Atormac
briv
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 601  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  » Next article
  » Previous article 
  » Table of Contents
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (470 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 »  Introduction
 »  Materials and Me...
 »  Results
 »  Discussion
 »  References
 »  Article Tables

 Article Access Statistics
    Viewed3900    
    Printed155    
    Emailed2    
    PDF Downloaded236    
    Comments [Add]    
    Cited by others 15    

Recommend this journal

 


 
ORIGINAL ARTICLE
Year : 2010  |  Volume : 58  |  Issue : 3  |  Page : 403-406

Predictors of major neurological improvement after intravenous thrombolysis in acute ischemic stroke: A hospital-based study from south India


Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082, India

Date of Acceptance04-Feb-2010
Date of Web Publication17-Jul-2010

Correspondence Address:
Subhash Kaul
Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.66085

Rights and Permissions

 » Abstract 

Background : Despite the increasing use of recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke, uncertainty persists about the short- and long-term outcome of the thrombolysed patients. Objective : To identify predictors of major neurological improvement at 24 h after intravenous rt-PA administration in patients of acute ischemic stroke and their relationship with outcome at 12 months. Materials and Methods : We analyzed the data of the patients with acute ischemic stroke treated as per the National Institute of Neurological Disorders and Stroke (NINDS) criteria with intravenous rt-PA between January 2000 and June 2009 at a tertiary care center in south India. Major neurological improvement was defined by an 8-point improvement in National Institute of Health Stroke Scale (NIHSS) score or an NIHSS score of 0 or 1 at 24 h. Good outcome was defined as a 12-month modified Rankin Scale (mRS) of 0 to 1. Results : Of the 72 patients with acute ischemic stroke treated with intravenous rt-PA, 23 (32%) patients had major neurological improvement at 24 h. Age <60 years (OR 1.9, 95% CI 1.7 to3.2), admission glucose levels <8 mmol/L (OR 3.87, 95% CI 1.9 to 9.2) and mild to moderate baseline stroke severity (NIHSS median score 10+ 6) were associated with major neurological improvement after adjusting for co variables. Major neurological improvement at 24 h was an independent predictor of good outcome (mRS=1) at 12 months (OR 13.9, 95% CI 6.84 to 40.2). Conclusions : Age <60 years, glucose levels <8 mmol/L and mild to moderate stroke severity (NIHSS median score 10±6) was associated with major neurological improvement after intravenous rt-PA. Major neurological improvement at 24 h after the administration of intravenous thrombolysis independently predicted good outcome at 12 months.


Keywords: Acute ischemic stroke, intravenous rt-PA, major neurological outcome, mRS


How to cite this article:
Boddu DB, Srinivasarao Bandaru V, Reddy PG, Madhusudan M, Rukmini M K, Suryaprabha T, Jabeen S A, Suvarna A, Jayalakshmi SS, Meena A K, Borgohain R, Kaul S. Predictors of major neurological improvement after intravenous thrombolysis in acute ischemic stroke: A hospital-based study from south India. Neurol India 2010;58:403-6

How to cite this URL:
Boddu DB, Srinivasarao Bandaru V, Reddy PG, Madhusudan M, Rukmini M K, Suryaprabha T, Jabeen S A, Suvarna A, Jayalakshmi SS, Meena A K, Borgohain R, Kaul S. Predictors of major neurological improvement after intravenous thrombolysis in acute ischemic stroke: A hospital-based study from south India. Neurol India [serial online] 2010 [cited 2021 Sep 19];58:403-6. Available from: https://www.neurologyindia.com/text.asp?2010/58/3/403/66085



