Symptomatic Intracranial Atherosclerosis in an Australian Context: Common and Underdiagnosed in Multiple Ethnic Groups
Stroke: Vascular and Interventional Neurology
Abstract
Background
Intracranial atherosclerosis (ICAD) is a common cause of stroke globally. We calculated the proportion of patients with stroke with symptomatic intracranial atherosclerosis in an Australian multiethnic setting, as well as diagnostic rates by stroke physicians and radiologists.
Methods
This was a multicenter retrospective cohort study based in Melbourne, Australia. Demographic data (including self‐reported ethnicity) and data on vascular risk factors were collected. Symptomatic ICAD was independently identified by 2 blinded stroke neurologists using multiplanar reformats and maximum intensity projections of routinely acquired thin slice computed tomography angiography data, with disagreements resolved by a third blinded stroke neurologist. This diagnostic reference standard was compared to the proportion of patients with ICAD identified in the radiology report and stroke team clinical notes.
Results
Of 1328 patients included (mean age, 73 years; 43% female), the proportion of patients with centrally read symptomatic ICAD was 14%, of whom 39% were diagnosed by the stroke clinical team and 65% by the reporting radiologist. Patients of Asian ethnicity more commonly had symptomatic ICAD than patients of European ethnicity (21% versus 14%; odds ratio, 1.5 [95% CI, 1.0–2.23]).
Conclusion
Intracranial atherosclerosis is common and underdiagnosed in an Australian tertiary stroke care unit setting in patients from multiple ethnic backgrounds.
Graphical Abstract

Non‐standard Abbreviation and Acronym
- ICAD
- intracranial atherosclerosis
Clinical Perspective
What Is New?
•
This article is the first investigation of intracranial atherosclerosis (ICAD) epidemiology in a population with substantial numbers of patients of both European and Asian ethnicity; we found that 14% of patients with ischemic stroke in an Australian setting had symptomatic ICAD.
•
ICAD was significantly more common among patients of Asian ethnicity, although still a major contributor to stroke in patients of European ethnicity.
•
We found that only 39% of ICAD cases were diagnosed by the treating stroke team, with the presence of multiple competing stroke causes associated with ICAD being overlooked.
What Are the Clinical Implications?
•
Stroke physicians should have a high index of suspicion for intracranial atherosclerosis as it is a significant contributor to the ischemic stroke burden, requires specific management, and is likely currently underdiagnosed.
•
Stroke physicians should still consider ICAD in patients who have another potential cause, such as carotid atherosclerosis or atrial fibrillation, as these causes share risk factors and are likely synergistic.
•
The frequent use of computed tomography angiogram in the modern era affords an excellent opportunity to diagnose ICAD, particularly when the vasculature is reviewed in multiple planes and using maximal intensity projections.
Intracranial atherosclerosis (ICAD) is a major contributor to the global stroke burden. Reported rates of symptomatic ICAD are higher in Asian populations (16.2%–33.7%) than European populations (7.4%–12.1%).1 The epidemiology of the disease has never been studied in a population containing substantial numbers of patients from both ethnic groups. Melbourne, Australia, is an example of such a multiethnic population. According to the 2016 census, 36% of people in greater Melbourne were born overseas, with 44% of these born in Asia.2
Intracranial atherosclerosis is readily diagnosable in many stroke centers, as computed tomography (CT) angiography is routinely performed for patients with suspected stroke. CT‐angiography has been shown to be highly sensitive in diagnosing ICAD when compared with catheter angiograms, especially when maximal intensity projections are used.3, 4, 5 The accuracy of stroke physicians and radiologists in diagnosing ICAD has not previously been investigated.
The only standardized criteria for diagnosing ICAD are from the comparison of WASID (Warfarin and Aspirin for Symptomatic Intracranial Arterial Stenosis) trial.6 These criteria do not capture ICAD cases where there is complete occlusion, <30% stenosis, or positive remodeling.
This study aimed to evaluate the diagnosis of ICAD using CT‐angiography in an Australian tertiary hospital stroke unit setting. We assessed the proportion of symptomatic ICAD among patients with ischemic stroke overall, and by ethnicity. We also assessed the proportion of ICAD cases that were prospectively identified by stroke physicians and radiologists.
