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Original Article
Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: A transcranial Doppler study Sujay Sada, Yugandhar Reddy, Sampath Rao, Suvarna Alladi, Subash Kaul Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
Abstract
Address for correspondence: Dr. Subash Kaul, Department of Neurology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad ‑ 500 034, Telangana, India. E‑mail: [email protected] Received : 05-03-2014 Review completed : 02-06-2014 Accepted : 28-09-2014
Introduction: Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a non‑invasive bedside screening method for assessing cerebral blood flow. Aim: To investigate the prevalence of MCA stenosis in asymptomatic but high‑risk individuals for stroke. Materials and Methods: Prospective study between December 2011 and December 2013. Vascular risk factors considered included: hypertension (HTN), diabetes mellitus, smoking, alcohol consumption, coronary artery disease (CAD), peripheral vascular disease (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine through the temporal windows by use of a standardized protocol. Results: Of the 427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean age was 54.2 ± 7.6 years. The frequency of the risk factors was: HTN 287 (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%), smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had normal intracranial arteries. On univariate analysis, subjects with higher age, HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial arterial stenosis (P 140 mm of Hg or diastolic blood pressure >90 mm of Hg, a clear history of HTN or on medication, or both. Subjects with DM were those with documented diabetes in their medical record, or fasting plasma glucose above 126 mg/dL or those who have taken drugs used for diabetes treatment. 511
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History of smoking included self‑reported habit of past or current smoking. We defined habitual alcohol drinking when subjects self‑reported habitual alcohol drinking in the past or present. [26] Cardiovascular disease included history of Myocardial infarction or angina. PVD meant past history of PVD or present active PVD. Fasting cholesterol >200 mg/dl was taken as hypercholesterolemia.[27] Obesity was defined as BMI of >30 kg/m2.[28] TCD examination TCD was performed with portable machine (Multi‑dop®B + DWL), which is a 2 MHz, power motion single‑channel TCD. We studied the bilateral middle cerebral arteries through the temporal windows by use of a standardized protocol.[29] The locations of the arterial segment under study are illustrated in Figure 1. We recorded insonation depth, peak systolic velocity, end diastolic velocity, mean flow velocity for all vessels. Cerebral arteries that could not be insonated because of poor acoustic windows were excluded from the study. We diagnosed the presence of intracranial arterial stenosis according to the peak flow velocity based on published criteria which was validated against MR angiography and clinical outcomes.[23] Briefly, the criteria for stenosis of arteries were defined by the peak systolic flow velocity more than 140 cm/sec for the middle cerebral artery (MCA).[30]
sample T test. Chi square test was also used for comparing sex in the intracranial stenotic arterial group. Univariate and multivariate analyses were also done to know the predictors of intracranial arterial stenosis.
Results We examined a total of 427 subjects, of which 53 (12.4%) were excluded from the study because of poor/incomplete echo window for TCD and remaining 374 subjects were analyzed. Males were 264 (70.6%) and females were 110 (29.4%). Mean age was 54.2 ± 7.6 (Range 41-85 yrs). The overall risk factors were HTN in 287 (76.7%), DM in 220 (58.8%), CAD in 120 (32.1%), hypercholesterolemia in 181 (48.4%), smoking in 147 (39.3%), alcohol in 99 (26.5%), obesity in 198 (52.9%) and peripheral arterial disease in 7 (1.9%) as shown in Table 1. Twenty‑seven (7.2%) of 374 patients had intracranial arterial stenosis and 347 (92.8%) had normal intracranial arteries. TCD on a patient with peak systolic flow velocity >140 cm/sec is shown in Figure 2.
Statistical analysis Data was entered in a spreadsheet and statistical evaluation was done using the IBM SPSS Statistics 20. Descriptive statistical values like mean and standard deviation (SD) were calculated for parameters required. Chi square test was used for various risk factors comparing between normal intracranial arterial group and stenotic intracranial arterial group. Mean age between stenotic and non stenotic group was compared using Independent
Mean age was 58.3 ± 4.3 years. The overall risk factors in stenotic group were HTN 26 (96.3%), DM 20 (74.1%), CAD 20 (74.1%), hypercholesterolemia 18 (66.6%), smoking 16 (59.3%), alcohol 10 (37%), obesity 19 (70.4%) and peripheral arterial disease 1 (3.7%) as shown in Table 2. The differences in patient characteristics between those with and without intracranial arterial stenosis are shown in Table 2. Stenotic group had higher mean age and higher number of HTN, DM, CAD, smokers, alcoholics, hypercholesterolemia, PVD and obese subjects compared to non‑stenotic group. The P value with Chi square test was calculated for various factors between non‑stenotic versus stenotic group, which showed statistical significance (P 0.05).
stenosis. Overall prevalence of intracranial arterial stenosis was 7.2% (27 of 374) in this study.
