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Table of Contents    
ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1282-1284

Intracranial Large Artery Disease is Independently Associated with Poor Functional Outcome in a Cohort of Ethnic South Asian Ischemic Stroke Patients


1 Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus, Singapore
2 Department of Neurology, Singapore General Hospital, Singapore
3 National University Singapore, Singapore

Date of Submission25-Apr-2016
Date of Decision31-Aug-2016
Date of Acceptance05-Jan-2017
Date of Web Publication30-Oct-2021

Correspondence Address:
Deidre A De Silva
Department of Neurology, National Neuroscience Institute, Singapore General Hospital Campus
Singapore
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.329581

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 » Abstract 


Background: Intracranial large artery disease (ICLAD) in ischemic stroke patients is associated with an increased risk for recurrent stroke; however, it is not known if ICLAD influences functional status following stroke. We studied the 6-month functional outcome in south Asian ischemic stroke patients and compared those with and without ICLAD.
Materials and Methods: This is a prospective cohort study of consecutive south Asian ischemic stroke patients. ICLAD was assessed with transcranial color-coded Doppler ultrasound or magnetic resonance angiography. Functional outcomes were obtained via telephone interviews with poor outcome defined as modified Rankin scale of 3–6.
Results: Of 216 ischemic stroke patients studied, 203 (93.9%) had follow-up data, of whom 50.7% (103) had ICLAD. Patients with ICLAD had a higher prevalence of hypertension (P < 0.001), hyperlipidemia (P = 0.047), ischemic heart disease (P = 0.030), and extracranial carotid disease (P = 0.005). A higher proportion of patients with ICLAD had poor functional outcome at 6 months (30.1%) versus those without ICLAD (13.0%) (P = 0.004). After adjusting for age, sex, hypertension, hyperlipidemia, diabetes, ischemic heart disease, atrial fibrillation, extracranial carotid stenosis, and recurrent vascular events, patients with ICLAD were 3.01 (95% confidence interval: 1.35–7.10) times more likely than those without ICLAD to have poor functional outcome.
Conclusions: The presence of ICLAD rendered poorer functional prognosis after stroke. These findings support the specific evaluation of the benefits of known acute stroke treatments such as thrombolysis, as well as investigation of potential novel strategies such as acute stenting.


Keywords: Functional outcome, intracranial atherosclerosis, ischemic stroke
Key Message: Ischaemic stroke patients with intracranial large artery disease (ICLAD) are 3 times more likely to have poor functional outcome compared to those without ICLAD. This association is independent of other known prognostic factors and thus provides evidence for further research to optimise hyperacute treatment of stroke due to ICLAD.


How to cite this article:
De Silva DA, Wee CK, Woon FP, Chang HM, Wong MC. Intracranial Large Artery Disease is Independently Associated with Poor Functional Outcome in a Cohort of Ethnic South Asian Ischemic Stroke Patients. Neurol India 2021;69:1282-4

How to cite this URL:
De Silva DA, Wee CK, Woon FP, Chang HM, Wong MC. Intracranial Large Artery Disease is Independently Associated with Poor Functional Outcome in a Cohort of Ethnic South Asian Ischemic Stroke Patients. Neurol India [serial online] 2021 [cited 2021 Dec 3];69:1282-4. Available from: https://www.neurologyindia.com/text.asp?2021/69/5/1282/329581




Intracranial large arteries are a common site of disease in ischemic stroke, particularly among Asian patients including ethnic south Asians.[1],[2] There are no proven acute treatments specific for ischemic stroke caused by intracranial large artery disease (ICLAD)[3] and limited evidence of proven treatments such as stroke thrombolysis in subgroups with ICLAD. While ICLAD is associated with increased risk of recurrent stroke,[4],[5] data regarding the influence of ICLAD on functional status following acute stroke are lacking. We studied the 6-month functional outcomes of ischemic stroke patients of south Asian ethnicity comparing those with and without ICLAD.


 » Materials and Methods Top


This is a prospective cohort study of consecutive ethnic south Asians admitted for acute ischemic stroke from November 2003 to December 2007 to a 1400-bed tertiary care hospital in Singapore. Ischemic stroke was determined by the managing clinicians based on clinical presentation and imaging. Ethnicity was ascertained from patient interviews or as indicated in the patient's identification cards issued to all Singapore citizens and residents. Patients of mixed ethnicity were excluded. None of the patients received acute reperfusion therapy.