 » Introduction Top


The National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rt-PA) Stroke Study demonstrated that intravenous rt-PA improves outcomes in acute ischemic stroke, when administered within 3 h of symptom onset. [1] The absolute benefit in the likelihood of a normal or near-normal outcome ranged from 11-15%, depending on the functional outcome scale. [2],[3] A major neurological improvement was defined as a National Institute of Health Stroke Scale (NIHSS) score equal to 0 or 1 at 24 h or an improvement of ≥8 points compared to baseline. [4] The higher rate of major neurological improvement observed in the rt-PA group compared to the placebo was interpreted as a marker of treatment efficacy, [5],[6],[7],[8],[9],[10] and major neurological improvement in turn independently predicted good clinical outcome at three months. [4],[11],[12] In rt-PA-treated patients, age and time from stroke onset to treatment predicted both major neurological improvement at 24 h and three-month favorable outcome. [4] A recent meta-analysis showed that women have a better outcome at three months after rt-PA administration compared to men. [13] Female gender, glucose levels < 8 mmol/L, and absence of cortical involvement at 24 h in CT scan were reported to be associated with major neurological improvement at three months. [14] However, sparse data is available on early predictors for favorable outcome at 12 months. The identification of predictors of early major neurological improvement and good outcome at 12 months may help to improve patient selection, and to allow more accurate estimation of the prognosis.


 » Materials and Methods Top


This was a prospective study performed between January 2000 and June 2009 at Nizam's Institute of Medical Sciences, a tertiary care health center and a university hospital located in Hyderabad, the capital city of Andhra Pradesh, a province in south India. The study protocol was approved by the Ethics Committee of the university and informed written consent was obtained from all the participants. Data from consecutive patients with acute ischemic stroke treated with intravenous rt-PA were collected prospectively. Demographic variables, evaluation and treatment time, admission and 24-h NIHSS scores were recorded. For all patients, time of symptom onset was defined by the time they were "last seen to be well." The onset-to-door, onset-to-CT scan of the brain, and onset-to-needle time were obtained from the nursing records. Patients received rt-PA at the dose of 0.9 mg/kg; 10% as a bolus, and the rest as an infusion over 1 h. [1] A comprehensive work-up of all the patients was done to determine the stroke mechanism and subtype. Neuroimaging in addition to computed tomography (CT) brain scan also included magnetic resonance imaging (MRI) and MR angiography. Major neurological improvement was defined as NIHSS score equal to 0 or 1 at 24 h or an improvement ≥8 points compared to baseline. [4] Minor and major complications of rt-PA treatment after infusion and during hospital stay were assessed. Mortality during hospital stay and during follow-up was recorded and the possible cause of death was identified. All the patients who survived were followed on a regular basis for assessment of outcome. The predictive value of major neurological improvement for 12-month outcome was analyzed using the modified Rankin Scale (mRS) and Barthel Index (BI) score. Good outcome was defined as a mRS of ≤1 and BI score of ≥95.

Statistical analysis

Statistical analysis was done using SPSS 14.0 window software (statistical package for the Social sciences, SPSS Inc). Continuous variables were presented in titer of mean and +SD. The association between demographic characteristics, clinical and hemodynamic variables, and major neurological improvement was examined using logistic regression analysis. Major neurological improvement at 24 h was evaluated as an independent predictor of good outcome (mRS 0 to 1, BI ≥95) at 12 months in a multivariate analysis. All tests were two-sided and P value <0.05 was considered statistically significant.


 » Results Top


A total of 72 patients with acute stroke were treated with intravenous rt-PA during the study period. The mean age was 53 ± 12.3 years and 48 (66%) patients were men [Table 1]. The risk factors included: hypertension in 56 (77.7%), diabetes mellitus in 35 (48.6%), smoking in 38 (52.7%), and coronary artery disease (CAD) in 16 (22%) patients. The mechanism of stroke was: large vessel disease in 30 (41.6%), small artery disease in 17 (23.6%), cardioembolism in nine (12.5%), and stroke of other determined etiology in eight (11%) (hyperhomocysteinemia 5, Takayasu disease 1, systemic lupus erythematosus 1 and protein C and S deficiency 1) [Table 2]. Twenty-three patients (32%) had major neurological improvement at 24 h after rt-PA administration. There were no significant differences in the gender, vascular risk factors, CT scan abnormalities, and time to rt-PA between patients with major neurological improvement and those with no significant improvement. On univariate analysis, age <60 years (P=0.001), admission glucose level < 8.0 mmol/L (P=0.001) and median baseline NIHSS 10±6 (P=0.005) were associated with major neurological improvement [Table 3]. On multivariate logistic regression analysis, age <60 years (OR 1.9, 95% CI 1.7 -3.2), admission glucose levels <8 mmol/L (OR 3.87, 95% CI 1.9 - 9.2) and mild to moderate stroke severity (median baseline NIHSS 10±6) (OR 2.79, 95% CI 1.69 - 6.37) were independently associated with major neurological improvement after adjusting for gender, diabetes, and normal CT brain. Asymptomatic intracerebral hemorrhage (ICH) was observed in 3/23 (13%) patients with major neurological improvement and in 15/49 (30.6%) patients without major neurological improvement (P=0.47). Symptomatic ICH was found in 3/49 (6.1%) patients without major neurological improvement, in none of the patients with neurological improvement and in 3/72 (4.1%) patients, if both groups were combined.

