studies focusing on specific tumor entities should address the resection extent of diffuse gliomas and metastatic burden in patients with metastatic tumors.


SE occurrence in patients with brain tumors contributes significantly to an immediate decline in functional status, regardless of the type of tumor (malignant or non-malignant), presence or absence of tumor progression, and refractoriness of the SE episode. Therefore, effective prevention of SE events is imperative for preserving and maintaining functional status in individuals with brain tumors.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.


  1. Herman, S. T. (2002). Epilepsy after brain insult: Targeting epileptogenesis. Neurology, 59(9 Suppl 5), S21–S26.

    Article  PubMed  Google Scholar 

  2. Olafsson, E., Ludvigsson, P., Hesdorffer, D., Kjartansson, O., Hauser, W. A., & Gudmundsson, G. (2005). Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: A prospective study. The Lancet Neurology., 4(10), 627–634.

    Article  PubMed  Google Scholar 

  3. Seidel, S., Wehner, T., Miller, D., Wellmer, J., Schlegel, U., & Gronheit, W. (2022). Brain tumor related epilepsy: Pathophysiological approaches and rational management of antiseizure medication. Neurological Research and Practice., 4(1), 45.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hauser, W. A., Annegers, J. F., & Kurland, L. T. (1993). Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia, 34(3), 453–468.

    Article  PubMed  CAS  Google Scholar 

  5. van Breemen, M. S., Wilms, E. B., & Vecht, C. J. (2007). Epilepsy in patients with brain tumours: Epidemiology, mechanisms, and management. The Lancet Neurology., 6(5), 421–430.

    Article  PubMed  Google Scholar 

  6. Glantz, M. J., Cole, B. F., Forsyth, P. A., Recht, L. D., Wen, P. Y., Chamberlain, M. C., et al. (2000). Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 54(10), 1886–1893.

    Article  PubMed  CAS  Google Scholar 

  7. Maschio, M. (2012). Brain tumor-related epilepsy. Current Neuropharmacology, 10(2), 124–133.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Rossetti, A. O., & Stupp, R. (2010). Epilepsy in brain tumor patients. Current Opinion in Neurology., 23(6), 603–609.

    Article  PubMed  CAS  Google Scholar 

  9. Goonawardena, J., Marshman, L. A., & Drummond, K. J. (2015). Brain tumour-associated status epilepticus. Journal of Clinical Neuroscience, 22(1), 29–34.

    Article  PubMed  Google Scholar 

  10. Betjemann, J. P., & Lowenstein, D. H. (2015). Status epilepticus in adults. The Lancet Neurology., 14(6), 615–624.

    Article  PubMed  Google Scholar 

  11. Trinka, E., Cock, H., Hesdorffer, D., Rossetti, A. O., Scheffer, I. E., Shinnar, S., et al. (2015). A definition and classification of status epilepticus–report of the ILAE task force on classification of status Epilepticus. Epilepsia, 56(10), 1515–1523.

    Article  PubMed  Google Scholar 

  12. Kamppi, L., Mustonen, H., Kotisaari, K., & Soinila, S. (2018). The essence of the first 25 h in the treatment of generalized convulsive status epilepticus. Seizure., 55, 9–16.

    Article  PubMed  Google Scholar 

  13. Bauer, K., Rosenow, F., Knake, S., Willems, L. M., Kamppi, L., & Strzelczyk, A. (2023). Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes. Neurological Research and Practice, 5(1), 34.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Giovannini, G., Pasini, F., Orlandi, N., Mirandola, L., & Meletti, S. (2019). Tumor-associated status epilepticus in patients with glioma: Clinical characteristics and outcomes. Epilepsy & Behavior., 101(Pt B), 106370.

    Article  Google Scholar 

  15. Arik, Y., Leijten, F. S., Seute, T., Robe, P. A., & Snijders, T. J. (2014). Prognosis and therapy of tumor-related versus non-tumor-related status epilepticus: A systematic review and meta-analysis. BMC Neurology., 14, 152.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cavaliere, R., Farace, E., & Schiff, D. (2006). Clinical implications of status epilepticus in patients with neoplasms. Archives of Neurology., 63(12), 1746–1749.

