J Neurol DOI 10.1007/s00415-014-7471-z

ORIGINAL COMMUNICATION

Non-convulsive status epilepticus after ischemic stroke: a hospitalbased stroke cohort study Vincenzo Belcastro • Simone Vidale • Gaetano Gorgone • Laura Rosa Pisani • Luigi Sironi • Marco Arnaboldi • Francesco Pisani

Received: 10 May 2014 / Revised: 19 July 2014 / Accepted: 11 August 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract To evaluate in the setting of a stroke unit ward the usefulness of a prolonged ([6 h) video-EEG recording (PVEEG) in identifying non-convulsive status epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE were also evaluated. Patients with an acute ischemic stroke, referred to our unit, were included in this prospective observational study. A PVEEG recording was implemented after stroke in all patients during the first week: (a) promptly in those exhibiting a clear or suspected epileptic manifestation; (b) at any time during the routine activity in the remaining patients. After the first week, a standard EEG/PVEEG recording was hooked up only in presence of an evident or suspected epileptic manifestation or as control of a previous epileptic episode. NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It occurred early (within the first week) in 20/32 (62.5 %) patients and late in the remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n = 19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis, a significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic stroke and a delayed diagnosis V. Belcastro (&)
S. Vidale
L. Sironi
M. Arnaboldi Neurology Unit, S. Anna Hospital, Como, Italy e-mail: [email protected] G. Gorgone Neurology Unit, Treviglio-Caravaggio Hospital, Treviglio, Italy L. R. Pisani IRCCS Centro Neurolesi ‘‘Bonino-Pulejo’’, Messina, Italy F. Pisani Department of Neurosciences, University of Messina, Messina, Italy

could worsen patient prognosis. Since NCSE can be difficult to be diagnosed only on clinical grounds, implementation of a prompt PVEEG should be kept available in a stroke unit whenever a patient develop signs, although subtle, consistent with NCSE. Keywords Non-convulsive status epilepticus
Post-stroke seizures
Prolonged video-EEG recording

Introduction Stroke is the most common cause of symptomatic epilepsy in older adults and status epilepticus (SE) can be a presenting clinical feature of an acute stroke [1–6]. Values concerning the incidence of post-stroke seizures and development of epilepsy after stroke show a great variability in the literature. This variability is due to different reasons: small sample sizes, different study designs, heterogeneous terminology, different periods of follow-up, no specification on the ischemic/hemorrhagic nature of the lesion. Incidence values of ‘‘early’’ (i.e., within the first 7 days) seizures range from 3 to 15 % [1, 7–11], but values [30 % have been also reported in the literature [5]. ‘‘Late’’ seizures, i.e., those after the first week, have been reported to occur in a percentage ranging from 3 to 9 % with a gradual increase by increasing the time period after stroke, the higher values being observed at 10 years [1, 4, 5]. Similarly, post-stroke epilepsy has been seen to develop in 6.4 % of patients as a mean value, ranging from 1.5 % at 3 months to 12.4 % at 10 years after stroke [2]. Concerning the incidence of SE, it has been estimated to range from 0.2 to 1.4 % [9–14] with very small differences observed between ischemic and hemorrhagic stroke (0.2 vs. 0.3 %) [14]. Additionally, most of these data regard convulsive

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generalized SE (CGSE) and only few observations have been specifically reported on non-convulsive SE (NCSE) after stroke [6, 15]. In particular, in comatose patients with NCSE, 20 % of patients had an ischemic stroke [15]. NCSE has been defined as a state of ongoing (or nonrecovery between) seizures without convulsions, usually for more than 30 min [16]. It is a clinical entity very difficult to be detected in acute and critically ill patients, including those with stroke, because of its subtle, nonconvulsive manifestations associated with transient consciousness disturbances [16–20]. Using a hospital-based stroke cohort, the first aim of the present study was to evaluate in the setting of a stroke unit ward the usefulness of a prolonged, namely lasting for at least 6 h, video-EEG recording (PVEEG) in identifying episodes of NCSE after an acute ischemic stroke. Predictors of NCSE were also evaluated.

