Stroke, which occurs when blood flow to the region of the brain is interrupted, is a major cause of death and disability in the population. It is the second-most common cause of death worldwide. Ischemic stroke accounts for about 87% of all strokes. Atherosclerosis causing thrombosis and resultant narrowing or occlusion of vessels is the most common cause of ischemic stroke.[3, 4]
Racial differences in the distribution of cerebral atherosclerosis is well established in many studies.[5, 6, 7] Intracranial atherosclerotic stenosis is responsible for ischemic strokes in only 6%–10% of White patients but up to 29% of African-American and Asian patients, with 3-fold increased risk of intracranial atherothrombosis reported in South Asian patients.
Transient ischemic attack (TIA) is an important risk factor for recurrent stroke which is a major cause of increased mortality and morbidity. Hence, the importance of recognizing this event and prompt evaluation for disease extent to start early treatment which will reduce new or severe stroke subsequently. There has been an increasing focus on this secondary prevention of stroke in the recent years.[10, 11, 12]
Advances in low-frequency Doppler ultrasound as well as imaging resolution, color flow Doppler, and power Doppler have led to the use of these technologies for interrogation of intracranial circulation through the intact skull. Doppler combines the advantages of hemodynamic information, cost-effectiveness, and bedside application. It is safe, noninvasive, fast, and repeatable. Transcranial color-coded Doppler sonography (TCCS) may particularly be useful in patients who require repeated imaging.
This study was done to determine the accuracy of TCCS in evaluation of the cerebral arterial system in patients with ischemic stroke or TIA presenting to a tertiary care center in South India.
MATERIALS AND METHODS
Consecutive patients who presented to the neurology outpatient department during the study (March to October 2009) with a history of cerebral ischemia (TIA or ischemic stroke) and who were planned for magnetic resonance angiography (MRA) as part of evaluation were included in this study after obtaining informed consent.
The exclusion criteria included patients who have had a previous vascular surgery (endarterectomy) or endovascular procedures such as carotid stenting, age <35 years, hemorrhagic stroke, hyperacute stroke, and patients who lacked a suitable acoustic window for TCCS.
Using sensitivity of 94% (based on a previous review), precision index of 6, and 95% confidence interval, we calculated the sample size for those positive for intracranial disease on MRA to be 40 cases.
The risk factor profiles determined included age, gender, indicators of adiposity (body mass index [BMI], waist circumference [WC], and waist–hip ratio [WHR]), diabetes mellitus, hypertension, coronary artery disease, dyslipidemia, family history, smoking, and serum homocysteine levels. The National Cholesterol Education Program Adult Treatment Panel III uses a higher cutoff for WC, which may not be reflective of central obesity in our population; hence, the cutoffs we used were WC >90 and >80 in men and women, respectively. Men with WHR ≥0.93 and women with WHR ≥0.86 had significantly increased risks of ischemic stroke in simple and multivariate models. These were the cutoffs used in our study. The BMI was calculated with the Indian cutoffs based on the standards set by the Indian Health Ministry's consensus guidelines for the prevention and management of obesity and metabolic syndrome for the country. The cutoffs used were as follows: <18.4 – underweight, 18.5–22.9 – normal, 23–24.9 – overweight, and >25 – obese.
Hyperhomocysteinemia has been linked to various vascular events including carotid artery stenosis. This association has been described mostly for extracranial carotid artery stenosis.
The patients were classified into the subtypes of ischemic stroke based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, which is based on clinical symptoms as well as results of further investigations. Accordingly, stroke is classified as being due to (1) thrombosis or embolism due to atherosclerosis of a large artery, (2) embolism of cardiac origin, (3) occlusion of a small blood vessel, (4) other determined causes, and (5) undetermined cause (in case two possible causes or no cause identified, or incomplete investigation). Associated presence of leukoaraiosis (white matter hyperintensities) was also documented.
A neck Doppler was performed to evaluate atherosclerotic lesions in the common carotid artery, extracranial internal carotid artery (ICA), and vertebral arteries (VAs). The percentage degree of stenosis of the extracranial ICA was stratified based on the consensus panel gray scale and Doppler US criteria for diagnosis of ICA stenosis. Neck Doppler was performed on Xario SSA 660A, Toshiba Medical Systems Corporation, using an 8–12 MHz linear probe.
TCCS was performed on GE Logiq 500 Pro, GE Healthcare India, with 1.9–3 MHz sector array transducer. The bilateral terminal internal carotid artery (TICA) segments, middle cerebral artery (MCA-M1 and M2 branches), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were imaged through the transtemporal window with the patient in lying-down position [Figure 1], and the bilateral terminal VAs and proximal basilar artery (BA) were imaged through the transforaminal also called the transoccipital window with patients in either sitting or lying down, lateral position depending on the clinical condition of the patient [Figure 2]. The angle-corrected velocities were measured from the spectral display. Depending on the peak systolic velocity (PSV) recorded, Ralf W. Baumgartner criteria was used for stratifying ≥50%/< 50% stenosis in the various vascular segments as ≥155/≥120 cm/s for ACA, ≥220/≥155 cm/s for MCA main stem (M1), ≥145/≥100 cm/s for PCA, ≥140/≥100 cm/s for BA, and ≥120/≥90 cm/s for VA, respectively.
