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Siddiqi AZ, Ignacio K, Kaveeta C, Bala F, Ademola A, Tkach A, Buck BH, Catanese L, Hunter G, Dowlatshahi D, Shamy M, Zafar A, Field TS, Appireddy R, Wadhwa A, Sajobi T, Swartz R, Almekhlafi M, Demchuk A, Menon B, Singh N. Safety and Efficacy of Intravenous Thrombolysis by Infarct Type in Patients with No Visible Occlusion: A Secondary Analysis of the AcT Trial. J Am Heart Assoc 2025; 14:e037577. [PMID: 39704225 PMCID: PMC12054515 DOI: 10.1161/jaha.124.037577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 11/11/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND About 25% of patients with acute ischemic stroke have lacunar infarct on follow-up imaging. In this secondary analysis from the AcT (Alteplase Compared With Tenecteplase) trial, we assessed if there is variation in safety or efficacy of intravenous thrombolysis by infarct type in patients with no visible occlusion. We also determined if this effect differed between tenecteplase and alteplase. METHODS AND RESULTS This is a secondary analysis from the AcT trial. Lacunar infarct was defined as single, ≤15 mm, and in regions supplied by perforating arterioles on 24-hour imaging. Outcomes included symptomatic intracerebral hemorrhage at 24 hours, any hemorrhage on imaging, and 90-day modified Rankin Scale score. Mixed-effects regression models adjusted for age, sex, stroke severity, thrombolytic type, and onset-to-needle time were used. Of 1577 patients, 456/29.9% had no visible occlusion and interpretable follow-up imaging (magnetic resonance imaging: 41.2%). Of these 93 (20.4%) (magnetic resonance imaging: 62.3%) had lacunar infarct, 171 (37.5%) (magnetic resonance imaging: 67.4%) had nonlacunar infarct, and 192 (42.1%) (magnetic resonance imaging: 7.3%) had no visible infarct. Four patients (2.3%) in the group with nonlacunar infarct and none in the groups with lacunar infarct and no visible infarct developed symptomatic intracerebral hemorrhage. Any intracranial hemorrhage was highest (21; 12.4%) in the group with nonlacunar infarct. There was no significant interaction between thrombolytic type and treatment outcomes. CONCLUSIONS In the AcT trial, safety of intravenous thrombolysis was similar across all infarct types in patients with no visible occlusion but functional outcomes were worst in patients with nonlacunar infarct. Safety and functional outcomes after intravenous thrombolysis were better in the groups with lacunar infarct and no visible infarct as compared with the overall trial population.
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Affiliation(s)
- A. Zohaib Siddiqi
- Division of Neurology, Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada
| | - Katrina Ignacio
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryABCanada
| | - Chitapa Kaveeta
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryABCanada
- Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
| | - Fouzi Bala
- Department of RadiologyTours University HospitalToursFrance
| | - Ayoola Ademola
- Department of Community Health Sciences and O’Brien Institute for Public HealthUniversity of CalgaryABCanada
| | | | - Brian H. Buck
- Division of Neurology, Department of MedicineUniversity of AlbertaEdmontonABCanada
| | - Luciana Catanese
- Hamilton Health Sciences and McMaster UniversityHamiltonONCanada
| | | | - Dar Dowlatshahi
- Department of Medicine (Neurology)Ottawa Hospital Research Institute and University of OttawaONCanada
| | - Michel Shamy
- Department of Medicine (Neurology)Ottawa Hospital Research Institute and University of OttawaONCanada
| | | | - Thalia S. Field
- Vancouver Stroke Program and the Division of NeurologyUniversity of British ColumbiaVancouverBCCanada
| | - Ramana Appireddy
- Division of Neurology, Department of MedicineQueen’s UniversityKingstonONCanada
| | - Ankur Wadhwa
- Division of Neurology, Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada
| | - Tolulope Sajobi
- Department of Community Health Sciences and O’Brien Institute for Public HealthUniversity of CalgaryABCanada
| | - Rick Swartz
- Department of Medicine (Division of Neurology), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences CentreUniversity of TorontoONCanada
| | - Mohammed Almekhlafi
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryABCanada
- Department of Community Health Sciences and O’Brien Institute for Public HealthUniversity of CalgaryABCanada
- Department of RadiologyUniversity of CalgaryABCanada
| | - Andrew Demchuk
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryABCanada
- Hotchkiss Brain InstituteCalgaryCanada
| | - Bijoy Menon
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryABCanada
- Department of Community Health Sciences and O’Brien Institute for Public HealthUniversity of CalgaryABCanada
- Department of RadiologyUniversity of CalgaryABCanada
- Hotchkiss Brain InstituteCalgaryCanada
| | - Nishita Singh
- Division of Neurology, Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada
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Kobayashi Y, Kondo Y, Yamamoto K, Hirayama S, Kuasano Y, Tazawa KI, Shimizu Y, Sato A, Sekijima Y. Tissue plasminogen activator for acute branch atheromatous disease exhibits transient improvement and worsening. J Neurol Sci 2024; 465:123201. [PMID: 39217764 DOI: 10.1016/j.jns.2024.123201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/17/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke. Although initial improvement is observed when administered for branch atheromatous disease (BAD), some cases subsequently worsen. Clinical data on the characteristics of these patients is lacking, and the benefits of tPA are unclear. OBJECTIVE To analyze rebound cases and elucidate the clinical characteristics and outcomes associated with tPA administration in BAD. METHODS This multicenter retrospective study was conducted in Japan. Worsening after initial improvement of a condition is termed as rebound, and such cases were compared with other types of ischemic stroke in patients with and without rebound. The characteristics of patients with BAD who rebounded were examined. RESULTS The study included 93 patients. Among the patients who were administered tPA, the NIHSS scores at 24 h and 7 days post-tPA were significantly higher in patients with BAD than in patients with other types of infarcts. The group with BAD exhibited a significantly higher rate of rebound than other groups (37.5 % vs. 0 %, P < 0.001). However, no differences were observed in outcomes between patients who experienced rebound after tPA administration and those who did not. CONCLUSIONS Reevaluation and changing the strategy of tPA use in patients with BAD may be necessary. However, this study does not totally discourage its use, as specific patients can benefit.
