TOAST classification of stroke

David Goldemund M.D.
Updated on 20/04/2024, published on 28/12/2022

  • the exact etiology of ischemic stroke has implications for both prognosis and management
  • a classification system for ischemic stroke subtype, mainly based on etiology, was developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST)
  • the TOAST classification identifies five ischemic stroke subtypes:
    • 1 – large-artery atherosclerosis (LAA)
    • 2 – cardioembolic stroke (CE)
    • 3 – small-vessel disease (SVD) / penetrating artery disease (PAD)
    • 4 – stroke of other determined cause
    • 5 – stroke of undetermined cause (cryptogenic stroke)
  • diagnosis is based on clinical features and data from brain imaging (CT/MRI), vascular imaging (CTA/MRA, neurosonology, DSA), cardiac imaging, and laboratory tests
  • the prevalence of each group varies depending on the mean age of the patient cohort
    • cryptogenic stroke and TOAST 4 are predominant in younger age groups
    • arteriolopathy and cardioembolic stroke are more prevalent in older age groups (reflecting the increased incidence of atrial fibrillation and other cardiac diseases.)
  • one large-scale application of the TOAST classification is the Get with the Guidelines-Stroke (GWTG-Stroke) registry; however, the TOAST subtypes entered into the registry were accurate in only 61% of patients  (Rathburn, 2024)
  • several other improved classification systems have been introduced:

TOAST 1 – Large Artery Atherosclerosis (macroangiopathy)

  • medium and large arteries are affected
  • stroke is caused by atherothrombosis or thromboembolism
  • significant stenosis (> 50%) or occlusion of a relevant extra- or intracranial artery due to atherosclerosis   Significant internal carotid artery stenosis on CTA  Large artery atherosclerosis (TOAST 1)  → assessment of atherosclerotic plaques
  • cortical lesion on brain CT/MRI   Trombembolic stroke in patient with ICA stenosis and embolic occlusion of M2 branch of MCA
  • subcortical lesion > 1.5 cm on brain CT/MRI (originally published)

    • it is known that even smaller lesions can be caused by branch artery atherosclerosis (see CISS classification)
  • stroke mechanisms in TOAST 1:
    • progressive narrowing to complete arterial occlusion (symptoms vary depending on the quality of the collateral circulation)
    • artery to artery embolism
    • combination of both mechanisms (embolism occurring at the time of the ICA occlusion)

Issues discussed regarding TOAST 1

  • a specific and probably underdiagnosed cause of thromboembolism originates from unstable (complicated) non-stenosing (< 50%) plaques in CCA, ICA,  aorta, and intracranial arteries  [Harloff, 2010]
  • additionally, small infarcts resulting from atherosclerotic plaques in the ostium of perforating arteries should be included here ⇒  branch artery disease (BAD) / branch occlusive disease (BOD)   
    • BAD can be detected using high-resolution MRI
    • this concept is already incorporated in both the CISS and SSS-TOAST classifications
  • significance of plaque composition and morphology is increasingly acknowledged
    • evidence of intraplaque hemorrhage (IPH), thrombus, thin or ruptured fibrous cap, or a large lipid-rich and/or necrotic core (visible on high-resolution MRI) correlates with an increased risk of cerebrovascular events, irrespective of stenosis severity  [Kopczak, 2020] [Kamel, 2019
    • these findings may support the classification of atherothrombotic etiology (TOAST 1)
  • no significant atherosclerosis in major cerebral arteries
  • presence of a potential cardioembolic source (especially any high-risk factor)

TOAST 2 – Cardioembolic stroke

  • at least one significant potential cardioembolic source must be identified
  • high-risk sources:
    • atrial fibrillation (AFib)
    • mechanical valve
    • thrombus in the left atrium/ventricle
    • atrial myxoma   Myxoma
    • endocarditis   Endocarditis on TEE
  • clinical and neuroimaging findings are similar to those of TOAST 1
    • there is no specific “cardioembolic brain imaging pattern”
    • cardioembolic etiology is supported by infarcts/TIAs occurring in different vascular territories (including silent lesions)  Cardioembolic stroke with multiple territory embolisation Cardioembolic strokes in different territories
  • a stroke in a patient with a medium-risk source of embolism and no other identifiable cause of stroke is classified as a possible cardioembolic stroke
  • presence of significant stenosis in relevant extra- and/or intracranial arteries