Patients and methods The Institutional Review Board of the S. Anna Hospital, Como, Italy, approved the study and granted a waiver of informed consent. The present investigation is a prospective observational study. Patient population Patients, referred to the Stroke Unit of S. Anna Hospital of Como between January 2010 and September 2013, were included in this study according to the following inclusion criteria: (1) acute ischemic stroke defined by the occurrence of acute neurologic signs and symptoms of vascular origin lasting 24 h or longer and documented through brain CT/MRI; (2) no other concomitant causes potentially responsible of acute seizures (for example: alcohol withdrawal, psychotropic drugs, electrolyte disturbance, previous brain lesions). A direct interview was required, except for aphasic or uncooperative patients, for whom the interview was released by his relatives. Patients with: (1) a previous history of seizures; (2) recurrent stroke; (3) i.v. or p.o. treatment with antiepileptic (AEDs) or sedative drugs, including barbiturates, benzodiazepines and propofol, prior to video-EEG execution; (4) hemorrhagic transformation of the ischemic area were excluded from analysis. EEG recording and epilepsy characterization Given that [50 % of epileptic seizures/SE occur in the first days after stroke [4, 5, 7–10, 13], a PVEEG recording, including ECG tracing, was implemented in all patients admitted to our Stroke Unit within the first week

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after stroke onset: it was hooked up as soon as an epileptic activity was clear or suspected or at any time during the routine activity in the remaining patients. Additional conventional (i.e., of *30 min) EEG recordings, or even PVEEG when clinically judged more appropriate, were made after the first week only in presence of clear or suspected epileptic seizures/SE or as control of a previous epileptic episode. EEG was recorded digitally using caps with 21 fixed gel electrodes placed according to the International 10–20 system. EEGs were immediately evaluated by board-certified electroencephalographers. Seizures were divided into convulsive and non-convulsive. Convulsive seizures (CSz) were described as ‘‘tonic–clonic,’’ ‘‘clonic’’ or ‘‘tonic’’ (including also synonyms like ‘‘jerking’’ or ‘‘twitching’’). SE was reported as convulsive (CSE) for CSz lasting longer than 5 min or if 2 or more fits occurred without a return to baseline in between. Non-convulsive seizures (NCSz) were considered those characterized by subtle movements like slow facial twitching and eye deviation. NCSE was defined as 30 min of continuous seizure activity without major motor phenomena and according to the criteria of Young et al. [16]. At least one of the following three primary EEG criteria and at least one of the four secondary EEG criteria had to be fulfilled. Primary criteria were (1) repetitive focal or generalized spikes, sharp waves, spikeand-wave or sharp-and-slow wave complexes at a frequency of [3/s; (2) repetitive focal or generalized spikes, sharp waves, spike-and-wave or sharp-and-slow wave complexes at a frequency of [3/s and secondary significant improvement in clinical state or baseline EEG after administration of AEDs; or (3) sequential rhythmic waves and secondary criteria (1), (2), (3) with or without significant improvement in clinical state or baseline EEG after administration of AEDs. Secondary EEG criteria were the following discharge patterns with a duration of [10 s: (1) incrementing onset with increase in voltage and/or increase or slowing of frequency; (2) decrementing offset with decrease in voltage or frequency; (3) postdischarge slowing or voltage attenuation; or (4) significant improvement in clinical state or baseline EEG after administration of AEDs. Patients with EEG showing only bilateral periodic discharges or stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) were excluded. The presence of periodic lateralized epileptiform discharges (PLEDs), an EEG pattern usually observed in patients with acute stroke, was not the reason for exclusion. NCSE was coded into two categories: ‘‘early’’ referred to that occurring within a week after stroke and considered to be provoked by the acute brain insult; ‘‘late’’ that developing after the first week [10]. Video recordings were