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Affiliation(s)
- Yuya Kobayashi
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano 396-8555, Japan; Department of Neurology, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan.
| | - Yasufumi Kondo
- Department of Neurology, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan
| | - Kanji Yamamoto
- Department of Neurology, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan
| | - Shuichi Hirayama
- Department of Neurosurgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan
| | - Yoshikazu Kuasano
- Department of Neurosurgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan
| | - Ko-Ichi Tazawa
- Department of Neurology, Nagano Red Cross Hospital, 5-22-1, Wakasato, Nagano 380-8582, Japan
| | - Yusaku Shimizu
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano 396-8555, Japan
| | - Atsushi Sato
- Department of Neurosurgery, Ina Central Hospital, 1313-1, Ina, Nagano 396-8555, Japan
| | - Yoshiki Sekijima
- Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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Shen Y, Li F, Cao L, Wang Y, Xiao J, Zhou X, Tian T. Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study. Genes (Basel) 2022; 13:genes13091584. [PMID: 36140752 PMCID: PMC9498627 DOI: 10.3390/genes13091584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/26/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022] Open
Abstract
Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; p = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
| | - Fuju Li
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
| | - Lina Cao
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
| | - Yunyun Wang
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
| | - Jing Xiao
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
| | - Xiaoyi Zhou
- Center for Disease Control and Prevention of Nantong, Nantong 226007, China
- Correspondence: (X.Z.); (T.T.); Tel.: +86-1891-439-6755 (X.Z.); +86-1599-655-5458 (T.T.)
| | - Tian Tian
- Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China
- Correspondence: (X.Z.); (T.T.); Tel.: +86-1891-439-6755 (X.Z.); +86-1599-655-5458 (T.T.)
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Marcelinus K, Liu H, Zhang K, Zong C, Yang H, Song B, Gao Y, Xu Y. Efficacy and Safety of Alteplase on Treatment of Acute Single Small Subcortical Infarction. Curr Neurovasc Res 2022; 19:255-266. [PMID: 36043775 DOI: 10.2174/1567202619666220829111211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/22/2022] [Accepted: 07/28/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Single Small Subcortical Infarction (SSSI) is an isolated small infarction in the territory of perforating artery with a maximum diameter of 20 mm in axial Diffusion-Weighted Imaging (DWI). About 20 to 30% of SSSI patients were reported to have Early Neurological Deterioration (END) in the acute phase, which brought adverse effects on long-term outcomes. The effect of the alteplase on the outcome of SSSI, especially END and long-term outcomes, was ambiguous. OBJECTIVE The study aims to find out the efficacy and safety of intravenous recombinant tissue Plasminogen Activator (rt-PA) on long-term and short- outcomes of patients with SSSI as compared to patients who received standard medical care. METHODS The patients were retrospectively screened from a stroke registry of the neurology department of 1st Affiliated Hospital of Zhengzhou University from January 2013 to December 2020. Based on treatment modality, patients were dichotomized into alteplase and standard medical care groups. To minimize confounding factors in subgroups, a propensity score matching analysis was done. The primary outcome was the favorable functional outcome 3 months after stroke onset, defined by attaining a score of ≤2 points on the modified Rankin scale (mRS), secondary outcome was the prevention of occurrence of END, defined as an increase of ≥2 points in the total score or ≥1point on motor subunit in the National Institutes of Health Stroke Scale (NIHSS) score within 72 hours after admission, safety features were symptomatic intracranial hemorrhage (sICH) or death. Multivariate analysis was employed to find the efficacy and safety of alteplase in the treatment of SSSI. RESULTS A total of 717 patients with anterior circulation SSSI were selected, and 132 were included in the final analysis. Forty-five patients were treated with alteplase within 4.5 hours and 87 with standard medical care, and 44 pairs were successfully matched by propensity score. Pre-match data showed that the alteplase thrombolysis group showed a higher proportion of favorable outcomes at 3-month follow-up [OR=0.315, 95%CI:0.106, 0.931, P = 0.037] but did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.033, 95%CI:0.417,2.554, P = 0.943]. Post-match data showed that the alteplase group also showed a higher proportion of favorable outcomes at 3-month follow-up [OR = 0.247, 95%CI: 0.074, 0.830, P = 0.024]; however, it did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.241, 95%CI: 0.433,3.554, P = 0.688]. There was one case of asymptomatic ICH in alteplase treated patients. CONCLUSION Patients with SSSI in the anterior circulation are more likely to achieve 3 months favorable outcomes than those who were treated with standard medical care; however, treatment with alteplase may not prevent the occurrence of END.