Major neurological improvement at 24 h as a predictor of good outcome at three months

Among the 23 patients with major neurological improvement at 24 h, one patient was lost to follow-up and two had nine months follow-up. Of the remaining 20 patients, 18 (90%) had good outcome (mRS 0 to 1) at 12 months. In 49 patients without major neurological improvement at 24 h, six patients were dead (myocardial infarction - 2, ICH - 2, malignant cerebral edema - 1 and sepsis -1) and five patients were lost to follow-up at 12 months. Out of the remaining 38 patients, good outcome was found in nine patients (23.6%). Major neurological improvement at 24 h predicted good outcome (mRS≤1, P<0.0001; BI score> 95, P=0.0001) at 12 months [Table 4]. After a multivariate analysis, major neurological improvement at 24 h continued to be a strong and independent predictor of good outcome (mRS≤1) at 12 months (OR 13.9, 95% CI 6.84 to 40.2) after adjusting for gender, vascular risk factors and brain CT scan abnormality.


 » Discussion Top


In this study major neurological improvement was observed in 32% patients, similar to the NINDS trial. [1] Age <60 years, glucose levels < 8 mmol/L and mild to moderate stroke severity (10±6) were independently associated with major neurological improvement. The presence of major neurological improvement at 24 h was predictive of good outcome at 12 months after adjusting for gender, stroke risk factors and brain CT scan abnormality. The association between time to treatment and major neurological improvement seems biologically plausible because earlier treatment should result in earlier recanalization and a greater salvage of tissue at risk of infarction. [4],[6]

A recent pooled analysis of randomized controlled rt-PA trials demonstrated that women benefit more from rt-PA administration than men. [13],[14] However, in the present study female gender was not preferentially associated with major neurological improvement at 24 h after intravenous rt-PA. In this study, younger age (<60 years) was associated with major neurological improvement, similar to an earlier study. [15] This relationship is likely to be a biological effect. Baseline glucose <8 mmol/L and mild to moderately severe stroke (median NIHSS score 10± 6) were also associated with major neurological improvement. These observations are in conformity with NINDS sub-study. [15] In the final multivariate model of the NINDS trial, treatment with rt-PA, diabetes, age, baseline NIHSS score, admission mean arterial pressure, and thrombus or hypodensity/mass effect on baseline CT scan were independently associated with three-month favorable outcome in both rt-PA and placebo-treated patients. [15] One of the worst feared complications of rt-PA is symptomatic ICH. Interestingly, the rate of overall symptomatic ICH in our series was 4.1%, which was lower than reported in NINDS study (6.4%). [1] Being able to predict good outcome at 24 h after intravenous rt-PA, may have implications for clinical management and discharge planning, which could significantly reduce costs associated with longer length of hospital stay. [16],[17]

This study has a limitation of having small numbers of subjects in each of the predictive variable subgroups, thereby lowering the power to detect predictive relationships with major neurological improvement. Nevertheless, the findings do help in the identification of predictors to prognosticate the outcome at 12 months, to a reasonable degree. Also, the present results are based on the window period of 3 h for intravenous thrombolysis, and are not directly applicable to the window period upto 4.5 h (according to ECASS III study). [18]

To conclude, this outcome based study about the use of rt-PA in acute ischemic stroke clearly showed that, age <60 years, base line glucose levels < 8 mmol/L and mild to moderate stroke severity (median NIHSS 10±6) were associated with major neurologic improvement after intravenous rt-PA. Major neurologic improvement at 24hours after intravenous thrombolysis was independently predictive of good outcome in terms of personal independence at the end of 12 months.

