Professional Documents
Culture Documents
a
Epilepsy Unit, Neurology Department, Vall dHebron University Hospital, Universitat Autonoma de Barcelona, Barcelona; bNeurology
Department, Vall dHebron University Hospital, Universitat Autonoma de Barcelona, Barcelona; and cNeurophysiology Department, Vall
dHebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
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M. GONZALEZ-CUEVAS ET AL.
mortality [10]. Another recent study found that the SE [19]. Patients with post-anoxic SE or incomplete
serum concentrations of procalcitonin levels measured clinical data were excluded.
at SE onset are independently associated with unfa- In addition to demographic characteristics, the type
vorable outcome [11]. of status (convulsive or non-convulsive), a previous
A simple clinical tool for predicting individual out- history of seizures, seizure semiology, level of con-
comes before obtaining the results of diagnostic tests sciousness before treatment, SE etiology and baseline
was proposed by Rossetti et al. [12]. These researchers mRS collected at arrival at the emergency department
developed a simple clinical score for the prognosis of were identified by interview of the patients family
SE in adults (Status Epilepticus Severity Score, or and by the patients history.
STESS) to use prior to initiating treatment. The score Seizure semiology was classified according to the
consists of four variables that are available at presen- worst manifestation prior to treatment (in descending
tation: history of seizures, age, seizure type and con- order of gravity: non-convulsive SE in coma, general-
sciousness impairment. It was concluded that the ized convulsive, complex partial, myoclonic or absence
STESS could identify patients with a high probability or simple partial). Level of consciousness prior to
of survival after SE. Later, a prospective study by the treatment was categorized as alert, somnolent or con-
same group confirmed that the STESS is able to reli- fused, stuporous and comatose. SE etiology was clas-
ably identify SE patients who are likely to survive and sified according to the last report of the International
proposed that, in these cases, an early aggressive treat- League Against Epilepsy [19] as being acute
ment could not be routinely justified, to reduce the symptomatic, remote symptomatic, progressive symp-
inherent risks that are related to an aggressive treat- tomatic or idiopathic/cryptogenic. Clinical outcome
ment plan. However, the STESS has low predictive was assessed at hospital discharge (dead or alive).
value for bad outcomes and has a ceiling eect espe- The mRS was scored as follows: 0, no symptoms; 1,
cially in patients older than 65 years without pre-exist- no significant disability despite symptoms (i.e. able to
ing epilepsy [12,13]. carry out all usual duties and activities); 2, slight dis-
The modified Rankin Scale (mRS) is an objective, ability (i.e. unable to carry out all previous activities
reliable measure of disability or dependence in daily but able to look after own aairs without assistance);
activities of a patient. It is commonly used in the eval- 3, moderate disability (i.e. requiring some help but able
uation of patients with neurological emergencies, such to walk without assistance); 4, moderately severe dis-
as stroke or SE, as a tool to measure their functional ability (i.e. unable to walk without assistance and
state [14,15]. This state may on many occasions be unable to attend to own bodily needs without assis-
influenced by the presence of dierent comorbidities, tance); 5, severe disability (i.e. bedridden, incontinent
and some recent studies have suggested that coexisting and requiring constant nursing care and attention) [17].
comorbidities might be associated with poor short- The STESS relies on the assessment of age, where
term prognosis in SE [1618]. under 65 years of age is 0 points and 65 years of age
Therefore, it is hypothesized that the patients base- or older is 2 points; previous history of seizures is 0
line mRS may be a prognostic factor that determines and no previous seizures 1; severity of seizure type
the short-term outcome of SE and that the inclusion (simple partial, complex partial, absence, myoclonic as
of the baseline functional condition of the patient (i.e. complicating idiopathic generalized epilepsy 0; gener-
the mRS) in the STESS can improve the prediction of alized convulsive 1; non-convulsive SE in coma 2);
mortality. and level of consciousness (alert or somnolent/con-
fused 0; stuporous or comatose 1). A score of 02 is
defined as favorable, which indicates a low risk of
Methods
death, and a score of 3 points or higher is defined as
A retrospective registry of all adult patients (16 years unfavorable [12].
of age and older) who experienced SE and were A prognosis was made according to the likelihood
admitted to our hospital between March 2011 and of patient death before hospital discharge.