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Affiliation(s)
- Kilanga Marcelinus
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Hongbing Liu
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Ke Zhang
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Ce Zong
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Hongxun Yang
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Bo Song
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yuan Gao
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.,National Health Council Key Laboratory of Prevention and Treatment of Cerebrovascular Disease.,Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, China
| | - Yuming Xu
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.,National Health Council Key Laboratory of Prevention and Treatment of Cerebrovascular Disease.,Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou University, Zhengzhou, China
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Vynckier J, Maamari B, Grunder L, Goeldlin MB, Meinel TR, Kaesmacher J, Hakim A, Arnold M, Gralla J, Seiffge DJ, Fischer U. Early Neurologic Deterioration in Lacunar Stroke: Clinical and Imaging Predictors and Association With Long-term Outcome. Neurology 2021; 97:e1437-e1446. [PMID: 34400585 DOI: 10.1212/wnl.0000000000012661] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 07/06/2021] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND AND OBJECTIVES To determine the rate and predictors of early neurologic deterioration (END) in patients with lacunar strokes and its implications for management and outcome. METHODS We enrolled consecutive patients with MRI-defined lacunar stroke who presented within 12 hours after symptom onset from a prospective stroke database (2015-2019). END was defined as any persisting increase in NIH Stroke Scale (NIHSS) score of ≥2 points within 24 hours after admission and favorable outcome as modified Rankin Scale (mRS) score of 0 to 2 at 90 days. We assessed the association of END with clinical and imaging variables, acute treatment, and outcome using multivariable regression, calculating adjusted odds ratios (aORs). RESULTS Sixty-one of 365 (16.7%) patients with acute lacunar stroke (median age 71.8 years, 39.5% female, median NIHSS score on admission 3) had END. Lower NIHSS score on admission (per point, aOR 0.81, p = 0.006), capsular warning syndrome (aOR 7.00, p < 0.001), ventral pontine infarct (aOR 3.49, p = 0.008), and hypoperfusion lesion on imaging (aOR 2.13, p = 0.026) were associated with END. Acute dual antiplatelet therapy was associated with reduced risk of END (aOR 0.10, p = 0.04). Patients with END had less favorable outcome at 90 days (aOR 0.13 p < 0.001), but IV thrombolysis (IVT) was associated with favorable outcome at 90 days (aOR 3.95, p = 0.002). DISCUSSION One in 6 patients with lacunar stroke has END, and patients at high risk of END can be identified with radiologic and clinical variables. Targeted therapeutic trials for this population seem justified. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that early neurologic deterioration in patients with acute lacunar stroke predicts poorer functional outcome at 90 days as determined by the mRS.
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Affiliation(s)
- Jan Vynckier
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland.
| | - Basel Maamari
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Lorenz Grunder
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Martina Béatrice Goeldlin
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Thomas Raphael Meinel
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Johannes Kaesmacher
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Arsany Hakim
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Marcel Arnold
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Jan Gralla
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - David Julian Seiffge
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
| | - Urs Fischer
- From the Department of Neurology (J.V., B.M., L.G., M.B.G., T.R.M., J.K., M.A., J.G., D.J.S., U.F.), Institute of Diagnostic and Interventional Neuroradiology (L.G., J.K., A.H., J.G.), and Institute of Diagnostic Interventional and Pediatric Radiology (L.G., J.K., J.G.), Inselspital, Bern University Hospital and University of Bern, Switzerland
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Karaszewski B, Wyszomirski A, Jabłoński B, Werring DJ, Tomaka D. Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis. Transl Stroke Res 2021; 12:406-415. [PMID: 33641037 PMCID: PMC8055574 DOI: 10.1007/s12975-021-00890-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 12/14/2020] [Accepted: 01/11/2021] [Indexed: 12/26/2022]
Abstract
Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29-1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31-2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.
