Abstracts
Objective
Status epilepticus (SE) is associated with significant morbidity and mortality, and there is some controversy concerning predictive indicators of outcome. Our main goal was to determine mortality and to identify factors associated with SE prognosis.
Method
This prospective study in a tertiary-care university hospital, included 105 patients with epileptic seizures lasting more than 30 minutes. Mortality was defined as death during hospital admission.
Results
The case-fatality rate was 36.2%, which was higher than in previous studies. In univariate analysis, mortality was associated with age, previous epilepsy, complex focal seizures; etiology, recurrence, and refractoriness of SE; clinical complications, and focal SE. In multivariate analysis, mortality was associated only with presence of clinical complications.
Conclusions
Mortality associated with SE was higher than reported in previous studies, and was not related to age, specific etiology, or SE duration. In multivariate analysis, mortality was independently related to occurrence of medical complications.
status epilepticus; epilepsy; mortality; prognosis
Objetivos
Status epilepticus (SE) está associado com morbidade e mortalidade importantes. Diversos estudos avaliaram determinantes de prognóstico relacionados com SE, havendo controvérsias neste sentido. O objetivo deste estudo foi avaliar mortalidade no SE e seus fatores determinantes.
Método
Estudo prospectivo, em Ribeirão Preto, incluiu 105 pacientes, entre fevereiro e dezembro de 2000. Mortalidade foi definida como óbito no período de internação hospitalar.
Resultados
O índice de mortalidade foi de 36.2%, superior ao verificado em estudos prévios. Em análise univariada, mortalidade foi associada com idade, antecedente de epilepsia, presença de crises focais complexas, etiologia, recorrência e refratariedade do SE, presença de complicações clínicas e classificação focal do SE. Em análise multivariada, a ocorrência de complicações clínicas relacionou-se significativamente com prognóstico.
Conclusões
Em nossa amostra, a mortalidade foi mais elevada do que previamente descrito na literatura, não relacionada com idade, etiologia ou duração do SE, mas, em análise multivariada, com complicações médicas durante o tratamento.
status epilepticus; epilepsia; mortalidade; prognóstico
Epileptic seizures are self-limited, lasting, in general, less than to 2 minutes. Status
epilepticus (SE) is manifested by continuous or recurrent epileptic seizures without
full recovery of motor, sensory and/or cognitive functions, and has multiple etiologies
and a diverse prognosis. The duration of seizures in SE varies from 5 to 30 minutes,
depending on the definition11 .Guidelines on epidemiologic studies on epilepsy. Commission on
Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia.
1993;34(4):592-6. 10.1111/j.1528-1157.1993.tb00433.x
https://doi.org/10.1111/j.1528-1157.1993...
. It is one
of the most frequent neurological emergencies, with an estimated annual incidence of
from 6.2 to 61/100,000 people22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
,33 .Chin RF, Neville BG, Scott RC. A systematic review of the
epidemiology of status epilepticus. Eur J Neurol. 2004;11(12):800-10.
http://dx.doi.org/10.1111/j.1468-1331.2004.00943.x
https://doi.org/10.1111/j.1468-1331.2004...
.
SE is associated with long-term mortality that is nearly three times greater than that
of the general population44 .Logroscino G, Hesdorffer DC, Cascino GD, Annegers J, Bagiella E,
Hauser WA. Long-term mortality after a first episode of status epilepticus.
Neurology. 2002;58(4):537-41.
http://dx.doi.org/10.1212/WNL.58.4.537
https://doi.org/10.1212/WNL.58.4.537...
. Indeed,
despite new advances in medical treatment, short-term mortality remains high, ranging
from 3 to 40%, depending on the sampling methods, age, specific etiology, or
refractoriness of SE55 .Sutter R, Kaplan PW, Rüegg S. Outcome predictors for status
epilepticus-what really counts. Nat Rev Neurol. 2013;9(9):525-34.
http://dx.doi.org/10.1038/nrneurol.2013.154
https://doi.org/10.1038/nrneurol.2013.15...
.
Several studies agree that the most important factors related to mortality in SE are
older age, acute symptomatic etiology such as central nervous system (CNS) infection,
acute stroke, metabolic disturbances, and anoxia, and long seizure duration.
Anti-epileptic drug (AED) withdrawal in previously epileptic patients is typically
associated with low mortality22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
,66 .Logroscino G; Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A,
Galobardes B et al. Mortality after a first episode of status epilepticus in the
United States and Europe. Epilepsia. 2005;46(suppl s11):46-8.
http://dx.doi.org/10.1111/j.1528-1167.2005.00409.x
https://doi.org/10.1111/j.1528-1167.2005...
.
For other characteristics, such as gender, history of prior epilepsy, refractory SE,
adequacy of medical treatment, presence of medical complications, level of
consciousness, and electroencephalographic pattern, there is no consensus in the
literature22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
. A better understanding
of SE prognostic factors would assist in making treatment-related decisions.