 
 » References Top

1.The NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.  Back to cited text no. 1      
2.Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA, et al. Use of tissue- type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 2000;283:1151-8.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Bravata DM, Kim N, Concato J, Krumholz HM, Brass LM. Thrombolysis for acute stroke in routine clinical practice. Arch Intern Med 2002;162:1994-2001.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Brown DL, Johnston KC, Wagner DP, Haley EC Jr. Predicting major neurological improvement with intravenous recombinant tissue plasminogen activator treatment of stroke. Stroke 2004;35:147-50.   Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Brandt T, von Kummer R, M?ller-K?ppers M, Hacke W. Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 1996;27:875-81.  Back to cited text no. 5      
6.Molina CA, Montaner J, Abilleira S, Arenillas JF, Ribs M, Huertas R,et al. Time course of tissue plasminogen activator-induced recanalization in acute cardioembolic stroke: a case- control study. Stroke 2001;32: 2821-7.  Back to cited text no. 6      
7.Alexandrov AV, Demchuk AM, Felberg RA, Christou I, Barber PA, Burgin WS, et al. High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial Doppler monitoring. Stroke 2000;31:610-4.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Demchuk AM, Burgin WS, Christou I, Felberg RA, Barber PA, Hill MD, et al. Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator. Stroke 2001;32:89-93.   Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Felberg RA, Okon NJ, El-Mitwalli A, Burgin WS, Grotta JC, Alexandrov AV. Early dramatic recovery during intravenous tissue plasminogen activator infusion: clinical pattern and outcome in acute middle cerebral artery stroke. Stroke 2002;33:1301-7.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Alexandrov AV, Burgin WS, Demchuk AM, El-Mitwalli A, Grotta JC. Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement. Circulation 2001;103:2897-902.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Johnston KC, Connors AF Jr, Wagner DP, Knaus WA, Wang X, Haley EC Jr. A predictive risk model for outcomes of ischemic stroke. Stroke 2000;31:448-55.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]  
12.Marler JR, Tilley BC, Lu M, Brott TG, Lyden PC, Grotta JC, et al. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000;55:1649-55.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Kent DM, Price LL, Ringleb P, Hill MD, Selker HP. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke 2005;36:62-5.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]  
14.Saposnik G, Legge SD, Webster F, Hachinski V. Predictors of major neurologic improvement after thrombolysis in acute stroke. Neurology 2005;65:1169-74.   Back to cited text no. 14      
15.NINDS t-PA Stroke Study Group. Generalized efficacy of t-PA for acute stroke: subgroup analysis of the NINDS rt-PA stroke trial. Stroke 1997;28:2119-25.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Martinez-Vila E, Irimia P. The cost of stroke. Cerebrovasc Dis 2004;17:124-9.   Back to cited text no. 16      
17.Saposnik G, Webster F, O'Callaghan C, Hachinski V. Optimizing discharge planning: clinical predictors of longer stay after recombinant tissue plasminogen activator for acute stroke. Stroke 2005;36:147-150.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke. N Engl J Med 2008;59:1317-29.  Back to cited text no. 18      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Lack of improvement following endovascular therapy in patients with acute ischemic stroke
Yuezhou Cao,Shuiping Wang,Wen Sun,Qiliang Dai,Wusheng Zhu,Qin Yin,Yunyun Xiong,Minmin Ma,Wenjie Zi,Shiquan Yang,Yunfei Han,Wei Li,Gelin Xu,Xinfeng Liu
International Journal of Neuroscience. 2017; 127(2): 176