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Affiliation(s)
- Bartosz Karaszewski
- Department of Adult Neurology, Division of Neurology, Faculty of Medicine, Medical University of Gdansk, Poland, Gdansk, Poland.
- Department of Adult Neurology, University Clinical Center in Gdansk, Poland, Debinki 7, 80-211, Gdansk, Poland.
- Main Expert in Stroke Medicine for the Polish Ministry of Health, Warsaw, Poland.
| | - Adam Wyszomirski
- Department of Adult Neurology, Division of Neurology, Faculty of Medicine, Medical University of Gdansk, Poland, Gdansk, Poland
| | - Bartosz Jabłoński
- Department of Adult Neurology, Division of Neurology, Faculty of Medicine, Medical University of Gdansk, Poland, Gdansk, Poland
- Department of Adult Neurology, University Clinical Center in Gdansk, Poland, Debinki 7, 80-211, Gdansk, Poland
| | - David J Werring
- Stroke Research Centre, University College London, Queen Square Institute of Neurology, London, UK
| | - Dominika Tomaka
- Department of Adult Neurology, University Clinical Center in Gdansk, Poland, Debinki 7, 80-211, Gdansk, Poland
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Zhong X, Yan X, Liang H, Xia R, Chen B, Zhao HJ. Evaluation of eight-style Tai chi on cognitive function in patients with cognitive impairment of cerebral small vessel disease: study protocol for a randomised controlled trial. BMJ Open 2021; 11:e042177. [PMID: 33558352 PMCID: PMC7871699 DOI: 10.1136/bmjopen-2020-042177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Cerebral small vessel disease (CSVD) is a critical factor that causes cognitive decline and progresses to vascular dementia and acute cerebrovascular events. Tai chi has been proven to improve nerve plasticity formation and directly improve cognitive function compared with other sports therapy, which has shown its unique advantages. However, more medical evidence needs to be collected in order to verify that Tai chi exercises can improve cognitive impairment due to CSVD. The main purposes of this study are to investigate the effect of Tai chi exercise on neuropsychological outcomes of patients with cognitive impairment related to CSVD and to explore its mechanism of action with neuroimaging, including functional MRI (fMRI) and event-related potential (P300). METHODS AND ANALYSIS The design of this study is a randomised controlled trial with two parallel groups in a 1:1 allocation ratio with allocation concealment and assessor blinding. A total of 106 participants will be enrolled and randomised to the 24-week Tai chi exercise intervention group and 24-week health education control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 12 and 24 weeks after randomisation. At the same time, fMRI and P300 will be measured the structure and function of brain regions related to cognitive function at baseline and 24 weeks after randomisation. Recruitment is currently ongoing (recruitment began on 9 November 2020). The approximate completion date for recruitment is in April 2021, and we anticipate to complete the study by December 2021. ETHICS AND DISSEMINATION Ethics approval was given by the Medical Ethics Committee of the Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine (approval number: 2019-058-04). The findings will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION NUMBER ChiCTR2000033176; Pre-results.
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Affiliation(s)
- Xiaoyong Zhong
- Department of Neurology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Xinghui Yan
- Department of Physical Education, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Hui Liang
- Department of Neurology, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Rui Xia
- College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Bin Chen
- Department of Rehabilitation, The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Hong-Jia Zhao
- The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
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8
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Barow E, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Ford I, Galinovic I, Nickel A, Puig J, Roy P, Wouters A, Magnus T, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G. Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial. JAMA Neurol 2020; 76:641-649. [PMID: 30907934 DOI: 10.1001/jamaneurol.2019.0351] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.
