TOAST classification of stroke

Created 23/03/2021, last revision 12/05/2023

  • 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)
  • the 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 from brain imaging (CT/MRI), vascular imaging (CTA/MRA, neurosonology, DSA), cardiac imaging, and laboratory tests
  • the representation of each group depends on the mean age of the patient sample
    • cryptogenic stroke and TOAST 4 predominate in younger age groups
    • arteriolopathy and cardioembolic stroke predominate at an older age (increased incidence of atrial fibrillation and other heart diseases)
  • 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)

  • 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)

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, 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 presented in the CISS and SSS-TOAST classifications
  • the importance of plaque composition and morphology is increasingly recognized
    • 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) is associated with an increased risk of cerebrovascular events regardless of stenosis severity  [Kopczak, 2020] [Kamel, 2019
    • these findings may support an 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 potential and significant cardioembolic source must be identified
    • cardiac sources are divided into high-risk and intermediate-risk groups based on their propensity for embolization
  • 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 TOAST 1
    • there is no specific cardioembolic pattern
    • 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
  • + 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)
  • it is 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)
  • 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)
  • CADASIL   Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
  • CARASIL   CARASIL - arc sign (Roeben, 2016)
  • Fabry  Pulvinar sign and leukoencephalopathy in Fabry disease
  • MELAS  Typical MRI lesions in MELAS
  • 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
  • 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 identified (e.g., atrial fibrillation in a patient with carotid stenosis > 50%, significant carotid stenosis + microangiopathy, etc.)
    • cryptogenic stroke (CS) – no etiology identified despite extensive evaluation
    • incomplete diagnostic evaluation

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TOAST classification of stroke