Distribution, Severity and Radiologic Features of Intracranial Stenosis in Asymptomatic Pakistanis

Research Article

Austin J Cerebrovasc Dis & Stroke. 2014;1(3): 1013.

Distribution, Severity and Radiologic Features of Intracranial Stenosis in Asymptomatic Pakistanis

Ayeesha K Kamal1*, Farzin Majeed2, Muhammad S Ilyas3, Munawar Hussain4, Kamran Masood4, Bilal Ahmed5, Hasan Rehman6, Zafar Sajjad7 and Scott E Kasner8

1Department of Neurology and Stroke Service, Aga Khan University, Pakistan

2Fogarty Cerebrovascular Research Fellow, Aga Khan University, Pakistan

3Department of Neurology, Dow University of Health Sciences, Pakistan

4Department of Radiology, Dow University of Health Sciences, Pakistan

5Department of Epidemiology and Biostatistics, Aga KhanUniversity, Pakistan

6Department of Medicine, Aga Khan University, Pakistan

7Department of Radiology, Aga Khan University, Pakistan

8Department of Neurology, University of Pennsylvania, USA

*Corresponding author: Ayeesha Kamran Kamal, Department of Neurology, Aga Khan University, Stadium Road –74800, Karachi, Pakistan

Received: July 15, 2014; Accepted: August 15, 2014; Published: August 19, 2014


Background: Intracranial atherosclerotic disease (ICAD) is the most common ischemic stroke subtype globally. It accounts for 30-50% of all ischemic strokes in Asians.

Aims: The aim of the study is to report the frequency of asymptomatic ICAD and its associated Magnetic Resonance Imaging (MRI) findings.

Methods: 200 adult participants were recruited from the Radiology Departments of two major diagnostic centers in Karachi. Eligible participants were confirmed for the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS). QVSFS negative subjects underwent MRI on a 1.5 Tesla scanner. Images were centrally reviewed on Di com Viewer 3.0 with electronic calipers to calculate the degree of ICAD.

Results: Mean age of subjects was 37.1 years (S.D 15.1) with50.5% men (n=101) and 49.5% women (n=99).Asymptomatic ICAD was found in34.5% (n=69) subjects. Of the 3800 intracranial arteries studied, 2.2% (n=88) had biological disease. 20.5% (n=18) of these vessels had atherosclerotic irregularities, 43.2% (n=38) had mild stenos is, 11.4% (n=10) had moderate stenos is, 5.7% (n=5) had severe stenos is while 19.3% (n=17) were completely occluded. The posterior cerebral artery (42% of stenosed arteries, n=37) was most affected. 23.5% (n=47) of subjects had peri-ventricular lucencies, 10.5% (n=21) had brain atrophy while 3.5% (n=7) had silent brain infarcts. There was a significant association between asymptomatic ICAD and peri ventricular lucencies (PR 1.59; 95% CI 1.35-1.99).

Conclusion: Asymptomatic ICAD is common in young Pakistanis, with no gender predilection; it preferentially affects the posterior circulation. Silent infarcts are rare compared to peri ventricular lucencies and atrophy.

Keywords: Stroke; Intracranial Stenosis; Developing Countries; Asymptomatic; Radiology; Prevention; Epidemiology


Two-thirds of stroke-related mortality worldwide is attributable to stroke in low and middle income countries [1]. Pakistan, currently the world’s sixth most populous nation [2,3], reports a1 in 4 lifetime prevalence of stroke symptoms over the age of 35 years [4]. Intracranial atherosclerotic disease (ICAD) is a major subtype of ischemic stroke [5] with an estimated prevalence of 20-54% amongst South Asians [6]. In fact, about 30-50% of all ischemic strokes in Asians occur due to ICAD [7].

The Karachi Intracranial Stenosis Study (KISS) [8], that looked at symptomatic ICAD stroke in hospitalized patients reported that 80% patients had significant concomitant asymptomatic stenosis (> 70% stenosis).


There is a relative paucity of data on asymptomatic ICAD especially from regions where it is most prevalent and wherein the window for intervention for primary prevention lies. The aim of the asymptomatic ICAD study is to determine the frequency of ICAD in those without clinically evident stroke and its associated Magnetic Resonance Angiography (MRA) findings. Findings from this study will help us determine the magnitude of asymptomatic ICAD in the Pakistani population and with it identifies the need to act early and focus on primary prevention.


We have summarized this study in this paper and provided relevant details. The entire study protocol is accessible at www. clinicaltrials.gov at Study ID: NCT0207287.

Study Design and Setting

A prospective cross-sectional study was carried out from March to June 2013 at the Radiology Departments of Aga Khan University [9] and Dow University of Health Sciences (DUHS) in Karachi.

Participating centers

Aga Khan University is a private not for profit academic center with a fee for service system. The Dow University Radiology Center is public sector, government funded and subsidized entity. Radiology departments in both centers are equipped with 1.5 Tesla MRI scanners.

City /Country setting

These centers are located in Karachi, Pakistan’s largest city with inhabitants of all ethnicities; Karachi has a population of 13 million inhabitants [10] and these centers cover the bulk of MRI scanning for the city and the country with combined volumes of greater than 2000 scans per month. These are general volumes of patient turnover.