TOAST 3 – Small artery disease (arteriolopathy, microangiopathy)

  • lacunar strokes
  • leukoaraiosis
  • clinical presentation: lacunar stroke / subcortical ischemic encephalopathy
  • + presence of traditional vascular risk factors (hypertension, dyslipidemia, diabetes, etc.)
  • brainstem or subcortical lesion on CT/MRI (diameter < 1.5 cm)  Lacunar infarction in the left thalamus
  • leukoencephalopathy on CT/MRI   Leucoencephalopathy on FLAIR  (→ FAZEKAS scaleARWMC scale)
  • caused by lipohyalinosis (the main feature of lipohyalinosis is the thickening of the vessel wall with narrowing of the lumina; eventually, vessel occlusion and infarction may occur)
  • distinguish non-arteriolopathic occlusion of perforating arteries  Nonarteriolopathic pontine infarction on the basis of probable Branch Artery Disease (BAD) or embolization.
    • atherosclerosis of the parent artery near the perforator origin – Branch Artery Disease (BAD) / Branch Occlusive Disease (BOD)
      • infarcts tend to be larger compared to classic arteriolopathy
      • high-resolution MRI can be used for diagnosis
    • embolization (from proximal arterial segments or from the heart)
  • genetic small vessel diseases should be classified as TOAST 4
  • presence of significant stenosis in relevant extra- and/or intracranial arteries
  • presence of a significant cardioembolic source
  • hemispheric infarction on CT/MRI

TOAST 4 – Stroke of other determined etiology

→ vasculitis overview

  • bony stroke
    • rare bone or cartilage anomalies affecting arteries supplying the brain
    • may be considered in patients with recurrent ischemic stroke of unknown cause in the same vascular territory
    • in addition to conventional vascular imaging, the dynamic imaging modalities with the patient’s head rotated or reclined may confirm the diagnosis  (e.g., Bow hunter´s syndrome)
  • Susac syndrome (retino-cochleo-cerebral vasculopathy)
    • rare microangiopathy of the cochlea, retina, and brain of unknown etiology (probably vasculitic in origin)   Susac syndrome - "string of pearls" in internal capsule
  • fat embolism
    • typically occurs after trauma (long bone fractures) and surgery (including plastic surgery with fat removal)
  • air embolism (microscopic x macroscopic) Macroscopic air embolization after endovascular surgery
    • a consequence of the incorrect insertion of a venous catheter into an artery [Riebau, 2004]
    • improper extraction of the central venous catheter (CVC) [Brockmeyer, 2009]
    • repeated IV applications in combination with pulmonary AV shunt or PFO
    • during catheterization
  • embolization of cholesterol particles from plaques should be assessed as TOAST 1 → Cholesterol Embolization Syndrome (CES)  Retinal cholesterol embolization (Hollenhorst crystals)
    • spontaneous x iatrogenic
  • diffuse lesions Diffuse cerebral edema due to hypoperfusion during surgery in ECC (Extra Corporeal Circulation)  or border zone (watershed) infarcts Border zone infarcts (BZI)
  • etiology
    • systemic hypotension
      • cardiac failure
      • extracorporeal circulation (ECC) surgery
    • hypoperfusion in carotid occlusion/stenosis (⇒ TOAST 1! )
  • various mechanisms ( e.g., vasospasm, cardioembolism in endocarditis)
  • oral contraceptives (usually in combination with a hypercoagulable state and/or smoking)
  • cocaine, crack, amphetamines, LSD, and heroin (drugs often cause IC bleeding)
  • sympathomimetics, ergotamine, sumatriptan
  • various mechanisms (most usually due to a hypercoagulable state or cardioembolism)
  • specific causes of stroke in pregnancy:
    • preeclampsia/eclampsia
    • amniotic fluid embolization (AFE)
    • choriocarcinoma
    • postpartum cerebral angiopathy
    • postpartum/peripartum cardiomyopathy (PPCM)

TOAST 5 – Stroke of undetermined etiology

  • the cause of the stroke could not be determined with sufficient certainty
    • ≥2 potential causes of stroke were identified (such as atrial fibrillation in a patient with > 50% carotid stenosis or significant carotid stenosis combined with microangiopathy)
    • cryptogenic stroke (CS) – no identifiable etiology despite an extensive evaluation
    • incomplete diagnostic evaluation

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TOAST classification of stroke