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Status epilepticus mimicking stroke recurrence
YEBEH-106509; No of Pages 6 Epilepsy & Behavior xxx (xxxx) xxx
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Status epilepticus mimicking stroke recurrence Giada Pauletto a, Francesco Bax b,c,⁎, Gian Luigi Gigli b,c,d, Simone Lorenzut a, Lorenzo Verriello a, Elisa Corazza b,c, Mariarosaria Valente b,c a
Neurology Unit, Udine University Hospital, Udine, Italy Clinical Neurology Unit, University of Udine, Udine, Italy Department of Medicine (DAME), University of Udine, Udine, Italy d Department of Mathematics, Informatics and Physics (DMIF), University of Udine, Udine, Italy b c
a r t i c l e
i n f o
Article history: Received 31 May 2019 Revised 14 August 2019 Accepted 16 August 2019 Available online xxxx Keywords: Status epilepticus Epilepsy Stroke Poststroke epilepsy Aphasic status ILAE status epilepticus classification
a b s t r a c t Aim of the study: The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (either ischemic or hemorrhagic), who developed status epilepticus (SE) mimicking a stroke relapse. Materials and methods: We performed a retrospective cohort study of patients brought to hospital by the emergency service between December 2016 and January 2018 with a stroke code as possible candidates for intravenous thrombolysis and who had already have a previous stroke. Among them, patients admitted for negative symptoms and finally discharged with a diagnosis of SE mimicking stroke were selected and their clinical characteristics collected. All patients underwent routine blood sample analysis, head computed tomography (CT) scan and, when indicated, CT angiography and CT-perfusion imaging of the head. After admission in our stroke unit, an Electroencephalogram (EEG) was performed within 3 h in patients suspected with SE, then classified according to International League Against Epilepsy (ILAE) classification (2015). Outcome measures were SE duration, antiepileptic drugs (AEDs) administered, mortality at 12 months, Engel scale, and modified Rankin scale (m-RS) at 6 months. A second cohort included those consecutive patients discharged with a true stroke relapse in the same considered time span. Clinical characteristics of these two cohorts were compared using Mann–Whitney test or Student t-test (Confidence Interval (C.I.) 95%, p b 0.05) for continuous variable and Fisher exact test or Pearson-Chi test for dichotomic variables (p b 0.05). Survival rates were calculated, and a Log-Rank test was performed to evaluate differences in survival distribution. Only in the group with SE, m-RS at 6 months and recurrence of SE were also evaluated. Results: Eleven patients were discharged with a diagnosis of SE mimicking stroke and 65 patients with stroke relapse. Temporal lobe localization was significantly more represented in group with SE (p = 0.036) while there was no difference regarding age, sex, and National Institutes of Health Stroke Scale (NIHSS). The m-RS was significantly higher in patients with hemorrhage relapse, mainly due to the high incidence of amyloid angiopathy in this subgroup. Status epilepticus recurred in 36.4% of patients, presenting with the same clinical features, and most patients (62.5%) achieved a good seizure control at 6 months (Engel scale = 1). A difference in mortality at 12 months (all cause considered) appeared only when distinguishing strokes between ischemic and hemorrhagic (Chi-Square: 10.711, p b 0.005). Discussion and conclusion: Status epilepticus is not infrequent in patients with previous stroke and may present with negative neurological symptoms, thus mimicking a stroke recurrence. EEG should be considered as a potential diagnostic tool in the acute stroke setting, at least in patients with previous stroke. This article is part of the Special Issue “Seizures & Stroke” © 2019 Elsevier Inc. All rights reserved.
1. Introduction 1.1. Background Status epilepticus (SE) following stroke is not infrequent in clinical practice, its incidence being estimated at around 1.5% of patients experiencing stroke [1]. Nevertheless, when presenting with negative ⁎ Corresponding author at: Clinical Neurology Unit, University of Udine, Udine, Italy. E-mail address: [email protected] (F. Bax).
symptoms such as aphasia or hemiparesis, it may mimic stroke relapse, thus posing a diagnostic challenge in patients with previous stroke. Failure in recognizing SE can lead to incorrect treatment, diagnostic delay and potential treatment adverse effects (i.e., bleeding during thrombolysis) which, in the end, may lead to a poorer clinical outcome. Currently, there is no clear evidence concerning which clinical or instrumental (i.e., laboratory and radiological) findings could guide the physician in distinguishing these two insidious entities. Some authors [2] suggested that lower NIHSS at presentation, female sex, and younger age are more indicative of a nonstroke etiology. In addition, they
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Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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estimated that up to 10.6% of stroke mimics are represented by epilepsy. To help clinical decision-making, perfusion-computed tomography (CT) (P-CT) of the head has been proposed as a helpful tool in distinguishing stroke from seizures; however, these findings derive from a small prospective comparative study which did not consider patients with status epilepticus [3]. At today, there is a poor understanding of the clinical features of patients who develop SE mimicking stroke (especially those with previous stroke), and consequently, no standardized diagnostic workup is available. Therefore, patients presenting with SE mimicking stroke relapse are at risk of delayed or incorrect medical treatment and potentially exposed to a poorer clinical outcome than those with a true stroke relapse.
32-channel SystemPLUS for Brian Quick by Micromed™. Since no ictal EEG pattern is specific for SE and it may evolve throughout the duration of the status itself [4], we considered the initial prevalent pattern when classifying SE. Two independent neurophysiologists (G.P. and L.V.) blinded to patient's outcome reviewed the EEG recordings. 2.4. Blood analysis and neuroradiological data According to our local stroke protocol, all patients underwent blood sampling (including complete blood count, C-reactive protein, serum creatinine, International Normalized Ratio (INR), activated Partial Thromboplastin Time (a-PTT) dosage) and neuroradiological study with CT scan, CT-angiography, and CT-perfusion when indicated.