METHOD
We retrospectively studied all 105 patients older than 1 month of age who were
diagnosed with SE and admitted to the Hospital das Clínicas da Faculdade de Medicina
de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), a tertiary-care
hospital, between February and December 2000. SE was defined as a clinical or
electrographic seizure lasting more than 30 minutes or recurrent seizures without
full recovery of consciousness for 30 minutes or more11 .Guidelines on epidemiologic studies on epilepsy. Commission on
Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia.
1993;34(4):592-6. 10.1111/j.1528-1157.1993.tb00433.x
https://doi.org/10.1111/j.1528-1157.1993...
. Serial 18- or 21-channel electroencephalograms (EEGs)
(Nihon Kohden, Japan), were obtained from all patients following the 10-20
International System of electrode placement. After discharge or death, medical
records were reviewed, including demographic data, medical history, prior history of
epilepsy, SE classification, seizure duration, SE etiology, EEG patterns, treatment,
response to treatment, and prognosis during the hospital stay. There was no
follow-up after discharge.
The sample was divided into two groups by prognosis. Those in group I survived until hospital discharge, and those in group II died while inpatients. Patients younger than 1 month of age and patients diagnosed with pseudo-status epilepticus were excluded from the study.
Patients were divided into three categories based on clinical semiology following the
Classification of Epileptic Seizures (i.e., focal, secondarily generalized, and
generalized SE)77 .Proposal for revised clinical and electroencephalographic
classification of epileptic seizures. Epilepsia. 1981;22(4):489-501.
http://dx.doi.org/10.1111/j.1528-1157.1981.tb06159.x
https://doi.org/10.1111/j.1528-1157.1981...
. Clinical
presentation was described as generalized tonic-clonic seizure (GTCS), focal complex
seizure (FCS), focal simple seizure (FSS), absence seizure, tonic seizure, epileptic
spams, delirium, or confusional state. SE was further characterized as convulsive or
nonconvulsive by semiology.
Refractory SE was defined as absence of clinical and/or EEG control if seizures occurred after use of first and second line-drugs (e.g., IV diazepam, phenytoin, or phenobarbital). Third-line treatment included IV continuous midazolam and/or thiopentone. Refractory patients were given ventilator support when necessary.
SE etiology was classified as follows88 .Hauser WA. Status epilepticus: epidemiologic considerations.
Neurology. 1990;40(5 Suppl 2):9-13.,99 .DeLorenzo RJ, Towne AR, Pellock JM, Ko D. Status epilepticus in
children, adults, and elderly. Epilepsia.1992;33(suppl
4):S15-25.,1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1111 .Shinnar S, Pellock JM, Moshé SL, Maytal J, O’Dell C, Driscoll SM et
al. In whom does status epilepticus occur: age-related differences in children.
Epilepsia. 1997;38(8):907-14.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb01256.x
https://doi.org/10.1111/j.1528-1157.1997...
:
-
Acute symptomatic: SE occurring during within 7 days of an acute disease, such as CNS infection, brain trauma, cerebrovascular disease, toxic or metabolic insults.
-
Febrile: SE in a previously neurologically healthy child where the only provocative factor was a febrile disease with axillary temperature ≥ 38ºC and not related to CNS infection.
-
Progressive symptomatic: SE related to progressive diseases such as brain neoplasms or neurodegenerative disorders including innate metabolic errors.
-
Remote symptomatic: SE in an individual with prior (> 7 days) neurological disease, including cerebrovascular disorders or brain trauma, in the absence of acute insult.
-
Acute on remote symptomatic: SE occurring during an acute neurological insult (e.g., fever, toxic or metabolic insults, alcohol or drug withdrawal), in an individual with a remote symptomatic etiology.
-
Previous epilepsy with low antiepileptic drug (AED) levels or AED withdrawal: SE occurring in a previously epileptic individual with documented low AED level and/or history of AED noncompliance or change in therapy.
-
Cryptogenic: SE occurring in the absence of a known acute or remote etiologic factor.
SE groups were stratified by etiology and refractoriness to SE only (febrile, cryptogenic, low AED level, acute on remote symptomatic, and symptomatic) and SE plus (acute symptomatic, progressive, and refractory SE of any etiology).
Ictal EEG pattern evolution was evaluated in serial EEG recordings and classified as
discrete seizures (DS), merging seizures (MS), continuous ictal discharge (CD), CD
with flat periods (CDF), and periodic lateralized epileptic discharges (PLED) as
described by Treiman1212 .Treiman DM. Electroclinical features of status epilepticus. J Clin
Neurophysiol. 1995;12(4):343-62.
http://dx.doi.org/10.1097/00004691-199512040-00005
https://doi.org/10.1097/00004691-1995120...
. The
initial ictal pattern of each patient was analyzed.
Patients were treated according to the existing institutional protocol, which, besides support measures, consisted of (1) diazepam IV (10-20 mg bolus); (2) phenytoin IV (10-30 mg/kg infused at maximum dose of 50 mg/min); (3) phenobarbital IV (20-30 mg/kg). Following first- and second-line treatments, the options included (1) midazolam or (2) thiopental IV continuous.