In univariate analysis, associated indicators for stenosis include HTN (OR 8.6, P 0.05) as shown in Table 3. Multivariate analysis, HTN and CAD are independent risk factors for intracranial arterial
Ischemic stroke is a heterogeneous disease with a variety of pathophysiological mechanisms. Stroke prevention is of paramount importance. Recent successes in stroke prevention underscore the importance of targeting therapy specifically to remedy the underlying mechanisms, such as carotid stenosis and atrial fibrillation. Presence of intracranial stenosis is of clinical significance because it is an additional independent predictor for survival and recurrent events. Knowledge of intracranial disease in the symptomatic and especially the asymptomatic high risk population may be useful for evaluating future treatment modalities. There are marked differences in the distribution of arterial lesions among different populations. In white individuals, carotid stenosis is a common cause of cerebral ischemia. In contrast, intracranial large artery stenosis is the predominant vascular lesion found in patients of Asian, African, or Hispanic ancestry.[5,31‑34] Previous studies found that intracranial large artery disease was prevalent among 69% to 84% of ethnic South Asians with large artery stroke.[1,2,35] Because of the large populations in Asia and Africa, intracranial large artery occlusive disease may be regarded perhaps numerically as the most common vascular cause of stroke in the world.
Table 1: Baseline characteristics of study population
Number; n=374 (%)
Variable Men Women HTN Diabetes Smokers Alcoholics CAD Hypercholesterolemia Obesity PVD
264 (70.6) 110 (29.4) 287 (76.7) 220 (58.8) 147 (39.3) 99 (26.5) 120 (32.1) 181 (48.4) 198 (52.9) 7 (1.9)
HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Table 2: Demographic characteristics and various risk factors among non‑stenotic group and stenotic group
Parameters No. of men No. of women Mean age (SD) Age range HTN Diabetics Smokers Alcoholics CAD Hypercholesterolemia PVD Obesity
Non‑Stenotic group (%)
Stenotic group (%)
245 (70.6) 102 (29.4) 53.9±7.7 41–85 261 (75.2) 200 (57.6) 131 (37.8) 89 (25.6) 100 (28.8) 163 (46.9) 6 (0.01) 198 (52.9)
19 (70.3) 8 (29.7) 58.3±4.3 49−68 26 (96.3) 20 (74.1) 16 (59.3) 10 (37) 20 (74.1) 18 (66.6) 1 (3.7) 19 (70.4)
P value
0.003 0.013 0.095 0.028 0.196 0.0001 0.049 0.466 0.06
SD ‑ Standard deviation, HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Table 3: Odds ratio of various risk factors in intracranial stenotic group
Variable HTN Diabetics Smokers Alcoholics Hypercholesterolemia CAD PVD Obesity
Odds ratio
95%CI
8.6 2.1 2.4 1.7 2.3 7 2.8 2.2
1.1-64 0.8-5 1-5.3 0.7-3.9 1-5 2.8-17.2 0.3-18.9 0.9-5.2
HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Neurology India | Sep-Oct 2014 | Vol 62 | Issue 5
Discussion
The present study is a prospective study to assess the prevalence of intracranial arterial stenosis in patients asymptomatic for stroke with various vascular risk factors. This is the first study from India about intracranial arterial stenosis in asymptomatic patients. The overall prevalence of intracranial arterial stenosis in this study was 7.2%. Previous studies have shown asymptomatic intracranial arterial steno‑occlusion ranging from 6.9% to 16.4%.[13,36‑39] High prevalence in present study is probably because all studied patients had at least one vascular risk factor and majority of the patients have more than one vascular risk factor. Intracranial stenosis is the most common stroke mechanism found in 26% of patients in our stroke registry and likely to be the common mechanism in other parts of India (personal communication). Detecting these patients at an asymptomatic stage will help to treat these patients aggressively to prevent the stroke. Association of intracranial stenosis with CAD in our patients emphasizes the need to screen for CAD in these patients. We have found that higher mean age, HTN, CAD, smoking and hypercholesterolemia 513
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were significant factors associated with intracranial arterial stenosis. These factors are well established factors for atherosclerosis. Our data is in agreement with previous community‑based studies in China by Wong et al.,[6,11,13,38] non‑community‑based studies in Thailand by Suwanwela et al. and Japan by Uehara et al.,[39,40] which reported that age, HTN, DM, CAD and hyperlipidemia were risk factors for intracranial stenosis. In this study, the frequency of DM was more in stenotic group compared to non‑stenotic group but it was not of statistical significance. Probably this was due to the small sample size. In our study, DM, alcohol, PVD and obesity were not significant factors for intracranial arterial stenosis. This is also similar with most of the previous studies reported by Wong et al.[11,13] Univariate and multivariate analyses were also done in this study. Univariate analysis found HTN, hypercholesterolemia CAD and smoking as risk factors for the development of intracranial arterial stenosis. But multivariate analysis showed only HTN and CAD as independent risk factors for the development of intracranial arterial stenosis, which is almost similar to the previous published studies on this subject.[11,13] This study design is cross‑sectional and only provides a snapshot of the health status as we did not know if the risk factors were present before or after the development of MCA stenosis. TCD is the only diagnostic tool used for this study without confirmation with angiography. We did not follow the stenosis group to assess rate of development of stroke over a period of time. In this study, the poor/incomplete window was found in 12.4%, which is similar to that reported previously.[11,13] This poor/incomplete window may over estimate or under estimate true prevalence of stenosis. The risk factor assessment was based on self‑reported response during the interview and minimal tests. Moreover, the study was conducted in a tertiary health care center. Further population‑based studies are needed to confirm the prevalence of intracranial arterial stenosis. Nevertheless, this study provides an estimate of the burden of intra cranial atherosclerosis and allows clinical trials of various approaches to prevent stroke in this high‑risk population.