1.2. Aim 2.5. Outcome measures The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (both ischemic and hemorrhagic) who developed stroke-mimicking SE. 2. Materials and methods 2.1. Study design and population This is a single-center retrospective cohort study considering the time interval between December 2016 and January 2018. We reviewed patients transported to our hospital by the emergency service with a stroke code and identified as possible candidates for intravenous thrombolysis. Among them, patients with history of previous stroke (either ischemic or hemorrhagic) were selected. In this subgroup, we identified patients with a diagnosis of SE, and the following data were collected: age at admission, sex, stroke type, hemisphere and lobe involvement, NIHSS at onset, neuroradiological findings, acute and chronic treatment with antiepileptic drugs (AEDs), previous history of stroke, previous history of seizures, epilepsy or poststroke epilepsy (PSE), modified Rankin scale (m-RS) at discharge and at 6 months, and survival at 12 months. Characteristics of SE were classified according to ILAE 2015 criteria by Trinka et al. [4], using the four-axis proposed (semeiology, etiology, electroencephalographic correlates when applicable, and age). Duration of SE was roughly estimated, considering the time of symptom onset reported from the emergency room medical records. A second cohort was composed by those patients who were referred with a stroke code between the time span considered and who were diagnosed with a recurrent stroke (ischemic or hemorrhagic) but did not develop SE. Age at admission, sex, stroke type, hemisphere, and lobe involvement of the new stroke, NIHSS at onset, m-RS at discharge, and survival at 12 months were collected. The study was approved by our local ethical committee. 2.2. Exclusion criteria We excluded from the study those patients aged under 18 years old at admission, those with incomplete follow-up, and those who denied consent for the use of sensitive data. Patients with PSE after previous stroke were not excluded because this condition does not exclude stroke recurrence and acute thrombolytic treatment. 2.3. EEG recordings EEG recordings to allow the diagnosis of SE were all initiated in stroke unit within the first 3 h from admission when SE was suspected, and a prolonged monitoring was carried on to assess the clinical evolution of their SE and response to AED therapy [5]. EEG pattern was compatible with SE since the beginning of the recording in all patients, according to the EEG patterns referred by Trinka et al. [4]. EEG recordings were obtained according to the 10/20 International System, with simultaneous video-recording. All EEG monitoring were recorded with a
Resolution of SE was described as a complete clinical and EEG recovery. Time to SE resolution was calculated. Type of AEDs needed to interrupt SE and therapy at discharge were reported. Seizure frequency was categorized at 6 months after hospital discharges using a simplified version of the Engel Classification of Seizures (Class I: seizure-free or only auras since surgery; Class II: rare seizures; Class III: meaningful seizure improvement; and Class IV: no seizure improvement or worsening) [6]. Survival at 12 months and m-RS at discharge were obtained for both cohorts of patients. 2.6. Statistical analysis General characteristics of study cohorts were described using mean and SD (or median and range if not normally distributed) for continuous variables and percentages for categorical variable. Data were tested for normal distribution using the Kolmogorov–Smirnov test. An independent samples t-test, or Mann–Whitney U when appropriate, were conducted to compare age, NIHSS, and m-RS at discharge in patients with SE mimicking stroke and patients with a true stroke relapse. A χ-square test for dichotomic variables was used to compare the remaining clinical characteristics among the cohorts. Survival curves were calculated, and a log rank test was run to determine differences in the survival distribution of the three different cohorts (SE mimicking stroke, ischemic stroke relapse, or hemorrhagic stroke relapse). Statistical significance level was set at 5%. SPSS software ver.13 (SPSS Inc. in Chicago) was used for statistical analysis. 3. Results 3.1. Study population and baseline characteristic of patients In the time span considered, among patients discharged from our stroke unit, 11 patients fulfilled our inclusion criteria for stroke-mimicking SE and 65 additional patients were diagnosed with stroke relapse. Clinical characteristics and demographics of patients with strokemimicking SE are summarized in Table 1. All patients presented at onset with negative symptoms (nonconvulsive). They were equally distributed among sexes; mean age and NIHSS at admission were 75.3 y.o. (SD ± 11.4) and 8.5 (SD ± 3), respectively. Previous stroke type was mostly ischemic (63.6%), and left temporal lobe was the site most involved. Status epilepticus marked the clinical onset of symptomatic epilepsy in 64% of patients while in the remaining patients, SE developed in the setting of an already diagnosed PSE. None of the patients was treated with thrombolysis. Status epilepticus semeiology was as follows: the majority of patients (seven) presented with aphasic status (B2-b.b). Four patients presented with ictal paresis (A3-a), and in 3 cases, it evolved to repeated focal motor seizures (A3-e status) with unmistakable Jacksonian march observed only in one instance. Impaired awareness was clearly described in four patients, tonic deviation of gaze and head appeared in two cases. Among the patients with aphasic status, four had
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
G. Pauletto et al. / Epilepsy & Behavior xxx (xxxx) xxx Table 1 Clinical characteristics and demographics of patients with SE mimicking stroke. Variables
n°/mean (CI 95%)
Patients with SE Age in years Sex • Male • Female Previous cerebrovascular event • Ischemic • Hemorrhagic (intraparenchymal) Hemisphere involvement • Right • Left Lobe involvement • Temporal • Nontemporal Previous seizures or PSE SE semeiologya • A3-e (ictal paresis) • B2-b.b (aphasic status) EEG main features • Continuous spiking • Spikes and waves • Rhythmic delta activity Duration of SE from diagnosis (in hours) NIHSS at onset — mean ± SD SE relapse Engel Scale at 6 months • =1 • N1 Modified Rankin Scale — mean ± SD • At discharge • At 6 months
11 75.3 y.o. ± 11.4 (67.6–82.9)
3
Table 2 Clinical characteristics and demographics of patients with stroke relapse. (%)
5 6
45.5 54.5
7 4
63.6 36.4
2 9
18.2 81.8
7 4 4
63.6 36.4 36.4
4 (3 evolving to A3-a) 7 5 3 3 13.5 h (2;148)b 8.5 ± 3 (CI 6.48; 10.61) 4
45.4 27.3 27.3
36.4
5 3
62.5 37.5
3 ± 1.84 (CI 1.76–4.24) 3.54 ± 2.11 (CI 2.12–4.97)
a According to the Definition and Classification of Status Epilepticus by Trinka et al. [4]. See text for details. b Median value, minimum and maximum values.