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Affiliation(s)
- Ewgenia Barow
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Florent Boutitie
- Hospices Civils de Lyon, Service de Biostatistique, Lyon, France.,Université Lyon 1, Villeurbanne, France.,Centre National de la Recherche Scientifique, Unité de Mixte de Recherche 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Bastian Cheng
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tae-Hee Cho
- Department of Stroke Medicine, Université Claude Bernard Lyon 1, CREATIS Centre National de la Recherche Scientifique Unité de Mixte de Recherche 5220, Institut National de la Santé et de la Recherche Médicale U1206, Institut National des Sciences Appliquées-Lyon, Lyon, France.,Hospices Civils de Lyon, Lyon, France
| | - Martin Ebinger
- Centrum für Schlaganfallforschung Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.,Neurologie der Rehaklinik Medical Park Humboldtmühle, Berlin, Germany
| | - Matthias Endres
- Centrum für Schlaganfallforschung Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.,Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Jochen B Fiebach
- Centrum für Schlaganfallforschung Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Jens Fiehler
- Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ian Ford
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom
| | - Ivana Galinovic
- Centrum für Schlaganfallforschung Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Alina Nickel
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Josep Puig
- Department of Radiology, Institut de Diagnostic per la Image, Hospital Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona, Salt, Girona, Spain
| | - Pascal Roy
- Hospices Civils de Lyon, Service de Biostatistique, Lyon, France
| | - Anke Wouters
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium.,Department of Neurosciences, Experimental Neurology, Katholieke Universiteit Leuven, Leuven, Belgium.,Vlaams Instituut voor Biotechnologie, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium
| | - Tim Magnus
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Vincent Thijs
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.,Department of Neurology, Austin Health, Heidelberg, Victoria, Australia
| | - Robin Lemmens
- Department of Neurology, University Hospitals Leuven, Leuven, Belgium.,Department of Neurosciences, Experimental Neurology, Katholieke Universiteit Leuven, Leuven, Belgium.,Vlaams Instituut voor Biotechnologie, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium
| | - Keith W Muir
- Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, United Kingdom
| | - Norbert Nighoghossian
- Department of Stroke Medicine, Université Claude Bernard Lyon 1, CREATIS Centre National de la Recherche Scientifique Unité de Mixte de Recherche 5220, Institut National de la Santé et de la Recherche Médicale U1206, Institut National des Sciences Appliquées-Lyon, Lyon, France.,Hospices Civils de Lyon, Lyon, France
| | - Salvador Pedraza
- Department of Radiology, Institut de Diagnostic per la Image, Hospital Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona, Salt, Girona, Spain
| | - Claus Z Simonsen
- Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - Christian Gerloff
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Götz Thomalla
- Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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9
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Das AS, Regenhardt RW, Feske SK, Gurol ME. Treatment Approaches to Lacunar Stroke. J Stroke Cerebrovasc Dis 2019; 28:2055-2078. [PMID: 31151838 PMCID: PMC7456600 DOI: 10.1016/j.jstrokecerebrovasdis.2019.05.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 04/15/2019] [Accepted: 05/02/2019] [Indexed: 12/12/2022] Open
Abstract
Lacunar strokes are appropriately named for their ability to cavitate and form ponds or "little lakes" (Latin: lacune -ae meaning pond or pit is a diminutive form of lacus meaning lake). They account for a substantial proportion of both symptomatic and asymptomatic ischemic strokes. In recent years, there have been several advances in the management of large vessel occlusions. New therapies such as non-vitamin K antagonist oral anticoagulants and left atrial appendage closure have recently been developed to improve stroke prevention in atrial fibrillation; however, the treatment of small vessel disease-related strokes lags frustratingly behind. Since Fisher characterized the lacunar syndromes and associated infarcts in the late 1960s, there have been no therapies specifically targeting lacunar stroke. Unfortunately, many therapeutic agents used for the treatment of ischemic stroke in general offer only a modest benefit in reducing recurrent stroke while adding to the risk of intracerebral hemorrhage and systemic bleeding. Escalation of antithrombotic treatments beyond standard single antiplatelet agents has not been effective in long-term lacunar stroke prevention efforts, unequivocally increasing intracerebral hemorrhage risk without providing a significant benefit. In this review, we critically review the available treatments for lacunar stroke based on evidence from clinical trials. For several of the major drugs, we summarize the adverse effects in the context of this unique patient population. We also discuss the role of neuroprotective therapies and neural repair strategies as they may relate to recovery from lacunar stroke.
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Affiliation(s)
- Alvin S Das
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Robert W Regenhardt
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Steven K Feske
- Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Mahmut Edip Gurol
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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10
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Paek YM, Lee JS, Park HK, Cho YJ, Bae HJ, Kim BJ, Park JM, Lee SJ, Cha JK, Park TH, Lee KB, Lee J, Lee BC, Kim JT, Kim DE, Shin DI, Kim WJ, Sohn SI, Choi JC, Hong KS. Intravenous thrombolysis with tissue-plasminogen activator in small vessel occlusion. J Clin Neurosci 2019; 64:134-140. [PMID: 30952555 DOI: 10.1016/j.jocn.2019.03.036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 02/12/2019] [Accepted: 03/21/2019] [Indexed: 10/27/2022]
Abstract
Intravenous tissue-plasminogen activator (IV-TPA) treatment in acute ischemic stroke (AIS) patients due to small vessel occlusion (SVO) has been debated because of its small expected benefit and symptomatic intracranial hemorrhage (SICH) risk. Furthermore, data on subgroups of SVO patients are limited. From a prospective multicenter stroke registry database, AIS patients due to SVO within 24 h from onset were selected. Efficacy outcomes were 3-month modified Rankin Scale (mRS) score 0-1 proportion and mRS score distribution. Additionally, subgroup analyses were conducted by age, sex, initial National Institute Health Stroke Scale (NIHSS) score, and presenting limb paresis. This study included 2482 patients: 193 in the IV-TPA group and 2289 in the control group. After adjusting covariates, IV-TPA treatment was associated with an increased mRS 0-1 outcome (adjusted OR [95% CI], 1.56 [1.06-2.29]; P = 0.0249), but was not significantly associated with a favorable mRS shift (1.33 [0.98-1.81]; P = 0.0709). SICH and 3-month death occurred in three (1.6%) and none in the IV-TPA group versus one (0.04%) and 16 (0.7%) in the control group. In subgroup analyses, the IV-TPA effect appeared significantly greater in patients aged ≥80 versus <80 for mRS score distribution (Pinteraction = 0.012). This study showed that, in SVO patients, IV-TPA within 4.5 h may improve functional outcome with a low SICH risk. The benefit appeared more substantial in patients aged ≥80.