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screened to determine clinical correlates for NCSE and episodes of electroencephalographic seizures. Level of consciousness, evaluated before pharmacological treatment and upon EEG initiation, was categorized on clinical grounds as alert/somnolent/stuporous/comatose. Each patient was monitored through video-EEG recording for at least 6 h following SE resolution, and a further conventional EEG recording was made after 24 h. Antiepileptic drug treatment When a true diagnosis of SE was made, pharmacological treatment was promptly started and its effect evaluated through both EEG and clinical monitoring. As a standard therapeutic approach, i.v. administered drugs were: lorazepam (0.1 mg/kg within 1–2 min), diazepam (10 mg, 5 mg/min) or phenytoin (PHT) (18 mg/kg, 5 mg/kg/min). According to the recent literature suggestions [21], levetiracetam (LEV) 25 mg/kg over 15 min or lacosamide (LCM) as initial bolus dose of 400 mg over 30 min was used in patients with concomitant medical conditions in whom the use of traditional AEDs was judged potentially unsafe because of their adverse effects (hypotension, QT prolongation, arrhythmias, respiratory complications). During i.v. treatment, patients were monitored through video-EEG, ECG, heart rate and blood pressure measurements. SE was considered fully controlled only after both clinical and electrographic resolution. Stroke characterization Based on history and the results of diagnostic studies including brain imaging, Doppler sonography, echocardiograms, and electrocardiograms, patients were classified according to stroke syndrome, etiology and severity. Clinical syndrome classification was assessed using the Oxfordshire Community Stroke Project (OCSP) criteria [22]. Stroke etiology was classified using the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria [23]. Stroke severity was assessed at admission using the National Institutes of Health (NIH) stroke scale (NIHSS) score [24]. Neuroimaging data (CT or MRI) were evaluated according to the arterial territory circulation involved (anterior or posterior) and lesion size (large, medium, small, or lacunar). A large lesion was required to have a diameter [3 cm on neuroimages; a small lesion a diameter \1 cm; a lacunar lesion was a CT hypodense area or T2 MRI hyperintense area \1 cm in maximum diameter deeply located in the cerebral hemispheres or in the brainstem. Finally, functional disability was obtained using the modified Rankin scale (mRS) [25] and mortality was assessed during hospitalization.

Statistical analysis Distribution of gender, vascular risk factors, functional disability, OCSP and TOAST criteria were summarized as frequencies and percentages and comparisons were made using the Pearson Chi-square test or Fisher exact test, as appropriate. Age and NIHSS score were indicated as median and interquartile range, and were investigated using the Mann–Whitney U test. Univariate and multivariate logistic regression models were used to evaluate the following potential determinants of NCSE: stroke syndrome, stroke etiology, size of infarction, NIHSS score, age, gender, vascular risk factors. In the analysis, the size of infarction was expressed as a three-level ordinal variable, according to the classification above mentioned. Multivariate models were constructed using all variables resulted significant in the univariate analysis. Measures of association were odds ratios (ORs) with 95 % confidence intervals. Each covariate was tested independently and with the main interaction terms. Finally, the ROC analysis was performed to check the goodness of fit of the implemented logistic regression final model. Statistical significance was chosen at the 5 % level. All statistics were implemented using STATA version 12 (StataCorp, USA).

Results Cohort characteristics A total of 1,362 patients were admitted to our Stroke Unit between January 2010 and September 2013: 1,034 (76 %) have an ischemic stroke; 227 (16.6 %) have an intracerebral hemorrhage (ICH); 101 (7.4 %) have a subarachnoid hemorrhage. Of the 1,034 patients with ischemic stroke, 72 (7 %) were excluded from the analysis because of a hemorrhagic transformation of the ischemic area. Moreover, 73 patients were also excluded from the analysis because of a previous history of seizures, sedative medication prior to PVEEG recording, a history of recurrent stroke or EEG recordings showing only bilateral periodic discharges. The final cohort consisted of 889 patients. The characteristics of the sample are summarized in Table 1. Seizures and status epilepticus Overall 59/889 (6.6 %) patients exhibited epileptic manifestations. Early CSz and CSE occurred in 41/889 (4.6 %) patients: seizures were tonic–clonic in 14, clonic without impairment of consciousness in 13, and clonic with automatisms in 6; focal motor SE occurred in four patients and CSE in the remaining four. Sixteen out of these 41 patients also developed late CSzs (n = 12) or focal motor

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J Neurol Table 1 Demographic and clinical characteristics of the screened population

Variable

NCSE (n = 32)

No NCSE (n = 857)

Overall (n = 889)

66.5 (61.0–78) 16 (50)

65.0 (58.0–77.0) 550 (64.1)

65.0 (58.0–77.0) 566 (63.6)

Demographic data Age (years) Male Stroke severity indicators NIHSS mRS [2

13.0 (9.0–15.0)* 12 (37.5)

3.0 (2.0–7.0)

4.0 (2.0–8.0)

343 (40.0)

355 (39.5)

Large size infarct B1 cm

2 (6.3)*

447 (52.2)

449 (50.5)

[1 cm

9 (28.1)*

284 (33.1)

293 (33.0)

[3 cm

21 (65.7)*

126 (14.7)