nonfluent aphasia (i.e., Broca aphasia) and three global aphasia but no patient presented with Wernicke aphasia. In three cases, aphasia was associated with limb paresis; since aphasia was the main feature, we classified them as aphasic status according to Trinka et al.'s classification (i.e., B2b.b) [4]. Our patients respect Rosenbaum revised criteria for epileptic aphasia [7,8] except for the fact that no standardized behavioral testing was routinely administered because of the retrospective design. The majority of subjects presented with the reappearance of previous stroke symptoms or worsening of a pre-existing neurological deficit, especially hemiparesis or monoparesis. A median time of 14.3 months elapsed from stroke to SE occurrence. EEG prevalent patterns at the beginning of the recording were continuous spiking (45.4%), spikes and waves (27.3%), and rhythmic delta slowing (27.3%). Lateralized periodic discharges (LPDs) were found in 2 patients as EEG evolution of the SE. Intermittent rhythmic delta activities (IRDAs) were not recorded, and quasiperiodic epileptiform activity was observed in 1 case as evolution of SE as well. We acknowledge that EEG abnormalities may change throughout the evolution of SE, thus, these data must be considered as a rough estimation. Interobserver reliability for EEG recording was 97.12% (weighted Cohen's Kappa: 0.908, p b 0.00019). Status epilepticus was the clinical onset of PSE in 64% of patients, and 36% of patients developed SE in the context of an already diagnosed PSE. Head CT scan at admission was performed in all patients, resulting negative except for signs of the previous stroke. Perfusion imaging was not performed because of poor collaboration of this type of patients. Clinical characteristics and demographics of patients with stroke relapse are summarized in Table 2. They were equally distributed among sexes, mean age and NIHSS at admission were 75.4 y.o. (SD ± 9.1) and 8.5 (SD ± 3), respectively. Previous stroke type was mostly ischemic (63.6%), and nontemporal lobe localization was the most represented. Characteristics according to stroke type are extensively shown in Table 2.
Variables Patients with stroke relapse • Total • Previous ischemic • Previous hemorrhagic Age in years (mean ± SD) • Overall • Ischemic • Hemorrhagic Sex (male) • Overall • Ischemic • Hemorrhagic New cerebrovascular event (all considered) • Ischemic • Hemorrhagic • Both Hemisphere involvement (left) • Overall • Ischemic • Hemorrhagic Lobe involvement (temporal) • Overall • Ischemic • Hemorrhagic NIHSS at onset • Overall • Ischemic • Hemorrhagic Modified Rankin Scale at discharge — mean ± SD • Overall • Ischemic • Hemorrhagic a
n°/mean (CI 95%)
(%)
65 53 12
100 81.5 18.5
75.4 y.o. ± 9.1 (73.15–77.71) 75.7 y.o. ± 9.8 (73.07–78.48) 73.9 y.o. ± 5.9 (70.30–77.54) 32 25 7
49.2 47.2 58.3
51 13 1
78.5 20.0 1.5
33 28 5
50.7 54.9 45.5a
22 17 5
33.8 32.1 41.7
9.5 ± 7 (7.46–11.59) 8.3 ± 7.5 (6.45–10.57) 12.4 ± 6.9 (8.03–16.81)
3.2 ± 1.9 (2.77–3.75) 2.9 ± 1.9 (2.42–3.51) 4.6 ± 1.4 (3.67–5.50)
Valid percentage over 11 patients as one had bilateral stroke.
Comparison of clinical characteristics among the cohorts is shown in Table 3. Only temporal lobe localization was significantly different (p = 0.046), but this statistical significance was lost when comparing SE and hemorrhagic relapse, probably due to low sample size. 3.2. Outcome measures Levetiracetam and lacosamide were the first and second choices of second-line AEDs used intravenously to stop SE because they were easier to handle in this population and guaranteed a direct oral switch. Phenytoin was not used mainly because of cardiac comorbidities and the high risk of pharmacological interactions. Benzodiazepines (i.e., lorazepam 4 mg intravenous (iv) and diazepam 8 mg iv) were used in 3 patients as first-line intravenous AED. Because of the lack of a sustained response, intravenous therapy was switched to levetiracetam and/or lacosamide. The first bolus of AED was sufficient to stop clinical symptoms and EEG epileptic activity in the majority of patients, nevertheless, a second AED was needed in 4 patients. Engel scale at 6 months was N 1 only in 3 patients (37.5%). Modified Rankin scale at discharge did not differ between SE and stroke relapse (p = 0.562), although a significant difference appeared when considering the hemorrhagic relapse subgroup (p = 0.037), indicating worse disability in the latter group. Survival analysis showed a significant difference in overall survival due to all causes at 12 months. Kaplan–Meier curves are shown in Figs. 1 and 2. 4. Discussion Status epilepticus is a neurological emergency that needs urgent and proper treatment. Today, we lack complete understanding of the clinical features of patients who develop SE mimicking stroke, in particular,
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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Table 3 Clinical characteristics comparison of patients with SE and stroke relapse. Age, NIHSS, and m-RS are indicated as mean; sex, hemisphere, and lobe involvement, previous cerebrovascular event and m-RS N 2 at discharge are indicated as number of cases (%). Variable
Age in years Sex — male
SE
75.3 5 (45.5%) Hemisphere 9 (left) (81.8%) Lobe (temporal) 7 (63.6%) Previous event — 7 ischemic stroke 8.5 NIHSS at admission (mean) m-RS at 3 discharge
Stroke relapse (ischemic)
Mann–Whitney†/Fisher exact test§ (p b 0.05)
SE
Stroke relapse (hemorrhagic)
Mann–Whitney†/Fisher exact test § (p b 0.05)
SE
Stroke relapse (all considered)
Mann–Whitney†/Fisher exact test§ (p b 0.05)
75.7 25 (47.2%)
0.881a 0.917b
73.9 7 (58.3%)
0.728a 0.537b
0.966a 0.817b
0.100 §
5 (45.5%)
0.089 §
33 (50.7%)
0.098 §
17 (32.1%)
0.046 §
5 (41.7%)
0.220 §
22 (33.8%)
0.046 §
53
0.001 §
0
/
75.3 5 (45.5%) 9 (81.8%) 7 (63.6%) 7
75.4 32 (49.2%)
28 (54.9%)
75.3 5 (45.5%) 9 (81.8%) 7 (63.6%) 7
53
0.229 §
8.3
0.235†
8.5
12.4
0.192†
8.5
9.5
0.501†
2.96
0.935 †
3
4.58
0.033 †
3
3.26
0.562 †
The bold and italics refer to the significant statistics (p b 0.05). a t-Test. b Pearson-Chi test.
among those with previous cerebrovascular events. Common risk factors for poststroke SE are the same of poststroke seizures – i.e., cortical involvement, hemorrhagic transformation, posterior temporal lobe involvement, alcohol abuse, greater neurological deficit, and sodium imbalance – and SE often marks the clinical onset of a PSE [9–11]. Moreover, SE usually arises in the acute phase of the stroke, and patients with poststroke SE have a poorer outcome than those with stroke alone, especially if SE occurred up to 3 months from the cerebrovascular event [9,12,13]. In previous studies on stroke mimics, the population was heterogeneous, including among stroke mimics are also migraine attacks and conversion disorders [14]. Unlike previous works, our population is more homogeneous, considering only postvascular SE; it is also older than those previously described, and probably for this reason, age, similarly to sex, is not significantly different between SE and new stroke (p N 0.05). There was no statistically significant difference in NIHSS at admission when comparing SE with stroke relapse (even in subanalysis considering different stroke types). This difference with previous studies may be explained by the fact that all the patients with SE had already suffered from stroke.
