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A clinical score for AbstractThe authors derived a clinical score to predict mortality in status

epilepticus (SE) from analysis of a retrospective SE cohort, using four variables


prognosis of status available at presentation: history of seizures, age, seizure type, and conscious-
epilepticus in adults ness impairment. Validation on a small prospective SE series (34 patients)
resulted in sensitivity, 1.000; specificity, 0.643; negative predictive value,
1.000; and unweighted accuracy, 0.822. This simple clinical score may reliably
identify patients surviving after SE.
NEUROLOGY 2006;66:17361738

Andrea O. Rossetti, MD; Giancarlo Logroscino, MD, PhD; and Edward B. Bromfield, MD

Status epilepticus (SE) has an important clinical im- minutes and clinically divided into simple-partial, complex-
partial, generalized convulsive, and subtle status (if only the
pact, with a short-term mortality of 7 to 39%.1-3 Cur- EEG allowed the diagnosis in comatose subjects); no absence SE
rently, there is no consensus about the best strategy was observed.9 We assessed the receiver operating characteristic
for treating specific forms of SE: the compromise be- curves (ROCs), in which the sensitivity (proportion of patients
tween Scylla, or the danger related to untreated with fatal outcome having a positive test) is plotted against the
inverse of the specificity (the latter defined as proportion of pa-
SE,4,5 and Charybdis, or the damage induced by pos- tients without fatal outcome having a negative test). The ROC
sibly unnecessary aggressive treatments,6 may prove allows the identification of the best test cutoff value: the un-
difficult. Accordingly, a simple tool to predict the risk weighted accuracy (averaged specificity and sensitivity) is maxi-
of death at the onset of the SE episode, before the mized toward the upper left corner.
The negative predictive value (NPV: proportion of subjects
results of diagnostic procedures are available, would with a negative test who do not have a fatal outcome) was then
be helpful. analyzed. It depends on the prevalence of the disease (in this case,
Several studies have focused on prognostic factors short-term fatal outcome) among the tested population, and there-
fore has more practical impact than sensitivity or specificity. The
for short-term outcome of SE, but no validated model optimal score for this clinical setting should aim at a high NPV
summarizing these findings has been proposed. Our (i.e., patients with low-risk score should not have a fatal outcome),
goal was to find a clinical test to apply before treat- with, at the same time, an acceptable accuracy.
ment initiation, in which patients with a good prog- We validated the best score on a series of 34 consecutive adult
patients with SE (using the same definition as before and exclud-
nostic profile have a high likelihood of surviving. ing anoxia) prospectively collected in our center over 14 months.
Table 2 summarizes the comparison of demographic and clinical
Methods. We developed a clinical score for death at hospital characteristics between the two series. The score was calculated
discharge based on previous works identifying risk factors for on admission and the survival assessed at hospital discharge.
short-term mortality in SE. Death represents a nondebatable con- Statistical analysis was performed with a STATA software
dition, as opposed to other forms of poor outcome (e.g., persistent package (version 9). ROCs were calculated using a nonparametric
vegetative state). Older age and acute symptomatic etiology have approach. Dichotomous categorical variables were analyzed with
been consistently linked to bad outcome in multivariate analy- two-sided Fishers exact tests, without correction for multiple com-
sis.3,7 Extent of consciousness impairment also correlates indepen- parisons; significance was set at p 0.05.
dently with prognosis.8,9 Subtle status often results from
deleterious brain damage and predicts a dismal prognosis.5 Con-
Results. The figure summarizes the ROCs and the epi-
versely, gender, ethnicity, and latency to treatment initiation have
conflicting predictive values in the literature.3,7 demiologic variables for each score, applied to the retro-
We therefore retained age, extent of consciousness impair- spective cohort. Comparison of the areas did not show any
ment, and seizure type. Because in most cases, etiology is not difference (p 0.823). The position of the cutoff points in
available at presentation, we considered seizure history as a the curves of the scores, however, varies: for score 1, the
surrogate.
These four variables were used to formulate three possible point closest to the upper left corner corresponds to a cutoff
scores, by varying the relative impact of age and consciousness 4 (NPV 0.943, accuracy 0.718); for score 2 to a cutoff
impairment (table 1). The other two variables were kept constant; of 3 (NPV 0.960, accuracy 0.731), and for score 3 to a
seizure type was treated as ordinal. cutoff of 3 (NPV 0.943, accuracy 0.714). Even if the
These models were applied on an SE database of 127 episodes
highest NPV is found at a cutoff of 2 for score 1, the
occurring in 107 adult patients, excluding anoxic causes.9 SE was
defined as ongoing or repetitive seizures without intercurrent nor- accuracy in this case is unacceptably low, implying that too
malization of consciousness or return to baseline for at least 30 many false-positive results might impair its clinical useful-
ness. Therefore, the best compromise between NPV and
accuracy appears to be score 2 at a cutoff 3. Interest-
ingly, in the retrospective cohort, a majority with a score
From the Department of Neurology (A.O.R., E.B.B.), Brigham and Womens above this cutoff was treated with coma induction for re-
Hospital, and Harvard School of Public Health (G.L.), Harvard Medical
fractory SE (p 0.016), but their mortality was higher
School, Boston, MA.
than in those with a low score (p 0.001).
Disclosure: The authors report no conflicts of interest. The application of score 2 (with a cutoff 3) to the
Received September 21, 2005. Accepted in final form December 8, 2005. prospective cohort results in the following: sensitivity
1.000; specificity 0.643; positive predictive value
Address correspondence and reprint requests to Dr. Edward B. Bromfield,
Division of Epilepsy and EEG, Department of Neurology, Brigham and
(PPV) 0.375; NPV 1.000; accuracy 0.822. In other
Womens Hospital, 75 Francis Street, Boston, MA 02115; e-mail: words, six of six subjects with fatal outcome and 18 of 28
ebromfield@partners.org surviving patients were correctly identified.
1736 Copyright 2006 by AAN Enterprises, Inc.
Table 1 Status epilepticus outcome scores (assessed before
treatment initiation)

