ASCO phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) assigns a degree of likelihood of causal relationship to every potential disease (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but the disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke describing all underlying diseases in every patient. In this new evolution of ASCO called ASCOD, we have added a ‘D' for dissection, recognizing that dissection is a very frequent disease in young stroke patients. We have also simplified the system by leaving out the ‘levels of diagnostic evidence', which has been integrated into grades 9 and 0. Moreover, we have also changed the cutoff for significant carotid or intracranial stenosis from 70% to more commonly used 50% luminal stenosis, and added a cardiogenic stroke pattern using neuroimaging. ASCOD captures and weights the overlap between all underlying diseases present in ischemic stroke patients.

Keywords:
Stroke etiology and classification, Stroke subtype

In 2009, we proposed a new system to phenotype patients with ischemic stroke, called ASCO (A for atherosclerosis; S for small-vessel disease, C for cardiac pathology, and O for other causes) to better describe the overlap between diseases underlying a cerebral ischemic event in a stroke patient [1]. Previous stroke subtype classification only considered size and location of cerebral infarction (Oxford classification) or the disease deemed to be directly causally related to the ischemic stroke, neglecting other underlying diseases not deemed to be causally related, although present, such as TOAST and CCS classifications [2].

Based on experience with ASCO during the past few years [3,4,5,6,7,8,9,10,11,12], we now propose an updated version called ASCOD phenotyping.

In ASCOD, every patient should be graded into 5 predefined phenotypes: A (atheroclerosis); S (small-vessel disease); C (cardiac pathology); O (other cause), and D (dissection). As done in the former ASCO classification [1], three degrees of causality between the index ischemic stroke and each category are considered (table 1). To determine the degree of causality, a number of diagnostic tests must be performed. These diagnostic tests are detailed for each category in table 2. If the disease is not detected after a minimum workup has been performed, the grade is 0. In case of incomplete workup (e.g. a minimal workup has not been performed) to rule out the disease, the grade is 9 (tables 1, 2).

Table 1

Method of classification

Method of classification
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Method of classification
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Table 2

Grades of predefined ASCOD phenotypes

Grades of predefined ASCOD phenotypes
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Grades of predefined ASCOD phenotypes
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In this updated version now called ASCOD phenotyping, we have added a ‘D' for dissection, recognizing that dissection is a very frequent causal disease in young ischemic stroke patients. We have also simplified the grading system by leaving out the ‘levels of diagnostic evidence'. This has caused some modifications with regard to technical issues including brain imaging findings, in particular concerning grades C and D. ‘Levels of evidence' has now been integrated into grade 9 defined as insufficient workup for each category (table 2). Technical limitations (e.g. poor bone windows for US-TCD or inability to perform MRI) are not necessarily in conflict with full workup. For grade 0 (disease is absent), a separate definition states what is needed to rule out the disease (table 2).

We have also modified the cutoff for significant carotid and intracranial stenosis, from 70% in the previous ASCO, to the more commonly accepted 50% luminal stenosis [13] in ASCOD as well as introduced some additional diagnostic and technical requirements.

ASCOD describes all 5 main diseases underlying ischemic stroke that are present or not in a given patient.

Compared to other stroke-subtyping classifications that categorize ischemic stroke in rigid groups into known cause of stroke and undetermined or cryptogenic stroke, ignoring other underlying diseases not deemed to be causally related, ASCOD grades all diseases present in a given patient, captures the overlap between the diseases, and weights the potentially causal relationship between every disease detected and the ischemic stroke [3,4,5,6,7].

By considering every specific disease underlying the ischemic stroke, ASCOD allows a comprehensive analysis of cohorts of patients with ischemic stroke, particularly for the purpose of clinical trials, phenotype-genotype analyses, or evaluation of the pertinence of a new diagnostic test or a new biomarker. ASCOD may help analyze clinical trials and perhaps select patients in future randomized trials.

One of the main advantages of the ASCOD phenotyping is the lack of an ‘undetermined' or ‘cryptogenic' group or ‘embolic stroke of unknown source' (that could also be named ‘embolic stroke of undetected potential sources'). These categories in causative classification systems are too ‘cryptic', too difficult to define (in fact they are only ‘negatively' defined) and differ from one neurologist or general practitioner to another, which is frustrating for the patients. With the ASCOD system, the only message to the patient is a positive one. In a patient who has no ASCOD 1 category, we can say that we found specific diseases (grades 2 or 3), but that we are unable to establish a direct causal relationship between these diseases and the ischemic stroke. However, we can treat these diseases according to guideline recommendations to reduce the risk of recurrence.

1.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG: A new approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis 2009;27:502-508.
2.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG: Classification of stroke subtypes. Cerebrovasc Dis 2009;27:493-501.
3.
Wolf ME, Sauer T, Alonso A, Hennerici MG: Comparison of the new ASCO classification with the TOAST classification in a population with acute ischemic stroke. J Neurol 2012;259:1284-1289.
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Chatzikonstantinou A, Wolf ME, Hennerici MG: Ischemic stroke in young adults: classification and risk factors. J Neurol 2012;259:653-659.
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Chatzikonstantinou A, Krissak R, Schaefer A, Schoenberg SO, Fink C, Hennerici MG: Coexisting large and small vessel disease in patients with ischemic stroke of undetermined cause. Eur Neurol 2012;68:162-165.
6.
Wolf ME, Sauer T, Hennerici MG, Chatzikonstantinou A: Characterization of patients with recurrent ischaemic stroke using the ASCO classification. Eur J Neurol 2013;20:812-817.
7.
Sirimarco G, Lavallée PC, Labreuche J, Meseguer E, Cabrejo L, Guidoux C, Klein IF, Olivot J-M, Abboud H, Adraï V, Kusmierek J, Ratani S, Touboul P-J, Mazighi M, Steg PG, Amarenco P: Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping. Submitted.
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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.
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Larrue V, Berhoune N, Massabuau P, Calviere L, Raposo N, Viguier A, Nasr N: Etiologic investigation of ischemic stroke in young adults. Neurology 2011;76:1983-1988.
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Shang Wy, Liu Jy: Stroke subtype classification: a comparative study of ASCO and modified TOAST. J Neurol Sci 2012;15;314:66-70.
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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.
12.
Amort M, Fluri F, Weisskopf F, Gensicke H, Bonati LH, Lyrer PA, Engelter ST: Etiological classifications of transient ischemic attacks: subtype classification by TOAST, CCS and ASCO - A pilot study. Cerebrovasc Dis 2012;33:508-516.
13.
von Reutern GM, Goertler MW, Bornstein NM, Del Sette M, Evans DH, Hetzel A, Kaps M, Perren F, Razumovky A, von Reutern M, Shiogai T, Titianova E, Traubner P, Venketasubramanian N, Wong LK, Yasaka M, Neurosonology Research Group of the World Federation of Neurology: Grading carotid stenosis using ultrasonic methods. Stroke 2012;43:916-921.
© 2013 S. Karger AG, Basel
2013
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