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Affiliation(s)
- Young Min Paek
- Department of Neurology, Ilsan Paik Hospital Inje University, Goyang, Republic of Korea
| | - Ji Sung Lee
- Clinical Research Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hong-Kyun Park
- Department of Neurology, Ilsan Paik Hospital Inje University, Goyang, Republic of Korea
| | - Yong-Jin Cho
- Department of Neurology, Ilsan Paik Hospital Inje University, Goyang, Republic of Korea.
| | - Hee-Joon Bae
- Department of Neurology, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea
| | - Beom Joon Kim
- Department of Neurology, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea
| | - Jong-Moo Park
- Department of Neurology, Eulji General Hospital, Seoul, Republic of Korea
| | - Soo Joo Lee
- Department of Neurology, Eulji University Hospital, Daejeon, Republic of Korea
| | - Jae-Kwan Cha
- Department of Neurology, Dong-A University Hospital, Busan, Republic of Korea
| | - Tai Hwan Park
- Department of Neurology, Seoul Medical Center, Seoul, Republic of Korea
| | - Kyung Bok Lee
- Department of Neurology, Soonchunhyang University Hospital Seoul, Seoul, Republic of Korea.
| | - Jun Lee
- Department of Neurology, Yeungnam University Medical Center, Daegu, Republic of Korea
| | - Byung-Chul Lee
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
| | - Joon-Tae Kim
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea.
| | - Dong-Eog Kim
- Department of Neurology, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| | - Dong-Ick Shin
- Department of Neurology, Chungbuk National University Hospital, Cheongju, Republic of Korea.
| | - Wook-Joo Kim
- Department of Neurology, Ulsan University College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Sung-Il Sohn
- Department of Neurology, Dongsan Medical Center Keimyung University, Daegu, Republic of Korea.
| | - Jay Chol Choi
- Department of Neurology, Jeju National University, Jeju, Republic of Korea.
| | - Keun-Sik Hong
- Department of Neurology, Ilsan Paik Hospital Inje University, Goyang, Republic of Korea.
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11
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Matusevicius M, Paciaroni M, Caso V, Bottai M, Khurana D, de Bastos M, Martins SC, Krespi Y, Cooray C, Toni D, Ahmed N. Outcome after intravenous thrombolysis in patients with acute lacunar stroke: An observational study based on SITS international registry and a meta-analysis. Int J Stroke 2019; 14:878-886. [PMID: 30935349 DOI: 10.1177/1747493019840947] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Intravenous thrombolysis (IVT) for lacunar stroke (LS) is debated, as the underlying pathophysiological mechanism may not be thrombogenic. AIMS To investigate outcomes after IVT in LS in the SITS International Stroke Thrombolysis Register and perform a meta-analysis. METHODS LS was identified by both baseline NIHSS-subscores and discharge ICD-10 codes, and contrasted by IVT to non-IVT treated. IVT patients were predominantly from Europe, non-IVT patients predominantly from South America and Asia. Outcome measurements were functional independence (modified Rankin Scale [mRS] score ≤2), excellent outcome (mRS ≤ 1), and mortality at three months. Matched-control comparisons of symptomatic intracerebral hemorrhage (SICH) between IVT-treated LS and IVT-treated non-LS patients were performed. Additionally, we performed a meta-analysis. RESULTS Median age for IVT-treated LS patients (n = 4610) was 66 years vs. 64 years and NIHSS score was 6 vs. 3, compared to non-IVT-treated LS (n = 1221). Univariate outcomes did not differ; however, IVT-treated LS patients had higher adjusted odds ratios (aOR) for functional independence (aOR = 1.65, 95% CI = 1.28-2.13) but similar mortality at three months (aOR = 0.57, 0.29-1.13) than non-IVT-LS. Propensity-score matched analysis showed that IVT-treated LS patients had a 7.1% higher chance of functional independency than non-IVT LS patients (p < 0.001). IVT-treated LS patients had lower odds for SICH (aOR = 0.33, 0.19-0.58 per SITS, aOR = 0.40, 0.27-0.57 per ECASS-2) than matched non-LS controls, which was mirrored in the meta-analysis. CONCLUSIONS Our adjusted results show that IVT treatment in LS patients was associated with better functional outcome than non-IVT-treated LS and less SICH than IVT-treated non-LS patients.