Unlike Winkler et al. [15], we did not find a significant correlation with the left hemisphere, and this may be due to limited sample size. An interesting finding of our study is temporal lobe localization in SE (p = 0.046); we hypothesize that temporal lobe was most frequently involved because of its vascularization (mainly medial and posterior cerebral arteries who are frequently stroke sites) and to its high epileptogenic potential. The site of the first vascular lesion (ischemic or hemorrhagic) – which becomes an epileptogenic focus – explains why these patients may be initially suspected with a relapsing stroke, due to the frequently overlapping neurological symptoms. Since most patients with status epilepticus (7 out of 11) presented with aphasic status, the main feature prompting further investigations (i.e., EEG recording) was the patient attitude towards the aphasia. In our experience, stroke aphasia is associated with more emotional involvement (i.e., patient usually struggling to express himself and appearing frustrated of not being understood) while in aphasic status, patients usually seem more emotionally detached and confused. Moreover, some patients developed clonic movements (face and limbs),
Fig. 1. Kaplan–Meier curve for all-cause mortality at 12 months among patients with SE and patients with stroke relapse. Log-Rank (Mantel–Cox) 2.602 (p = 0.107).
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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Fig. 2. Kaplan–Meier curve for all-cause mortality at 12 months among patients with SE and patients with stroke relapse according to stroke type. Log-Rank (Mantel–Cox) 10.711 (p = 0.005).
strengthening our suspicion of an epileptic cause of the disturbance. In three cases, aphasia was associated with limb paresis thus, indicating a stroke recurrence as more probable; in these cases, as already outlined above, the characteristics of the aphasia lead us to perform an urgent EEG. Overall survival from all causes at 1 year was not different when comparing SE and stroke relapse. However, if we consider stroke subtypes, an intergroup significant difference was found (p b 0.05), with mortality being higher among hemorrhagic strokes, followed by SE, and ischemic stroke. In line with current literature, SE was the clinical onset of a PSE in the majority of patients [16]. Status epilepticus was controlled by therapy in almost all patients, and at 6 months, the Engel class was 1 in the majority of patients, indicating good seizure control. However, relapse of SE was not infrequent, and it was a cause of new hospitalizations. Four patients were lost at follow-up because they died, among them, one patient developed superrefractory status epilepticus and died without SE resolution, three patients died because of medical conditions different from SE (lung cancer, septic status, and malignant arrhythmia). Previous works have discussed epileptic seizures as stroke mimics. It is possible that some of these papers may have included patients with SE, but lack of a prolonged EEG monitoring may have hampered SE recognition [14,15,17]. However, to our knowledge, this is the first study evaluating SE alone as stroke mimic, using a standardized classification [4].
5. Limitations We are aware of the following limitations of the study: retrospective design and single center experience, limited sample size, and possible underestimation of SE (especially if patients were admitted during nighttime or weekends when EEG monitoring was more difficult to organize). The lack of perfusion studies is due to the retrospective design of our work and poor patient cooperation; however, we would like to clarify that our Hospital Stroke Unit protocol includes perfusion studies mainly in the case of undetermined stroke onset-time or in the presence of early signs of ischemia. Magnetic Resonance Imaging (MRI) scan is usually not performed in the case of stroke code, at our Institution.
6. Conclusion Status epilepticus is not uncommon in patients with previous stroke, and it may present with negative symptoms mimicking a new cerebrovascular event. Patients with previous stroke with temporal lobe involvement are more prone to develop SE. Relapse is not infrequent and may lead to multiple hospital admissions. EEG should be considered as a diagnostic tool in the clinical management of acute suspected stroke, at least in those patients with a previous stroke. Moreover, as shown in a recent review [18], in the context of patients with previous stroke or PSE, new negative neurological symptoms must raise suspicion of SE or of epileptic origin of the disturbance. Prospective and multicenter studies are needed to better characterize the magnitude of the problem and identify patient more at risk for poststroke SE and SE recurrence. Acknowledgments None. References [1] Velioglu SK, Ozmenoglu M, Boz C, Alioglu Z. Status epilepticus after stroke. Stroke. 2001;31:1160–72. [2] Quenardelle V, Lauer-Ober V, Zinchenko I, Bataillard M, Rouyer O, Beaujeux R, et al. Stroke mimics in a stroke care pathway based on MRI screening. Cerebrovasc Dis. 2016;42:205–12. [3] Kubiak-Balcerewicz K, Fiszer U, Naganska E, Siemianowski C, Sobieszek A, WitakGrybowska A, et al. Differentiating stroke and seizure in acute setting-perfusion computed tomography? J Stroke Cerebrovasc Dis. 2017;26(6):1321–7. [4] Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus — report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23. [5] Ericson EJ, Gerard EE, Macken MP, Schuele SU. Aphasic status epilepticus: electroclinical correlation. Epilepsia. 2011;52(8):1452–8. [6] Engel J, Cascino GD, Ness PCV, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel J, editor. Surgical treatment of the epilepsies. NY: Raven Press; 1993. [7] Rosenbaum DH, Siegel M, Barr WB, Rowan AJ. Epileptic aphasia. 1986;36:822–5. [8] Grimes DA, Guberman A. De novo aphasic status epilepticus. Epilepsia. 1997;38(8): 945–9. [9] Belcastro V, Vidale S, Gorgone G, Pisani LR, Sironi L, Arnaboldi M, et al. Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke cohort study. J Neurol. 2014;261(11):2136–42.
