Background: Ischemic cerebrovascular disease (ICVD) comprises multiple etiological phenotypes that share common clinical characteristics. Etiological classification of patients with ICVD is of major clinical interest to achieve optimal medical treatment and predict prognosis. The TOAST classification system has been widely used to describe stroke etiology but provides restricted phenotypic homogeneity within groups. The ASCO classification system has introduced a new approach in phenotypic classification, and aims to describe clinical characteristics without merging concurrent comorbidities. Inflammatory processes have been suggested to mediate stroke etiology and pathology. The Acute Inflammatory Stroke Study (AISS), a hospital-based cohort, is here introduced and described by TOAST and ASCO classification systems. The aim of this first analysis of AISS was to investigate long-term mortality in relation to ischemic stroke subtypes, and clinical and biochemical markers. Methods: AISS consecutively follows patients on 6 occasions up to 1 year after stroke onset. Complete workup according to ASCO comprised CT or MRI of the head, ECG, duplex of the extracranial arteries or CT/MR angiography and ultrasound of the heart. Level 2 evidence was required in each domain to obtain a comparable system to TOAST (ASCO2). Clinical and biochemical characteristics and mortality rates were documented and compared by the two classification systems. Results: Of 142 patients consecutively evaluated and recruited in the study, a total of 101 ICVD patients (ischemic stroke, n = 84; transient ischemic attack, n = 17) were included in the final analysis. Agreement between ASCO2 and TOAST was very good. During the mean observation period of 28 months, 26 patients died. The 1- and 4-year mortality rates were 0 and 4% for large artery atherosclerosis (LAA); 23 and 36% for cardioembolism (CE); 0% for small artery occlusion (SAO); 63 and 100% for the subtype with unknown etiology due to incomplete workup (Unknown), and 12 and 29% for the cryptogenic subtype. As for the ASCO2 groups, the 1- and 4-year mortality rates were 0 and 6% in LAA, 25 and 36% in CE, 0% in SAO, 0 and 14% in LAA + CE, 0% in SAO + CE, 16 and 36% in the subgroup with undetermined etiology despite complete workup, and 56 and 100% in Unknown. Regression analysis showed that age, white blood cell count, fibrinogen and bilirubin, but not etiological subgroup, were independent predictors of mortality. Conclusion: Our findings indicate that clinical and biochemical markers may differentiate phenotypically homogeneous etiological subtypes and predict long-term mortality. Further studies with larger patient numbers are needed to investigate possible causative mechanisms.

1.
Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke 1990;21:637-676.
2.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG: Classification of stroke subtypes. Cerebrovasc Dis 2009;27:493-501.
3.
Strong K, Mathers C, Bonita R: Preventing stroke: saving lives around the world. Lancet Neurol 2007;6:182-187.
4.
Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU: Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke 2001;32:2735-2740.
5.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.
6.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG: New approach to stroke subtyping: The A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis 2009;27:502-508.
7.
Marnane M, Duggan CA, Sheehan OC, Merwick A, Hannon N, Curtin D, Harris D, Williams EB, Horgan G, Kyne L, McCormack PM, Duggan J, Moore A, Crispino-O'Connell G, Kelly PJ: 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. Stroke 2010;41:1579-1586.
8.
Shang W, Liu J: Stroke subtype classification: a comparative study of ASCO and modified TOAST. J Neurol Sci 2012;314:66-70.
9.
Cotter PE, Belham M, Martin PJ: Towards understanding the cause of stroke in young adults utilising a new stroke classification system (A-S-C-O). Cerebrovasc Dis 2012;33:123-127.
10.
Ohira T, Shahar E, Chambless LE, Rosamond WD, Mosley TH Jr, Folsom AR: Risk factors for ischemic stroke subtypes: the Atherosclerosis Risk in Communities study. Stroke 2006;37:2493-2498.
11.
McColl BW, Allan SM, Rothwell NJ: Systemic infection, inflammation and acute ischemic stroke. Neuroscience 2009;158:1049-1061.
12.
Tuttolomondo A, Di Sciacca R, Di Raimondo D, Serio A, D'Aguanno G, La Placa S, Pecoraro R, Arnao V, Marino L, Monaco S, Natale E, Licata G, Pinto A: Plasma levels of inflammatory and thrombotic/fibrinolytic markers in acute ischemic strokes: relationship with TOAST subtype, outcome and infarct site. J Neuroimmunol 2009;215:84-89.
13.
Alvarez-Perez FJ, Castelo-Branco M, Alvarez-Sabin J: Usefulness of measurement of fibrinogen, D-dimer, D-dimer/fibrinogen ratio, C reactive protein and erythrocyte sedimentation rate to assess the pathophysiology and mechanism of ischaemic stroke. J Neurol Neurosurg Psychiatry 2011;82:986-992.
14.
Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977;33:159-174.
15.
Mogensen UB, Olsen TS, Andersen KK, Gerds TA: Cause-specific mortality after stroke: relation to age, sex, stroke severity, and risk factors in a 10-year follow-up study. J Stroke Cerebrovasc Dis 2012, E-pub ahead of print.
16.
Li C, Hedblad B, Rosvall M, Buchwald F, Khan FA, Engstrom G: Stroke incidence, recurrence, and case-fatality in relation to socioeconomic position: a population-based study of middle-aged Swedish men and women. Stroke 2008;39:2191-2196.
17.
Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO: Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke 2000;31:1062-1068.
18.
Pinto A, Tuttolomondo A, Di Raimondo D, Fernandez P, Licata G: Risk factors profile and clinical outcome of ischemic stroke patients admitted in a Department of Internal Medicine and classified by TOAST classification. Int Angiol 2006;25:261-267.
19.
Olindo S, Cabre P, Deschamps R, Chatot-Henry C, René-Corail P, Fournerie P, Saint-Vil M, May F, Smadja D: Acute stroke in the very elderly: epidemiological features, stroke subtypes, management, and outcome in Martinique, French West Indies. Stroke 2003;34:1593-1597.
20.
Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C: Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study. Stroke 2011;42:10-16.
21.
Herishanu Y, Abramsky O, Lavy S: Hyperbilirubinaemia in acute ischaemic stroke. J Neurol Sci 1971;14:417-420.
22.
Pineda S, Bang OY, Saver JL, Starkman S, Yun SW, Liebeskind DS, Kim D, Ali LK, Shah SH, Ovbiagele B: Association of serum bilirubin with ischemic stroke outcomes. J Stroke Cerebrovasc Dis 2008;17:147-152.
23.
Sevastos N, Savvas SP, Rafailidis PI, Manesis EK: Cholestasis in acute stroke: An investigation on its prevalence and etiology. Scand J Gastroenterol 2005;40:862-866.
24.
Lin JP, Vitek L, Schwertner HA: Serum bilirubin and genes controlling bilirubin concentrations as biomarkers for cardiovascular disease. Clin Chem 2010;56:1535-1543.
25.
Perlstein TS, Pande RL, Creager MA, Weuve J, Beckman JA: Serum total bilirubin level, prevalent stroke, and stroke outcomes: NHANES 1999-2004. Am J Med 2008;121:781-788, e781.
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