Conclusions The overall prevalence of intracranial arterial stenosis is 7.2% in high‑risk non‑stroke population in a sample from the South Indian city of Hyderabad. Higher mean age, HTN, CAD, smoking and hypercholesterolemia were significant risk factors for intracranial arterial stenosis. HTN and CAD are independent risk factors for the development of intracranial arterial stenosis. 514
References 1. 2. 3.
4. 5. 6. 7. 8.
9. 10. 11. 12. 13. 14.
15.
16. 17. 18. 19. 20. 21.
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. Moussouttas M, Aguilar L, Fuentes K, Anyanwu B, Manassarians H, Papamitsakis N, et al. Cerebrovascular disease among patients from the Indian subcontinent. Neurology 2006;67:894‑6. Hussain S, Sukumaran S, Vajpayee A, Khan SU, Rahman KM, Chaturvedi S, et al. Pattern of intracranial versus extacranial atherosclerotic cerebrovascular disease in Indian patients with stroke – an angiography study. XVI European Stroke Conference Glasgow, United Kingdom 29 May – 1 June 2007. Li H, Wong KS. Racial distribution of intracranial and extracranial atherosclerosis. J Clin Neurosci 2003;10:30‑4. Gorelick PB, Caplan LR, Hier DB, Parker SL, Patel D. Racial differences in the distribution of anterior circulation occlusive disease. Neurology 1984;34:54‑9. Wong KS, Li H. Long‑term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003;34:2361‑6. Wong KS. Global burden of intra cranial atherosclerosis. Int J Stroke 2006;1:158‑9. Kaul S, Sunitha P, Suvarna A, Meena AK, Uma M, Reddy JM. Subtypes of Ischemic Stroke in a Metropolitan City of South India (One year data from a hospital based stroke registry). Neurol India 2002;50 Suppl: 8‑S14. Bogousslavsky J, Barnett HJ, Fox AJ, Hachinski VC, Taylor W. Atherosclerotic disease of the middle cerebral artery. Stroke 1986;17:1112‑20. Hermes P. The importance of Doppler studies in asymptomatic intracranial and extracranial arterial disease. Keio J Med 2002;51:189‑92. Wong KS, Ng PW, Tang A, Liu R, Yeung V, Tomlinson B. Prevalence of asymptomatic intracranial atherosclerosis in high‑risk patients. Neurology 2007;68:2035‑8. Wong KS, Huang YN, Yang HB, Gao S, Li H, Liu JY, et al. A door‑to‑door survey of intracranial atherosclerosis in Liangbei County, China. Neurology 2007;68:2031‑4. Lee IS, Yoon BW, Bac HJ. Correlation between coronary artery disease and atherosclerotic intracranial stenosis. Neurology 1998;50:Suppl 4:A296. Bendszus M, Koltzenburg M, Burger R, Warmuth‑Metz M, Hofmann E, Solymosi L. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: A prospective study. Lancet 1999;354:1594‑7. Bash S, Villablanca JP, Jahan R, Duckwiler G, Tillis M, Kidwell C. Intracranial vascular stenosis and occlusive disease: Evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol 2005;26:1012‑21. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982;57:769‑74. de Bray JM, Joseph PA, Jeanvoine H, Maugin D, Dauzat M, Plassard F. Transcranial Doppler evaluation of middle cerebral artery stenosis. J Ultrasound Med 1988;7:611‑6. Rother J, Schwartz A, Rautenberg W, Hennerici M. Middle cerebral artery stenosis: Assessment by magnetic resonance angiography and transcranial Doppler ultrasound. Cerebrovasc Dis 1994;4:273‑9. Rorick MB, Nichols FT, Adams RJ. Transcranial Doppler correlation with angiography in detection of intracranial stenosis. Stroke 1994;25:1931‑4. Sliwka U, Klötzsch C, Popescu O, Brandt K, Schmidt P, Berlit P, et al. Do chronic middle cerebral artery stenoses represent an embolic focus? A multirange transcranial Doppler study. Stroke 1997;28:1324‑7. Felberg RA, Christou I, Demchuk AM, Malkoff M, Alexandrov AV. Screening for intracranial stenosis with transcranial Doppler: The accuracy of mean flow velocity thresholds. J Neuroimaging 2002;12:9‑14. Neurology India | Sep-Oct 2014 | Vol 62 | Issue 5