Assessment of ICLAD of internal carotid artery, middle cerebral artery, anterior cerebral artery, vertebrobasilar arteries, and/or posterior cerebral artery[6] was performed with transcranial color-coded Doppler ultrasound (TCCD) or magnetic resonance angiography (MRA). ICLAD on TCCD was defined by previously established criteria.[7] If there were poor acoustic/bone windows, we used MRA to assess ICLAD, which was defined as ≥50% luminal narrowing with or without loss of signal at the stenotic region.[6] ICLAD was present if one or more vessels fulfilled the criteria. Extracranial carotid disease was assessed by Duplex ultrasonography; severe disease was defined as stenosis of ≥70% by the North American Symptomatic Carotid Endarterectomy Trial[8] criteria or complete occlusion.

Telephone interviews with the patients or their caregivers were conducted by a trained research assistant at 6 months to ascertain functional status, scored with the modified Rankin scale (mRS) and incidence of recurrent vascular events (stroke, myocardial infarction, and vascular death). Poor functional outcome was defined as mRS 3–6.

Statistical analysis was performed using the Statistical Package for the Social Sciences software for Windows Version 21.0 (IBM Corp, Armonk, New York, USA). Chi-square test was used for comparison of dichotomous variables. Regression analyses were performed adjusting for covariates of age, sex, hypertension, hyperlipidemia, diabetes, ischemic heart disease (IHD); factors associated with stroke etiology, namely extracranial carotid disease and atrial fibrillation (AF); and recurrent vascular events. This study was approved by the hospital's ethics committee and written consent was obtained from all patients.


 » Results Top


Among 240 consecutive south Asian ischemic stroke patients, 216 (90.0%) had ICLAD assessment, of whom 203 (93.9%) had follow-up data. The median age of these 203 patients was 64 years [interquartile range (IQR): 54–72); 70.4% (143) were males; 78.8% (160) had hypertension, 76.4% (155) had hyperlipidemia, 61.6% (125) had diabetes, 37.9% (77) had IHD, 4.9% (10) had AF; and 35.0% (71) were smokers.

The prevalence of ICLAD was 50.7% (103). Median age of patients with ICLAD (64, IQR: 56–72 years) was similar to those without ICLAD (62, IQR: 53–72 years) (P = 0.393). Patients with ICLAD had a higher prevalence of hypertension (91.2% vs. 66.0%; P < 0.001), hyperlipidemia (82.5% vs. 70.0%; P = 0.047), IHD (45.6% vs. 30.0%; P = 0.030), and extracranial carotid disease (16.7% vs. 4.0%; P = 0.005). Baseline National Institute of Health Stroke Scale (NIHSS) was higher in ICLAD patients (median NIHSS = 4; IQR 2–6) vs. non-ICLAD (median NIHSS = 3, IQR 1–4; P = 0.039). There were no differences in sex distribution between patients with ICLAD versus those without ICLAD (males 66.9% vs. 74.0%; P = 0.286), diabetes (66.9% vs. 56.0%; P = 0.115), prevalence of AF (5.0% vs. 4.8%; P = 1.000), or smoking (33.0% vs. 37.0%; P = 0.560).

In the overall cohort, 21.7% (44) had poor functional status and 8.9% (18) had a subsequent vascular event at six months poststroke. A higher proportion of patients with ICLAD had poor functional status (30.1% vs. 13.0%; P = 0.004). Subsequent vascular event rates were similar across both groups (ICLAD 10.6% vs. non-ICLAD 7.0%; P = 0.461). After adjusting for age, sex, hypertension, hyperlipidemia, diabetes, IHD, AF, extracranial carotid stenosis, and recurrent vascular events, the likelihood of poor functional outcome was higher for patients with ICLAD [odds ratio (OR) 3.01, 95% confidence interval 1.35–7.10; P = 0.008] compared to those without ICLAD [Table 1].
Table 1: Regression Analysis of Prognostic Factors for Poor Outcome (modified Rankin Score 3-6) at six months following Ischemic Stroke

