Early seizures after ischemic stroke: focus on thrombolysis

CNS Spectrums ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Gergely Feher ◽  
Zsuzsanna Gurdan ◽  
Katalin Gombos ◽  
Katalin Koltai ◽  
Gabriella Pusch ◽  
...  

Introduction.Stroke is a significant underlying cause of epilepsy. Seizures due to ischemic stroke (IS) are generally categorized into early seizures (ESs) and late seizures (LSs). Seizures in thrombolysis situations may raise the possibility of other etiology than IS.Aim.We overtook a systematic review focusing on the pathogenesis, prevalence, risk factors, detection, management, and clinical outcome of ESs in IS and in stroke/thrombolysis situations. We also collected articles focusing on the association of recombinant tissue-type plasminogen activator (rt-PA) treatment and epileptic seizures.Results.We have identified 37 studies with 36,775 participants. ES rate was 3.8% overall in patients with IS with geographical differences. Cortical involvement, severe stroke, hemorrhagic transformation, age (<65 years), large lesion, and atrial fibrillation were the most important risk factors. Sixty-one percent of ESs were partial and 39% were general. Status epilepticus (SE) occurred in 16.3%. 73.6% had an onset within 24 h and 40% may present at the onset of stroke syndrome. Based on EEG findings seizure-like activity could be detected only in approximately 18% of ES patients. MRI diffusion-weighted imaging and multimodal brain imaging may help in the differentiation of ischemia vs. seizure. There are no specific recommendations with regard to the treatment of ES.Conclusion.ESs are rare complications of acute stroke with substantial burden. A significant proportion can be presented at the onset of stroke requiring an extensive diagnostic workup.

2014 ◽  
Vol 3 (7) ◽  
pp. 204798161454321
Author(s):  
Ratnesh Mehra ◽  
Chiu Yuen To ◽  
Omar Qahwash ◽  
Boyd Richards ◽  
Richard D Fessler

Background Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? Purpose To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. Material and Methods We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Results Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. Conclusion The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS.


2020 ◽  
Vol 11 ◽  
pp. 129 ◽  
Author(s):  
Yu Shimizu ◽  
Katsuhiro Tsuchiya ◽  
Norihiro Fujisawa

Background: Diffuse alveolar hemorrhage (DAH) is a rare and frequently life-threatening complication of a variety of conditions. DAH may result from coagulation disorders, inhaled toxins, or infections. We report a series of patients who developed DAH after receiving a tissue-type plasminogen activator (tPA) for acute cerebral infarction. We aimed to find risk factors of DAH in patients receiving tPA and the effectiveness of activated recombinant factor VII (rFVIIa) treatment for the same. Case Description: A total of 1023 acute ischemic stroke (AIS) patients who received tPA in our department from January 2006 to December 2018 were enrolled in this study. Four of the 1023 patients (0.39%) developed DAH. The modified Rankin scale was used to assess clinical severity. Infarction volume was assessed upon follow-up using DWI (diffusion-weighted imaging). Atherothrombotic brain infarction cases were excluded from the study. The age, sex, occlusion site, area of infarction, emphysema, intracranial hemorrhage, and neurological outcomes were analyzed. Patients who developed DAH were more likely to have a history of emphysema. We administered rFVIIa to three DAH patients with good prognosis. Conclusion: The inclusion/exclusion criteria of tPA were based on the AHA/ASA Guidelines for the early management of patients with AIS.These patients had no evidence of infections, bronchoscopy, autoimmune diseases, HIV, and transplantations. Our study suggests that systemic administration of rFVIIa for DAH is effective. Emphysema may be a risk factor for the development of DAH following tPA. When we use tPA for emphysema patients, we must be careful about DAH enough.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Masato Osaki ◽  
Masatoshi Koga ◽  
Mayumi Fukuda ◽  
Yuya shigehatake ◽  
Kazuyuki Nagatsuka ◽  
...  