[Downloaded free from http://www.neurologyindia.com on Thursday, November 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for journal Sada, et al.: Prevalence of middle cerebral artery stenosis in asymptomatic subjects more than 40 years age group
22. Gao S, Lam WW, Chan YL, Liu JY, Wong KS. Optimal values of flow velocity on transcranial Doppler in grading middle cerebral artery stenosis in comparison with magnetic resonance angiography. J Neuroimaging 2002;12:213‑8. 23. Bang OY, Cho JH, Han BI, Joo IS, Kim DI, Huh K. Transcranial Doppler findings in middle cerebral arterial occlusive disease in relation to degree of stenosis and presence of concomitant stenoses. J Clin Ultrasound 2003;31:142‑51. 24. Tsivgoulis G, Sharma VK, Lao AY, Malkoff MD, Alexandrov AV. Validation of transcranial Doppler with computed tomography angiography in acute cerebral ischemia. Stroke 2007;38:1245‑9. 25. Dawber TR. The Framingham study: The epidemiology of atheroscerotic disease. Cambridge: Harvard University Press; 1980. 26. Kiechl S, Willeit J, Egger G, Oberhollenzer M, Aichner F. Alcohol consumption and carotid atherosclerosis: Evidence of dose‑dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study. Stroke 1994;25:1593‑8. 27. Rodríguez Artalejo F, Guallar‑Castillón P, Gutiérrez‑Fisac JL, Ramón Banegas J, del Rey Calero J. Socioeconomic level, sedentary lifestyle, and wine consumption as possible explanations for geographic distribution of cerebrovascular disease mortality in Spain. Stroke 1997;28:922‑8. 28. World Health Organisation Technical report series 894: “Obesity: Preventing and managing the global epidemic” Geneva: World Health Organisation 2000. PDF ISBN92‑4‑120894. 29. Aaslid R. Transcranial Doppler sonography. Vienna and Newyork: Springer‑Verlag; 1986. 30. Boddu DB, Sharma VK, Bandaru VC, Jyotsna Y, Padmaja D, Suvarna A, et al. Validation of transcranial Doppler with magnetic resonance angiography in acute cerebral ischemia. J Neuroimaging 2011;21:e34‑40. 31. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: A review. Stroke 1986;17:648‑55. 32. Nishimaru K, McHenry LC Jr, Toole JF. Cerebral angiographic and
33. 34. 35. 36.
37.
38. 39. 40.
clinical differences in carotid system transient ischemic attacks between American Caucasian and Japanese patients. Stroke 1984;15:56‑9. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race‑ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 1995;26:14‑20. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 1996;27:1974‑80. Wong KS, Huang YN, Gao S, Lam WW, Chan YL, Kay R. Intracranial stenosis in Chinese patients with acute stroke. Neurology 1998;50:812‑3. Yoon BW, Bae HJ, Kang DW, Lee SH, Hong KS, Kim KB, et al. Intracranial cerebral artery disease as a risk factor for central nervous system complications of coronary artery bypass graft surgery. Stroke 2001;32:94‑9. Uehara T, Tabuchi M, Hayashi T, Kurogane H, Yamadori A. Asymptomatic occlusive lesions of carotid and intracranial arteries in Japanese patients with ischemic heart disease: Evaluation by brain magnetic resonance angiography. Stroke 1996;27:393‑7. Uehara T, Tabuchi M, Mori E. Frequency and clinical correlates of occlusive lesions of cerebral arteries in Japanese patients without stroke. Evaluation by MR angiography. Cerebrovasc Dis 1998;8:267‑72. Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebral arteries: Intracranial versus extracranial. Neuroepidemiology 2003;22:37‑40. Uehara T, Tabuchi M, Mori E. Risk factors for occlusive lesions of intracranial arteries in stroke‑free Japanese. Eur J Neurol 2005;12:218‑22.
How to cite this article: Sada S, Reddy Y, Rao S, Alladi S, Kaul S. Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: A transcranial Doppler study. Neurol India 2014;62:510-5. Source of Support: Nil, Conflict of Interest: None declared.