Study population

We recruited adult Pakistani patients >18 years who presented to the participating centers for MRI Brain for indications other than transient ischemic attack (TIA) or stroke(headache, epilepsy, rhino sinusitis etc.). Subjects were required to have no clinical history of stroke or TIA, confirmed by a negative result on the Questionnaire to Verify Stroke-free Status (QVSFS).

Data collection procedures/ study flow

Non-probability purposive sampling was used to recruit consecutive patients prospectively from the two study sites. All eligible participants were screened for presence of stroke symptoms via QVSFS by trained data collectors after which an informed consent was taken for enrollment into the study. A previously tested Urdu version of QVSFS was used [4,11,12]. QVSFS consists of eight questions, six of which are related to stroke symptoms namely hemiplegia, hemi-anesthesia, hemianopia, loss of vision in one eye, inability to speak and inability to understand [13]. Those who consented to the study and were QVSFS negative were subject to detailed interview and an additional 5 minute Time of flight MRA without contrast was performed. Images were then collected on Compact Disks (CD) for centralized image viewing and quantification. The reviewers were experienced investigators who had previously systematically reviewed vasculature and were unaware of the medical history of the participant.

Data collection tools/ variables

A standardized Data collection form (DCF) was used to collect baseline demographic information.

A magnetic resonance imaging (MRI) reading form adapted from the work of Ward law [14,15] was used to review imaging findings. Modifications made to the form included using angiographic data to record information on cerebral vasculature. In each subject, 19 arteries (bilateral anterior cerebral arteries (A1&A2), bilateral middle cerebral arteries (M1&M2), bilateral posterior cerebral arteries, bilateral vertebral arteries, bilateral internal carotid artery- petrous bilateral internal carotid artery- cavernous, bilateral internal carotid artery- supraclinoid and basilar artery) were examined for the number, degree, and distribution of stenosis. Biologically relevant disease ranging from atherosclerotic irregularity to measurable stenosis was noted and measured. The following radiologic variables were noted : stroke [16], acute stroke lesions [17], silent brain infarcts [18], cortical infarcts [19], lacunar infarcts [19], atrophy [20], leukoaraiosis [21], arterial review [22,23]. All radiologic data were directly archived into a centralized computer using Dicom 3.0 software. The method used to calculate stenosis was adapted from the one used in the Warfarin versus Aspirin in Symptomatic Intracranial Disease [24] study which is as follows:

Percentage stenosis= [1- (Dstenosis/D normal)*100[14, 25]

Where D stenosis is the diameter of the artery at the site of the most severe stenosis, and D normal is the diameter of the proximal normal artery.

The software allowed zooming, panning, measurements, annotations and segmentation of the images. It has the ability to rotate (90, 180 degrees) and flip (horizontal, vertical) images. It also provides angle values which helps in measuring stenosis around corners. Intracranial occlusive lesions were rated by giving them 1 of 5 grades depending on the narrowness of the arteries as follows: <25% as atherosclerotic disease, 25% to 49% reduction as mild stenosis,50% to 74% reduction as moderate stenosis, 75% to 99% reduction as severe stenosis, and no opening graded as complete occlusion [17]. Any vessel that was congenitally absent or atretic was not counted as stenosed.

Peri ventricular lucency was classified according to the 3 point system proposed by van Swieten et al. [21].

Silent brain infarcts were defined as vascular disease manifesting as infarcts as detected on MRI in the absence of transient ischemic attack or stroke [18].

Ethical approval and human subjects’ protections

All participants provided written informed consent. This was taken after explaining the risks and benefits associated with taking part in the study. Ethical approval was taken from AKU Ethical Review Committee and the Institutional review board of DUHS. (ERC number 2327 CHS ERC 12 and IRB 360/DUHS 2012). All scans were reviewed within 24 hours by the radiology faculty and there was provision in the study to report any critical incidental findings like aneurysms first to the referring physician and in his absence or inability to contact , the report was communicated to the patient with an urgent specialist referral. All gathered data was numerically coded so as not to reveal the identity of the participants. All electronic transfer within centers was done through decoded CDs that were centralized to a single password protected workstation for analysis.

Sample size estimation

A minimum sample size of 200 participants was required in order to achieve 80 % power for detecting a minimum difference of 20% in the prevalence of radiological findings between asymptomatic ICAD positive and ICAD negative persons assuming a 1:3 ratio in patients with ICAD versus no ICAD and at a level of significance of 5%.

Statistical analysis

For categorical variables (brain atrophy, silent brain infarcts and peri-ventricular lucencies proportions were calculated. The independent contribution of any ICAD-associated finding was examined in the Univariate Cox proportional hazards model, which was used to calculate prevalence ratios. In order to compute the statistically adjusted Prevalence Ratios (PR), multivariable Cox regression analysis was done. The level of significance of ≤ 0.05 was set for the analysis. Statistical analyses were conducted using Statistical Package for Social Sciences (SPSS); Version 19.


Mean age of the participants was 37.1 years (S.D 15.1 years) with nearly 62% (n=124) of the participants being younger than 40 years. There was a roughly equal proportion of males (50.5%, n=101) and females (49.5%, n=99) in the study (Table I – Demographic Data).