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Status epilepticus mimicking stroke recurrence Giada Pauletto a, Francesco Bax b,c,⁎, Gian Luigi Gigli b,c,d, Simone Lorenzut a, Lorenzo Verriello a, Elisa Corazza b,c, Mariarosaria Valente b,c a
Neurology Unit, Udine University Hospital, Udine, Italy Clinical Neurology Unit, University of Udine, Udine, Italy Department of Medicine (DAME), University of Udine, Udine, Italy d Department of Mathematics, Informatics and Physics (DMIF), University of Udine, Udine, Italy b c
a r t i c l e
i n f o
Article history: Received 31 May 2019 Revised 14 August 2019 Accepted 16 August 2019 Available online xxxx Keywords: Status epilepticus Epilepsy Stroke Poststroke epilepsy Aphasic status ILAE status epilepticus classification
a b s t r a c t Aim of the study: The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (either ischemic or hemorrhagic), who developed status epilepticus (SE) mimicking a stroke relapse. Materials and methods: We performed a retrospective cohort study of patients brought to hospital by the emergency service between December 2016 and January 2018 with a stroke code as possible candidates for intravenous thrombolysis and who had already have a previous stroke. Among them, patients admitted for negative symptoms and finally discharged with a diagnosis of SE mimicking stroke were selected and their clinical characteristics collected. All patients underwent routine blood sample analysis, head computed tomography (CT) scan and, when indicated, CT angiography and CT-perfusion imaging of the head. After admission in our stroke unit, an Electroencephalogram (EEG) was performed within 3 h in patients suspected with SE, then classified according to International League Against Epilepsy (ILAE) classification (2015). Outcome measures were SE duration, antiepileptic drugs (AEDs) administered, mortality at 12 months, Engel scale, and modified Rankin scale (m-RS) at 6 months. A second cohort included those consecutive patients discharged with a true stroke relapse in the same considered time span. Clinical characteristics of these two cohorts were compared using Mann–Whitney test or Student t-test (Confidence Interval (C.I.) 95%, p b 0.05) for continuous variable and Fisher exact test or Pearson-Chi test for dichotomic variables (p b 0.05). Survival rates were calculated, and a Log-Rank test was performed to evaluate differences in survival distribution. Only in the group with SE, m-RS at 6 months and recurrence of SE were also evaluated. Results: Eleven patients were discharged with a diagnosis of SE mimicking stroke and 65 patients with stroke relapse. Temporal lobe localization was significantly more represented in group with SE (p = 0.036) while there was no difference regarding age, sex, and National Institutes of Health Stroke Scale (NIHSS). The m-RS was significantly higher in patients with hemorrhage relapse, mainly due to the high incidence of amyloid angiopathy in this subgroup. Status epilepticus recurred in 36.4% of patients, presenting with the same clinical features, and most patients (62.5%) achieved a good seizure control at 6 months (Engel scale = 1). A difference in mortality at 12 months (all cause considered) appeared only when distinguishing strokes between ischemic and hemorrhagic (Chi-Square: 10.711, p b 0.005). Discussion and conclusion: Status epilepticus is not infrequent in patients with previous stroke and may present with negative neurological symptoms, thus mimicking a stroke recurrence. EEG should be considered as a potential diagnostic tool in the acute stroke setting, at least in patients with previous stroke. This article is part of the Special Issue “Seizures & Stroke” © 2019 Elsevier Inc. All rights reserved.
1. Introduction 1.1. Background Status epilepticus (SE) following stroke is not infrequent in clinical practice, its incidence being estimated at around 1.5% of patients experiencing stroke [1]. Nevertheless, when presenting with negative ⁎ Corresponding author at: Clinical Neurology Unit, University of Udine, Udine, Italy. E-mail address: [email protected] (F. Bax).
symptoms such as aphasia or hemiparesis, it may mimic stroke relapse, thus posing a diagnostic challenge in patients with previous stroke. Failure in recognizing SE can lead to incorrect treatment, diagnostic delay and potential treatment adverse effects (i.e., bleeding during thrombolysis) which, in the end, may lead to a poorer clinical outcome. Currently, there is no clear evidence concerning which clinical or instrumental (i.e., laboratory and radiological) findings could guide the physician in distinguishing these two insidious entities. Some authors [2] suggested that lower NIHSS at presentation, female sex, and younger age are more indicative of a nonstroke etiology. In addition, they
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Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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estimated that up to 10.6% of stroke mimics are represented by epilepsy. To help clinical decision-making, perfusion-computed tomography (CT) (P-CT) of the head has been proposed as a helpful tool in distinguishing stroke from seizures; however, these findings derive from a small prospective comparative study which did not consider patients with status epilepticus [3]. At today, there is a poor understanding of the clinical features of patients who develop SE mimicking stroke (especially those with previous stroke), and consequently, no standardized diagnostic workup is available. Therefore, patients presenting with SE mimicking stroke relapse are at risk of delayed or incorrect medical treatment and potentially exposed to a poorer clinical outcome than those with a true stroke relapse.
32-channel SystemPLUS for Brian Quick by Micromed™. Since no ictal EEG pattern is specific for SE and it may evolve throughout the duration of the status itself [4], we considered the initial prevalent pattern when classifying SE. Two independent neurophysiologists (G.P. and L.V.) blinded to patient's outcome reviewed the EEG recordings. 2.4. Blood analysis and neuroradiological data According to our local stroke protocol, all patients underwent blood sampling (including complete blood count, C-reactive protein, serum creatinine, International Normalized Ratio (INR), activated Partial Thromboplastin Time (a-PTT) dosage) and neuroradiological study with CT scan, CT-angiography, and CT-perfusion when indicated.