Statistical analysis
Continuous variables were compared using the Mann-Whitney test and categorical variables were compared using Pearson’s chi-square. Odds ratios (ORs) were determined by logistic regression and reported with 95% confidence intervals (CIs). Statistical significance was established at the 0.05 level. Multivariate analysis was used to determine independent mortality risk factors. All statistical analyses was done using SSPS for Windows, version 10 (SSPS, Inc., Chicago, USA).
RESULTS
During the study period, 105 SE patients were admitted to HCFMRP-USP. Their mean age was 30.0 ± 26.8 years; 42 patients (40%) were women, and the male-female ratio was 1.5:1. The mortality rate was 36.2%, with 38 patients dying during their hospital stay. Following clinical or ECG criteria, SE was not stopped until death in 10 patients (9.5%). Overall, there were 125 SE episodes.
Univariate analysis
Table 1 summarizes the findings of univariate analysis. SE survivors were younger in group I (mean age = 24.9 ± 23.9 years) than in group II (39.3 ± 29.3 years; Z = 2.14, p = 0.032). The mortality rate was higher in the elderly (≥ 65, 64.7%) than in children (< 12 years of age, 25.7%), and adults (34.7%). There was no difference in gender-related mortality (33.3% in men and 40.4% in women). Fifty-five patients (52.4%) had a history of prior epilepsy, and they had a mortality rate of 18.2% compared with 56.0% in those without a history of epilepsy (p < 0.001). The most frequent seizure type was FCS (37.1%), followed in descending order by GTCS (28.6%) and FCC evolving to GTCS (14.3%). FCC had the highest mortality rate (51.3%; p = 0.015). Compared with other seizure types, GTCS had a lower mortality rate (20%; p = 0.033). There were no significant differences in mortality among other seizure types. No patients with absence seizure died. Convulsive SE predominated (86.7%) in this sample, and there was no difference in the mortality rates of patients with convulsive (36.3%) and nonconvulsive (35.7%) SE.
The SE etiologies of the study patients are shown in Table 1. Acute symptomatic SE etiology predominated (32.4%), followed by acute on remote symptomatic SE (19.0%), AED noncompliance in previously epileptic patients (19.0%), remote symptomatic SE (16.2%), progressive symptomatic SE (7.6%), cryptogenic SE (3.6%), and febrile SE (1.9%). The mortality rate was significantly higher in acute symptomatic SE (53%; p = 0.015), and lower in the AED noncompliance group (5%; p = 0.011).
As for SE classification (Table 1), focal SE (46.7%) was the most frequent, followed by secondary generalized SE (42.9%), and generalized SE (10.5%). Mortality was the highest in those with focal SE (49%; p = 0.012). SE recurrence in the same hospital admission was observed in 11.4% of patients, and the mortality was higher in this group (66.7% versus 32.2%; p = 0.020). Refractory SE was diagnosed in 36.2% of patients, and they had a higher mortality rate (57.9 versus 23.8%; p = 0.001).
Fifty-one patients (48.6%) were included in the SE-only group and 56 (51.4%) in the SE-plus group. Mortality was greater in the SE-plus than in the SE-only group (55.4% versus 14.3%; p < 0.001). Ictal EEG patterns were identified in 55.2% of patients, with PLED having a significantly higher mortality rate (60%; OR = 3.16; p = 0.045). As PLED predominated among elderly patients, there was no difference in ictal pattern-related mortality when the analysis was controlled for age.
Severe clinical complications occurred in 67.6%, of patients, and 48 (45.7%) had more than one complication (Table 2). The most common complications were respiratory failure with mechanical ventilation, arterial hypotension, and pneumonia. Other complications, such as cardiac arrhythmias, and urinary tract infections, were rare in this sample. Clinical complications were more frequent among refractory SE individuals (97.2 versus 52.2%; p < 0.0001) and in the SE plus group (49.0% versus 83.9%; p < 0.0001; Table 3). Mortality was higher in individuals with clinical complications (50.7 versus 5.9%; p < 0.001).
Multivariate analysis
In multivariate analysis, only the presence of medical complications was related to a higher mortality rate (p = 0.013; OR = 11.8; CI = 1.7-82.1).
DISCUSSION
Comparing mortality related to SE in different study populations is difficult because
of differences in methodology, definition (seizure duration of 5 versus 30 minutes),
study design (prospective versus retrospective), population (pediatric versus
adults, community versus university hospital), treatment (lack of medication or
medical facilities in different countries), and follow-up period (short- versus
long-term follow-up)22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
.
The short-term mortality rate in our sample (36.2%) was higher than the 7.6 to 33%
reported in the five most important previous SE epidemiology studies44 .Logroscino G, Hesdorffer DC, Cascino GD, Annegers J, Bagiella E,
Hauser WA. Long-term mortality after a first episode of status epilepticus.