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Original Article
Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: A transcranial Doppler study Sujay Sada, Yugandhar Reddy, Sampath Rao, Suvarna Alladi, Subash Kaul Department of Neurology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India
Abstract
Address for correspondence: Dr. Subash Kaul, Department of Neurology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad ‑ 500 034, Telangana, India. E‑mail: [email protected] Received : 05-03-2014 Review completed : 02-06-2014 Accepted : 28-09-2014
Introduction: Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a non‑invasive bedside screening method for assessing cerebral blood flow. Aim: To investigate the prevalence of MCA stenosis in asymptomatic but high‑risk individuals for stroke. Materials and Methods: Prospective study between December 2011 and December 2013. Vascular risk factors considered included: hypertension (HTN), diabetes mellitus, smoking, alcohol consumption, coronary artery disease (CAD), peripheral vascular disease (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine through the temporal windows by use of a standardized protocol. Results: Of the 427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean age was 54.2 ± 7.6 years. The frequency of the risk factors was: HTN 287 (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%), smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had normal intracranial arteries. On univariate analysis, subjects with higher age, HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial arterial stenosis (P 140 mm of Hg or diastolic blood pressure >90 mm of Hg, a clear history of HTN or on medication, or both. Subjects with DM were those with documented diabetes in their medical record, or fasting plasma glucose above 126 mg/dL or those who have taken drugs used for diabetes treatment. 511
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History of smoking included self‑reported habit of past or current smoking. We defined habitual alcohol drinking when subjects self‑reported habitual alcohol drinking in the past or present. [26] Cardiovascular disease included history of Myocardial infarction or angina. PVD meant past history of PVD or present active PVD. Fasting cholesterol >200 mg/dl was taken as hypercholesterolemia.[27] Obesity was defined as BMI of >30 kg/m2.[28] TCD examination TCD was performed with portable machine (Multi‑dop®B + DWL), which is a 2 MHz, power motion single‑channel TCD. We studied the bilateral middle cerebral arteries through the temporal windows by use of a standardized protocol.[29] The locations of the arterial segment under study are illustrated in Figure 1. We recorded insonation depth, peak systolic velocity, end diastolic velocity, mean flow velocity for all vessels. Cerebral arteries that could not be insonated because of poor acoustic windows were excluded from the study. We diagnosed the presence of intracranial arterial stenosis according to the peak flow velocity based on published criteria which was validated against MR angiography and clinical outcomes.[23] Briefly, the criteria for stenosis of arteries were defined by the peak systolic flow velocity more than 140 cm/sec for the middle cerebral artery (MCA).[30]
sample T test. Chi square test was also used for comparing sex in the intracranial stenotic arterial group. Univariate and multivariate analyses were also done to know the predictors of intracranial arterial stenosis.
Results We examined a total of 427 subjects, of which 53 (12.4%) were excluded from the study because of poor/incomplete echo window for TCD and remaining 374 subjects were analyzed. Males were 264 (70.6%) and females were 110 (29.4%). Mean age was 54.2 ± 7.6 (Range 41-85 yrs). The overall risk factors were HTN in 287 (76.7%), DM in 220 (58.8%), CAD in 120 (32.1%), hypercholesterolemia in 181 (48.4%), smoking in 147 (39.3%), alcohol in 99 (26.5%), obesity in 198 (52.9%) and peripheral arterial disease in 7 (1.9%) as shown in Table 1. Twenty‑seven (7.2%) of 374 patients had intracranial arterial stenosis and 347 (92.8%) had normal intracranial arteries. TCD on a patient with peak systolic flow velocity >140 cm/sec is shown in Figure 2.
Statistical analysis Data was entered in a spreadsheet and statistical evaluation was done using the IBM SPSS Statistics 20. Descriptive statistical values like mean and standard deviation (SD) were calculated for parameters required. Chi square test was used for various risk factors comparing between normal intracranial arterial group and stenotic intracranial arterial group. Mean age between stenotic and non stenotic group was compared using Independent
Mean age was 58.3 ± 4.3 years. The overall risk factors in stenotic group were HTN 26 (96.3%), DM 20 (74.1%), CAD 20 (74.1%), hypercholesterolemia 18 (66.6%), smoking 16 (59.3%), alcohol 10 (37%), obesity 19 (70.4%) and peripheral arterial disease 1 (3.7%) as shown in Table 2. The differences in patient characteristics between those with and without intracranial arterial stenosis are shown in Table 2. Stenotic group had higher mean age and higher number of HTN, DM, CAD, smokers, alcoholics, hypercholesterolemia, PVD and obese subjects compared to non‑stenotic group. The P value with Chi square test was calculated for various factors between non‑stenotic versus stenotic group, which showed statistical significance (P 0.05).
stenosis. Overall prevalence of intracranial arterial stenosis was 7.2% (27 of 374) in this study.
