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Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Efficacy and Safety of Alteplase on Treatment of Acute Single Small Subcortical Infarction

Author(s): Kilanga Marcelinus, Hongbing Liu, Ke Zhang, Ce Zong, Hongxun Yang, Bo Song, Yuan Gao* and Yuming Xu*

Volume 19, Issue 3, 2022

Published on: 19 October, 2022

Page: [255 - 266] Pages: 12

DOI: 10.2174/1567202619666220829111211

Price: $65

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.

Keywords: Single small subcortical infarction, Early neurological deterioration, functional outcome, Intracerebral hemorrhage, small vessel disease, modified Rankin scale

[1]
Jeong HG, Kim BJ, Yang MH, Han MK, Bae HJ. Neuroimaging markers for early neurologic deterioration in single small subcortical infarction. Stroke 2015; 46(3): 687-91.
[http://dx.doi.org/10.1161/STROKEAHA.114.007466] [PMID: 25677600]
[2]
Davalos A, Castillo J. Progressing stroke. In: Fisher M, Bogousslavsky J, Eds. Current Review of Cerebrovascular Disease. Philadelphia, PA: Current Medicine Inc. 1999; pp. 149-60.
[3]
Thanvi B, Treadwell S, Robinson T. Early neurological deterioration in acute ischaemic stroke: Predictors, mechanisms and management. Postgrad Med J 2008; 84(994): 412-7.
[http://dx.doi.org/10.1136/pgmj.2007.066118] [PMID: 18832401]
[4]
Mayer SA, Sacco RL, Shi T, Mohr JP. Neurologic deterioration in noncomatose patients with supratentorial intracerebral hemorrhage. Neurology 1994; 44(8): 1379-84.
[http://dx.doi.org/10.1212/WNL.44.8.1379] [PMID: 8058133]
[5]
Kwan J, Hand P. Early neurological deterioration in acute stroke: Clinical characteristics and impact on outcome. QJM 2006; 99(9): 625-33.
[http://dx.doi.org/10.1093/qjmed/hcl082] [PMID: 16905751]
[6]
Martí-Vilalta JL, Arboix A. The Barcelona stroke registry. Eur Neurol 1999; 41(3): 135-42.
[http://dx.doi.org/10.1159/000008036] [PMID: 10202244]
[7]
Yamamoto H, Bogousslavsky J, van Melle G. Different predictors of neurological worsening in different causes of stroke. Arch Neurol 1998; 55(4): 481-6.
[http://dx.doi.org/10.1001/archneur.55.4.481] [PMID: 9561975]
[8]
Mohr JP, Caplan LR, Melski JW, et al. The Harvard cooperative stroke registry: A prospective registry. Neurology 1978; 28(8): 754-62.
[http://dx.doi.org/10.1212/WNL.28.8.754] [PMID: 567291]
[9]
Tei H, Uchiyama S, Ohara K, et al. Deteriorating ischemic stroke in 4 clinical categories classified by the oxfordshire community stroke project. Stroke 2000; 31: 2049-54.
[http://dx.doi.org/10.1161/01.STR.31.9.2049]
[10]
Hwang YH, Seo JG, Lee HW, Park SP, Suh CK. Early neurological deterioration following intravenous recombinant tissue plasminogen activator therapy in patients with acute lacunar stroke. Cerebrovasc Dis 2008; 26(4): 355-9.
[http://dx.doi.org/10.1159/000151638] [PMID: 18728362]
[11]
Barow E, Boutitie F, Cheng B, et al. Functional outcome of intravenous thrombolysis in patients with lacunar infarcts in the wake-up trial. JAMA Neurol 2019; 76(6): 641-9.
[http://dx.doi.org/10.1001/jamaneurol.2019.0351] [PMID: 30907934]
[12]
Fuentes B, Sanchez PM, Alonso M, et al. Efficacy of intravenous thrombolysis according to stroke subtypes: The madrid stroke network data. Eur J Neurol 2012; 19(12): 1568-74.
[http://dx.doi.org/10.1111/j.1468-1331.2012.03790.x]
[13]
Hsia AW, Sachdev HS, Tomlinson J, Hamilton SA, Tong DC. Efficacy of IV tissue plasminogen activator in acute stroke: Does stroke subtype really matter? Neurology 2003; 61(1): 71-5.
[http://dx.doi.org/10.1212/01.WNL.0000071228.56362.36] [PMID: 12847159]
[14]
Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke: The standard treatment with alteplase to reverse stroke (STARS) study. JAMA 2000; 283(9): 1145-50.
[http://dx.doi.org/10.1001/jama.283.9.1145] [PMID: 10703776]
[15]
Eggers CCJ, Bocksrucker C, Seyfang L. The efficacy of thrombolysis in lacunar stroke - evidence from the Austrian Stroke Unit Registry. Eur J Neurol 2017; 24(6): 780-7.
[http://dx.doi.org/10.1111/ene.13288] [PMID: 28449276]
[16]
Paek YM, Lee JS, Park HK, et al. Intravenous thrombolysis with tissue-plasminogen activator in small vessel occlusion. J Clin Neurosci 2019; 64: 134-40.
[http://dx.doi.org/10.1016/j.jocn.2019.03.036] [PMID: 30952555]
[17]
Hill MD, Buchan AM. Thrombolysis for acute ischemic stroke: Results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005; 172(10): 1307-12.
[http://dx.doi.org/10.1503/cmaj.1041561] [PMID: 15883405]
[18]
Griebe M, Fischer E, Kablau M, et al. Thrombolysis in patients with lacunar stroke is safe: An observational study. J Neurol 2014; 261(2): 405-11.
[http://dx.doi.org/10.1007/s00415-013-7212-8] [PMID: 24366651]