    Article  PubMed  Google Scholar 

  17. Purwien, L., Schubert-Bast, S., Kieslich, M., Ronellenfitsch, M. W., Merker, M., Czabanka, M., et al. (2023). Trends and differences in status epilepticus treatment of children and adults over 10 years: A comparative study of medical records (2012–2021) from a University Hospital in Germany. CNS Drugs, 37(11), 993–1008.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Knake, S., Rosenow, F., Vescovi, M., Oertel, W. H., Mueller, H. H., Wirbatz, A., et al. (2001). Incidence of status epilepticus in adults in Germany: A prospective, population-based study. Epilepsia, 42(6), 714–718.

    Article  PubMed  CAS  Google Scholar 

  19. von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gotzsche, P. C., Vandenbroucke, J. P., et al. (2007). The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. Lancet, 370(9596), 1453–1457.

    Article  Google Scholar 

  20. Ferlisi, M., & Shorvon, S. (2012). The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain, 135(Pt 8), 2314–2328.

    Article  PubMed  Google Scholar 

  21. Shorvon, S., & Ferlisi, M. (2011). The treatment of super-refractory status epilepticus: A critical review of available therapies and a clinical treatment protocol. Brain, 134(Pt 10), 2802–2818.

    Article  PubMed  Google Scholar 

  22. Malter, M. P., & Neuneier, J. (2022). Super-refractory status epilepticus in adults. Neurological Research and Practice, 4(1), 35.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Leitinger, M., Trinka, E., Gardella, E., Rohracher, A., Kalss, G., Qerama, E., et al. (2016). Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: A retrospective study. The Lancet Neurology., 15(10), 1054–1062.

    Article  PubMed  Google Scholar 

  24. Charlson, M. E., Pompei, P., Ales, K. L., & MacKenzie, C. R. (1987). A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Diseases., 40(5), 373–383.

    Article  PubMed  CAS  Google Scholar 

  25. Banks, J. L., & Marotta, C. A. (2007). Outcomes validity and reliability of the modified Rankin scale: Implications for stroke clinical trials: A literature review and synthesis. Stroke, 38(3), 1091–1096.

    Article  PubMed  Google Scholar 

  26. Rossetti, A. O., Logroscino, G., Milligan, T. A., Michaelides, C., Ruffieux, C., & Bromfield, E. B. (2008). Status Epilepticus Severity Score (STESS): A tool to orient early treatment strategy. Journal of Neurology., 255(10), 1561–1566.

    Article  PubMed  Google Scholar 

  27. Beuchat, I., Rosenow, F., Kellinghaus, C., Trinka, E., Unterberger, I., Ruegg, S., et al. (2022). Refractory status epilepticus: Risk factors and analysis of intubation in the multicenter SENSE registry. Neurology, 99(16), e1824–e1834.

    Article  PubMed  Google Scholar 

  28. Cornwall, C. D., Kroigard, T., Kristensen, J. S. S., Callesen, H. E., & Beier, C. P. (2023). Outcomes and treatment approaches for super-refractory status epilepticus: A systematic review and meta-analysis. JAMA Neurology., 80(9), 959–968.

    Article  PubMed  Google Scholar 

  29. Guterman, E. L., Betjemann, J. P., Aimetti, A., Li, J. W., Wang, Z., Yin, D., et al. (2021). Association between treatment progression, disease refractoriness, and burden of illness among hospitalized patients with status epilepticus. JAMA Neurology., 78(5), 588–595.

    Article  PubMed  Google Scholar 

  30. Beuchat, I., Novy, J., Rosenow, F., Kellinghaus, C., Ruegg, S., Tilz, C., et al. (2024). Staged treatment response in status epilepticus: Lessons from the SENSE registry. Epilepsia,  65(2), 338-349.

    Article  PubMed  Google Scholar 

  31. Lattanzi, S., & Meletti, S. (2024). Refractory status epilepticus: Is there room for grading refractoriness? Epilepsia, 65(2), 527-528.

    Article  PubMed  Google Scholar 

  32. Rossetti, A. O., Hurwitz, S., Logroscino, G., & Bromfield, E. B. (2006). Prognosis of status epilepticus: Role of aetiology, age, and consciousness impairment at presentation. Journal of Neurology, Neurosurgery and Psychiatry, 77(5), 611–615.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Kaneoka, A., Fujimoto, S. H., Tamura, K., Inaji, M., & Maehara, T. (2023). Nonconvulsive status epilepticus characteristics in glioma patients: A retrospective study. Discover Oncology, 14(1), 30.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Vilaseca-Jolonch, A., Abraira, L., Quintana, M., Sueiras, M., Thonon, V., Toledo, M., et al. (2020). Tumor-associated status epilepticus: A prospective cohort in a tertiary hospital. Epilepsy & Behavior., 111, 107291.

