Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin population stroke study.
OBJECTIVE
Reliable etiologic classification of ischemic stroke may enhance clinical trial design and identification of subtype-specific environmental and genetic risk factors. Although new classification systems (Causative Classification System [CCS] and ASCO [A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause]) have been developed to improve subtype assignment, few comparative data exist from large studies. We hypothesized that both CCS and ASCO would reduce the proportion of patients classified as cause undetermined compared with the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) scheme in a large population-based stroke study.


METHODS
A single rater classified all first-ever ischemic strokes in the North Dublin Population Stroke Study, a population-based study of 294 529 North Dublin residents. Published algorithms for TOAST, CCS, and ASCO were applied.


RESULTS
In 381 first-ever ischemic stroke patients, CCS assigned fewer patients as cause undetermined (26.2% versus 39.4%; P<0.000001), with increased assignment of cardio-aortic embolism (relative increase 6.9%; P=0.004), large artery atherosclerosis (relative increase 44.1%; P=0.00006), small artery occlusion (relative increase 27.3%; P=0.00006), and other causes (relative increase 91.7%; P=0.001) compared with TOAST. When ASCO grade 1 evidence was applied, fewer patients were classified as small artery disease (relative decrease 29.1%; P=0.007) and more as large artery/atherothrombotic (relative increase 17.6%; P=0.03). ASCO grade 1 did not reduce the proportion of cause undetermined cases compared with TOAST (42.3% versus 39.4%; P=0.2). Agreement between systems ranged from good (kappa=0.61 for TOAST/ASCO grade 1 small artery category) to excellent (kappa=0.95 for TOAST/CCS and ASCO grade 1/CCS cardio/aorto-embolism category). Application of ASCO grades 1 to 3 indicated evidence of large artery/atherosclerosis (73.3%), cardio-embolism (31.3%), small artery (64.7%), and other cause (12%) in TOAST-undetermined cases.


CONCLUSIONS
Both CCS and ASCO schemes showed good-to-excellent agreement with TOAST, but each had specific characteristics compared with TOAST for subtype assignment and data retention. The feasibility of a single combined classification system should be considered.
Marnane
Michael
M
Neurovascular Clinical Science Unit, Mater University Hospital/University College Dublin, Ireland. mmarnane@gmail.com
Duggan
Caroline A
CA
Sheehan
Orla C
OC
Merwick
Aine
A
Hannon
Niamh
N
Curtin
Denis
D
Harris
Dawn
D
Williams
Emma B
EB
Horgan
Gillian
G
Kyne
Lorraine
L
McCormack
Patricia M E
PM
Duggan
Joseph
J
Moore
Alan
A
Crispino-O'Connell
Gloria
G
Kelly
Peter J
PJ
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000704:Analysis of Variance; D002545:Brain Ischemia / Q000145:classification* / Q000209:etiology; D002318:Cardiovascular Diseases / Q000145:classification / Q000150:complications*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D020521:Stroke / Q000145:classification* / Q000209:etiology