In univariate analysis, associated indicators for stenosis include HTN (OR 8.6, P 0.05) as shown in Table 3. Multivariate analysis, HTN and CAD are independent risk factors for intracranial arterial
Ischemic stroke is a heterogeneous disease with a variety of pathophysiological mechanisms. Stroke prevention is of paramount importance. Recent successes in stroke prevention underscore the importance of targeting therapy specifically to remedy the underlying mechanisms, such as carotid stenosis and atrial fibrillation. Presence of intracranial stenosis is of clinical significance because it is an additional independent predictor for survival and recurrent events. Knowledge of intracranial disease in the symptomatic and especially the asymptomatic high risk population may be useful for evaluating future treatment modalities. There are marked differences in the distribution of arterial lesions among different populations. In white individuals, carotid stenosis is a common cause of cerebral ischemia. In contrast, intracranial large artery stenosis is the predominant vascular lesion found in patients of Asian, African, or Hispanic ancestry.[5,31‑34] Previous studies found that intracranial large artery disease was prevalent among 69% to 84% of ethnic South Asians with large artery stroke.[1,2,35] Because of the large populations in Asia and Africa, intracranial large artery occlusive disease may be regarded perhaps numerically as the most common vascular cause of stroke in the world.
Table 1: Baseline characteristics of study population
Number; n=374 (%)
Variable Men Women HTN Diabetes Smokers Alcoholics CAD Hypercholesterolemia Obesity PVD
264 (70.6) 110 (29.4) 287 (76.7) 220 (58.8) 147 (39.3) 99 (26.5) 120 (32.1) 181 (48.4) 198 (52.9) 7 (1.9)
HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Table 2: Demographic characteristics and various risk factors among non‑stenotic group and stenotic group
Parameters No. of men No. of women Mean age (SD) Age range HTN Diabetics Smokers Alcoholics CAD Hypercholesterolemia PVD Obesity
Non‑Stenotic group (%)
Stenotic group (%)
245 (70.6) 102 (29.4) 53.9±7.7 41–85 261 (75.2) 200 (57.6) 131 (37.8) 89 (25.6) 100 (28.8) 163 (46.9) 6 (0.01) 198 (52.9)
19 (70.3) 8 (29.7) 58.3±4.3 49−68 26 (96.3) 20 (74.1) 16 (59.3) 10 (37) 20 (74.1) 18 (66.6) 1 (3.7) 19 (70.4)
P value
0.003 0.013 0.095 0.028 0.196 0.0001 0.049 0.466 0.06
SD ‑ Standard deviation, HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Table 3: Odds ratio of various risk factors in intracranial stenotic group
Variable HTN Diabetics Smokers Alcoholics Hypercholesterolemia CAD PVD Obesity
Odds ratio
95%CI
8.6 2.1 2.4 1.7 2.3 7 2.8 2.2
1.1-64 0.8-5 1-5.3 0.7-3.9 1-5 2.8-17.2 0.3-18.9 0.9-5.2
HTN ‑ Hypertension, CAD ‑ Coronary artery disease, PVD ‑ Peripheral vascular disease
Neurology India | Sep-Oct 2014 | Vol 62 | Issue 5
Discussion
The present study is a prospective study to assess the prevalence of intracranial arterial stenosis in patients asymptomatic for stroke with various vascular risk factors. This is the first study from India about intracranial arterial stenosis in asymptomatic patients. The overall prevalence of intracranial arterial stenosis in this study was 7.2%. Previous studies have shown asymptomatic intracranial arterial steno‑occlusion ranging from 6.9% to 16.4%.[13,36‑39] High prevalence in present study is probably because all studied patients had at least one vascular risk factor and majority of the patients have more than one vascular risk factor. Intracranial stenosis is the most common stroke mechanism found in 26% of patients in our stroke registry and likely to be the common mechanism in other parts of India (personal communication). Detecting these patients at an asymptomatic stage will help to treat these patients aggressively to prevent the stroke. Association of intracranial stenosis with CAD in our patients emphasizes the need to screen for CAD in these patients. We have found that higher mean age, HTN, CAD, smoking and hypercholesterolemia 513
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were significant factors associated with intracranial arterial stenosis. These factors are well established factors for atherosclerosis. Our data is in agreement with previous community‑based studies in China by Wong et al.,[6,11,13,38] non‑community‑based studies in Thailand by Suwanwela et al. and Japan by Uehara et al.,[39,40] which reported that age, HTN, DM, CAD and hyperlipidemia were risk factors for intracranial stenosis. In this study, the frequency of DM was more in stenotic group compared to non‑stenotic group but it was not of statistical significance. Probably this was due to the small sample size. In our study, DM, alcohol, PVD and obesity were not significant factors for intracranial arterial stenosis. This is also similar with most of the previous studies reported by Wong et al.[11,13] Univariate and multivariate analyses were also done in this study. Univariate analysis found HTN, hypercholesterolemia CAD and smoking as risk factors for the development of intracranial arterial stenosis. But multivariate analysis showed only HTN and CAD as independent risk factors for the development of intracranial arterial stenosis, which is almost similar to the previous published studies on this subject.[11,13] This study design is cross‑sectional and only provides a snapshot of the health status as we did not know if the risk factors were present before or after the development of MCA stenosis. TCD is the only diagnostic tool used for this study without confirmation with angiography. We did not follow the stenosis group to assess rate of development of stroke over a period of time. In this study, the poor/incomplete window was found in 12.4%, which is similar to that reported previously.[11,13] This poor/incomplete window may over estimate or under estimate true prevalence of stenosis. The risk factor assessment was based on self‑reported response during the interview and minimal tests. Moreover, the study was conducted in a tertiary health care center. Further population‑based studies are needed to confirm the prevalence of intracranial arterial stenosis. Nevertheless, this study provides an estimate of the burden of intra cranial atherosclerosis and allows clinical trials of various approaches to prevent stroke in this high‑risk population.