Methods
This was a multicenter retrospective cohort study. Data were collected from the Royal Melbourne Hospital, Austin, and Alfred hospitals in 2019 to 2020. The study was approved by the human ethics research committee. Data are available on reasonable request.
All patients admitted to the participating stroke units with ischemic stroke were reviewed. Patients who did not have an imaging‐confirmed ischemic stroke, did not have a CT‐angiogram, or were transferred from another hospital were excluded from the analysis.
Images were independently reviewed by 2 stroke neurologists, blinded to the findings of the other reviewer. In cases of disagreement, a third stroke neurologist was used as a tie‐breaker. CT‐angiograms were reviewed for evidence of intracranial atherosclerosis. All CT‐angiograms were reviewed in 3 planes, in both thin slice and maximal intensity projection reformats. Patients were categorized as having intracranial atherosclerosis if they had vessel stenosis >30% using comparison of WASID trial criteria,6 significant vascular calcification in atypical locations, or evidence of previous ICAD in a now‐occluded vessel. Because of its frequency, carotid siphon calcification was not considered sufficient to diagnose ICAD. Cases where there was another known cause for stenosis, such as dissection or vasculitis, were excluded from the ICAD group. Symptomatic intracranial atherosclerosis was defined as atherosclerosis in the same territory as the presenting stroke. Diagnostic rates by radiologists were assessed by reviewing radiology reports. Diagnostic rates by stroke physicians were assessed by reviewing discharge summaries and outpatient letters. Ethnicities were self‐reported and obtained from hospital records. Ethnicities were divided into European, Asian, Oceanian (including Indigenous Australian, Maori, Polynesian, and Micronesian ethnicities), African, Middle Eastern, and Hispanic.
Statistical Analysis
Statistical analyses were performed using IBM SPSS 29. The odds ratio (OR) for ICAD and ICAD diagnosis was calculated using logistic regression comparing Asian versus European ethnicities. European ethnicity was chosen as the reference category as most patients belong to this category and it had the lowest rate of symptomatic ICAD. Patients of other ethnicities were excluded from the logistic regression analysis because of insufficient numbers and were reported using descriptive statistics. Logistic regression was used to analyze the relationship between stroke unit diagnosis and age, sex, European or Asian ethnicity, vascular comorbidities, lesion location, degree of stenosis, stroke cause as diagnosed by the stroke team, presence of multiple stroke causes, pattern of infarction, and presence of carotid atherosclerosis.
Results
Of 2204 patients screened, 1328 were included in the final analysis after exclusion of 876 because of transfer from another hospital (600 [27%]), lack of a CT‐angiogram (271 [12%]), or lack of an imaging‐confirmed ischemic stroke (5 [0.2%]). The mean age of the patients was 73 years, and 43% were female. Among patients with available data, 29% (236/822) had diabetes, 16% (131/822) were smokers, 71% (585/822) had hypertension, and 53% (423/803) had hyperlipidemia.
There were 181 of 1328 (14%) patients with symptomatic intracranial atherosclerosis. Of 13 of 181 (7%) who were not diagnosed based on comparison of WASID trial criteria, 6 of 13 had complete occlusion with prior evidence of ICAD and 7 of 13 had significant calcification in atypical locations.
Of the cases identified retrospectively, 71 of 181 (39%) were prospectively identified by the stroke team and 116 of 181 (65%) by the reporting radiologist. The Table shows a breakdown of data by ethnicity. Ethnicity data were not available for 67 of 1328 (5%) patients. There were no significant associations between stroke team ICAD diagnosis and age, sex, European versus Asian ethnicity, vascular comorbidities, lesion location (see Table S1 in supplementary materials), degree of stenosis, stroke cause as diagnosed by the stroke team, pattern of infarction, and presence of carotid atherosclerosis.