    Article  Google Scholar 

  35. Fox, J., Ajinkya, S., Greenblatt, A., Houston, P., Lekoubou, A., Lindhorst, S., et al. (2019). Clinical characteristics, EEG findings and implications of status epilepticus in patients with brain metastases. Journal of the Neurological Sciences, 407, 116538.

    Article  PubMed  Google Scholar 

  36. Knudsen-Baas, K. M., Power, K. N., Engelsen, B. A., Hegrestad, S. E., Gilhus, N. E., & Storstein, A. M. (2016). Status epilepticus secondary to glioma. Seizure., 40, 76–80.

    Article  PubMed  Google Scholar 

  37. Marcuse, L. V., Lancman, G., Demopoulos, A., & Fields, M. (2014). Nonconvulsive status epilepticus in patients with brain tumors. Seizure., 23(7), 542–547.

    Article  PubMed  Google Scholar 

  38. Rosati, A., Tomassini, A., Pollo, B., Ambrosi, C., Schwarz, A., Padovani, A., et al. (2009). Epilepsy in cerebral glioma: Timing of appearance and histological correlations. Journal of Neuro-oncology, 93(3), 395–400.

    Article  PubMed  Google Scholar 

  39. Kortland, L. M., Knake, S., von Podewils, F., Rosenow, F., & Strzelczyk, A. (2017). Socioeconomic outcome and quality of life in adults after status epilepticus: A multicenter, longitudinal, matched case-control analysis from Germany. Frontiers in Neurology., 8, 507.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Roberg, L. E., Monsson, O., Kristensen, S. B., Dahl, S. M., Ulvin, L. B., Heuser, K., et al. (2022). Prediction of long-term survival after status epilepticus using the ACD score. JAMA Neurology., 79(6), 604–613.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Strzelczyk, A., Ansorge, S., Hapfelmeier, J., Bonthapally, V., Erder, M. H., & Rosenow, F. (2017). Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany. Epilepsia, 58(9), 1533–1541.

    Article  PubMed  Google Scholar 

  42. Brauchitsch, S., Strzelczyk, A., Rosenow, F., Neuhaus, E., Dubinski, D., Steinbach, J.P., Voss M. (2022) High end-of-life incidence of seizures and status epilepticus in patients with primary and secondary brain tumors. Journal of Neuro-Oncology, 160(2), 277–284.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Kortland, L. M., Alfter, A., Bahr, O., Carl, B., Dodel, R., Freiman, T. M., et al. (2016). Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany. Epilepsia, 57(12), 2056–2066.

    Article  PubMed  Google Scholar 

  44. Mevius, A., Joeres, L., Gille, P., Molzan, M., Foskett, N., Wilke, T., et al. (2023). Epidemiology, real-world treatment and mortality of patients with status epilepticus in Germany: Insights from a large healthcare database. Brain Commun., 5(3), fcad145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Urban, H., Willems, L. M., Ronellenfitsch, M. W., Rosenow, F., Steinbach, J. P., & Strzelczyk, A. (2020). Increased occurrence of status epilepticus in patients with brain metastases and checkpoint inhibition. Oncoimmunology., 9(1), 1851517.

    Article  PubMed  PubMed Central  Google Scholar 

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The authors would like to thank the study teams at both participating epilepsy centers. This data analysis was supported by the State of Hessen with a LOEWE grant to the CePTER Consortium ( Leena Kämppi received research funding from STIFTUNG MICHAEL. Pia S. Zeiner and Katharina J. Weber received funding from the Mildred Scheel Career Center Frankfurt (Deutsche Krebshilfe).


Open Access funding enabled and organized by Projekt DEAL. This study was supported by a LOEWE Grant from the State of Hessen for the Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

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Authors and Affiliations



JR, DZ, SK, HU; JK, KW, PZ, AP, EH, AK, EF, SA, RW, MS, TR, MWR, KM, LH, LM, MC, CN, LT, CG, JS, FR, and AS participated in the recruitment of patients and data collection. AS supervised the study. JR, DZ, LK, and AS performed the statistical analysis and created the charts and figures. All authors drafted the article, discussed the results, contributed to the final manuscript, and approved the final manuscript for publication.