March 2014 was analyzed. The local ethics committee
authorized the study without obtaining informed con-
Statistical analysis
sent from all patients.
Status epilepticus was defined as a condition result- Statistical analysis was undertaken using SPSS Statis-
ing either from the failure of the mechanisms respon- tics for Windows, version 17.0 (SPSS Inc, Chicago,
sible for seizure termination or from the initiation of USA).
mechanisms which lead to abnormally prolonged sei- Prognosis was assessed according to the clinical out-
zures after 5 min for tonic-clonic SE and 10 min focal come (alive or dead) at discharge. To determine
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CLINICAL SCORE FOR STATUS EPILEPTICUS 3
variables associated with mortality, statistical signifi- The demographics and the most relevant clinical
cance was assessed by Pearsons chi-squared or Fish- variables of the cohort were classified by outcome and
ers exact test for categorical variables and the are presented in Table 1. In the univariate analysis, it
Students t or MannWhitney U test for numerical was found that age, non-convulsive SE in coma,
variables. The cuto age with best sensitivity and speci- marked consciousness impairment, etiology, the
ficity to predict mortality was determined through a STESS and mRS were associated with higher mortal-
receiver operating characteristic (ROC) curve. ROC ity.
curves were also obtained to assess the capacity of the The use of anesthetic treatment was also included
mRS, the STESS and the modified STESS (mSTESS) in the univariate analysis, and even though mortality
to predict death. The predictive capacity was deter- was higher in patients requiring anesthetics this dier-
mined as the area under the ROC curve with a confi- ence was not statistically significant. Regarding age,
dence interval (CI) of 95%. A logistic regression model the best cuto point to predict mortality in our sam-
was performed to assess the mRS and STESS as inde- ple (ROC curve) was 70 years old (P = 0.003).
pendent predictors of death using the Hosmer and The results of the logistic regression analysis
Lemeshow statistic to assess the goodness of fit. The showed that the STESS (OR 1.863, 95% CI 1.345
score added to the STESS that was used to obtain the 2.577; P < 0.001) and mRS (OR 1.459, 95% CI
final mSTESS scale was based upon the coecient val- 1.0042.19; P = 0.047) were the only independent pre-
ues (b coecients) of the logistic regression after con- dictors of mortality. The data model had an excellent
sidering the results of the ROC curves for each cuto goodness of fit (Hosmer and Lemeshow test,
point of mRS used to predict mortality. Sensitivities, P = 0.240) with a regression coecient of the STESS
specificities, as well as positive and negative predictive [b 0.622, SE(b) 0.166] which is almost twice that of
values (PPVs and NPVs) were calculated to evaluate the mRS [b 0.378, SE(b) 0.190].
the prediction accuracy for the best cuto points of the Considering both the values of the coecients of
STESS and the mSTESS. The overall accuracy for the the logistic regression, where a higher weight in the
cuto point of each scale was obtained using the pro- STESS was observed, and the results of the ROC
portion of patients that were classified for the predic- curve of mRS that was used to predict mortality
tion of mortality. An ROC curve was also performed [where two good cutos were obtained, one very sen-
to establish cuto points of the mSTESS to classify sitive >0 (sensitivity 96.4%, specificity 23.1%) and the
patients into dierent risks of mortality. MantelHaen- other very specific >3 (sensitivity 21.4%, specificity
szel v2 tests were used to test the homogeneity of the 94.4%)], it was possible to divide the mRS into three
odds ratio (OR) across strata. A P value <0.05 was con- groups, to which the following scores were assigned:
sidered to be statistically significant. 0, mRS = 0; 1, mRS = 13; and 2, mRS > 3. These
scores were added to the STESS of each patient. The
cuto point of age to 70 years old was also modified
Results
following our ROC curve results regarding age.
