Causative Classification System for Ischemic Stroke (CCS)

1. Clinical evaluation (check all that apply)

a. There is prior history of ischemic stroke, transient ischemic attack, or transient monocular blindness from the territory of index artery within the month preceding the index stroke

b. Prior clinical events described in 1a are exclusively a cluster of repetitive and stereotypic lacunar transient ischemic attacks that started within the week preceding the index stroke

c. The patient presents with a lacunar syndrome

d. There is evidence of concurrent systemic embolism

2. Imaging evaluation of the brain (check all that apply)

a. Brain imaging has not been done (CT or MRI)

b. Brain imaging is negative for the presence of acute brain infarct or perfusion deficit consistent with clinical symptoms

c. There is a lacunar infarct as defined by a single acute infarct within the territory of penetrating arteries in the brainstem, deep gray matter, or internal capsule that is ≤20 mm in its greatest diameter and there is no known focal pathology in the parent artery at the site of the origin of the penetrating artery

d. There are multiple acute and subacute ischemic lesions in either right and left anterior or anterior and posterior circulations or both, in the absence of non-embolic occlusion or near occlusive stenosis of all relevant vessels

e. There are acute unilateral internal watershed infarcts

f. There are multiple temporally separate infarcts exclusively within the territory of the clinically relevant artery

3. Imaging evaluation of the cerebral vasculature (check all that apply)

a. Imaging evaluation of blood vessels has not been done

b. There is stenotic or occlusive vascular disease judged to be due to atherosclerosis in clinically-relevant arteries

1. Intracranial arteries
2. Extracranial arteries

c. The atherosclerotic plaque described in 3b has features consistent with thrombus formation, ulceration, near-occlusive stenosis or non-chronic occlusion

d. There is an atherosclerotic plaque causing mild stenosis in the absence of any detectable plaque ulceration or thrombosis in clinically-relevant extracranial or intracranial artery. There is also a prior history of two or more ischemic stroke, transient ischemic attack, or transient monocular blindness from the territory of index artery, at least one event within the last month

e. There is angiographic evidence of abrupt cut-off consistent with a blood clot within the clinically relevant and otherwise angiographically normal appearing intracranial artery

f. There is vascular imaging evidence that the clinically relevant occluded intracranial artery has been completely recanalized

4. Cardiac evaluation (check all that apply)

a. Cardiac evaluation has not been done

b. Cardiac evaluation reveals a high-risk source (check all that apply)

1. Left atrial thrombus
2. Left ventricular thrombus
3. Atrial fibrillation
4. Paroxysmal atrial fibrillation
5. Sick sinus syndrome
6. Atrial flutter
7. Recent myocardial infarction
8. Mitral stenosis or rheumatic valve disease
9. Bioprosthetic and mechanical heart valves
10. Chronic myocardial infarction together with low ejection fraction <28%
11. Dilated cardiomyopathy
12. Non bacterial thrombotic endocarditis
13. Infective endocarditis
14. Papillary fibroelastoma
15. Left atrial myxoma
16. Patent foramen ovale and concurrent systemic embolism

c. Cardiac evaluation reveals a low- or uncertain-risk source (check all that apply)

1. Mitral annular calcification
2. Patent foramen ovale
3. Atrial septal aneurysm
4. Atrial septal aneurysm and patent foramen ovale
5. Left ventricular aneurysm without thrombus
6. Left atrial smoke
7. Congestive heart failure with ejection fraction <30%
8. Complex atheroma in the ascending aorta or proximal arch
9. Apical akinesia
10. Wall motion abnormalities (hypokinesia, akinesia, dyskinesia) other than apical akinesia
11. Hypertrophic cardiomyopathy
12. Left ventricular hypertrophy
13. Left ventricular hypertrabeculation/non-compaction
14. Other

5. Evaluation for diagnosis of other (uncommon) causes of stroke (check all that apply)

a. Acute arterial dissection in relevant arteries

b. Cerebral vascular abnormalities in the relevant artery

c. Cerebral vasculitis

d. Cerebral venous thrombosis

e. Acute disseminated intravascular coagulation

f. Drug-induced stroke

g. Fibromuscular dysplasia

h. Heparininduced thrombocytopenia type II

i. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

j. Hyperviscosity syndromes

k. Hypoperfusion syndromes

l. Iatrogenic causes

m. Partially thrombosed cerebral aneurysm in a clinically relevant artery

n. MELAS

o. Meningitis

p. Migraine-induced stroke

q. Moyamoya disease

r. Primary antiphospholipid antibody syndrome

s. Primary infection of the arterial wall

t. Sickle cell disease

u. Sneddon`s syndrome

v. Thrombotic thrombocytopenic purpura — Hemolytic uremic syndrome

w. Segmental vasoconstriction or vasospasm

x. Abnormalities of thrombosis and hemostasis

y. Other causes