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Affiliation(s)
- Marius Matusevicius
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Maurizio Paciaroni
- Stroke Unit, Division of Cardiovascular Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Valeria Caso
- Stroke Unit, Division of Cardiovascular Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Matteo Bottai
- Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Dheeraj Khurana
- Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Mario de Bastos
- Neurology Department, Hospital Universitario de Caracas, Caracas, Venezuela
| | - Sheila Co Martins
- Neurology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Yakup Krespi
- MLP CARE Stroke Network, Istinye University, Istanbul, Turkey
| | - Charith Cooray
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Neurology, Karolinska University Hospital, Solna, Sweden
| | - Danilo Toni
- Emergency Department Stroke Unit, Sapienza University, Policlinico Umberto I Hospital, Rome, Italy
| | - Niaz Ahmed
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Neurology, Karolinska University Hospital, Solna, Sweden
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12
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Zivanovic Z, Gubi M, Vlahovic D, Milicevic M, Jovicevic M, Lucic A, Ruzicka-Kaloci S, Radovanovic B, Zikic TR, Zarkov M, Popovic N, Slankamenac P. Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis. J Stroke Cerebrovasc Dis 2018; 28:435-440. [PMID: 30409747 DOI: 10.1016/j.jstrokecerebrovasdis.2018.10.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 09/21/2018] [Accepted: 10/13/2018] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. MATERIALS AND METHODS In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. RESULTS Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P = .002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P = .01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P = .002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. CONCLUSION Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.
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Affiliation(s)
- Zeljko Zivanovic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Marina Gubi
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia.
| | - Dmitar Vlahovic
- Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Marija Milicevic
- Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Mirjana Jovicevic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Aleksandra Lucic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Svetlana Ruzicka-Kaloci
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | | | - Tamara Rabi Zikic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Marija Zarkov
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Nemanja Popovic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Petar Slankamenac
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; Clinic of Neurology, Clinical Centre of Vojvodina, Novi Sad, Serbia.
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13
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Iglesias-Rey R, Rodríguez-Yáñez M, Rodríguez-Castro E, Pumar JM, Arias S, Santamaría M, López-Dequidt I, Hervella P, Correa-Paz C, Sobrino T, Vivien D, Campos F, Castellanos M, Castillo J. Worse Outcome in Stroke Patients Treated with rt-PA Without Early Reperfusion: Associated Factors. Transl Stroke Res 2017; 9:347-355. [PMID: 29116527 PMCID: PMC6061244 DOI: 10.1007/s12975-017-0584-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 10/23/2017] [Accepted: 10/30/2017] [Indexed: 02/07/2023]
Abstract
Based on preclinical studies suggesting that recombinant tissue plasminogen activator (rt-PA) may promote ischemic brain injuries, we investigated in patients the possible risk of worse clinical outcome after rt-PA treatment as a result of its inability to resolve cerebral ischemia. Here, we designed a cohort study using a retrospective analysis of patients who received treatment with intravenous (4.5-h window) or intraarterial rt-PA, without or with thrombectomy. Controls were consecutive patients who did not receive recanalization treatment, who met all inclusion criteria. As a marker of reperfusion, we defined the variable of early neurological improvement as the difference between the score of the National Institute of Health Stroke Scale (NIHSS) (at admission and 24 h). The main variable was worsening of the patient’s functional situation in the first 3 months. To compare quantitative variables, we used Student’s t test or the Mann-Whitney test. To estimate the odds ratios of each independent variable in the patient’s worsening in the first 3 months, we used a logistic regression model. We included 1154 patients; 577 received rt-PA, and 577 served as controls. In the group of patients treated with rt-PA, 39.4% who did not present clinical reperfusion data developed worsening within 3 months after stroke compared with 3.5% of patients with reperfusion (P < 0.0001). These differences were not significant in the control group. In summary, administration of rt-PA intravenously or intraarterially without reperfusion within the first 24 h may be associated with a higher risk of functional deterioration in the first 3 months.