Features Score 1 Score 2 Score 3

Consciousness
Alert or somnolent/confused 0 0 0
Stuporous or comatose 2 1 1
Seizure type
SP or CP 0 0 0
GC 1 1 1
NCSEC 2 2 2
Age, y
65 0 0 0
65 1 2 1
History of seizures
Yes 0 0 0
No 1 1 1
Total 06 06 05

SP simple partial; CP complex partial; GC generalized


convulsive; NCSEC nonconvulsive status epilepticus with
coma.

Discussion. These results suggest that a simple


clinical score, consisting of four parameters assessed
before treatment and any diagnostic procedure, is a
reliable identifier of adult SE patients who survive:
in the prospective series, none of the patients with a
score below the cutoff died.
The validity of a clinical score correlates with the
representative nature of the populations on which it
was tested. Our prospective cohort is relatively
small, but results from consecutive recruitment of
patients with SE, and its demographic and clinical

Table 2 Demographic, etiologic, and clinical comparison of the


retrospective vs prospective cohorts

Retro Pro
Variable (127 episodes) (34 episodes) p

Female 65 (51%) 14 (41%) 0.33


Age 65 y 38 (30%) 12 (35%) 0.54
Previous seizures 82 (65%) 18 (53%) 0.24
Acute etiology 77 (61%) 19 (56%) 0.32
Generalized convulsive 61 (48%) 16 (47%) 1.00
or subtle SE
Stuporose or comatose 91 (72%) 22 (65%) 0.53
Time to treatment 62 (49%) 12 (35%) 0.18
initiation 1 h
Refractory SE 49 (39%) 13 (38%) 1.00
Dead 16 (13%) 6 (18%) 0.41

Refractory SE defined as resistant to benzodiazepines and phe-


nytoin, valproic acid, or phenobarbital and needing coma induc-
Figure. Receiver operating characteristics curve and quan-
tion for seizure management.
titative description of selected cutoff points of interest for
Retro retrospective; Pro prospective; SE status the three scores.
epilepticus.
June (1 of 2) 2006 NEUROLOGY 66 1737
characteristics are similar to population-based1,2 and treatments. Considering the therapeutic options for
hospital-based10 studies. The retrospective cohort SE in other settings, in particular coma induction, it
also has comparable features: table 2 and the similar is critical to identify patients at different levels of
values of sensitivity, specificity, PPV, NPV, and ac- risk. We believe that this tool may prove useful be-
curacy of the applied test underline this aspect. cause it can provide a rationale for planning the
Score 2 shows the best compromise between NPV level of monitoring and possibly modulating the ag-
and accuracy at the cutoff closest to the upper left gressiveness of treatment. Nevertheless, before its
corner of the ROC. Clinically, such a threshold ap- routine use in a controlled application, a large pro-
pears reasonable: patients in subtle status, a condi- spective survey is needed to confirm these results.
tion with high mortality,5 are automatically beyond
the cutoff, whereas older subjects without an addi-
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1738 NEUROLOGY 66 June (1 of 2) 2006

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