Conclusions The overall prevalence of intracranial arterial stenosis is 7.2% in high‑risk non‑stroke population in a sample from the South Indian city of Hyderabad. Higher mean age, HTN, CAD, smoking and hypercholesterolemia were significant risk factors for intracranial arterial stenosis. HTN and CAD are independent risk factors for the development of intracranial arterial stenosis. 514
References 1. 2. 3.
4. 5. 6. 7. 8.
9. 10. 11. 12. 13. 14.
15.
16. 17. 18. 19. 20. 21.
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. Moussouttas M, Aguilar L, Fuentes K, Anyanwu B, Manassarians H, Papamitsakis N, et al. Cerebrovascular disease among patients from the Indian subcontinent. Neurology 2006;67:894‑6. Hussain S, Sukumaran S, Vajpayee A, Khan SU, Rahman KM, Chaturvedi S, et al. Pattern of intracranial versus extacranial atherosclerotic cerebrovascular disease in Indian patients with stroke – an angiography study. XVI European Stroke Conference Glasgow, United Kingdom 29 May – 1 June 2007. Li H, Wong KS. Racial distribution of intracranial and extracranial atherosclerosis. J Clin Neurosci 2003;10:30‑4. Gorelick PB, Caplan LR, Hier DB, Parker SL, Patel D. Racial differences in the distribution of anterior circulation occlusive disease. Neurology 1984;34:54‑9. Wong KS, Li H. Long‑term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke 2003;34:2361‑6. Wong KS. Global burden of intra cranial atherosclerosis. Int J Stroke 2006;1:158‑9. Kaul S, Sunitha P, Suvarna A, Meena AK, Uma M, Reddy JM. Subtypes of Ischemic Stroke in a Metropolitan City of South India (One year data from a hospital based stroke registry). Neurol India 2002;50 Suppl: 8‑S14. Bogousslavsky J, Barnett HJ, Fox AJ, Hachinski VC, Taylor W. Atherosclerotic disease of the middle cerebral artery. Stroke 1986;17:1112‑20. Hermes P. The importance of Doppler studies in asymptomatic intracranial and extracranial arterial disease. Keio J Med 2002;51:189‑92. Wong KS, Ng PW, Tang A, Liu R, Yeung V, Tomlinson B. Prevalence of asymptomatic intracranial atherosclerosis in high‑risk patients. Neurology 2007;68:2035‑8. Wong KS, Huang YN, Yang HB, Gao S, Li H, Liu JY, et al. A door‑to‑door survey of intracranial atherosclerosis in Liangbei County, China. Neurology 2007;68:2031‑4. Lee IS, Yoon BW, Bac HJ. Correlation between coronary artery disease and atherosclerotic intracranial stenosis. Neurology 1998;50:Suppl 4:A296. Bendszus M, Koltzenburg M, Burger R, Warmuth‑Metz M, Hofmann E, Solymosi L. Silent embolism in diagnostic cerebral angiography and neurointerventional procedures: A prospective study. Lancet 1999;354:1594‑7. Bash S, Villablanca JP, Jahan R, Duckwiler G, Tillis M, Kidwell C. Intracranial vascular stenosis and occlusive disease: Evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol 2005;26:1012‑21. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982;57:769‑74. de Bray JM, Joseph PA, Jeanvoine H, Maugin D, Dauzat M, Plassard F. Transcranial Doppler evaluation of middle cerebral artery stenosis. J Ultrasound Med 1988;7:611‑6. Rother J, Schwartz A, Rautenberg W, Hennerici M. Middle cerebral artery stenosis: Assessment by magnetic resonance angiography and transcranial Doppler ultrasound. Cerebrovasc Dis 1994;4:273‑9. Rorick MB, Nichols FT, Adams RJ. Transcranial Doppler correlation with angiography in detection of intracranial stenosis. Stroke 1994;25:1931‑4. Sliwka U, Klötzsch C, Popescu O, Brandt K, Schmidt P, Berlit P, et al. Do chronic middle cerebral artery stenoses represent an embolic focus? A multirange transcranial Doppler study. Stroke 1997;28:1324‑7. Felberg RA, Christou I, Demchuk AM, Malkoff M, Alexandrov AV. Screening for intracranial stenosis with transcranial Doppler: The accuracy of mean flow velocity thresholds. J Neuroimaging 2002;12:9‑14. Neurology India | Sep-Oct 2014 | Vol 62 | Issue 5