147 (16.5)

Vascular risk factors Discrete variables (sex, large size infarct, vascular risk factors, OCSP and TOAST ischemic stroke subtypes) are indicated as number of cases (percentage). Age is indicated as median (interquartile range) and NIHSS score as geometric mean (standard error) mRS Modified Rankin Scale, NCSE non-convulsive status epilepticus, NIHSS NIH Stroke Scale, PACI partial anterior circulation infarct, POCI posterior circulation infarct, TACI total anterior circulation infarct, TIA transient ischemic attack * p \ 0.0001,   p = 0.0001 and à p = 0.001 in comparison to No NCSE patients

Hypertension

16 (50.0)

430 (50.1)

446 (50.1)

Diabetes

9 (28.1)

186 (21.7)

195 (21.7)

Cardiac arrhythmia

5 (15.6)

188 (15.6)

192 (21.4)

Smoking

2 (6.2)

310 (36.2)

312 (35.0)

Hyperlipidemia

8 (25)

276 (32.2)

284 (31.5)

TIA

5 (15.6)

120 (14.0)

125 (13.9)

15 (46.8)à

123 (14.3)

138 (15.5)

11 (34.3)

126 (14.7)

137 (15.4)

385 (41.5)

385 (45.0)

268 (31.2)

274 (30.8)

OCSP classification TACI PACI LACI POCI

6 (18.7)

TOAST classification Large artery atherothrombosis

13 (40.6) 

69 (8.0)

82 (9.2)

Cardioembolic

10 (31.2)

227 (26.5)

237 (26.6)

Lacunar

315 (36.7)

315 (35.4)

Cryptogenetic

7 (21.9)

214 (25.0)

221 (24.8)

Other

2 (6.2)

58 (6.8)

60 (6.8)

SE (n = 4) during the period of hospitalization. Two patients exhibited for the first time tonic–clonic Sz during the third week after stroke. Complex partial seizures, although suspected in eight additional patients on the basis of apparently not oriented motor manifestations and/or level of consciousness oscillations, were not firmly demonstrated through EEG recording. Similarly, electrical seizures not associated to clinical manifestations were not intercepted in our population of patients during hospitalization. In our cohort, NCSE was identified in 32/889 (3.6 %) patients: it occurred early in 20/32 (i.e., 62.5 %) and late in the remaining 12 patients. Early NCSE developed as continuation of a CSE in five patients and during the post-ictal phase of a tonic–clonic seizure in two patients. Late NCSE was diagnosed in 12 patients: during the second week in eight and during the third week in the remaining four. Seven of these 12 patients had already had early tonic–clonic seizures and two early focal motor SE; the remaining three patients developed NCSE without any previously identified epileptic activity. Impairment of

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0

0

consciousness and agitation were the main manifestations in 22/32 (68.8 %) patients and aphasia in the remaining 10 (31.2 %). Noteworthy, NCSE was diagnosed on the basis of a specific clinical suspect in 19 patients (59.4 %) and without any clinical suspect in the remaining 13 patients (40.6 %). In 6 out of these 13 patients, it was intercepted in the first week during PVEEG recording implemented as part of the routine activity, and in the other seven patients during PVEEG made to monitor the time course of a tonic– clonic seizure (1 patient in the first week), a CSE (3 patients in the first week), or made just as a control in 3 patients (1 in the second week and 2 in the third week) who had had previous CSzs. EEG features PVEEG was recorded for a mean duration of 9 h 22 min, range 6 h 15 min–13 h 27 min. PVEEG recording was implemented within the first 3 days in the majority of patients, namely 605, and