Neurology. 2002;58(4):537-41.
http://dx.doi.org/10.1212/WNL.58.4.537
https://doi.org/10.1212/WNL.58.4.537...
,1313 .Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA.
Incidence of status epilepticus in Rochester, Minnesota, 1965-1984. Neurology.
1998;50:735-41. http://dx.doi.org/10.1212/WNL.50.3.735
https://doi.org/10.1212/WNL.50.3.735...
,1414 .DeLorenzo RJ, House WA, Towne AR, Boggs JG, Pellock JM, Penberthy L
et al. A prospective, population-based epidemiologic study of status epilepticus
in Richmond, Virginia. Neurology. 1996;46(4):1029-35.
http://dx.doi.org/10.1212/WNL.46.4.1029
https://doi.org/10.1212/WNL.46.4.1029...
,1515 .Coeytaux A, Jallon P, Galobardes B, Morabia A. Incidence of status
epilepticus in French-speaking Switzerland (EPISTAR). Neurology.
2000;55(5):693-7. http://dx.doi.org/10.1212/WNL.55.5.693
https://doi.org/10.1212/WNL.55.5.693...
,1616 .Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A et
al. Incidence of status epilepticus in adults in Germany: a prospective,
population-based study. Epilepsia. 2001;42(6):714-8.
http://dx.doi.org/10.1046/j.1528-1157.2001.01101.x
https://doi.org/10.1046/j.1528-1157.2001...
. In addition, the mortality rate in this population
was higher than those in most recent studies in developing countries (7.3% in
Peru1717 .Maldonado A, Ramos W, Pérez J, Huamán LA, Gutiérrez EL. [Convulsive
status epilepticus: clinico-epidemiologic characteristics and risk factors in
Peru]. Neurologia. 2010;25(8):478-84.
http://dx.doi.org/10.1016/j.nrl.2010.07.010
https://doi.org/10.1016/j.nrl.2010.07.01...
, 10.5% in India22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, 12.1% in Singapore22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, 14.8% in Honduras22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, 15.9% in China22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, 19.8% in Brazil1818 .Garzon E, Fernandes RMf, Sakamoto AC. Analysis of clinical
characteristics and risk factors for mortality in human status epilepticus.
Seizure. 2003;12(6):337-45.
http://dx.doi.org/10.1016/S1059-1311(02)00324-2
https://doi.org/10.1016/S1059-1311(02)00...
, 24.8% in Senegal22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, 29% in India22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
, and 26.7% in Thailand22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
), but not in all (55.4% in Taiwan1919 .Tsai MH, Chuang YC, Chang HW, Chang WN, Lai SL, Huang CR et al.
Factors predictive of outcome in patients with de novo status epilepticus. QJM.
2009;102(1):57-62. http://dx.doi.org/10.1093/qjmed/hcn149
https://doi.org/10.1093/qjmed/hcn149...
).
Our study had important biases that might explain the higher mortality rate we
observed. HCFMRP-USP is the largest hospital in northern São Paulo state, serving as
a tertiary referral facility for an area comprising more than 1.5 million
inhabitants. This may have contributed to inclusion of fewer patients with SE
etiologies having a low mortality risk, such as febrile SE (around 50% of cases in
pediatric populations under 5 years of age)99 .DeLorenzo RJ, Towne AR, Pellock JM, Ko D. Status epilepticus in
children, adults, and elderly. Epilepsia.1992;33(suppl
4):S15-25.,1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1111 .Shinnar S, Pellock JM, Moshé SL, Maytal J, O’Dell C, Driscoll SM et
al. In whom does status epilepticus occur: age-related differences in children.
Epilepsia. 1997;38(8):907-14.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb01256.x
https://doi.org/10.1111/j.1528-1157.1997...
idiopathic or cryptogenic SE (representing 5 to 18% of
SE cases and with a mortality approaching 0%)1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1414 .DeLorenzo RJ, House WA, Towne AR, Boggs JG, Pellock JM, Penberthy L
et al. A prospective, population-based epidemiologic study of status epilepticus
in Richmond, Virginia. Neurology. 1996;46(4):1029-35.
http://dx.doi.org/10.1212/WNL.46.4.1029
https://doi.org/10.1212/WNL.46.4.1029...
,1515 .Coeytaux A, Jallon P, Galobardes B, Morabia A. Incidence of status
epilepticus in French-speaking Switzerland (EPISTAR). Neurology.
2000;55(5):693-7. http://dx.doi.org/10.1212/WNL.55.5.693
https://doi.org/10.1212/WNL.55.5.693...
,2020 .Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status
epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia.
1994;35(5):1104-12.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
https://doi.org/10.1111/j.1528-1157.1994...
and alcohol-related SE (2.8% in our sample compared
with 8.1 to 25% in other adult studies), which has reported mortality rates of 0 to
10%)22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
.We employed the 30-minute
criterion for SE diagnosis, in contrast to the 5-minute criterion used by some of
the recent studies mentioned above. SE mortality has been related to longer
duration1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,2020 .Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status
epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia.