Of the 162 patients who were registered as having SE, Finally a new score that was variable between 0 and 8
136 were included and 26 were excluded due to insu- points was obtained, the modified STESS (mSTESS;
cient clinical data (seven cases) or to hypoxic etiology Table 2). The STESS, mRS and mSTESS predictive
(19 cases). capacities are detailed in Fig. 1, where it is noted that
The mean age was 62.01 ! 17.62 (1995) years, the mSTESS has a greater capacity to predict mortal-
and 54.4% of patients were males. Also, 60.2% of ity (80.1%, 95% CI 70.6%89.6%) compared to
patients had a de novo SE episode. The total mortality STESS (74.3%, 95% CI 63.8%81.8%).
was 22.1%. The most common etiologies of SE were The best cuto point to predict mortality in the
acute symptomatic (47.1%) and remote symptomatic mSTESS was a score of 4. When the established cuto
(32.4%), which was mainly secondary to vascular of STESS 3 was compared, an improvement in the
(30.9%) and tumor (19.9%) lesions. Of the patients capacity to predict death was found with a higher over-
who died, 14% were due to status itself (homeostatic all accuracy (81.8% vs. 59.6%), as shown in Table 3.
failure), 34% were from complications during hospi- This new scale provides a better PPV than the
talization, mainly respiratory infections, and 52% died STESS, thereby allowing those patients with a higher
due to the etiology causing the status (17% acute risk of mortality to be better identified. Furthermore,
stroke, 6% intracranial hemorrhage, 10% subarach- in the ROC curve another cuto point was observed
noid hemorrhage, 10% meningitis, 3% encephalitis that allowed the patients with a very low risk of death
and 6% due to traumatic brain injury leading to brain (mSTESS < 02) to be qualified successfully, enabling
edema). three types of patients to be dierentiated according
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M. GONZALEZ-CUEVAS ET AL.
Age (mean, SD) 62.01 (!17.6) 60.1 ! 17.2 68.5 ! 17.6 0.022
Male 74 (54.4%) 56 (52.8%) 18 (60%) 0.486
History of previous seizures 54 (39.7%) 46 (43.4%) 8 (26.7%) 0.098
Seizure type
SP or CP 80 (58.8%) 68 (64.1%) 12 (40%) 0.018
GC 42 (30.9%) 33 (31.1%) 9 (30%) 0.906
NCSEC 14 (10.3%) 5 (4.7%) 9 (30%) <0.001
Consciousness
Alert or somnolent/confused 92 (67.6%) 82 (77.3%) 10 (33.3%) <0.001
Stuporous or comatose 44 (32.4%) 24 (22.6%) 20 (66.6%)
mRS (median, IQR) 1 (12) 1 (12) 2 (13) 0.002
Etiologies
Acute symptomatic 64 (47.1%) 43 (40.6%) 21 (70%) 0.004
Remote symptomatic 44 (32.4%) 41 (38.7%) 3 (10%) 0.003
Progressive symptomatic 11 (8.1%) 10 (9.4%) 1 (3.3%) 0.455
Cryptogenic/idiopathic 17 (12.5%) 12 (11.3%) 5 (16.7%) 0.531
STESS (median, IQR) 3 (13) 2 (13) 3.5 (25) <0.001
Anesthetic treatment 41 (30.1%) 28 (26.4%) 13 (43.3%) 0.075
CP, complex partial; GC, generalized convulsive; IQR, interquartile range; mRS, modified Rankin Scale; NCSEC, non-convulsive status epilep-
ticus with coma; SP, simple partial; STESS, Status Epilepticus Severity Score.