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between the forth and the seventh day in the remaining 284 patients. Ictal EEG features showed: (a) high-voltage, theta rhythmic activity with intermingled spikes over the temporo-occipital regions in eight patients; (b) high-voltage theta activity intermingled with sharp waves over frontal regions in seven patients; (c) bilateral, over frontal regions, continuous spike- and slow-wave discharges in six patients. Continuous focal sharp waves with change in amplitude, frequency and spatial distribution were observed in 11 patients. Treatment and epilepsy outcome Initial treatment of NCSE was efficacious in 21 patients in a time ranging from 30 to 60 min after i.v. administration: lorazepam (n = 4), diazepam (n = 9), LCM (n = 5) and PHT (n = 3). Eight patients did not show any response to initial diazepam treatment and were treated with PHT (n = 6) or LEV (n = 2) introduced as second-line treatment. None of these patients relapse. In three patients, NCSE was refractory to diazepam followed by PHT and LCM and a transfer to the intensive care unit was needed. A chronic treatment with AEDs was started in all SE patients. The following drugs were given to patients with NCSE: LEV in 24 patients, oxcarbazepine in six and phenobarbital in the remaining two patients. The present follow-up for 28 of these patients ranges from 2 to 43 months. In the control visits, usually planned every 6–8 weeks, a global neurological evaluation, seizure frequency recordings through ad hoc calendars, therapy adjustments and standard EEG execution have been performed. Of these patients, 25 developed post-stroke epilepsy with seizure frequency of 3–8 fits per month (18 patients) and \1 per month (7 patients). Three patients are seizure free (present follow-up 5, 13 and 16 months). Detailed data concerning long-term outcome of both epilepsy and stroke in our population will be object of a forthcoming article. No information has been obtained on the remaining four patients after discharge from hospital and until the preparation of the present manuscript. Stroke features and outcome Of the 32 patients with NCSE, a total anterior circulation infarct (TACI) was diagnosed in 15, a partial anterior circulation infarct (PACI) in 11 and a posterior circulation infarct (POCI) in 6 patients. Three patients with early NCSE received intravenous recombinant tissue plasminogen activator (t-PA). None of the patients developing NCSE died during the period of hospitalization, and all were discharged to rehabilitation or to home within 14–30 days after stroke onset. No differences in outcome

Table 2 Independent predictors of NCSE in patients with ischemic stroke SE

z

p

OR

95 % CI

TACI

0.24

-1.46

0.1

0.34

0.12

1.03

Large artery atherothrombosis

1.57

3.07

0.002

3.7

1.60

6.49

Infarct size NIHSS score

1.56 0.05

2.92 2.72

0.003 0.007

3.6 1.14

1.52 1.04

8.44 1.24

Variables not in equations: gender, age, hypertension, diabetes mellitus, cardiac arrhythmia, smoking, hyperlipidemia, TIA, PACI, POCI, other TOAST classification aetiologies CI confidence interval, OR odds ratio, SE standard error, NIHSS NIH Stroke Scale

of stroke between NCSE patients and the other patients were detected through the NIHH score and other functional assessment scales used (Barthel index, modified Rankin Scale). As above mentioned, detailed data on the long-term outcome of our population will be illustrated in a forthcoming study. Statistical significance Univariate analysis showed significant differences between patients with NCSE and those without NCSE with regard to etiology, clinical presentation and size of ischemic area (Table 1). Regarding stroke etiology, large artery atherothrombosis showed a different distribution between NCSE and non-NCSE groups (Table 1). In the multiple logistic regression models, we considered as predictors of the NCSE those variables resulting significant from the univariate analysis (Table 1). A significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology (Table 2). No significant differences between the expected and the observed regression matrix were observed (area under ROC curve = 0.87).

Discussion The results of the present study indicate that NCSE is not a rare event after an acute ischemic stroke and occurs in a percentage of 3–4 % of patients. In our cohort, significant predictors of NCSE were a large size infarct, large artery atherothrombosis and NIHSS score at admission. With regard to infarct area, it has been proposed that the ischemic penumbra of a stroke can contain electrically irritable tissue that provides a focus for seizure activity [26]. Enhanced release of glutamate, ionic imbalances associated to breakdown of membrane phospholipids, release of free fatty acids, reduced GABAergic function