1994;35(5):1104-12.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
https://doi.org/10.1111/j.1528-1157.1994...
,2121 .Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality
in status epilepticus. Epilepsia. 1994;35(1):27-34.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02908.x
https://doi.org/10.1111/j.1528-1157.1994...
. SE duration was longer in our sample due to
methodological issues (i.e, use of serial EEG instead of continuous EEG monitoring)
and to a higher incidence of refractory SE. Also the higher mortality might be
related to treatment issues; for example, delay in initiating medical treatment, as
the majority of patients had been transferred from other medical facilities, or the
lack of medication more effective in SE treatment, such as IV lorazepam.
Excluding the neonatal period, there is evidence that SE mortality increases with
age, independent of etiology, ranging from 0 to 8% in children, 14 to 25% in adults,
and over 35% in the elderly. In our sample, we observed a similar distribution, but
with higher mortality rates at every age: 25.7% in children, 34.7% in adults, and
64.7% in the elderly66 .Logroscino G; Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A,
Galobardes B et al. Mortality after a first episode of status epilepticus in the
United States and Europe. Epilepsia. 2005;46(suppl s11):46-8.
http://dx.doi.org/10.1111/j.1528-1167.2005.00409.x
https://doi.org/10.1111/j.1528-1167.2005...
,1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1313 .Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA.
Incidence of status epilepticus in Rochester, Minnesota, 1965-1984. Neurology.
1998;50:735-41. http://dx.doi.org/10.1212/WNL.50.3.735
https://doi.org/10.1212/WNL.50.3.735...
.
In other hospital samples, 30 to 44% of SE patients had a history of previous
epilepsy22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
. In our sample, 52.4%
had a history of epilepsy. We believe that this is related to a selection bias that
may be unique to our Epilepsy Center in Ribeirão Preto.
One of the best prognostic factors of SE is etiology, and the highest mortality rates
are observed in patients with acute symptomatic or progressive symptomatic
etiologies. Mortality rates in acute symptomatic SE range from 27 to 34%22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
,44 .Logroscino G, Hesdorffer DC, Cascino GD, Annegers J, Bagiella E,
Hauser WA. Long-term mortality after a first episode of status epilepticus.
Neurology. 2002;58(4):537-41.
http://dx.doi.org/10.1212/WNL.58.4.537
https://doi.org/10.1212/WNL.58.4.537...
,1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1111 .Shinnar S, Pellock JM, Moshé SL, Maytal J, O’Dell C, Driscoll SM et
al. In whom does status epilepticus occur: age-related differences in children.
Epilepsia. 1997;38(8):907-14.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb01256.x
https://doi.org/10.1111/j.1528-1157.1997...
,2222 .Claassen J, Lokin JK, Fitzsimmons BF, Mendelsohn FA, Mayer SA.
Predictors of functional disability and mortality after status epilepticus.
Neurology. 2002;58(1):139-42.
http://dx.doi.org/10.1212/WNL.58.1.139
https://doi.org/10.1212/WNL.58.1.139...
, which are lower than our findings (53%). Other
etiologies, such as febrile SE, are associated with lower mortality rates, from 0 to
3%99 .DeLorenzo RJ, Towne AR, Pellock JM, Ko D. Status epilepticus in
children, adults, and elderly. Epilepsia.1992;33(suppl
4):S15-25.,1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1111 .Shinnar S, Pellock JM, Moshé SL, Maytal J, O’Dell C, Driscoll SM et
al. In whom does status epilepticus occur: age-related differences in children.
Epilepsia. 1997;38(8):907-14.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb01256.x
https://doi.org/10.1111/j.1528-1157.1997...
,1414 .DeLorenzo RJ, House WA, Towne AR, Boggs JG, Pellock JM, Penberthy L
et al. A prospective, population-based epidemiologic study of status epilepticus
in Richmond, Virginia. Neurology. 1996;46(4):1029-35.
http://dx.doi.org/10.1212/WNL.46.4.1029
https://doi.org/10.1212/WNL.46.4.1029...
. In our sample, febrile SE also had a 0% mortality
rate.
In previously epileptic individuals, the predominant causes of SE are noncompliance
to treatment or change AED therapy, associated with 20 to 55% of cases. Mortality
rates in these patients are low, ranging from 0 to 6%66 .Logroscino G; Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A,
Galobardes B et al. Mortality after a first episode of status epilepticus in the
United States and Europe. Epilepsia. 2005;46(suppl s11):46-8.
http://dx.doi.org/10.1111/j.1528-1167.2005.00409.x
https://doi.org/10.1111/j.1528-1167.2005...
,1414 .DeLorenzo RJ, House WA, Towne AR, Boggs JG, Pellock JM, Penberthy L
et al. A prospective, population-based epidemiologic study of status epilepticus
in Richmond, Virginia. Neurology. 1996;46(4):1029-35.
http://dx.doi.org/10.1212/WNL.46.4.1029
https://doi.org/10.1212/WNL.46.4.1029...