1.2. Aim 2.5. Outcome measures The aim of the study was to evaluate the clinical characteristics of patients with previous stroke (both ischemic and hemorrhagic) who developed stroke-mimicking SE. 2. Materials and methods 2.1. Study design and population This is a single-center retrospective cohort study considering the time interval between December 2016 and January 2018. We reviewed patients transported to our hospital by the emergency service with a stroke code and identified as possible candidates for intravenous thrombolysis. Among them, patients with history of previous stroke (either ischemic or hemorrhagic) were selected. In this subgroup, we identified patients with a diagnosis of SE, and the following data were collected: age at admission, sex, stroke type, hemisphere and lobe involvement, NIHSS at onset, neuroradiological findings, acute and chronic treatment with antiepileptic drugs (AEDs), previous history of stroke, previous history of seizures, epilepsy or poststroke epilepsy (PSE), modified Rankin scale (m-RS) at discharge and at 6 months, and survival at 12 months. Characteristics of SE were classified according to ILAE 2015 criteria by Trinka et al. [4], using the four-axis proposed (semeiology, etiology, electroencephalographic correlates when applicable, and age). Duration of SE was roughly estimated, considering the time of symptom onset reported from the emergency room medical records. A second cohort was composed by those patients who were referred with a stroke code between the time span considered and who were diagnosed with a recurrent stroke (ischemic or hemorrhagic) but did not develop SE. Age at admission, sex, stroke type, hemisphere, and lobe involvement of the new stroke, NIHSS at onset, m-RS at discharge, and survival at 12 months were collected. The study was approved by our local ethical committee. 2.2. Exclusion criteria We excluded from the study those patients aged under 18 years old at admission, those with incomplete follow-up, and those who denied consent for the use of sensitive data. Patients with PSE after previous stroke were not excluded because this condition does not exclude stroke recurrence and acute thrombolytic treatment. 2.3. EEG recordings EEG recordings to allow the diagnosis of SE were all initiated in stroke unit within the first 3 h from admission when SE was suspected, and a prolonged monitoring was carried on to assess the clinical evolution of their SE and response to AED therapy [5]. EEG pattern was compatible with SE since the beginning of the recording in all patients, according to the EEG patterns referred by Trinka et al. [4]. EEG recordings were obtained according to the 10/20 International System, with simultaneous video-recording. All EEG monitoring were recorded with a
Resolution of SE was described as a complete clinical and EEG recovery. Time to SE resolution was calculated. Type of AEDs needed to interrupt SE and therapy at discharge were reported. Seizure frequency was categorized at 6 months after hospital discharges using a simplified version of the Engel Classification of Seizures (Class I: seizure-free or only auras since surgery; Class II: rare seizures; Class III: meaningful seizure improvement; and Class IV: no seizure improvement or worsening) [6]. Survival at 12 months and m-RS at discharge were obtained for both cohorts of patients. 2.6. Statistical analysis General characteristics of study cohorts were described using mean and SD (or median and range if not normally distributed) for continuous variables and percentages for categorical variable. Data were tested for normal distribution using the Kolmogorov–Smirnov test. An independent samples t-test, or Mann–Whitney U when appropriate, were conducted to compare age, NIHSS, and m-RS at discharge in patients with SE mimicking stroke and patients with a true stroke relapse. A χ-square test for dichotomic variables was used to compare the remaining clinical characteristics among the cohorts. Survival curves were calculated, and a log rank test was run to determine differences in the survival distribution of the three different cohorts (SE mimicking stroke, ischemic stroke relapse, or hemorrhagic stroke relapse). Statistical significance level was set at 5%. SPSS software ver.13 (SPSS Inc. in Chicago) was used for statistical analysis. 3. Results 3.1. Study population and baseline characteristic of patients In the time span considered, among patients discharged from our stroke unit, 11 patients fulfilled our inclusion criteria for stroke-mimicking SE and 65 additional patients were diagnosed with stroke relapse. Clinical characteristics and demographics of patients with strokemimicking SE are summarized in Table 1. All patients presented at onset with negative symptoms (nonconvulsive). They were equally distributed among sexes; mean age and NIHSS at admission were 75.3 y.o. (SD ± 11.4) and 8.5 (SD ± 3), respectively. Previous stroke type was mostly ischemic (63.6%), and left temporal lobe was the site most involved. Status epilepticus marked the clinical onset of symptomatic epilepsy in 64% of patients while in the remaining patients, SE developed in the setting of an already diagnosed PSE. None of the patients was treated with thrombolysis. Status epilepticus semeiology was as follows: the majority of patients (seven) presented with aphasic status (B2-b.b). Four patients presented with ictal paresis (A3-a), and in 3 cases, it evolved to repeated focal motor seizures (A3-e status) with unmistakable Jacksonian march observed only in one instance. Impaired awareness was clearly described in four patients, tonic deviation of gaze and head appeared in two cases. Among the patients with aphasic status, four had
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
G. Pauletto et al. / Epilepsy & Behavior xxx (xxxx) xxx Table 1 Clinical characteristics and demographics of patients with SE mimicking stroke. Variables
n°/mean (CI 95%)
Patients with SE Age in years Sex • Male • Female Previous cerebrovascular event • Ischemic • Hemorrhagic (intraparenchymal) Hemisphere involvement • Right • Left Lobe involvement • Temporal • Nontemporal Previous seizures or PSE SE semeiologya • A3-e (ictal paresis) • B2-b.b (aphasic status) EEG main features • Continuous spiking • Spikes and waves • Rhythmic delta activity Duration of SE from diagnosis (in hours) NIHSS at onset — mean ± SD SE relapse Engel Scale at 6 months • =1 • N1 Modified Rankin Scale — mean ± SD • At discharge • At 6 months
11 75.3 y.o. ± 11.4 (67.6–82.9)
3
Table 2 Clinical characteristics and demographics of patients with stroke relapse. (%)
5 6
45.5 54.5
7 4
63.6 36.4
2 9
18.2 81.8
7 4 4
63.6 36.4 36.4
4 (3 evolving to A3-a) 7 5 3 3 13.5 h (2;148)b 8.5 ± 3 (CI 6.48; 10.61) 4
45.4 27.3 27.3
36.4
5 3
62.5 37.5
3 ± 1.84 (CI 1.76–4.24) 3.54 ± 2.11 (CI 2.12–4.97)
a According to the Definition and Classification of Status Epilepticus by Trinka et al. [4]. See text for details. b Median value, minimum and maximum values.