GC 1
NCSEC 2
Age (years)
<70 0 0.4
70 2
History of seizures
Area under
SE 95% CI
Yes 0 ROC curve
STESS (06) 0.743 0.054 0.6380.818
No 1 0.2 mRS (05) 0.652 0.056 0.5420.762
mRS mSTESS (08) 0.801 0.049 0.7060.896
0 0
13 1
4 2 0.0
Total 08 0.0 0.2 0.4 0.6 0.8 1.0
1 - specificity
CP, complex partial; GC, generalized convulsive; mRS, modified
Rankin Scale; mSTESS, modified Status Epilepticus Severity Score; Figure 1 Capacity of the new scale versus the STESS to predict
NCSEC, non-convulsive status epilepticus with coma; SP, simple mortality.
partial; STESS, Status Epilepticus Severity Score.
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CLINICAL SCORE FOR STATUS EPILEPTICUS 5
Overall
Sensitivity (%) Specificity (%) PPV (%) NPV (%) accuracy (%) OR (CI 95%) P
CI, confidence interval; mSTESS, modified Status Epilepticus Severity Score; NPV, negative predictive value; OR, odds ratio; PPV, positive
predictive value; STESS, Status Epilepticus Severity Score.
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M. GONZALEZ-CUEVAS ET AL.
evaluated, one at discharge and one long-term out- Other functional scales, such as the Barthel scale,
come, and compared to baseline mRS. In the results it may be more reliable and less subjective in assessing
can be observed that patients who had a poor long- disability; however, these scales are longer and less
term outcome had a slightly higher median in mRS suitable for rapid patient assessment.
compared with patients with a good outcome [3 (14) One limitation of this study is that it is a retrospec-
vs. 2 (04)], but this dierence was not statistically sig- tive cohort series from a single center, and it has not
nificant (P = 0.233). However, this study focused only been validated. Another limitation is that mortality
on refractory SE [22]. was considered as the primary outcome and only clini-
In our series, it was observed that the baseline func- cal factors were considered. Electroencephalogram pat-
tional condition that was also defined by the mRS terns and other variables that might influence the
was independently associated with mortality in results such as seizure duration before initiation of
patients with SE. By adding this variable to the therapy and total duration of SE were ignored because
STESS (increasing the cuto point of age), a new the aim was to focus only on the factors that can be
score was obtained: the modified STESS (4 mSTESS, evaluated very early in the first assessment of the
NPV 87.0%, PPV 58.3%, overall accuracy 81.8%). patient. Also, like many clinical studies, only mortality
This new score not only allowed the prediction of on discharge was investigated and a longer period of
mortality to be improved but also allowed patients evaluation would be very interesting for future studies.
who had a very low risk of death (mSTESS 2) to be
classified.
Conclusions
With this new scale, it was observed that the ceiling
eect of the STESS decreases; e.g. a 70-year-old The STESS is a useful tool in predicting mortality in
patient without pre-existing epilepsy and a good base- patients with SE at admission; these predictions can
line situation (mRS = 0) would score 3 points on our be improved by adding baseline disability, as assessed
scale that would correspond to intermediate risk of by the mRS, and increasing the cuto point of age to
mortality and not as an unfavorable prognosis as in 70 years. A new proposal, the modified STESS, can
the STESS. In addition the higher value of PPV in be more accurate in the short-term prognosis of
our score allows us to better identify those patients patients with SE.
with a really higher risk of mortality.
On the other hand, a recent study performed for
Acknowledgements
intensive care unit patients with SE has shown that
the use of intravenous anesthetic drugs in SE was The authors thank the ER neurology and neurophysi-
associated with an increased relative risk of death ologist consultants of the Vall dHebron University
independent of possible confounders and without sig- Hospital, Spain, for their help with data acquisition.
nificant changes in risk by dierent grades of SE Furthermore, we want to thank Dr Andrea O. Ros-
severity and dierent SE etiologies [23]. The analyzed setti for reviewing the manuscript and for advice.
cohort of these studies was exclusively composed of
patients seen in intensive care units, thus potentially
Disclosure of conflicts of interest
limiting the generalizability. In our series, globally, a
higher mortality was observed in patients who The authors declare no financial or other conflicts of
required the use of anesthetics as part of treatment; interest.
however, this result was not statistically significant
(P = 0.075). Moreover the mortality in our series did
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