,1818 .Garzon E, Fernandes RMf, Sakamoto AC. Analysis of clinical
characteristics and risk factors for mortality in human status epilepticus.
Seizure. 2003;12(6):337-45.
http://dx.doi.org/10.1016/S1059-1311(02)00324-2
https://doi.org/10.1016/S1059-1311(02)00...
,2020 .Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status
epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia.
1994;35(5):1104-12.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
https://doi.org/10.1111/j.1528-1157.1994...
. In our sample, AED noncompliance, withdrawal, or
reduction was observed in 19.6% (43.6% of previously epileptic individuals), and the
mortality rate in this group was 11.5% (n = 3). Two deaths were related to
cardiorespiratory arrest during SE treatment.
Seizure duration was associated with a increased mortality in several studies66 .Logroscino G; Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A,
Galobardes B et al. Mortality after a first episode of status epilepticus in the
United States and Europe. Epilepsia. 2005;46(suppl s11):46-8.
http://dx.doi.org/10.1111/j.1528-1167.2005.00409.x
https://doi.org/10.1111/j.1528-1167.2005...
,2020 .Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status
epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia.
1994;35(5):1104-12.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
https://doi.org/10.1111/j.1528-1157.1994...
,2323 .Neligan A, Shorvon SD. Prognostic factors, morbidity and mortality
in tonic-clonic status epilepticus: a review. Epilepsy Res. 2011;93(1):1-10.
http://dx.doi.org/10.1016/j.eplepsyres.2010.09.003
https://doi.org/10.1016/j.eplepsyres.201...
, but there is no consensus in this finding1010 .Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA.
Short-term mortality after a first episode of status epilepticus. Epilepsia.
1997;38(12):1344-9.
http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
https://doi.org/10.1111/j.1528-1157.1997...
,1818 .Garzon E, Fernandes RMf, Sakamoto AC. Analysis of clinical
characteristics and risk factors for mortality in human status epilepticus.
Seizure. 2003;12(6):337-45.
http://dx.doi.org/10.1016/S1059-1311(02)00324-2
https://doi.org/10.1016/S1059-1311(02)00...
. We were not able to correlate SE duration with
mortality. SE duration was longer in our sample than in others, mainly due to a high
incidence of FCS with electroencephalographic SE after control of clinical seizures
(subtle SE). As continuous EEG was not available, it was difficult to determine when
seizures were controlled.
The reported incidence of refractory SE is 9 to 38%, and mortality in that group is
generally higher than in other SE patients, from 16 to 100%2424 .Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of
refractory status epilepticus with pentobarbital, propofol, or midazolam: a
systematic review. Epilepsia. 2002;43(2):146-53.
http://dx.doi.org/10.1046/j.1528-1157.2002.28501.x
https://doi.org/10.1046/j.1528-1157.2002...
. The incidence (36.2%) and mortality rate (57.9%)
of refractory SE in our sample were similar to those in other studies.
The presence and severity of medical comorbidities is associated with a poor
prognosis in SE, and can be related to seizure duration, SE etiology, and medical
treatment. As medical complications can be related to longer SE duration, more
aggressive and prompt medical treatment may be the most effective way to prevent the
development of complications. In this sample, severe medical complications were
described in 67.6% of patients, a higher incidence than other studies2020 .Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status
epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia.
1994;35(5):1104-12.
http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
https://doi.org/10.1111/j.1528-1157.1994...
,2525 .Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S et
al. A comparison of lorazepam, diazepam, and placebo for the treatment of
out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631-7.
http://dx.doi.org/10.1056/NEJMoa002141
https://doi.org/10.1056/NEJMoa002141...
. This was the only independent prognostic factor
in multivariate analysis. Yaffe and Lowenstein2626 .Yaffe K, Lowenstein DH. Prognostic factors of pentobarbital therapy
for refractory generalized status epilepticus. Neurology. 1993;43(5):895-900.
http://dx.doi.org/10.1212/WNL.43.5.895
https://doi.org/10.1212/WNL.43.5.895...
reported a higher survival rate among refractory SE
patients without medical complications. Respiratory insufficiency with orotracheal
intubation was associated with a high mortality rate in SE2727 .Sagduyu A, Tarlaci S, Sirin H. Generalized tonic-clonic status
epilepticus: causes, treatment, complications and predictors of case fatality. J
Neurol. 1998;245(10):640-6.
http://dx.doi.org/10.1007/s004150050260
https://doi.org/10.1007/s004150050260...
. Occurrence of medical complications, such as
arterial hypotension, multiple organ failure, and cardiac arrhythmias, was
associated with high mortality in univariate analysis, but not in multivariate
analysis2222 .Claassen J, Lokin JK, Fitzsimmons BF, Mendelsohn FA, Mayer SA.
Predictors of functional disability and mortality after status epilepticus.