nonfluent aphasia (i.e., Broca aphasia) and three global aphasia but no patient presented with Wernicke aphasia. In three cases, aphasia was associated with limb paresis; since aphasia was the main feature, we classified them as aphasic status according to Trinka et al.'s classification (i.e., B2b.b) [4]. Our patients respect Rosenbaum revised criteria for epileptic aphasia [7,8] except for the fact that no standardized behavioral testing was routinely administered because of the retrospective design. The majority of subjects presented with the reappearance of previous stroke symptoms or worsening of a pre-existing neurological deficit, especially hemiparesis or monoparesis. A median time of 14.3 months elapsed from stroke to SE occurrence. EEG prevalent patterns at the beginning of the recording were continuous spiking (45.4%), spikes and waves (27.3%), and rhythmic delta slowing (27.3%). Lateralized periodic discharges (LPDs) were found in 2 patients as EEG evolution of the SE. Intermittent rhythmic delta activities (IRDAs) were not recorded, and quasiperiodic epileptiform activity was observed in 1 case as evolution of SE as well. We acknowledge that EEG abnormalities may change throughout the evolution of SE, thus, these data must be considered as a rough estimation. Interobserver reliability for EEG recording was 97.12% (weighted Cohen's Kappa: 0.908, p b 0.00019). Status epilepticus was the clinical onset of PSE in 64% of patients, and 36% of patients developed SE in the context of an already diagnosed PSE. Head CT scan at admission was performed in all patients, resulting negative except for signs of the previous stroke. Perfusion imaging was not performed because of poor collaboration of this type of patients. Clinical characteristics and demographics of patients with stroke relapse are summarized in Table 2. They were equally distributed among sexes, mean age and NIHSS at admission were 75.4 y.o. (SD ± 9.1) and 8.5 (SD ± 3), respectively. Previous stroke type was mostly ischemic (63.6%), and nontemporal lobe localization was the most represented. Characteristics according to stroke type are extensively shown in Table 2.
Variables Patients with stroke relapse • Total • Previous ischemic • Previous hemorrhagic Age in years (mean ± SD) • Overall • Ischemic • Hemorrhagic Sex (male) • Overall • Ischemic • Hemorrhagic New cerebrovascular event (all considered) • Ischemic • Hemorrhagic • Both Hemisphere involvement (left) • Overall • Ischemic • Hemorrhagic Lobe involvement (temporal) • Overall • Ischemic • Hemorrhagic NIHSS at onset • Overall • Ischemic • Hemorrhagic Modified Rankin Scale at discharge — mean ± SD • Overall • Ischemic • Hemorrhagic a
n°/mean (CI 95%)
(%)
65 53 12
100 81.5 18.5
75.4 y.o. ± 9.1 (73.15–77.71) 75.7 y.o. ± 9.8 (73.07–78.48) 73.9 y.o. ± 5.9 (70.30–77.54) 32 25 7
49.2 47.2 58.3
51 13 1
78.5 20.0 1.5
33 28 5
50.7 54.9 45.5a
22 17 5
33.8 32.1 41.7
9.5 ± 7 (7.46–11.59) 8.3 ± 7.5 (6.45–10.57) 12.4 ± 6.9 (8.03–16.81)
3.2 ± 1.9 (2.77–3.75) 2.9 ± 1.9 (2.42–3.51) 4.6 ± 1.4 (3.67–5.50)
Valid percentage over 11 patients as one had bilateral stroke.
Comparison of clinical characteristics among the cohorts is shown in Table 3. Only temporal lobe localization was significantly different (p = 0.046), but this statistical significance was lost when comparing SE and hemorrhagic relapse, probably due to low sample size. 3.2. Outcome measures Levetiracetam and lacosamide were the first and second choices of second-line AEDs used intravenously to stop SE because they were easier to handle in this population and guaranteed a direct oral switch. Phenytoin was not used mainly because of cardiac comorbidities and the high risk of pharmacological interactions. Benzodiazepines (i.e., lorazepam 4 mg intravenous (iv) and diazepam 8 mg iv) were used in 3 patients as first-line intravenous AED. Because of the lack of a sustained response, intravenous therapy was switched to levetiracetam and/or lacosamide. The first bolus of AED was sufficient to stop clinical symptoms and EEG epileptic activity in the majority of patients, nevertheless, a second AED was needed in 4 patients. Engel scale at 6 months was N 1 only in 3 patients (37.5%). Modified Rankin scale at discharge did not differ between SE and stroke relapse (p = 0.562), although a significant difference appeared when considering the hemorrhagic relapse subgroup (p = 0.037), indicating worse disability in the latter group. Survival analysis showed a significant difference in overall survival due to all causes at 12 months. Kaplan–Meier curves are shown in Figs. 1 and 2. 4. Discussion Status epilepticus is a neurological emergency that needs urgent and proper treatment. Today, we lack complete understanding of the clinical features of patients who develop SE mimicking stroke, in particular,
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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Table 3 Clinical characteristics comparison of patients with SE and stroke relapse. Age, NIHSS, and m-RS are indicated as mean; sex, hemisphere, and lobe involvement, previous cerebrovascular event and m-RS N 2 at discharge are indicated as number of cases (%). Variable
Age in years Sex — male
SE
75.3 5 (45.5%) Hemisphere 9 (left) (81.8%) Lobe (temporal) 7 (63.6%) Previous event — 7 ischemic stroke 8.5 NIHSS at admission (mean) m-RS at 3 discharge
Stroke relapse (ischemic)
Mann–Whitney†/Fisher exact test§ (p b 0.05)
SE
Stroke relapse (hemorrhagic)
Mann–Whitney†/Fisher exact test § (p b 0.05)
SE
Stroke relapse (all considered)
Mann–Whitney†/Fisher exact test§ (p b 0.05)
75.7 25 (47.2%)
0.881a 0.917b
73.9 7 (58.3%)
0.728a 0.537b
0.966a 0.817b
0.100 §
5 (45.5%)
0.089 §
33 (50.7%)
0.098 §
17 (32.1%)
0.046 §
5 (41.7%)
0.220 §
22 (33.8%)
0.046 §
53
0.001 §
0
/
75.3 5 (45.5%) 9 (81.8%) 7 (63.6%) 7
75.4 32 (49.2%)
28 (54.9%)
75.3 5 (45.5%) 9 (81.8%) 7 (63.6%) 7
53
0.229 §
8.3
0.235†
8.5
12.4
0.192†
8.5
9.5
0.501†
2.96
0.935 †
3
4.58
0.033 †
3
3.26
0.562 †
The bold and italics refer to the significant statistics (p b 0.05). a t-Test. b Pearson-Chi test.
among those with previous cerebrovascular events. Common risk factors for poststroke SE are the same of poststroke seizures – i.e., cortical involvement, hemorrhagic transformation, posterior temporal lobe involvement, alcohol abuse, greater neurological deficit, and sodium imbalance – and SE often marks the clinical onset of a PSE [9–11]. Moreover, SE usually arises in the acute phase of the stroke, and patients with poststroke SE have a poorer outcome than those with stroke alone, especially if SE occurred up to 3 months from the cerebrovascular event [9,12,13]. In previous studies on stroke mimics, the population was heterogeneous, including among stroke mimics are also migraine attacks and conversion disorders [14]. Unlike previous works, our population is more homogeneous, considering only postvascular SE; it is also older than those previously described, and probably for this reason, age, similarly to sex, is not significantly different between SE and new stroke (p N 0.05). There was no statistically significant difference in NIHSS at admission when comparing SE with stroke relapse (even in subanalysis considering different stroke types). This difference with previous studies may be explained by the fact that all the patients with SE had already suffered from stroke.