Background and purpose: Extraischemic hematoma (EIH) is defined as hemorrhage that appears in regions of the brain without visible ischemic damage. The frequency, clinical features, disease-related factors, and prognosis of patients with EIH after IV recombinant tissue-type plasminogen activator (rt-PA) are not well known. We aimed to elucidate EIH and associated factors after IV rt-PA for acute ischemic stroke. Methods: We studied consecutive stroke patients who received IV rt-PA from 2005 through 2011. EIH was defined as any extra-ischemic hemorrhages identified on the follow-up CT within the initial 36 h after rt-PA. Results: Of the total 266 patients (177 men, 73±13 years old) studied, EIH was identified in 11 (4%, 5 men, 77±7 yo, 1 multiple EIH); 8 patients in the parenchyma (5 subcortex, 1 thalamus, 1 corona radiate, 1 cerebellum), 2 in the intraventricule, 1 in the subdural space, and 1 in the subarachnoidal space. As compared with 47 patients with hemorrhagic transformation (HT) from the index infarct (30 men, 73±10 yo) and 208 with “no hemorrhage” (NH, 142 men, 73±14 yo), Fazekas grade of periventricular hyperintensity (PVH) was higher [median 2 in EIH, 1 in HT, 1 in NH; P<0.001), DWI-ASPECTS was lower [7, 7.5, 9; P<0.001), and reduced eGFR (<60 ml/min/1.73 m2) was more common in patients with EIH (82%, 32%, 38%; P=0.007). On multivariate analysis, higher grade of PVH (OR 5.06, 95%CI 1.92-16.09 per 1 point; P<0.001) and reduced eGFR (OR 6.94, 95%CI 1.40-54.69; P=0.02) were associated with EIH. Percentages of the mRS 5-6 at 3 months were 46% in EIH, 36% in HT, and 16% in NH (P=0.001). EIH was an independent predictor of the mRS 5-6 (OR 4.90, 95%CI 1.11-22.35; P=0.036), along with older age, lower DWI-ASPECTS, higher NIHSS score, and prior antithrombotic use. Of 132 patients undergoing T2*-WI before or within several days after thrombolysis, microbleeds were more common in patients with EIH (86%) than the others (19% in HT, 24% in NH, P<0.001). Conclusions: EIH developed in 4% of the stroke patients after IV rt-PA. Severe PVH and renal dysfunction were associated with the occurrence of EIH. Severe PVH might indicate prevalent existence of microbleeds. EIH was predictive of unfavorable outcome following IV rt-PA.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Robert J Stanton ◽  
Eleni Antzoulatos ◽  
Elisheva R Coleman ◽  
Felipe De Los Rios La Rosa ◽  
Stacie L Demel ◽  
...  

Background: Hemorrhagic transformation (HT) of ischemic stroke can have devastating consequences, leading to longer hospitalizations, increased morbidity and mortality. We sought to identify the rate of HT in stroke patients not treated with tPA within a large, biracial population. Methods: The GCNKSS is a population-based stroke epidemiology study from five counties in the Greater Cincinnati region. During 2015, we captured all hospitalized strokes by screening ICD-9 codes 430-436 and ICD-10 codes I60-I68, and G45-46. Study nurses abstracted all potential cases and physicians adjudicated cases, including classifying the degree of HT. Patients treated with thrombolytics were excluded. Incidence rates per 100,000 and associated 95% confidence intervals (CI) were estimated for HT cases, age and sex adjusted to the 2000 US population. Multiple logistic regression was used to examine risk factors associated with HT. Results: In 2015, there were 2301 ischemic strokes included in the analysis. Of these 104 (4.5%) had HT; 23 (22.1%) symptomatic, 55 (52.9%) asymptomatic and 26 (25%) unknown. Documented reasons for not receiving tPA in these patients were: time (71, 68.3%), anticoagulant use (1, 1.0%), other (18,17.3%) and unknown (14, 13.5%), which were not significantly different compared to those without HT. Only 29/104 (18.3%) had HT classified as PH-1 or PH-2. The age, sex and race-adjusted rate of HT was 9.8 (7.9, 11.6) per 100,000. The table shows rates of potential risk factors and the adjusted odds of developing HT. 90 day all-cause case fatality for patients with HT was significantly higher, 27.9% vs. 15.7%, p<0.0001. Conclusion: We found that 4.5% of non-tPA treated IS patients had HT. These patients had more severe strokes, were more likely to have abnormal coagulation tests or anticoagulant use, and were more likely to die within 90 days. We also report the first population-based incidence rate of HT in non-tPA treated of 9.8/100,000, a rate similar to the incidence of SAH.