Neurology. 2002;58(1):139-42.
http://dx.doi.org/10.1212/WNL.58.1.139
https://doi.org/10.1212/WNL.58.1.139...
.
EEG is essential for SE diagnosis, especially in nonconvulsive or subtle SE, and to
guide its treatment, but its relevance for SE prognosis is not clear22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
. Of the different ictal EEG
patterns, only PLED has been associated with increased mortality2828 .Garzon E, Fernandes RM, Sakamoto AS. Serial EEG during human status
epilepticus: evidence for PLED as an ictal pattern. Neurology.
2001;57(7):1175-83. http://dx.doi.org/10.1212/WNL.57.7.1175
https://doi.org/10.1212/WNL.57.7.1175...
,2929 .Nei M, Lee JM, Shanker VL, Sperling MR. The EEG and prognosis in
status epilepticus. Epilepsia. 1999;40(2):157-63.
http://dx.doi.org/10.1111/j.1528-1157.1999.tb02069.x
https://doi.org/10.1111/j.1528-1157.1999...
, but a number of studies failed to find an
association of EEG patterns with prognosis and mortality22 .Neligan A, Shorvon SD. Frequency and prognosis of convulsive status
epilepticus of different causes: a systematic review. Arch Neurol.
2010;67(8):931-40.
http://dx.doi.org/10.1001/archneurol.2010.169
https://doi.org/10.1001/archneurol.2010....
. Our data found no association between EEG patterns
and mortality. In our sample, PLED was related to a higher mortality rate, but this
finding was associated with a higher prevalence of PLED in elderly patients.
In conclusion, this prospective study, conducted in a Brazilian University Hospital, found an SE-related mortality rate (36.2%), which is higher than that reported by most previous studies. Mortality was independently associated with medical complications that occurred during hospitalization.
References
-
1Guidelines on epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia. 1993;34(4):592-6. 10.1111/j.1528-1157.1993.tb00433.x
» https://doi.org/10.1111/j.1528-1157.1993.tb00433.x -
2Neligan A, Shorvon SD. Frequency and prognosis of convulsive status epilepticus of different causes: a systematic review. Arch Neurol. 2010;67(8):931-40. http://dx.doi.org/10.1001/archneurol.2010.169
» https://doi.org/10.1001/archneurol.2010.169 -
3Chin RF, Neville BG, Scott RC. A systematic review of the epidemiology of status epilepticus. Eur J Neurol. 2004;11(12):800-10. http://dx.doi.org/10.1111/j.1468-1331.2004.00943.x
» https://doi.org/10.1111/j.1468-1331.2004.00943.x -
4Logroscino G, Hesdorffer DC, Cascino GD, Annegers J, Bagiella E, Hauser WA. Long-term mortality after a first episode of status epilepticus. Neurology. 2002;58(4):537-41. http://dx.doi.org/10.1212/WNL.58.4.537
» https://doi.org/10.1212/WNL.58.4.537 -
5Sutter R, Kaplan PW, Rüegg S. Outcome predictors for status epilepticus-what really counts. Nat Rev Neurol. 2013;9(9):525-34. http://dx.doi.org/10.1038/nrneurol.2013.154
» https://doi.org/10.1038/nrneurol.2013.154 -
6Logroscino G; Hesdorffer DC, Cascino G, Hauser WA, Coeytaux A, Galobardes B et al. Mortality after a first episode of status epilepticus in the United States and Europe. Epilepsia. 2005;46(suppl s11):46-8. http://dx.doi.org/10.1111/j.1528-1167.2005.00409.x
» https://doi.org/10.1111/j.1528-1167.2005.00409.x -
7Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981;22(4):489-501. http://dx.doi.org/10.1111/j.1528-1157.1981.tb06159.x
» https://doi.org/10.1111/j.1528-1157.1981.tb06159.x -
8Hauser WA. Status epilepticus: epidemiologic considerations. Neurology. 1990;40(5 Suppl 2):9-13.
-
9DeLorenzo RJ, Towne AR, Pellock JM, Ko D. Status epilepticus in children, adults, and elderly. Epilepsia.1992;33(suppl 4):S15-25.