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with functional and structural impairment of GABAergic interneurons have been described to occur in the ischemic area after an acute insult [27, 28]. Cortical location and large size infarct have been constantly found to be associated with post-stroke seizures [2, 9, 11], a finding that has emerged also from the present study. On the basis of the cascade of synaptic and intracellular events shared by seizure and vascular brain injuries, it can be hypothesized that post-stroke NCSE could be triggered by acute cellular biochemical disturbances occurring with acute ischemic stroke. In the present study, large artery atherothrombosis was another significant predictor of NCSE. Large artery atherothrombosis is more common in cortical than lacunar infarcts, implying that an embolic etiology would be more common in TACIs and PACIs than in LACIs [29]. Notably, in our NCSE group, TACI was diagnosed in 15/32 (46.8 %) and PACI in 11/32 (34.3 %) patients while lacunar infarct was completely absent. These observations reinforce the crucial role of cortical involvement in seizure genesis. A clinically relevant aspect is the possible impact of NCSE on outcome of patients with ischemic stroke. Previous studies have shown that NCSE is a risk factor for the development of refractory SE, poor outcome, and increased mortality independently of the underlying pathology [16, 30]. In one of these studies, for example, the mortality rate in an intensive care unit was high: more than half of the patients with NCSE, 13/23 (57 %) died [16]. Specific data on NCSE after an ischemic stroke are difficult to be extrapolated from published studies because of a number of reasons, including no reported distinction between CSE and NCSE in the analysis, combination of both patients with ischemic stroke and ICH, focus mainly on EEG activity, generic report on patients with acute insults as seen in medical intensive care units [8, 16–18, 20, 31]. In our cohort, cases of death were not observed during hospitalization and until the present follow-up. Additionally, NCSE patients did not show, as compared to patients without NCSE, differences concerning outcome and complications until the present follow-up. The NIHSS score was a significant predictor of NCSE. Interpretation of NIHSS score is difficult since the impairment of consciousness, which is a hallmark of NCSE, could have increased itself NIHSS score at admission. In fact, early NCSE occurred in 62.5 % of our 32 NCSE patients, this value being in agreement with that reported in critically ill patients, in whom seizures activity was observed in the first 24 h after the insult in a large majority of patients (88 %) [20]. Additionally, as above mentioned, SE has been seen to be a possible presenting clinical feature of an acute stroke [1–3]. On this basis, it can be hypothesized that a percentage of our patients might have at admittance a

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condition of NCSE which has not been detected. In patients with ischemic stroke, values concerning the incidence of SE range between 1 and 10 % [20] and NCSE has been reported to occur in 30 % of patients developing post-stroke SE [13]. In our cohort, 5 out of 20 patients developed early NCSE as continuation of CSE and in two patients it occurred in the post-ictal phase of a tonic–clonic seizure. These values are very close to those reported in other studies [17, 32] and emphasize the importance to have the possibility in a stroke unit to implement a VEEG recording longer than a conventional one, which lasts about 20–30 min on average. In a population of 110 patients, the first seizures were detected in slightly more than half of the cases within the first hour of recording [33]. The second relevant finding deriving from the present study, concerning EEG, is that the diagnosis of NCSE has been made during a routine EEG recording and without any clinical suspect or any previous epileptic manifestation in a considerable proportion of patients. This result, in line with a large body of literature observations [18, 31, 32], provides further support in favor of the view that the incidence of NCSE after an ischemic stroke is underappreciated and that this pathology is more frequent than thought in the past. As above mentioned, in fact, NCSE is a clinical entity which goes easily unnoticed especially in elderly patients and in patients with acute brain disorders in whom impairment of consciousness is frequent as a consequence of various pathologies [32–36]. In particular, in patients with an acute ischemic stroke diagnosis of NCSE might be made difficult because of various factors: (1) NCSE occurs more frequently in the first days after stroke onset when impairment of consciousness is a common expression of stroke itself, (2) NCSE can occur just after CSz/CSE and might be easily interpreted as a post-ictal state, (3) manifestations of NCSE can be so subtle as no to raise the suspect of an epileptic activity. Our study has different limitations: (1) the single-institution approach makes the study vulnerable to bias; (2) the relatively small sample size of NCSE group does not necessarily represent all the characteristics of patients suffering from acute stroke and developing NCSE; (3) cases of NCSE before and after PVEEG implementation could have been easily missed. The latter limit, in particular, has been also emphasized by various authors [36, 37].

Conclusions This population-based study shows that implementation of a PVEGG should be permanently available in a stroke unit. In this setting, a conventional EEG recording is of limited diagnostic value because of the intermittent nature of subtle, difficult-to-detect seizures and PVEEG

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recording increases the possibility to diagnose NCSE. An increased awareness that NCSE is a possible, not rare event after an ischemic stroke and that it can most frequently occur with subtle signs can contribute to speed a diagnosis of NCSE. A quick diagnosis of this condition is crucial to implement a prompt treatment and hence to avoid possible clinical complications in patients with ischemic stroke [33, 37]. Acknowledgments We would like to acknowledge the contribution of Neurology EEG technologists of S. Anna Hospital in connecting these patients to the PVEEG at all odd hours. Conflicts of interest

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