Ethnicity | Symptomatic ICAD | Diagnosed by treating stroke team | Diagnosed by reporting radiologist |
---|---|---|---|
European | 145/1062 (14%) (OR 1.0) | 51/145 (35%) (OR 1.0) | 89/145 (61%) (OR 1.0) |
Asian | 23/112 (21%) (OR 1.5 [95% CI, 1.0–2.23]) | 13/23 (57%) (OR 2.4 [95% CI, 0.98–5.85]) | 19/23 (83%) (OR 5.02 [95% CI, 1.64–15.32]) |
Oceanian | 1/23 (4%) | 0/1 (0%) | 1/1 (100%) |
Middle Eastern | 6/32 (16%) | 4/6 (67%) | 4/6 (67%) |
African | 5/28 (18%) | 3/5 (60%) | 3/5 (60%) |
Hispanic | 0/4 (0%) | NA | NA |
Unknown | 1/67 (1%) | 0/1 (0%) | 0/1 (0%) |
Total | 181/1328 (14%) | 71/181 (39%) | 116/181 (64%) |
John Wiley & Sons, Ltd.
ICAD indicates intracranial atherosclerosis; and OR, odds ratio.
The stroke teams were significantly more likely to overlook the diagnosis of ICAD if there was a competing cause, such as carotid atherosclerosis or atrial fibrillation: 58 of 123 (47%) of ICAD cases were diagnosed where there were no competing causes, compared with 13 of 58 (22%) cases where there were multiple possible causes (OR, 0.3 [95% CI, 0.2–0.7]). We found that symptomatic ICAD is more common among Australian patients of Asian ethnicity than those of European ethnicity (21% versus 14%; OR, 1.5 [95% CI. 1.0–2.23).
Discussion
In this multicenter study, we found that ≈1 in 7 patients with ischemic stroke had symptomatic intracranial atherosclerosis, despite a predominance of European ethnicity (80% of patients).
Symptomatic ICAD is commonly reported as more common among Asian patients than European patients, although the reason for this difference is currently poorly understood. There is likely a genetic component, but our understanding of the specific genes that predispose to ICAD is currently limited.7 There are important environmental differences between European and Asian populations that likely contribute to ICAD, most significantly smoking rates, diabetes prevalence, and access to medical care.8 We found that symptomatic ICAD is more common among Australian patients of Asian ethnicity than those of European ethnicity (21% versus 14%; OR, 1.5 [95% CI. 1.0‐2.23), but less common than rates reported by most Asian ICAD epidemiology studies (16.2%–33.7%). This is consistent with the understanding that ICAD is a multifactorial disease with multiple genetic and environmental factors, some of which may be mitigated by the Australian environment.
We found higher rates of symptomatic ICAD in patients of European ethnicity compared with previous European studies: 6.9% in Oxfordshire, United Kingdom,9 and 2% in Germany,10 proportions more comparable to clinically diagnosed ICAD in our study. Additionally, CT‐angiography is more sensitive for ICAD than time‐of‐flight magnetic resonance angiography3 or transcranial Doppler11 used in those studies, particularly when multiplanar reconstructions maximal intensity projections are used (Figure ).11 This may also explain the underdiagnosis of ICAD by stroke neurologists in our study as, in the clinical setting, assessment of intracranial vessels is typically based on axial thin slice CT‐angiography. An additional explanation is that many of these previous studies adopted a definition of ICAD that only included stenoses of 50% to ‐99%. In contrast, our study additionally included patients with vessel occlusion if there was previous evidence of ICAD in the same location, lesions with significant positive remodeling, and 30% to 50% stenoses.

The underdiagnosis of ICAD in an Australian tertiary stroke setting is an important finding of this study. Only 39% of symptomatic ICAD cases were diagnosed by the stroke team. We found that the presence of alternative potential causes of stroke increased the likelihood of ICAD being overlooked by the stroke team. However, ICAD is an important risk factor for future stroke, deserving dedicated management. Diagnosis of ICAD may lead to altered blood pressure targets, prolonged dual‐antiplatelet therapy, more intensive lipid‐lowering therapy, and intracranial stenting.9 Although it did not reach significance, there was a strong trend toward ICAD being more likely to be diagnosed in Asian‐ancestry patients compared with European‐ancestry patients. This may reflect that ICAD is well‐recognized to occur commonly in Asian patients, but less well‐recognized as an important cause of stroke in European patients.
Limitations of this study include that we relied on clinical context to differentiate ICAD from other causes of intracranial stenosis, and some stenoses may have been misclassified. The definition of symptomatic atherosclerosis included any case where the stroke was in the same territory as the ICAD lesion, which may have led to the inclusion of bystander lesions. Patient numbers in ethnicities other than European were small, limiting the precision of estimates in those groups. CT angiogram has similar sensitivity to catheter angiograms in identifying ICAD. However, unlike black‐blood vessel wall magnetic resonance imaging, CT angiogram does not identify positive remodeling and can also lead to measurement errors in the internal carotid artery attributable to bony artefact.4 Finally, we only assessed stroke team diagnosis using outpatient letters and discharge summaries. It is possible that some ICAD was diagnosed but not related in these communications.
Conclusions
In conclusion, symptomatic intracranial atherosclerosis was present in ≈1 in 7 Australian patients with stroke, and more common in patients of Asian ethnicity. ICAD was substantially underdiagnosed, especially in patients with multiple potential causes of stroke.
Disclosures
None.
Sources of Funding
None.
Acknowledgements
None.
Supplemental Material
Table S1: Anatomic Location of Intracranial Atherosclerosis.
- Download
- 183.31 KB
REFERENCES
1.
Wong LK. Global burden of intracranial atherosclerosis. Int J Stroke. 2006;1:158–159.
2.
Australian Bureau of Statistics 2016, Census; 2016. Accesed 01/03/2024. https://www.abs.gov.au/websitedbs/censushome.nsf/home/2016
3.
Bash S, Villablanca JP, Jahan R, Duckwiler G, Tillis M, Kidwell C, Saver J, Sayre J. Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography. AJNR Am J Neuroradiol. 2005;26:1012–1021.
4.
Skutta B, Fürst G, Eilers J, Ferbert A, Kuhn FP. Intracranial stenoocclusive disease: double‐detector helical CT angiography versus digital subtraction angiography. AJNR Am J Neuroradiol. 1999;20:791–799.
5.
Duffis EJ, Jethwa P, Gupta G, Bonello K, Gandhi CD, Prestigiacomo CJ. Accuracy of computed tomographic angiography compared to digital subtraction angiography in the diagnosis of intracranial stenosis and its impact on clinical decision‐making. J Stroke Cerebrovasc Dis. 2013;22:1013–1017.
6.
Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol. 2000;21:643–646.
7.
Liu M, Gutierrez J. Genetic risk factors of intracranial atherosclerosis. Curr Atheroscler Rep. 2020;22:13.
8.
Saraf U, Prabhakaran S, Arun K, Babiker A, Rajendran A, Kesavadas C, Sylaja PN. Comparison of risk factors, treatment, and outcome in patients with symptomatic intracranial atherosclerotic disease in India and the United States. Ann Indian Acad Neurol. 2020;23:265–269.
9.
Hurford R, Wolters FJ, Li L, Lau KK, Küker W, Rothwell PM, Cohort OVSP. Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population‐based cohort study. Lancet Neurol. 2020;19:413–421.
10.
Weber R, Kraywinkel K, Diener HC, Weimar C, Collaboration GSS. Symptomatic intracranial atherosclerotic stenoses: prevalence and prognosis in patients with acute cerebral ischemia. Cerebrovasc Dis. 2010;30:188–193.
11.
Suwanwela NC, Suwanwela N, Phanthumchinda K. Comparison of transcranial Doppler ultrasound and computed tomography angiography in symptomatic middle cerebral artery stenosis. Australas Radiol. 2000;44:174–177.
Information & Authors
Information
Published In
Stroke: Vascular and Interventional Neurology
Copyright
© 2024 The Author(s). Stroke: Vascular and Interventional Neurology published by Wiley Periodicals LLC on behalf of American Heart Association; The Society for Vascular and Interventional Neurology. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Versions
You are viewing the most recent version of this article.
History
Received: 13 April 2024
Accepted: 5 September 2024
Published online: 16 December 2024
Published in print: January 2025
Keywords
Authors
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to access the full text.
eLetters(0)
eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.