-
10Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA. Short-term mortality after a first episode of status epilepticus. Epilepsia. 1997;38(12):1344-9. http://dx.doi.org/10.1111/j.1528-1157.1997.tb00073.x
» https://doi.org/10.1111/j.1528-1157.1997.tb00073.x -
11Shinnar S, Pellock JM, Moshé SL, Maytal J, O’Dell C, Driscoll SM et al. In whom does status epilepticus occur: age-related differences in children. Epilepsia. 1997;38(8):907-14. http://dx.doi.org/10.1111/j.1528-1157.1997.tb01256.x
» https://doi.org/10.1111/j.1528-1157.1997.tb01256.x -
12Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol. 1995;12(4):343-62. http://dx.doi.org/10.1097/00004691-199512040-00005
» https://doi.org/10.1097/00004691-199512040-00005 -
13Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Incidence of status epilepticus in Rochester, Minnesota, 1965-1984. Neurology. 1998;50:735-41. http://dx.doi.org/10.1212/WNL.50.3.735
» https://doi.org/10.1212/WNL.50.3.735 -
14DeLorenzo RJ, House WA, Towne AR, Boggs JG, Pellock JM, Penberthy L et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996;46(4):1029-35. http://dx.doi.org/10.1212/WNL.46.4.1029
» https://doi.org/10.1212/WNL.46.4.1029 -
15Coeytaux A, Jallon P, Galobardes B, Morabia A. Incidence of status epilepticus in French-speaking Switzerland (EPISTAR). Neurology. 2000;55(5):693-7. http://dx.doi.org/10.1212/WNL.55.5.693
» https://doi.org/10.1212/WNL.55.5.693 -
16Knake S, Rosenow F, Vescovi M, Oertel WH, Mueller HH, Wirbatz A et al. Incidence of status epilepticus in adults in Germany: a prospective, population-based study. Epilepsia. 2001;42(6):714-8. http://dx.doi.org/10.1046/j.1528-1157.2001.01101.x
» https://doi.org/10.1046/j.1528-1157.2001.01101.x -
17Maldonado A, Ramos W, Pérez J, Huamán LA, Gutiérrez EL. [Convulsive status epilepticus: clinico-epidemiologic characteristics and risk factors in Peru]. Neurologia. 2010;25(8):478-84. http://dx.doi.org/10.1016/j.nrl.2010.07.010
» https://doi.org/10.1016/j.nrl.2010.07.010 -
18Garzon E, Fernandes RMf, Sakamoto AC. Analysis of clinical characteristics and risk factors for mortality in human status epilepticus. Seizure. 2003;12(6):337-45. http://dx.doi.org/10.1016/S1059-1311(02)00324-2
» https://doi.org/10.1016/S1059-1311(02)00324-2 -
19Tsai MH, Chuang YC, Chang HW, Chang WN, Lai SL, Huang CR et al. Factors predictive of outcome in patients with de novo status epilepticus. QJM. 2009;102(1):57-62. http://dx.doi.org/10.1093/qjmed/hcn149
» https://doi.org/10.1093/qjmed/hcn149 -
20Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia. 1994;35(5):1104-12. http://dx.doi.org/10.1111/j.1528-1157.1994.tb02562.x
» https://doi.org/10.1111/j.1528-1157.1994.tb02562.x -
21Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia. 1994;35(1):27-34. http://dx.doi.org/10.1111/j.1528-1157.1994.tb02908.x
» https://doi.org/10.1111/j.1528-1157.1994.tb02908.x -
22Claassen J, Lokin JK, Fitzsimmons BF, Mendelsohn FA, Mayer SA. Predictors of functional disability and mortality after status epilepticus. Neurology. 2002;58(1):139-42. http://dx.doi.org/10.1212/WNL.58.1.139
» https://doi.org/10.1212/WNL.58.1.139 -
23Neligan A, Shorvon SD. Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review. Epilepsy Res. 2011;93(1):1-10. http://dx.doi.org/10.1016/j.eplepsyres.2010.09.003
» https://doi.org/10.1016/j.eplepsyres.2010.09.003 -
24Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia. 2002;43(2):146-53. http://dx.doi.org/10.1046/j.1528-1157.2002.28501.x
» https://doi.org/10.1046/j.1528-1157.2002.28501.x -
25Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631-7. http://dx.doi.org/10.1056/NEJMoa002141
» https://doi.org/10.1056/NEJMoa002141 -
26Yaffe K, Lowenstein DH. Prognostic factors of pentobarbital therapy for refractory generalized status epilepticus. Neurology. 1993;43(5):895-900. http://dx.doi.org/10.1212/WNL.43.5.895
» https://doi.org/10.1212/WNL.43.5.895 -
27Sagduyu A, Tarlaci S, Sirin H. Generalized tonic-clonic status epilepticus: causes, treatment, complications and predictors of case fatality. J Neurol. 1998;245(10):640-6. http://dx.doi.org/10.1007/s004150050260
» https://doi.org/10.1007/s004150050260 -
28Garzon E, Fernandes RM, Sakamoto AS. Serial EEG during human status epilepticus: evidence for PLED as an ictal pattern. Neurology. 2001;57(7):1175-83. http://dx.doi.org/10.1212/WNL.57.7.1175
» https://doi.org/10.1212/WNL.57.7.1175 -
29Nei M, Lee JM, Shanker VL, Sperling MR. The EEG and prognosis in status epilepticus. Epilepsia. 1999;40(2):157-63. http://dx.doi.org/10.1111/j.1528-1157.1999.tb02069.x
» https://doi.org/10.1111/j.1528-1157.1999.tb02069.x
Publication Dates
-
Publication in this collection
Aug 2015
History
-
Received
13 Jan 2015 -
Received
8 Mar 2015 -
Accepted
30 Mar 2015