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 » Discussion Top


This study reveals the novel finding that ICLAD was associated with poor function at 6 months following stroke, independent of demographics, risk factors, other etiologies of stroke, and recurrent vascular events. The poorer functional outcome in patients with ICLAD could in part be accounted by their higher initial NIHSS, which was observed in this study and other published research.[9],[10]

Based on our findings of poorer functional outcome and more severe baseline neurological deficits in stroke patients with ICLAD, the specific benefits and roles of acute reperfusion treatments including intravenous thrombolysis and mechanical thrombectomy should be investigated. There are data suggesting greater potential benefit from acute stroke reperfusion treatments in patients with ICLAD,[11] possibly due to better collaterals and larger areas of penumbra with less severe hypoperfusion.[12]

The main strengths of our study are the prospective consecutive recruitment of patients and the good follow-up rate. Though the sample size was relatively small, this study was sufficiently powered to show the independent association between ICLAD and poorer functional outcomes. The main limitations are that this study did not annotate if the ICLAD was related to the index stroke, asymptomatic or remotely symptomatic, and the severity of ICLAD. Other limitations are use of MRA or TCCD for ICLAD assessment instead of the gold standard digital subtraction angiography, and follow-up assessment by telephone rather than in-person visits.


 » Conclusions Top


In conclusion, ischemic stroke patients with ICLAD have poorer functional outcome at 6 months compared to those without ICLAD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Wong LK. Global burden of intracranial atherosclerosis. Int J Stroke 2006;1:158-9.  Back to cited text no. 1
    
2.
De Silva DA, Woon FP, Lee MP, Chen CP, Chang HM, Wong MC. South Asian patients with ischemic stroke: Intracranial large arteries are the predominant site of disease. Stroke 2007;38:2592-4.  Back to cited text no. 2
    
3.
Gorelick PB, Wong KS, Bae HJ, Pandey DK. Large artery intracranial occlusive disease: A large worldwide burden but a relatively neglected frontier. Stroke 2008;39:2396-9.  Back to cited text no. 3
    
4.
Mazighi M, Tanasescu R, Ducrocq X, Vicaut E, Bracard S, Houdart E, et al. Prospective study of symptomatic atherothrombotic intracranial stenoses: The GESICA study. Neurology 2006;66:1187-91.  Back to cited text no. 4
    
5.
Wong KS, Li H. Long-term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003;34:2361-6.  Back to cited text no. 5
    
6.
Korogi Y, Takahashi M, Nakagawa T, Mabuchi N, Watabe T, Shiokawa Y, et al. Intracranial vascular stenosis and occlusion: MR angiographic findings. AJNR Am J Neuroradiol 1997;18:135-43.  Back to cited text no. 6
    
7.
Wong KS, Li H, Chan YL, Ahuja A, Lam WW, Wong A, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease. Stroke 2000;31:2641-7.  Back to cited text no. 7
    
8.
North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-53.  Back to cited text no. 8
    
9.
Wang Y, Zhao X, Liu L, Soo YOY, Pu Y, Pan Y, et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: The Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke 2014;45:663-9.  Back to cited text no. 9
    
10.
Kang J, Kim N, Oh CW, Kwon OK, Jung CK, Kim WJ, et al. Symptomatic steno-occlusion of cerebral arteries and subsequent ischemic events in patients with acute ischemic stroke. J Stroke Cerebrovasc Dis 2014;23:e347-53.  Back to cited text no. 10
    
11.
Kim SJ, Ryoo S, Kim GM, Chung CS, Lee KH, Bang OY. Clinical and radiological outcomes after intracranial atherosclerotic stroke: A comprehensive approach comparing stroke subtypes. Cerebrovasc Dis 2011;31:427-34.  Back to cited text no. 11
    
12.
Kim SJ, Seok JM, Bang OY, Kim G-M, Kim KH, Jeon P, et al. MR mismatch profiles in patients with intracranial atherosclerotic stroke: A comprehensive approach comparing stroke subtypes. J Cereb Blood Flow Metab 2009;29:1138-45.  Back to cited text no. 12
    



 
 
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