Stroke ◽  
2018 ◽  
Vol 49 (9) ◽  
pp. 2163-2172 ◽  
Author(s):  
Isaac García-Yébenes ◽  
Alicia García-Culebras ◽  
Carolina Peña-Martínez ◽  
David Fernández-López ◽  
Jaime Díaz-Guzmán ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yasuhiro Suzuki ◽  
Nobuo Nagai ◽  
Desire Collen ◽  
Roger Lijnen ◽  
Kazuo Umemura

Background: Tissue-type plasminogen activator (t-PA) is approved for treatment of ischemic stroke patients, but it may increase the risk of intracranial bleeding (ICB). Matrix metalloproteinases (MMPs), which can be activated through the plasminogen/plasmin system, may contribute to ICB after ischemic stroke. Objectives: To explore the contribution of plasminogen, MMP-3 and MMP-9 to ICB associated with t-PA treatment after ischemic stroke. Methods: Using a thrombotic middle cerebral artery occlusion (MCA-O) model, ICB was studied in mice with genetic deficiencies of plasminogen (Plg −/ − ), stromelysin-1 (MMP-3 −/ − ) or gelatinase B (MMP-9 −/ − ) and their corresponding wild-type (WT) littermates. t-PA (10 mg/kg) or its equivalent volume of solvent was administered intravenously 4 hours after MCA-O. The induction of MMP-3 and MMP-9 was also studied in C57BL/6 WT mice. Results: In MMP-3 +/+ WT mice given solvent, ICB was 4.3 ± 2.9 mm 3 (mean ± SD), which was significantly increased with tPA treatment to 9.7 ± 4.7 mm 3 (P<0.05), whereas ICB in MMP-3 −/ − mice was not altered by t-PA treatment (5.7 ± 2.7 mm 3 , as compared to 5.1 ± 1.8 mm 3 without tPA; n = 7–9 in each group). ICB induced by t-PA was significantly less in Plg −/ − (5.7 ± 3.9 mm 3 ) than in WT mice (8.8 ± 3.2 mm 3 , p<0.05) but ICB by t-PA in MMP-9 −/ − (8.3 ± 2.3 mm 3 ) was comparable with that in WT (8.3 ± 3.1 mm 3 ; n=8 –12 in each group). Administration of the broad-spectrum MMP inhibitor GM6001 after t-PA treatment reduced ICB significantly in MMP-3 +/+ (from 6.4 ± 1.9 mm 3 to 4.1 ± 1.9 mm 3 , p<0.05) but not in MMP-3 −/ − mice (2.2 ± 0.6 mm 3 without versus 2.9 ± 1.5 mm 3 with GM6001; n=6 – 8 in each group). MMP-3 expression was significantly enhanced at the ischemic hemisphere; with placebo treatment, it was expressed only in neurons, whereas it was upregulated in endothelial cells with t-PA treatment. Although MMP-9 expression was also significantly enhanced at the ischemic brain, the amount and the distribution were comparable in mice with and without t-PA treatment. Conclusions: Our data with gene deficient mice suggest that plasminogen and MMP-3 are relatively more important than MMP-9 for the increased ICB induced by t-PA treatment of ischemic stroke.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hong Chang ◽  
Xiaojuan Wang ◽  
Yuchen Qiao ◽  
Jie Zhao ◽  
Haiqing Song

Background and objective: Rapid administration of intravenous recombinant tissue-type plasminogen activator (rt-PA) is the standard treatment for patients with acute ischemic stroke (AIS). While hemorrhage represents as an important and unpredictable complication of thrombolytic treatment, few studies have specifically assessed the prevalence and predictors of bleeding complications among AIS patients in Asia. We assessed characteristics of hemorrhagic complications after intravenous thrombolysis in Chinese AIS patients. Methods: This single-academic-center study retrospectively evaluated 351 acute ischemic stroke patients who received rt-PA intravenously from April 2011 to April 2016. The occurrence and characteristics of any hemorrhagic complications, as well as their associated risk factors were recorded and summarized. Multivariate logistic regression was conducted to analyze significant predictors of bleeding. Results: 134 (38.1%) patients experienced one hemorrhagic event in one or more locations The top seven common sites were gingiva (49.3%), skin (18.3%), urinary system (10.4%), digestive tract (7.5%), intra-cranial cavity (7.5%), mouth (4.4%) and nasal cavity (2.2%). All the gingival bleeding occurred during 1 to 24 hours after thrombolysis and was the first sign of bleeding. Intracranial hemorrhage (both symptomatic and asymptomatic) occurred in 16 patients, of whom 4 presented first with gingival bleeding. Multivariate analysis showed that high systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were independent risk factors for hemorrhage post thrombolysis (P<0.05). Conclusions: One out of three AIS patients in this study had a bleeding complication. The most common site of initial hemorrhage after intravenous thrombolysis was gingival, which frequently occurred as the initial bleeding site within 24 hours after thrombolysis. Consistent with literature, elevated SBP and higher NIHSS were the two key predictors of bleeding risk.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Nobuyuki Ohara ◽  
Junya Kobayashi ◽  
Toshiaki Goda ◽  
Takeshi Ikegami ◽  
Kotaro Watanabe ◽  
...  

