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      Risk Factors for Epilepsy After Thrombolysis for Ischemic Stroke: A Cohort Study

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          Abstract

          The effects of thrombolysis in seizure and epilepsy after acute ischemic stroke have been poorly explored. In this study, we examine risk factors and consequences of intravenous rt-PA for treatment of acute ischemic stroke. In a retrospective cohort study we evaluate risk factors for seizure and epilepsy after stroke thrombolysis, as well as the impact of seizures and epilepsy in outcome of stroke patients. In our cohort, mean age of patients was 67.2 years old ( SD = 13.1) and 79 of them (51.6%) were male and. Initial NIHSS mean score were 10.95 ( SD = 6.25). Three months NIHSS mean score was 2.09 ( SD = 3.55). Eighty seven (56.9%) patients were mRS of 0–1 after thrombolysis. Hemorrhagic transformation was observed in 22 (14.4%) patients. Twenty-one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation (OR = 3.26; 95% CI = 1.08–9.78; p = 0.035) and with mRS ≥ 2 at 3 months after stroke (OR = 3.51; 95% CI = 1.20–10.32; p = 0.022). Hemorrhagic transformation (OR = 3.55; 95% CI = 1.11–11.34; p = 0.033) and mRS ≥ 2 at 3 months (OR = 5.82; 95% CI = 1.45–23.42; p = 0.013) were variables independently associated with post-stroke epilepsy. In our study, independent risks factors for poor outcome in stroke thrombolysis were age (OR = 1.03; 95% CI = 1.01–1.06; p = 0.011), higher NIHSS (OR = 1.08; 95% CI = 1.03–1.14; p = 0.001), hemorrhagic transformation (OR = 2.33; 95% CI = 1.11–4.76; p = 0.024), seizures (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018) and large cortical area (ASPECTS ≤ 7) (OR = 2.04; 95% CI = 1.04–3.84; p = 0.036). Concluding, in this retrospective cohort study, the neurological impairment after thrombolysis (but not before) and hemorrhagic transformation remained independent risk factors for seizures or post-stroke epilepsy after thrombolysis. Moreover, we observed that seizures emerged as an independent risk factor for poor outcome after thrombolysis therapy in stroke patients (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018).

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          Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

          Stephen M Davis, Geoffrey Donnan, Mark W. Parsons … (2008)
          Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.
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            Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

            M Fiorelli, S Lorenzano, S. Bastianello … (1999)
            The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.
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              Prediction of late seizures after ischaemic stroke with a novel prognostic model (the SeLECT score): a multivariable prediction model development and validation study

              Marian Galovic, Nico Döhler, Barbara Erdélyi-Canavese … (2018)
              Article 0 comments Cited 88 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Neurol
                Journal ID (iso-abbrev): Front Neurol
                Journal ID (publisher-id): Front. Neurol.
                Title: Frontiers in Neurology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-2295
                Publication date (Electronic): 23 January 2020
                Publication date Collection: 2019
                Volume: 10
                Electronic Location Identifier: 1256
                Affiliations
                [1] 1Graduate Program in Medicine: Medical Sciences, Universidade Federal Do Rio Grande Do Sul , Porto Alegre, Brazil
                [2] 2Basic Research and Advanced Investigations in Neurology, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul , Porto Alegre, Brazil
                [3] 3Division of Neurology, Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil
                [4] 4CETER–Center for Epilepsy Surgery, Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil
                Author notes

                Edited by: Luiz Eduardo Betting, São Paulo State University, Brazil

                Reviewed by: Lécio Figueira Pinto, University of São Paulo, Brazil; Elaine Keiko Fujisao, Self-employed, Londrina, Brazil

                *Correspondence: Marino Muxfeldt Bianchin mbianchin@ 123456hcpa.edu.br

                This article was submitted to Epilepsy, a section of the journal Frontiers in Neurology

                Article
                DOI: 10.3389/fneur.2019.01256
                PMC ID: 6989601
                PubMed ID: 32038448
                SO-VID: 0afba770-4bf9-40ad-8f9e-8f9d4825ce2d
                Copyright © Copyright © 2020 Brondani, de Almeida, Cherubini, Secchi, de Oliveira, Martins and Bianchin.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 08 February 2019
                Date accepted : 12 November 2019
                Page count
                Figures: 0, Tables: 7, Equations: 0, References: 82, Pages: 10, Words: 8040
                Categories
                Subject: Neurology
                Subject: Original Research

                ScienceOpen disciplines: Neurology
                Keywords: reperfusion therapy,post-stroke epilepsy,acute seizures,stroke outcome,rt-pa
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: reperfusion therapy, post-stroke epilepsy, acute seizures, stroke outcome, rt-pa

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