TOAST classification of stroke

Created 23/03/2021, last revision 30/01/2023

  • the exact etiology of ischemic stroke has implications for prognosis and management
  • a system for classifying ischemic stroke subtypes mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST)
  • TOAST classification identifies five subtypes of stroke:
    • 1 – large-artery atherosclerosis (LAA)
    • 2 – cardioembolic stroke (CE)
    • 3 – small-vessel disease (SVD) / penetrating artery disease (PAD)
    • 4 – a stroke of other determined cause
    • 5 – a stroke of undetermined cause (cryptogenic stroke)
  • diagnosis is based on clinical features and data obtained from brain imaging (CT/MRI), vessel imaging (CTA/MRA, neurosonology, DSA), cardiac imaging, and laboratory tests
  • representation of each group depends on the mean age of the patients’ sample
    • cryptogenic stroke and TOAST 4 predominate at a younger age
    • arteriolopathy and cardioembolic strokes predominate at an older age (increased occurrence of AFib and cardiac diseases)
  • other improved classification systems have been introduced:

→ ischemic stroke diagnosis and classification

TOAST 1 – Large Artery Atherosclerosis (macroangiopathy)

  • medium-sized and large arteries are affected
  • stroke is caused by atherothrombosis or thromboembolism
  • significant stenosis (> 50%) or occlusion of relevant extra- or intracranial artery due to atherosclerosis  Large artery atherosclerosis (TOAST 1)
  • 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 arteries atherosclerosis (see CISS classification)

Issues discussed regarding TOAST 1

  • a specific and probably underdiagnosed etiology is thromboembolism from an unstable (complicated) non-stenosing (< 50%) plaques in CCA, ICA,  aorta, and intracranial arteries  [Harloff, 2010]
  • in addition, minor infarcts resulting from atherosclerotic plaques in the ostium of perforating arteries should be included here – branch artery disease (BAD) / branch occlusive disease (BOD)   
  • the importance of plaque composition and morphology is increasingly recognized.
    • demonstration of intraplaque hemorrhage (IPH), thrombus, thin or ruptured fibrous cap, or a large lipid-rich and/or necrotic core (visible on high-resolution MRI) are associated with an increased risk of cerebrovascular events regardless of the severity of the stenosis  [Kopczak, 2020] [Kamel, 2019
    • these findings may support an atherothrombotic etiology (TOAST 1)
  • no significant atherosclerosis in major brain arteries
  • presence of potential cardioembolic source (especially any high-risk factor)

TOAST 2 – Cardioembolic stroke

  • at least one potential and significant cardioembolic source must be identified
    • cardiac sources are divided into high-risk and medium-risk groups based on their propensities for embolism
  • some high-risk sources:
    • atrial fibrillation (AFib)
    • mechanical valve
    • thrombus in the left atrium/ventricle
    • atrial myxoma   Myxoma
    • endocarditis   Endocarditis on TEE
  • clinical and brain imaging findings are similar to TOAST 1
    • no specific cardioembolic pattern, but cardioembolic etiology is supported by infarcts/TIAs in different vascular territories (including silent lesions on brain imaging)  Cardioembolic stroke with multiple territory embolisation Cardioembolic strokes in different territories
  • a stroke in a patient with a medium-risk cardiac source of embolism and no other 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
  • + 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)
  • 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 perforator origin – Branch Artery Disease (BAD) / Branch Occlusive Disease (BOD)
      • infarcts tend to be larger than in classic arteriolopathy
      • high resolution MRI can be used for diagnosis
    • embolization (from proximal arterial segments or from the heart)
  • presence of significant stenosis in relevant extra- and/or intracranial arteries
  • presence of a significant cardioembolic source
  • hemisferal infarction on CT/MRI

TOAST 4 – Stroke of other determined etiology

  • < 5% of stroke patients < 50 years of age   Primary CNS vasculitis
  • mainly PACNS and Takayasu arteritis are present at a younger age

→ see here

  • dissection Dissection in common carotid artery (CCA)
  • vasospasm Vasospasm on DSA
    • primary (idiopathic)
    • secondary (a consequence of complicated migraine, VSP provoked during angiography or by drugs, etc.)
  • reversible vasoconstriction syndrome (RCVS)
  • moya-moya angiopathy Moya-moya disease
    • multiple etiologies (e.g., Grange syndrome, ACTA2 mutations, vasculitis, etc.)
  • metabolic diseases
    • Fabry disease
    • homocystinuria
  • embolization from (pseudo) aneurysm (extra-/intracranial)   Aneurysm with intrasaccular thrombus (CTA)
  • migraine (probably due to vasospasm)
  • genetically linked diseases of the connective tissue
  • Sneddon syndrome

    • non-inflammatory thrombotic angiopathy affecting small to medium-sized arteries, clinically stroke + livedo racemosa
  • carotid artery web  Carotid artery web
  • Grange syndrome
  • dolichoectasia (usually in the basilar artery) Basilar artery dolichoectasia (CTA)
    • more often in older patients
  • CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)   Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
  • Fabry
  • HANAC (Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps)
  • HERNS (Hereditary endotheliopathy with retinopathy, nephropathy, and stroke) → more here
  • 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
  • hypercoagulable states
    • primary – most often antiphospholipid syndrome and APC resistance
    • secondary
      • oncohematological diseases (e.g., leukemia, polycythemia vera)
      • thrombotic thrombocytopenic purpura (TTP)
      • non-specific intestinal inflammation
      • nephrotic syndrome
  • hemoglobinopathies (typically sickle cell disease)
  • hematological malignancies
  • hyperviscosity syndrome (HVS)
  • 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)
    • 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 frequently cause IC hemorrhages)
  • sympathomimetics, ergotamine, sumatriptan

TOAST 5 – Stroke of undetermined etiology

  • cause of a stroke could not be determined with sufficient confidence
    • ≥2 potential causes of stroke identified (such as AFib in a patient with carotid stenosis > 50%, significant carotid stenosis + microangiopathy, etc.)
    • cryptogenic stroke (CS) – no etiology determined despite extensive evaluation
    • incomplete diagnostic evaluation

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TOAST classification of stroke