Background: The benefits of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke are time dependent, and national guidelines recommend door-to-needle (DTN) time within 60 minutes. Several strategies have been reported to be associated with reducing DTN times. However, effectiveness of such strategies has not been fully evaluated. Methods: In 2014, we assembled a multidisciplinary team called ‘Acute Stroke Team (AST)’ aiming for improving outcomes of patients with acute ischemic stroke, especially by reducing onset-to-treatment time. A new protocol was implemented to minimize delays: AST staff prenotification, parallel process workflow, and rapid acquisition of laboratory testing and brain imaging. AST reviewed all intravenous tPA cases and discussed the points of improvement. AST also organized both public and in-hospital lectures, and simulation training course. We compared patients received intravenous tPA within 4.5 hours from the symptom onset at our institute in the pre AST (April 2011 - August 2014) and post AST (September 2014 - July 2016) period. Using univariate methods and multivariable logistic regression, we assessed the associated factors with favorable outcomes. Results: In the pre and post AST period, 46 and 36 patients were treated with intravenous tPA, respectively. Compared with pre AST period, the median (interquartile range) DTN times was reduced from 71 (63-95) minutes to 55 (49-71) minutes (p<0.01), and the percentage of patients with DTN times within 60 minutes were improved from 22% to 64% (P<0.001) in the post AST period. By multivariable analysis, shorter DTN times (OR 0.98, 95% CI 0.95-0.99, p=0.025), lower age (OR 0.90, 95% CI 0.85-0.96, p=0.001) and lower NIHSS on admission (OR 0.88, 95% CI 0.82-0.95, p=0.001) were independently associated with independent ambulation at hospital discharge. Conclusions: Multidisciplinary team-based approach reduced DTN times. Reducing DTN times was associated with improving patient outcomes. Future efforts should focus on sustainability and safety of this approach.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Alvaro Garcia-Tornel ◽  
Marta Olive-Gadea ◽  
Marc Ribo ◽  
David Rodriguez-Luna ◽  
Jorge Pagola ◽  
...  

A significant proportion of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) present poor functional outcome despite recanalization. We aim to investigate computed tomography perfusion (CTP) patterns after EVT and their association with outcome Methods: Prospective study of anterior large vessel occlusion AIS patients who achieved complete recanalization (defined as modified Thrombolysis in Cerebral Ischemia (TICI) 2b - 3) after EVT. CTP was performed within 30 minutes post-EVT recanalization (POST-CTP): hypoperfusion was defined as volume of time to maximal arrival of contrast (Tmax) delay ≥6 seconds in the affected territory. Hyperperfusion was defined as visual increase in cerebral blood flow (CBF) and volume (CBV) with advanced Tmax compared with the unaffected hemisphere. Dramatic clinical recovery (DCR) was defined as a decrease of ≥8 points in NIHSS score at 24h or NIHSS≤2 and good functional outcome by mRS ≤2 at 3 months. Results: One-hundred and forty-one patients were included. 49 (34.7%) patients did not have any perfusion abnormality on POST-CTP, 60 (42.5%) showed hypoperfusion (median volume Tmax≥6s 17.5cc, IQR 6-45cc) and 32 (22.8%) hyperperfusion. DCR appeared in 56% of patients and good functional outcome in 55.3%. Post-EVT hypoperfusion was related with worse final TICI, and associated worse early clinical evolution, larger final infarct volume (p<0.01 for all) and was an independent predictor of functional outcome (OR 0.98, CI 0.97-0.99, p=0.01). Furthermore, POST-CTP identified patients with delayed improvement: in patients without DCR (n=62, 44%), there was a significant difference in post-EVT hypoperfusion volume according to functional outcome (hypoperfusion volume of 2cc in good outcome vs 11cc in poor outcome, OR 0.97 CI 0.93-0.99, p=0.04), adjusted by confounding factors. Hyperperfusion was not associated with worse outcome (p=0.45) nor symptomatic hemorrhagic transformation (p=0.55). Conclusion: Hypoperfusion volume after EVT is an accurate predictor of functional outcome. In patients without dramatic clinical recovery, hypoperfusion predicts good functional outcome and defines a “stunned-brain” pattern. POST-CTP may help to select EVT patients for additional therapies.


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