[19]
Zivanovic Z, Gubi M, Vlahovic D, et al. Patients with acute lacunar infarction have benefit from intravenous thrombolysis. J Stroke Cerebrovasc Dis 2019; 28(2): 435-40.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.020] [PMID: 30409747]
[20]
Kim DH, Lee DS, Nah HW, Cha JK. Clinical and radiological factors associated with unfavorable outcome after intravenous thrombolysis in patients with mild ischemic stroke. BMC Neurol 2018; 18(1): 30.
[http://dx.doi.org/10.1186/s12883-018-1033-4] [PMID: 29544461]
[21]
Simonsen CZ, Schmitz ML, Madsen MH, et al. Early neurological deterioration after thrombolysis: Clinical and imaging predictors. Int J Stroke 2016; 11(7): 776-82.
[http://dx.doi.org/10.1177/1747493016650454] [PMID: 27188241]
[22]
Terasawa Y, Iguchi Y, Kimura K, et al. Neurological deterioration in small vessel disease may be associated with increase of infarct volume. J Neurol Sci 2008; 269(1-2): 35-40.
[http://dx.doi.org/10.1016/j.jns.2007.12.014] [PMID: 18222484]
[23]
Nah HW, Kang DW, Kwon SU, Kim JS. Diversity of single small subcortical infarctions according to infarct location and parent artery disease: Analysis of indicators for small vessel disease and atherosclerosis. Stroke 2010; 41(12): 2822-7.
[http://dx.doi.org/10.1161/STROKEAHA.110.599464] [PMID: 20966406]
[24]
Wardlaw JM. What causes lacunar stroke? J Neurol Neurosurg Psychiatry 2005; 76(5): 617-9.
[http://dx.doi.org/10.1136/jnnp.2004.039982] [PMID: 15834013]
[25]
Zhang C, Wang Y, Zhao X, et al. Distal single subcortical infarction had a better clinical outcome compared with proximal single subcortical infarction. Stroke 2014; 45(9): 2613-9.
[http://dx.doi.org/10.1161/STROKEAHA.114.005634] [PMID: 25052317]
[26]
Hassan A, Hunt BJ, O’Sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain 2003; 126(2): 424-32.
[http://dx.doi.org/10.1093/brain/awg040] [PMID: 12538408]
[27]
Mustanoja S, Meretoja A, Putaala J, et al. Outcome by stroke etiology in patients receiving thrombolytic treatment: Descriptive subtype analysis. Stroke 2011; 42(1): 102-6.
[http://dx.doi.org/10.1161/STROKEAHA.110.597534] [PMID: 21106955]
[28]
Yang L, Cao W, Wu F, et al. Predictors of clinical outcome in patients with acute perforating artery infarction. J Neurol Sci 2016; 365: 108-13.
[29]
Zhu Y, Carmeliet P, Fay WP. Plasminogen activator inhibitor-1 is a major determinant of arterial thrombolysis resistance. Circulation 1999; 99(23): 3050-5.
[http://dx.doi.org/10.1161/01.CIR.99.23.3050] [PMID: 10368124]
[30]
Moser M, Nordt T, Peter K, et al. Platelet function during and after thrombolytic therapy for acute myocardial infarction with reteplase, alteplase, or streptokinase. Circulation 1999; 100(18): 1858-64.
[http://dx.doi.org/10.1161/01.CIR.100.18.1858] [PMID: 10545429]
[31]
Kim SK, Song P, Hong JM, et al. Prediction of progressive motor deficits in patients with deep subcortical infarction. Cerebrovasc Dis 2008; 25(4): 297-303.
[http://dx.doi.org/10.1159/000118373] [PMID: 18303247]
[32]
Wu X, Liu Y, Nie C, et al. Efficacy and safety of intravenous thrombolysis on acute branch atheromatous disease: A retrospective case-control study. Front Neurol 2020; 11: 581.
[http://dx.doi.org/10.3389/fneur.2020.00581]
[33]
Park MG, Oh EH, Kim BK, Park KP. Intravenous tissue plasminogen activator in acute branch atheromatous disease: Does it prevent early neurological deterioration? J Clin Neurosci 2016; 33: 194-7.
[http://dx.doi.org/10.1016/j.jocn.2016.04.011] [PMID: 27452127]
[34]
Duan Z, Fu C, Chen B, et al. Lesion patterns of single small subcortical infarct and its association with early neurological deterioration. Neurol Sci 2015; 36(10): 1851-7.
[http://dx.doi.org/10.1007/s10072-015-2267-1] [PMID: 26032577]
[35]
Liu C, Gao Y, Song B, et al. Elevated serum homocysteine associated with distal type of single small subcortical infarction. Curr Neurovasc Res 2020; 17(5): 629-35.
[http://dx.doi.org/10.2174/1567202617666201029145824]
[36]
Strbian D, Piironen K, Meretoja A, et al. Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms. Int J Stroke 2013; 8(5): 293-9.
[http://dx.doi.org/10.1111/j.1747-4949.2012.00808.x]
[37]
Pan YT, Lee JD, Lin YH, et al. Comparisons of outcomes in stroke subtypes after intravenous thrombolysis. Springerplus 2016; 5(1): 47.
[http://dx.doi.org/10.1186/s40064-016-1666-y] [PMID: 26835227]
[38]
Köhrmann M, Nowe T, Huttner HB, et al. Safety and outcome after thrombolysis in stroke patients with mild symptoms. Cerebrovasc Dis 2009; 27(2): 160-6.
[http://dx.doi.org/10.1159/000185607] [PMID: 19092237]

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