For intracranial TICA, elevation in PSV >120 cm/s was taken as the cutoff. Ratio with contralateral TICA or MCA of at least 2:1 also was taken as additional criteria for classification into ≥50% stenosis. Since there were no previous data available on velocity cutoffs for M2 stenosis, a value of ≥150/≥120 cm/s was taken in our study to classify as ≥50%/<50% stenosis in addition to the disturbed spectral flow pattern. Velocity in a single M2 branch which was well visualized was measured.
Unenhanced three-dimensional time of flight (TOF) MRA of the intracranial arteries was performed on 1.5 Tesla Magnetom Avanto, Siemens machine, and 3 Tesla Intera Achieva, Philips machines. The parameters used were repetition time (TR)/echo time (TE) (in milliseconds) of 24/8.6; 20° flip angle; 320 × 224 matrix; 0.6 mm section thickness with 0.12 mm slice gap on Siemens and TR/TE (in ms) of 25/3.4; 20° flip angle; 544 × 274 matrix; 1.4 mm section thickness with 0.7 mm slice gap for Philips machine, respectively.
The TCCS was performed by two observers in conjunction, and the observers included a radiology resident and a consultant neuroradiologist with >5 years of experience. The neck Doppler images recorded on picture archiving and communication systems (PACS) were first reviewed by the same observers followed by performance of TCCS. MRA images on the PACS were evaluated on a later day by the same observers. The stenosis grading was done by measurement of vessel caliber on the MRA source images.
Weighted kappa was computed to assess the agreement between TCCS and MRA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of color Doppler with respect to MRA was calculated. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) software (version 16, SPSS, Inc, Chicago, IL, USA).
The study was approved by the institutional review board.
Ninety patients satisfied the eligibility criteria for the study. The study group comprised of 78 males and 12 females. Majority (43.3%) of patients were in the age group of 50–60 years. The mean (standard deviation) age was 54.3 (9.9) years. The median time of the latest stroke episode in the patient from presentation was 3 months (range: <1–80 months).
Atherosclerotic risk factor profile
The atherosclerotic risk factors noted in the study population are shown in Table 1.
In patients who were smokers, the median pack years of smoking was 22.4 years (range: 1.8–156). Among patients who had intracranial atherosclerosis, 50% had diabetes and 68.8% had hypertension. Of the total of 1170 vascular segments studied by MRA, 1077 (92%) were successfully insonated. Suboptimal unilateral or bilateral temporal acoustic window was encountered in 13 (12.1%) patients.
The predominant subtype (TOAST) was small-artery occlusion (41.1%), followed by large-artery atherosclerosis (LAA) (33.3%), and stroke due to undetermined cause was 25.6%. Associated leukoaraiosis was found in 44.4% of patients. Leukoaraiosis was more prevalent in lacunar stroke subtype (64.9%).
Topographic distribution of cerebrovascular atherosclerosis
Intracranial atherosclerosis was found to be the predominant site of cerebral atherosclerotic disease in our study population, with 32/90 (35.6%) patients having significant intracranial arterial lesions. Isolated extracranial atherosclerosis was found in only 2/90 (2.2%), while combined intracranial and extracranial disease was found in 11/90 (12.2%). No significant proximal arterial lesion was found in 45/90 (50%) patients.
Distribution according to diseased vascular segments in intracranial circulation in our study population on MRA is shown in Table 2.
The distribution of diseased and normal vascular segments as evaluated on TCCS is shown in Table 3.
Comparison of transcranial color-coded Doppler sonography and magnetic resonance angiography
The weighted kappa values calculated to determine agreement between TCCS and MRA for assessment of various vascular segments in the intracranial circulation were 0.83 (good agreement between the two modalities) for ACA, 0.66 (fair agreement) for MCA, M1 segment, 0.45 (poor agreement) for MCA, M2 segment, 0.86 (good agreement) for TICA segment, 0.46 (poor agreement) for PCA segment, and 0.81 (good agreement) for VA segment.
The kappa value could not be computed for BA as there were not enough variables in the different disease categories to be compared.
The sensitivity, specificity, PPV, and NPVs for hemodynamically significant (≥50%) and normal/hemodynamically insignificant lesions (0%–49%) in the different vascular segments on TCCS in comparison to MRA are shown in Table 4.
As there were no hemodynamically significant (>50%) arterial lesions in the BA in our sample population, the accuracy parameters could not be assessed