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Affiliation(s)
- Ramón Iglesias-Rey
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain.
| | - Manuel Rodríguez-Yáñez
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Emilio Rodríguez-Castro
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - José Manuel Pumar
- Department of Neuroradiology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Susana Arias
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - María Santamaría
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Iria López-Dequidt
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Pablo Hervella
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Clara Correa-Paz
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Tomás Sobrino
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Denis Vivien
- Inserm, Inserm, UMR-S U1237, Physiopathology and Imaging of Neurological diseases, GIP Cyceron, Caen Normandie University, 14073, Caen, France
- CHU de Caen, Department of Clinical Research, Caen University Hospital, 14000, Caen, France
| | - Francisco Campos
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
| | - Mar Castellanos
- Department of Neurology, Biomedical Research Institute, University Hospital A Coruña, 15006, Corunna, Spain
| | - José Castillo
- Clinical Neurosciences Research Laboratory, Department of Neurology, Clinical University Hospital, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706, Santiago de Compostela, Spain
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Guillon B, Bourcier R, Toulgoat F, de Gaalon S, Gaultier-Lintia A, Sévin M. Gestione dell’infarto cerebrale acuto. Neurologia 2016. [DOI: 10.1016/s1634-7072(16)80382-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Okazaki S, Hornberger E, Griebe M, Gass A, Hennerici MG, Szabo K. MRI Characteristics of the Evolution of Supratentorial Recent Small Subcortical Infarcts. Front Neurol 2015; 6:118. [PMID: 26074870 PMCID: PMC4443727 DOI: 10.3389/fneur.2015.00118] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Accepted: 05/09/2015] [Indexed: 11/13/2022] Open
Abstract
Objective Morphological changes of recent small subcortical infarcts are not well defined. The purpose of the present study was to describe the MRI characteristics of the evolution for this stroke subtype. Methods We conducted a retrospective review of patients diagnosed with definite supratentorial recent small subcortical infarcts according to the ASCO classification with baseline and follow-up MRI (≥90 days of stroke onset). We investigated the incidence of cavity formation, the infarct volume change, and the positional relationship between infarct lesions and preexisting white matter hyperintensities (WMHs) of presumed vascular origin. Results We identified 62 patients with a median age of 71 years (range: 30–87). Median follow-up period was 26 months (range: 3–99). Cavity formation was observed in 38 infarct lesions (61%). Eighteen lesions (29%) were partially adjacent to WMHs and 7 (11%) were fused into WMHs. In a multiple logistic regression analysis, age [odds ratio per 5-year increase: 1.34; 95% confidence interval (CI): 1.03–1.80; p = 0.03] and baseline infarct volume (odds ratio per 1-ml increase: 4.7; 95% CI: 1.6–19.7; p = 0.003) were independent predictors of cavity formation. There was a significant volume reduction between baseline and follow-up infarct lesions (median volume reduction rate: 44%). Conclusion More than one-third of recent small subcortical infarcts do not lead to cavity formation and 40% of infarct lesions overlap with WMHs. Our data indicate the continuity between recent small subcortical infarcts and WMHs.
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Affiliation(s)
- Shuhei Okazaki
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
| | - Eva Hornberger
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
| | - Martin Griebe
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
| | - Achim Gass
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
| | - Michael G Hennerici
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
| | - Kristina Szabo
- Department of Neurology, UniversitätsMedizin Mannheim, University of Heidelberg , Mannheim , Germany
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Abstract
Cerebrovascular diseases are one of the favorite topics of manuscripts submitted to the Journal of Neurology. In this summary paper, we briefly present those manuscripts that in our opinion were most relevant in selected areas of vascular diseases of the brain.
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Affiliation(s)
- José M Ferro
- Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal,
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Haršány M, Tsivgoulis G, Alexandrov AV. Intravenous thrombolysis in acute ischemic stroke: standard and potential future applications. Expert Rev Neurother 2014; 14:879-92. [PMID: 24984941 DOI: 10.1586/14737175.2014.934676] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Acute ischemic stroke is a medical emergency requiring urgent treatment. Randomized clinical trial and Phase IV data have provided unequivocal evidence that intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) improves early functional outcomes by restoring brain perfusion. Moreover, these studies have shed substantial light on the factors which are associated with more favorable outcome with tPA and are related to the highest benefit-to-risk ratio. Stroke physicians should consider vascular imaging techniques to aid decision making with thrombolytic therapy. The presence of intracranial occlusion is the target of treatment with early recanalization being the goal. Successful use of intravenous thrombolysis depends on a sound understanding of the decision-making process and organization of the treating team who strives for early treatment initiation and strict adherence to the protocol. Intravenous rt-PA within 4.5 h of onset should now be a standard treatment of acute disabling ischemic stroke throughout the world. This review also summarizes intravenous thrombolysis contraindications as well as the safety of novel reperfusion therapies including tenecteplase, sonothrombolysis and the combination of alteplase with direct thrombin inhibitors or glycoprotein IIb/IIIa receptor antagonists.
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Affiliation(s)
- Michal Haršány
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic
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