Unlike Winkler et al. [15], we did not find a significant correlation with the left hemisphere, and this may be due to limited sample size. An interesting finding of our study is temporal lobe localization in SE (p = 0.046); we hypothesize that temporal lobe was most frequently involved because of its vascularization (mainly medial and posterior cerebral arteries who are frequently stroke sites) and to its high epileptogenic potential. The site of the first vascular lesion (ischemic or hemorrhagic) – which becomes an epileptogenic focus – explains why these patients may be initially suspected with a relapsing stroke, due to the frequently overlapping neurological symptoms. Since most patients with status epilepticus (7 out of 11) presented with aphasic status, the main feature prompting further investigations (i.e., EEG recording) was the patient attitude towards the aphasia. In our experience, stroke aphasia is associated with more emotional involvement (i.e., patient usually struggling to express himself and appearing frustrated of not being understood) while in aphasic status, patients usually seem more emotionally detached and confused. Moreover, some patients developed clonic movements (face and limbs),
Fig. 1. Kaplan–Meier curve for all-cause mortality at 12 months among patients with SE and patients with stroke relapse. Log-Rank (Mantel–Cox) 2.602 (p = 0.107).
Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509
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Fig. 2. Kaplan–Meier curve for all-cause mortality at 12 months among patients with SE and patients with stroke relapse according to stroke type. Log-Rank (Mantel–Cox) 10.711 (p = 0.005).
strengthening our suspicion of an epileptic cause of the disturbance. In three cases, aphasia was associated with limb paresis thus, indicating a stroke recurrence as more probable; in these cases, as already outlined above, the characteristics of the aphasia lead us to perform an urgent EEG. Overall survival from all causes at 1 year was not different when comparing SE and stroke relapse. However, if we consider stroke subtypes, an intergroup significant difference was found (p b 0.05), with mortality being higher among hemorrhagic strokes, followed by SE, and ischemic stroke. In line with current literature, SE was the clinical onset of a PSE in the majority of patients [16]. Status epilepticus was controlled by therapy in almost all patients, and at 6 months, the Engel class was 1 in the majority of patients, indicating good seizure control. However, relapse of SE was not infrequent, and it was a cause of new hospitalizations. Four patients were lost at follow-up because they died, among them, one patient developed superrefractory status epilepticus and died without SE resolution, three patients died because of medical conditions different from SE (lung cancer, septic status, and malignant arrhythmia). Previous works have discussed epileptic seizures as stroke mimics. It is possible that some of these papers may have included patients with SE, but lack of a prolonged EEG monitoring may have hampered SE recognition [14,15,17]. However, to our knowledge, this is the first study evaluating SE alone as stroke mimic, using a standardized classification [4].
5. Limitations We are aware of the following limitations of the study: retrospective design and single center experience, limited sample size, and possible underestimation of SE (especially if patients were admitted during nighttime or weekends when EEG monitoring was more difficult to organize). The lack of perfusion studies is due to the retrospective design of our work and poor patient cooperation; however, we would like to clarify that our Hospital Stroke Unit protocol includes perfusion studies mainly in the case of undetermined stroke onset-time or in the presence of early signs of ischemia. Magnetic Resonance Imaging (MRI) scan is usually not performed in the case of stroke code, at our Institution.
6. Conclusion Status epilepticus is not uncommon in patients with previous stroke, and it may present with negative symptoms mimicking a new cerebrovascular event. Patients with previous stroke with temporal lobe involvement are more prone to develop SE. Relapse is not infrequent and may lead to multiple hospital admissions. EEG should be considered as a diagnostic tool in the clinical management of acute suspected stroke, at least in those patients with a previous stroke. Moreover, as shown in a recent review [18], in the context of patients with previous stroke or PSE, new negative neurological symptoms must raise suspicion of SE or of epileptic origin of the disturbance. Prospective and multicenter studies are needed to better characterize the magnitude of the problem and identify patient more at risk for poststroke SE and SE recurrence. Acknowledgments None. References [1] Velioglu SK, Ozmenoglu M, Boz C, Alioglu Z. Status epilepticus after stroke. Stroke. 2001;31:1160–72. [2] Quenardelle V, Lauer-Ober V, Zinchenko I, Bataillard M, Rouyer O, Beaujeux R, et al. Stroke mimics in a stroke care pathway based on MRI screening. Cerebrovasc Dis. 2016;42:205–12. [3] Kubiak-Balcerewicz K, Fiszer U, Naganska E, Siemianowski C, Sobieszek A, WitakGrybowska A, et al. Differentiating stroke and seizure in acute setting-perfusion computed tomography? J Stroke Cerebrovasc Dis. 2017;26(6):1321–7. [4] Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus — report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–23. [5] Ericson EJ, Gerard EE, Macken MP, Schuele SU. Aphasic status epilepticus: electroclinical correlation. Epilepsia. 2011;52(8):1452–8. [6] Engel J, Cascino GD, Ness PCV, Rasmussen TB, Ojemann LM. Outcome with respect to epileptic seizures. In: Engel J, editor. Surgical treatment of the epilepsies. NY: Raven Press; 1993. [7] Rosenbaum DH, Siegel M, Barr WB, Rowan AJ. Epileptic aphasia. 1986;36:822–5. [8] Grimes DA, Guberman A. De novo aphasic status epilepticus. Epilepsia. 1997;38(8): 945–9. [9] Belcastro V, Vidale S, Gorgone G, Pisani LR, Sironi L, Arnaboldi M, et al. Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke cohort study. J Neurol. 2014;261(11):2136–42.
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Please cite this article as: G. Pauletto, F. Bax, G.L. Gigli, et al., Status epilepticus mimicking stroke recurrence, Epilepsy & Behavior, https://doi.org/ 10.1016/j.yebeh.2019.106509