Corresponding author

Correspondence to Adam Strzelczyk.

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Competing interests

S. Knake has received support from Angelini Pharma, Bial, Desitin Arzneimittel, Eisai, Epilog, Jazz (GW) Pharmaceuticals, Merck Serono and UCB (Zogenix) Pharma in the form of speaker honoraria; M.W. Ronellenfitsch has received support in the form of a research grant from UCB and an honorarium for advisory board participation from Alexion; L. Habermehl has received support from Jazz Pharma, Zogenix, and Angelini pharma in the form of reimbursed travelling expenses and training costs; S. Adeberg has received support from, Accuray Inc., AstraZeneca GmbH, Bristol Myers Squibb GmbH & Co., MSD, Novocure GmbH, Merck KGaA, and Fakultät Heidelberg in the form of honoraria /travel reimbursements; research cooperations with Novocure GmbH, and scientific advisory compensation from Accuray Inc., Sanofi Genzyme, Novartis, and Novocure GmbH; M. Sebastian has received support in the form of an institutional grant from AstraZeneca of the United Kingdom, travel grants from Takeda and Pfizer of Germany, and consulting fees and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Lilly, Roche, Boehringer Ingelheim, Amgen, Takeda, Johnson, Merck-Serono, GlaxoSmithKline, and Daiichi; Ch. Nimsky has received support as a scientific consultant for Brainlab and speaker honoraria from B. Braun, BK medical, and Brainlab. L. Timmermann has received support in the form of occasional consultation payments from Boston Scientific and speaker’s honoraria for symposia sponsored by Boston Scientific, AbbVIE, Novartis, Neuraxpharm, Teva, the Movement Disorders Society, and DIAPLAN. The institution of L.T., and not L.T. personally, received funding from Boston Scientific, the German Research Foundation, the German Ministry of Education and Research, the Otto-Loewi-Foundation, and the Deutsche Parkinson Vereinigung. Neither L.T. nor any member of his family holds stocks, stock options, patents, or financial interests in any of the above-mentioned companies or their competitors. L. Timmermann serves as the president of the German Neurological Society without payment or income. C. Grefkes reports that he is part of the editorial board of Neurological Research and Practice. J.P. Steinbach has received support in the form of honoraria for lectures, as well as advisory board participation compensation, consulting fees, and travel grants from Abbvie, Roche, Boehringer, Bristol-Myers Squibb, Medac, Mundipharma, or UCB; F. Rosenow has received support in the form of personal fees and non-financial support from UCB Pharma; personal fees from Angelini Pharma, Desitin Pharma, Eisai GMBH, Jazz Pharma, LMU Munich, Medilearn India, and Roche Pharma; and research grants from the German Research Foundation (DFG), BMBF—ERAPerMed Programme, European Union (FP7), Hessisches Ministerium für Wissenschaft und Kunst (LOEWE-Programme), Hessisches Ministerium für Soziales und Integration Detlev-Wrobel-Fonds for Epilepsy Research Frankfurt, Reiss-Stiftung, Dr. Senckenbergische-Stiftung, Ernst Max von Grunelius-Stiftung, Chaja Foundation, Dr. Schär Deutschland GmbH, Vitaflo Deutschland GmbH, Nutricia Milupa GmbH, and Desitin Pharma, outside of the submitted work; FR reports that he is part of the editorial board of Neurological Research and Practice. L. Kämppi has received support in the form of speaker honoraria from UCB and Merck and Eisai, congress/travel support from UCB and Angelini Pharma, and personal grants from the Michael Foundation, Finnish Neurology Association, and HUS Neurocenter; A. Strzelczyk has received support from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, Jazz (GW) Pharmaceuticals, Marinus Pharma, Precisis, Takeda, UCB (Zogenix) Pharma, and UNEEG Medical in the form of personal fees and grants. AS reports that he is part of the editorial board of Neurological Research and Practice. The remaining authors have no conflicts of interest.

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Additional file 1. Table S1.

Tumor localization; Table S2. Treatment characteristics with antiseizure medications (ASMs) and anesthetics.

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Rickel, J.K., Zeeb, D., Knake, S. et al. Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review. Neurol. Res. Pract. 6, 19 (2024).

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