[Pubmed] | [DOI]
2 Prediction of favorable outcome by percent improvement in patients with acute ischemic stroke treated with endovascular stent thrombectomy
Yuezhou Cao,Shuiping Wang,Wen Sun,Qiliang Dai,Wei Li,Jin Cai,Xinying Fan,Wusheng Zhu,Yunyun Xiong,Yunfei Han,Wenjie Zi,Shiquan Yang,Jia Chen,Xinfeng Liu
Journal of Clinical Neuroscience. 2017; 38: 100
[Pubmed] | [DOI]
3 Leukoaraiosis and Early Neurological Recovery after Intravenous Thrombolysis
Heidi McAlpine,Leonid Churilov,Peter Mitchell,Richard Dowling,Sarah Teo,Bernard Yan
Journal of Stroke and Cerebrovascular Diseases. 2014; 23(9): 2431
[Pubmed] | [DOI]
4 Early and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke
Leonard LL. Yeo,Prakash Paliwal,Hock L. Teoh,Raymond C. Seet,Bernard PL. Chan,Benjamin Wakerley,Shen Liang,Rahul Rathakrishnan,Vincent F. Chong,Eric YS. Ting,Vijay K. Sharma
Journal of Stroke and Cerebrovascular Diseases. 2013;
[Pubmed] | [DOI]
5 Rapid Neurological Recovery Post Thrombolysis: Mechanisms and Implications
Bejoy Machumpurath,Maya Reddy,Bernard Yan
Neuroscience & Medicine. 2013; 04(01): 36
[Pubmed] | [DOI]
6 Intravenous thrombolysis for acute cerebral ischaemia in old stroke patients ≥80 years of age
Boulouis, G. and Dumont, F. and Cordonnier, C. and Bodenant, M. and Leys, D. and Hénon, H.
Journal of Neurology. 2012; 259(7): 1461-1467
[Pubmed]
7 Intravenous thrombolysis for acute cerebral ischaemia in old stroke patients =80 years of age
Gregoire Boulouis,Frederic Dumont,Charlotte Cordonnier,Marie Bodenant,Didier Leys,Hilde Hénon
Journal of Neurology. 2012; 259(7): 1461
[Pubmed] | [DOI]
8 Outcome of Chlamydia pneumoniae associated acute ischemic stroke in elderly patients: A case–control study
V.C.S. Srinivasarao Bandaru,Demudu Babu Boddu,K. Rukmini Mridula,B. Akhila,Suvarna Alladi,V. Laxmi,Rammohan Pathapati,M. Neeraja,Subhash Kaul
Clinical Neurology and Neurosurgery. 2012; 114(2): 120
[Pubmed] | [DOI]
9 Outcome of Chlamydia pneumoniae associated acute ischemic stroke in elderly patients: A case-control study
Srinivasarao Bandaru, V.C.S. and Boddu, D.B. and Mridula, K.R. and Akhila, B. and Alladi, S. and Laxmi, V. and Pathapati, R. and Neeraja, M. and Kaul, S.
Clinical Neurology and Neurosurgery. 2012; 114(2): 120-123
[Pubmed]
10 Intravenous thrombolysis for acute ischemic stroke in Asia
Sharma, V.K. and Ng, K.W.P. and Venketasubramanian, N. and Teoh, H.L. and Chan, B.P.L.
Expert Review of Neurotherapeutics. 2012; 12(2): 209-217
[Pubmed]
11 Intravenous thrombolysis in acute ischemic stroke after POLKARD: One center analysis of program impact on clinical practice
Arkuszewski, M. and Targosz-Gajniak, M. and Swiat, M. and Patalong-Ogiewa, M. and Pieta, M. and Opala, G.
Advances in Medical Sciences. 2011; 56(2): 231-240
[Pubmed]
12 Current status of intravenous thrombolysis for acute ischemic stroke in Asia
Sharma, V.K. and Ng, K.W.P. and Venketasubramanian, N. and Saqqur, M. and Teoh, H.L. and Kaul, S. and Srivastava, P.M.V. and Sergentanis, T. and Suwanwela, N. and Nguyen, T.H. and Lawrence Wong, K.S. and Chan, B.P.L.
International Journal of Stroke. 2011; 6(6): 523-530
[Pubmed]
13 Intravenous thrombolysis in acute ischemic stroke after POLKARD: one center analysis of program impact on clinical practice
M Arkuszewski,M Targosz-Gajniak,M Swiat,M Patalong-Ogiewa,M Pieta,G Opala
Advances in Medical Sciences. 2011; 56(2)
[Pubmed] | [DOI]
14 Early outcome after intravenous thrombolysis in patients with acute ischemic stroke
Dharmasaroja, P.A., Muengtaweepongsa, S., Dharmasaroja, P.
Neurology India. 2011; 59(3): 351-354
[Pubmed]
15 Two-hour improvement of patients in the national institute of neurological disorders and stroke trials and prediction of final outcome
Hemmen, T.M., Ernstrom, K., Raman, R.
Stroke. 2011; 42(11): 3163-3167
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow