Demographics, Risk Factors, and Etiology of Posterior Cerebral Artery Stroke Causing Homonymous Hemianopia

Background: Posterior cerebral artery (PCA) strokes account for up to 10% of all ischemic strokes, often presenting with homonymous hemianopia. The proportion of these strokes attributed to various etiologies varies widely in previously published studies, owing largely to differing patient populations, definitions of stroke pathogenesis, and vascular territories involved. The Causative Classification System (CCS), an automated version of the Stop Stroke Study (SSS) Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system, allows for a more rigorous assignment of stroke etiology. Methods: We excerpted clinical and imaging data on 85 patients who had PCA stroke with homonymous hemianopia examined at the University of Michigan. We compared the stroke risk factor profile of our PCA cohort with that of 135 patients with stroke in the distribution of the internal carotid artery (ICA) and middle cerebral artery (MCA) in an unpublished University of Michigan registry. We applied the CCS web-based calculator to our PCA cohort to determine stroke etiology. Results: In our PCA cohort, 80.0% had at least 2 conventional stroke risk factors and 30.6% had 4 risk factors, most commonly systemic hypertension. The risk factor profile of our PCA cohort resembled that of our ICA/MCA cohort except that the mean age of our PCA cohort was more than a decade younger and had a significantly lower frequency of atrial fibrillation (AF) than our ICA/MCA cohort. In nearly half of the patients with AF in our PCA cohort, AF was diagnosed after the stroke. Among stroke etiologies in our PCA cohort, 40.0% were of undetermined cause, 30.6% were from cardioaortic embolism, 17.6% were from other determined causes, and only 11.8% were from supra-aortic large artery atherosclerosis. Strokes after endovascular or surgical interventions were prominent among other determined causes. Conclusions: Most patients in our PCA cohort had multiple conventional stroke risk factors, a finding not previously documented. Mean age at stroke onset and AF frequency were lower than in our ICA/MCA cohort, in agreement with previous studies. As some other studies have found, nearly 1/3 of strokes were attributed to cardioaortic embolism. Within that group, AF was often a poststroke diagnosis, a finding not previously highlighted. Compared with earlier studies, a relatively high portion of strokes were of undetermined etiology and of other determined etiologies, including stroke after endovascular or surgical interventions. Supra-aortic large artery atherosclerosis was a relatively uncommon explanation for stroke.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Demographics, Risk Factors, and Etiology of Posterior Cerebral Artery Stroke Causing Homonymous Hemianopia Elaine A. Liu, BA, Sadhana Murali, MD, Roberto Rivera-de Choudens, MD, Jonathan D. Trobe, MD Background: Posterior cerebral artery (PCA) strokes account for up to 10% of all ischemic strokes, often presenting with homonymous hemianopia. The proportion of these strokes attributed to various etiologies varies widely in previously published studies, owing largely to differing patient populations, definitions of stroke pathogenesis, and vascular territories involved. The Causative Classification System (CCS), an automated version of the Stop Stroke Study (SSS) Trial of Org 10,172 in Acute Stroke Treatment (TOAST) system, allows for a more rigorous assignment of stroke etiology. Methods: We excerpted clinical and imaging data on 85 patients who had PCA stroke with homonymous hemianopia examined at the University of Michigan. We compared the stroke risk factor profile of our PCA cohort with that of 135 patients with stroke in the distribution of the internal carotid artery (ICA) and middle cerebral artery (MCA) in an unpublished University of Michigan registry. We applied the CCS web-based calculator to our PCA cohort to determine stroke etiology. Results: In our PCA cohort, 80.0% had at least 2 conventional stroke risk factors and 30.6% had 4 risk factors, most commonly systemic hypertension. The risk factor profile of our PCA cohort resembled that of our ICA/MCA cohort except that the mean age of our PCA cohort was more than a decade younger and had a significantly lower frequency of atrial fibrillation (AF) than our ICA/MCA cohort. In nearly half of the patients with AF in our PCA cohort, AF was diagnosed after the stroke. Among stroke etiologies in our PCA cohort, 40.0% were of undetermined cause, 30.6% were from cardioaortic embolism, 17.6% were from other determined causes, and only 11.8% were from supra-aortic large artery atherosclerosis. Strokes after endovascular or surgical interventions were prominent among other determined causes. Conclusions: Most patients in our PCA cohort had multiple conventional stroke risk factors, a finding not previously documented. Mean age at stroke onset and AF frequency Medical Scientist Training Program (EAL), University of Michigan School of Medicine, Ann Arbor, Michigan; and Departments of Neurology (SM, JDT), Radiology (RR-dC), and Ophthalmology and Visual Sciences (JDT), University of Michigan, Ann Arbor, Michigan. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105; E-mail: jdtrobe@ umich.edu Liu et al: J Neuro-Ophthalmol 2023; 43: 387-392 were lower than in our ICA/MCA cohort, in agreement with previous studies. As some other studies have found, nearly 1/3 of strokes were attributed to cardioaortic embolism. Within that group, AF was often a poststroke diagnosis, a finding not previously highlighted. Compared with earlier studies, a relatively high portion of strokes were of undetermined etiology and of other determined etiologies, including stroke after endovascular or surgical interventions. Supra-aortic large artery atherosclerosis was a relatively uncommon explanation for stroke. Journal of Neuro-Ophthalmology 2023;43:387–392 doi: 10.1097/WNO.0000000000001948 © 2023 by North American Neuro-Ophthalmology Society P osterior cerebral artery (PCA) territory stroke comprises up to 10% of all ischemic stroke.1,2 In previously reported studies of cohorts ranging from 23 to 232 patients, the relative prevalence of etiologies has varied.1–13 Cardioaortic embolism has often been most frequent, accounting for 28.6%–65% of cases.1,2,4–6,9,10,12,13 Atrial fibrillation (AF) has ranged in frequency from 9.3% to 64%.1–3,5– 8,12,13 Some studies of PCA stroke have noted supraaortic large artery atherosclerosis to be the most frequent cause, representing 42.4%8 and 50.4%7 of cases. Still other studies have reported small artery occlusion as the predominant cause, accounting for 34.5%3 and 52.1%11 of cases. A definite cause for PCA stroke is not established in up to 32% of cases.1,2,4,5,7–13 The variability in reported relative prevalence of stroke causes may be ascribed to differences in baseline patient characteristics, inclusion criteria, definitions of stroke etiology, and variability in the location of the infarction within the domain of the posterior circulation. The Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification system,14 not widely used in past studies, offers a standardized means of categorizing stroke. Even so, the TOAST system has only moderate interexaminer reliability,15,16 which may partially explain why 3 separate PCA stroke publications reached different conclusions as to the primary stroke etiology. A Korean study found supra-aortic large artery atherosclerosis as predominant (42.4%),8 a study of the Lausanne Stroke Registry found cardioaortic embolism as predominant (39.4%),9 and a study of the 387 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Perugia stroke registry found small artery occlusion as predominant (52.1%).11 The TOAST classification was modified in 2005 as the Stop Stroke Study (SSS)–TOAST classification system to allow for advances in the understanding and management of ischemic stroke.17 In 2007, an automated version was developed as the Causative Classification System (CCS), which uses a web-based calculator to determine stroke etiology.18 The CCS allows for rapid analysis of patient data and exhibits high intraexaminer and interexaminer reliability.18 In this study, we applied the CCS to patients who had imaging evidence of visual cortex infarction causing homonymous hemianopia, the most common clinical manifestation of PCA stroke, occurring in up to 96% of cases.3– 5,7,9,10,13 We compared demographics and underlying risk factors in our PCA cohort with a University of Michigan unpublished cohort of patients with internal carotid artery (ICA) and middle cerebral artery (MCA) stroke. We also investigated the relationship between stroke etiology and underlying demographics and risk factors. METHODS With permission from the Michigan Medicine (University of Michigan) Institutional Review Board, we conducted a 2009–2020 electronic medical records (Epic) search of patients with “homonymous hemianopia,” “visual fields,” and “MRI” using the university’s Electronic Medical Record Search Engine (EMERSE).19 Patients were included only if medical records disclosed a homonymous hemianopia on automated visual field examination and MRI or CT documented ischemic stroke in the corresponding retrogeniculate visual pathway. Some patients also had ischemic stroke in the brainstem, cerebellum, thalamus, or temporal lobe, and a small number had ischemic stroke in the domain of the MCA. We obtained a cohort of 85 patients. We performed chart review to identify baseline characteristics and clinical features at the time of stroke diagnosis, including age and sex, presenting symptoms, statin/aspirin use, and conventional stroke risk factors, including systemic hypertension, low density lipoprotein (LDL) greater than 70, current or past tobacco use, basal metabolic index (BMI) greater than 30, obstructive sleep apnea, Type 2 diabetes, and stroke in a first-degree relative. If the medical record did not contain information about these conventional stroke risk factors, we labeled them as “unknown.” We also excerpted data from inpatient telemetry, shortterm outpatient cardiac monitoring, electrocardiography (EKG), and transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) performed at or after the time of stroke. In our PCA cohort, 83.5% had an EKG, 70.6% had a TTE, 25.9% had a TEE, and 15.3% had both TTE and TEE. We compared demographics and risk factors with those collected in an unpublished University of Michigan registry 388 of 135 patients with exclusively ICA/MCA strokes. These patients had undergone mechanical thrombectomy of the ICA or MCA. The board-certified neuroradiologist author (R.R.) reviewed the imaging studies performed closest to the time of the stroke. MRI studies were available on 81 patients and CT alone on 4 patients. MRA head studies were available on 28 patients, MRA neck on 21 patients, CTA head on 27 patients, and CTA neck on 24 patients. Vascular territories were defined according to validated anatomical maps widely used in clinical practice and previous studies.3,8,20–22 Stenoses and occlusions were judged by the presence of atherosclerosis or thrombus according to the definitions provided by the CCS criteria.18 Occlusions marked by abrupt arterial cut-offs were attributed to thrombus. Occlusions or stenoses were attributed to atherosclerotic disease if they exhibited an eccentric location or calcification and occurred in clinically relevant arteries. Clinical and imaging data were entered into the CCS18 to define the etiology of stroke. The CCS has 5 major etiologic categories: supra-aortic large artery atherosclerosis, cardioaortic embolism, small artery occlusion, other determined causes, and undetermined causes. Based on the quality of the data, the 4 determined etiologic categories are further divided into “evident,” “probable,” or “possible.” (see Supplemental Digital Content, Table S1, http:// links.lww.com/WNO/A745). Statistics were performed using the Student t test for continuous variables and the Fisher exact test for categorical variables. Statistical significance was set at P , 0.05. RESULTS Baseline Characteristics (Table 1) The clinical profile of our 85 patients with PCA stroke resembled that of the University of Michigan registry of 135 patients with ICA/MCA stroke, with 2 exceptions: 1) Our PCA cohort was significantly younger (P , 0.0001), with a mean age difference of 11.8 years, and 2) our PCA cohort had higher rates of LDL .70 (P = 0.0320). The most prevalent conventional risk factor in our PCA cohort was hypertension (75.3%), followed by LDL .70 (57.6%), tobacco use (55.3%), BMI .30 (35.3%), family history of stroke (24.7%), obstructive sleep apnea (23.5%), and Type 2 diabetes (22.3%). In this cohort, 98.8% had at least one conventional risk factor for ischemic stroke, 80.0% had at least 2 risk factors, 56.5% had at least 3 risk factors, and 37.7% had at least 4 risk factors. Stroke Etiologies (Table 2) No definite etiology could be determined in 40.0% of patients, 58.8% of whom had had an incomplete evaluation. Of those patients who had undergone a complete evaluation, over 1/3 had 2 possible stroke etiologies. No etiology was found in the remaining undetermined cases. Liu et al: J Neuro-Ophthalmol 2023; 43: 387-392 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Demographics and risk factors Internal Carotid Artery/ Middle Cerebral Artery Strokes (N = 135) P Mean: 60.5 median: 61 39 (45.9) 64 (75.3) 1 (1.2) Mean: 72.3, median: 74 76 (56.3%) 92 (68.1) ,0.0001* 0.1656† 0.2221† 49 (57.6) 16 (18.8) 47 (55.3) 2 (2.4) 30 (35.3) 10 (11.8) 21 (24.7) 10 (11.8) 20 (23.5) 2 (2.4) 69 (51.9) 8 (5.9) Unavailable 0.0320† Demographics and Risk Factors Posterior Cerebral Artery Strokes (N = 85) Age at time of stroke (y) Female Hypertension Hypertension status unknown LDL .70 LDL status unknown History of tobacco use Unknown tobacco use BMI .30 Unknown BMI Family history of stroke Unknown family history Obstructive sleep apnea Obstructive sleep apnea status unknown Type 2 diabetes Type 2 diabetes status unknown Unavailable Unavailable Unavailable 19 (22.3) 1 (1.2) 27 (20) 0.7333† *Student t test. † Fisher exact test. BMI, basal metabolic index; LDL, low density lipoprotein. Among the determined causes of stroke, cardioaortic embolism was most common, accounting for 30.6%. Other determined causes accounted for 17.6% of strokes. Supraaortic large artery atherosclerosis accounted for only 11.8%. Small artery occlusion did not account for any strokes because the visual cortex is considered by the CCS to be outside the domain of small penetrating arteries. Cardioaortic Embolism (Table 3) The most prevalent high-risk cardioaortic embolic factor was AF, occurring in 16 patients (18.8%). Nearly half of these patients received a diagnosis of AF after the occurrence of the stroke, by inpatient telemetry, inpatient EKG, or outpatient short-term cardiac monitoring. AF was significantly less frequent in our PCA cohort than in our ICA/ MCA cohort (18.8% vs 37%, P = 0.0042). Supra-Aortic Large Artery Atherosclerosis Among the 11.8% of patients whose stroke was attributable to supra-aortic large artery atherosclerosis, 100% underwent head vessel imaging, and 90% underwent neck vessel imaging. Within this group, 80% had intracranial atherosclerosis, and 20% had extracranial atherosclerosis. Other Determined Causes (Table 4) Iatrogenic etiologies, defined by endovascular and surgical interventions of the heart, proximal aorta, and cerebral vasculature, occurred in 7 patients (8.2%). Other determined causes were active malignancy (3.5%), severe Liu et al: J Neuro-Ophthalmol 2023; 43: 387-392 systemic hypotension (2.4%), abnormalities of thrombosis and hemostasis (2.4%), and acute arterial dissection (2.4%). Demographics and Risk Factors according to Etiology (Table 5) Compared with patients with a cardioaortic embolic etiology, patients with large artery atherosclerosis etiology tended to be male with decreased statin use and TABLE 2. Posterior cerebral artery stroke etiologies* Stroke Etiology Supra-aortic large artery atherosclerosis Evident Possible Cardioaortic embolism Evident Possible Small artery occlusion Other determined causes Evident Probable Possible Undetermined Complete evaluation Incomplete evaluation N (%) 10 (11.8) 8 (9.4) 2 (2.4) 26 (30.6) 10 (11.8) 16 (18.8) 0 (0)† 15 (17.6) 11 (12.9) 3 (3.5) 1 (1.2) 34 (40.0) 14 (16.5) 21 (23.5) *Based on the Causative Classification System (CCS).18 † Most patients in our cohort had cortically based infarcts and therefore do not meet the CCS criteria for small artery occlusive disease. 389 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Risk factors for cardioaortic embolic stroke etiology High-risk cardioaortic embolic factors N (%) Atrial fibrillation Diagnosed prestroke Diagnosed poststroke By inpatient telemetry By inpatient EKG By outpatient cardiac monitoring By outpatient EKG Dilated cardiomyopathy Left ventricular thrombus Other* Low-risk cardioaortic embolic factors Left ventricular hypertrophy Left atrium dilatation Patent foramen ovale Atrial septal aneurysm Apical akinesia Other† 16 (18.8) 9 7 1 1 4 1 4 (4.7) 2 (2.4) 7 (8.2) 17 (20.0) 16 (18.8) 13 (15.3) 3 (3.5) 3 (3.5) 4 (4.7) *Left atrial thrombus, atrial flutter, chronic myocardial infarction, nonbacterial thrombotic endocarditis, infective endocarditis, papillary fibroelastoma, bioprosthetic valve, 1 each. † Atrial septal aneurysm + patent foramen ovale, left ventricular aneurysm, complex atheroma, wall motion abnormality, 1 each. EKG, electrocardiography. increased Type 2 diabetes. Patients with a cardioaortic embolic etiology tended to have increased tobacco use, BMI .30, and obstructive sleep apnea. DISCUSSION In this study, most patients with PCA stroke had multiple conventional stroke risk factors, with 80.0% having at least 2 risk factors and 30.6% having 4 risk factors. No comparative information is available from our ICA/MCA cohort or from previous studies. In common with earlier studies, systemic hypertension was the most common conventional risk factor in our PCA and ICA/MCA cohorts.1,3,5–10,23–25 The patients in our PCA cohort were relatively young at stroke onset as compared with those in our ICA/MCA cohort. Their mean age of 60.5 years is consistent with previous publications reporting an age span of 58–73.9 years.2,3,5– 10,12,13 The mean age of our ICA/MCA cohort at 72.3 years is also consistent with previous literature of anterior circulation ischemic stroke, which has reported mean ages between 62.7 and 76 years.3,10,23–26 The youth of our patients with PCA stroke also agrees with a previous study directly comparing PCA and MCA strokes.3 Several other studies have shown that posterior circulation strokes occur at a younger age than anterior circulation strokes.10,23,24 Notably, 8 patients (9.4%) in our PCA cohort were younger than 40 years, over half of whom had a stroke of cardioaortic embolic etiology. None of 390 these patients had AF, but 4 had a patent foramen ovale and others had a left ventricular thrombus, papillary fibroelastoma, or dilated cardiomyopathy. Although previous studies have highlighted a predilection of stroke for the elderly population,27,28 our study found a younger population and an association with cardioembolic risk factors. AF was present in 18.8% of our PCA cohort, which falls within the reported frequency range between 9.3% and 64%,1–3,5–8,12,13 although most studies report between 9.3% and 26.7%.2,3,5,7,8,12,13 The 37% frequency of AF in our ICA/MCA cohort conforms to previous reported frequencies between 7.5% and 40.3% in anterior circulation strokes.3,10,23–25 Our finding of a decreased frequency of AF in the PCA cohort relative to the ICA/MCA cohort is consistent with a previous study that directly compared PCA with MCA stroke,3 as well as studies comparing posterior and anterior circulation strokes.10,23–25 Notably, nearly half of the AF cases in our PCA cohort were diagnosed only after the stroke had occurred, a previously unreported finding that supports the importance of cardiac evaluation in patients with PCA stroke. Indeed, a study that focused on patients diagnosed with embolic stroke of undetermined source found that subclinical AF was more frequent in PCA stroke than in stroke in other territories.29 An important finding of our study is that 40.0% of patients had a stroke of undetermined etiology. This percentage is higher than the range of 9.6%–26.9%8,9,11 disclosed in earlier PCA stroke studies that used the TOAST criteria without the CCS calculator. Studies that did not use TOAST have reported frequencies of up to 32%.1,2,4,5,7,10,12,13 The relatively high frequency in our study could be attributed to incomplete evaluations and to the fact that some patients had a stroke of more than one possible etiology. The relatively high cardioaortic embolism frequency of 30.6% in our study conforms to that of earlier studies. TABLE 4. Other determined causes of posterior cerebral artery stroke* Causes N (%) Iatrogenic† Malignancy Severe systemic hypotension Abnormalities of thrombosis and hemostasis Acute arterial dissection Other‡ 7 (8.2) 3 (3.5) 2 (2.4) 2 (2.4) 2 (2.4) 6 (7.1) *Based on the Causative Classification System.18 † Stroke within 14 days of endovascular and surgical interventions of heart, proximal aorta, cerebral vasculature, including carotid endarterectomy, cranial reconstruction, thrombectomy, cerebral aneurysm coiling, implantable cardioverter defibrillator placement, and cardiac catheterization. ‡ Drug-induced (cocaine and heroin), hyperviscosity (myelodysplastic syndrome), partially thrombosed cerebral aneurysm, primary antiphospholipid antibody syndrome, Sneddon syndrome, posterior reversible encephalopathy syndrome, 1 each. Liu et al: J Neuro-Ophthalmol 2023; 43: 387-392 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 5. Comparison between demographics and risk factors for 2 stroke etiologies Demographics and Risk Factors Age at time of stroke (y) Female On statin at time of stroke On aspirin at time of stroke Hypertension LDL . 