[Downloaded free from http://www.neurologyindia.com on Thursday, November 13, 2014, IP: 202.177.173.189] || Click here to download free Android application for journal Sada, et al.: Prevalence of middle cerebral artery stenosis in asymptomatic subjects more than 40 years age group
22. Gao S, Lam WW, Chan YL, Liu JY, Wong KS. Optimal values of flow velocity on transcranial Doppler in grading middle cerebral artery stenosis in comparison with magnetic resonance angiography. J Neuroimaging 2002;12:213‑8. 23. Bang OY, Cho JH, Han BI, Joo IS, Kim DI, Huh K. Transcranial Doppler findings in middle cerebral arterial occlusive disease in relation to degree of stenosis and presence of concomitant stenoses. J Clin Ultrasound 2003;31:142‑51. 24. Tsivgoulis G, Sharma VK, Lao AY, Malkoff MD, Alexandrov AV. Validation of transcranial Doppler with computed tomography angiography in acute cerebral ischemia. Stroke 2007;38:1245‑9. 25. Dawber TR. The Framingham study: The epidemiology of atheroscerotic disease. Cambridge: Harvard University Press; 1980. 26. Kiechl S, Willeit J, Egger G, Oberhollenzer M, Aichner F. Alcohol consumption and carotid atherosclerosis: Evidence of dose‑dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study. Stroke 1994;25:1593‑8. 27. Rodríguez Artalejo F, Guallar‑Castillón P, Gutiérrez‑Fisac JL, Ramón Banegas J, del Rey Calero J. Socioeconomic level, sedentary lifestyle, and wine consumption as possible explanations for geographic distribution of cerebrovascular disease mortality in Spain. Stroke 1997;28:922‑8. 28. World Health Organisation Technical report series 894: “Obesity: Preventing and managing the global epidemic” Geneva: World Health Organisation 2000. PDF ISBN92‑4‑120894. 29. Aaslid R. Transcranial Doppler sonography. Vienna and Newyork: Springer‑Verlag; 1986. 30. Boddu DB, Sharma VK, Bandaru VC, Jyotsna Y, Padmaja D, Suvarna A, et al. Validation of transcranial Doppler with magnetic resonance angiography in acute cerebral ischemia. J Neuroimaging 2011;21:e34‑40. 31. Caplan LR, Gorelick PB, Hier DB. Race, sex and occlusive cerebrovascular disease: A review. Stroke 1986;17:648‑55. 32. Nishimaru K, McHenry LC Jr, Toole JF. Cerebral angiographic and
33. 34. 35. 36.
37.
38. 39. 40.
clinical differences in carotid system transient ischemic attacks between American Caucasian and Japanese patients. Stroke 1984;15:56‑9. Sacco RL, Kargman DE, Gu Q, Zamanillo MC. Race‑ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 1995;26:14‑20. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 1996;27:1974‑80. Wong KS, Huang YN, Gao S, Lam WW, Chan YL, Kay R. Intracranial stenosis in Chinese patients with acute stroke. Neurology 1998;50:812‑3. Yoon BW, Bae HJ, Kang DW, Lee SH, Hong KS, Kim KB, et al. Intracranial cerebral artery disease as a risk factor for central nervous system complications of coronary artery bypass graft surgery. Stroke 2001;32:94‑9. Uehara T, Tabuchi M, Hayashi T, Kurogane H, Yamadori A. Asymptomatic occlusive lesions of carotid and intracranial arteries in Japanese patients with ischemic heart disease: Evaluation by brain magnetic resonance angiography. Stroke 1996;27:393‑7. Uehara T, Tabuchi M, Mori E. Frequency and clinical correlates of occlusive lesions of cerebral arteries in Japanese patients without stroke. Evaluation by MR angiography. Cerebrovasc Dis 1998;8:267‑72. Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebral arteries: Intracranial versus extracranial. Neuroepidemiology 2003;22:37‑40. Uehara T, Tabuchi M, Mori E. Risk factors for occlusive lesions of intracranial arteries in stroke‑free Japanese. Eur J Neurol 2005;12:218‑22.
How to cite this article: Sada S, Reddy Y, Rao S, Alladi S, Kaul S. Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: A transcranial Doppler study. Neurol India 2014;62:510-5. Source of Support: Nil, Conflict of Interest: None declared.
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