70 History of tobacco use Obesity (BMI .30) Family history of stroke Obstructive sleep apnea Type 2 diabetes Number of conventional risk factors 0 1 2 3 4 5 6 Supra-Aortic Large Artery Atherosclerosis (N = 10) Cardioaortic Embolism (N = 26) Average: 63.5, median: 61 3 (30.0%) 1 (10) 4 (40) 7 (70) 8 (80) 4 (40) 2 (20) 2 (20) 1 (10) 3 (30) Average: 59.3, median: 64 11 (42.3%) 11 (42.3) 8 (30.8) 20 (76.9) 19 (73.1) 14 (53.8) 11 (42.3) 5 (19.2) 7 (26.9) 5 (19.2) 0 (0%) 3 (30) 1 (10) 2 (20) 4 (40) 0 (0) 0 (0) P 0.4194* 0.7062† 0.0545† 0.7039† 0.6856† .0.9999† 0.7112† 0.2591† .0.9999† 0.3968† 0.6576† 0 (0%) 2 (7.7) 8 (30.8) 5 (19.2) 8 (30.8) 2 (7.7) 1 (3.8) *Student t test. † Fisher exact test. BMI, basal metabolic index; LDL, low density lipoprotein. Non-TOAST studies have reported a frequency range between 21% and 61%,1–7,10,12,13 and TOAST studies have reported a range between 20% and 54.1%.8,9,11 Other determined causes of stroke in our PCA cohort accounted for 17.6% of cases, higher than the 0%–5.5%8,9,11 reported in previous TOAST studies. Non-TOAST studies of PCA stroke have reported a range of up to 22.9%,1–5,7,10,12,13 but with a less standardized method for how etiologic assignments were made. We highlight the fact that almost half of other determined causes of stroke in our cohort immediately followed endovascular and surgical intervention on the heart or cerebral vasculature or after severe systemic hypotension during surgical procedures, a finding not previously reported. Although perioperative stroke risk is generally below 2% in noncardiac, non-neurologic, and nonmajor surgeries, it may be as high as 10% in patients undergoing high-risk cardiac or brain surgery.30,31 In our study, malignancy, abnormalities of thrombosis and hemostasis, Sneddon syndrome, acute arterial dissection, and posterior reversible encephalopathy syndrome accounted for other determined causes of stroke, emphasizing the importance of a full clinical evaluation when no conventional etiology is apparent. The least frequent stroke etiology in our PCA cohort was supra-aortic large artery atherosclerosis (11.8%), on the low end in comparison with earlier TOAST studies, which have reported a range from 11% to 42.4%.8,9,11 PCA stroke studies not using the TOAST criteria have reported a similar range of 11.8%–40.9%.1–7,10,12,13 The highest prevalence of supra-aortic large atherosclerosis (42.4%) was noted Liu et al: J Neuro-Ophthalmol 2023; 43: 387-392 in a study of a Korean population known to have a relatively high prevalence of intracranial atherosclerosis.8 In past PCA stroke studies not defined by homonymous hemianopia that used the TOAST criteria, the relative etiologic prevalence of small artery occlusion has varied between 19.4% and 52.1%.8,9,11 One TOAST study of PCA stroke reported a frequency of small artery occlusion of 34.5%.3 As patients were included only if they had homonymous hemianopia, our study population was dominated by cortical infarcts. By CCS definition, that feature excluded small vessel disease as a possible etiologic category. Patients in our PCA cohort with a supra-aortic large artery atherosclerotic etiology tended to be predominantly men with Type 2 diabetes, as noted in previous studies.26,32,33 By contrast, patients with cardioaortic embolic etiology tended to have an increased frequency of BMI .30, obstructive sleep apnea, and tobacco use. Previous literature has shown an association between cardioembolic stroke and obstructive sleep apnea,34 highlighting the importance of sleep studies in this setting. We acknowledge several limitations to the conclusions from this study. Our PCA cohort was defined by clinical presenting symptoms and imaging evidence of infarction within the PCA territory, whereas our ICA/MCA cohort was defined by occlusion requiring thrombectomy. Thus, we are not evaluating the full scope of MCA strokes that can occur in the absence of an occlusion, and our comparisons with our PCA cohort may be skewed. Our analysis of risk factors across stroke etiologies did not reach statistical significance, likely 391 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution because of small group sizes. Input of data to the CCS has flaws. Interpretation of test results varies among examiners. For example, distinguishing atherosclerosis from other causes of vascular stenosis is a leading cause of disagreement. The relationship between prothrombotic abnormalities and stroke is unsettled. Finally, because of the difficulty in capturing every stroke etiology, the CCS is forced to include an unstandardized “other” category within the other determined causes of stroke that is not well defined. STATEMENT OF AUTHORSHIP Conception and design: E. A. Liu, S. Murali, R. 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