TOAST classification of stroke

Created 23/03/2021, last revision 21/09/2022

the exact etiology of ischemic stroke affects prognosis, outcome, 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 denotes five subtypes of ischemic stroke:
- 1 – large-artery atherosclerosis
- 2 – cardioembolism
- 3 – small-vessel disease
- 4 – a stroke of other determined cause
- 5 – a stroke of undetermined cause (cryptogenic stroke)
diagnosis is based on clinical features and data collected 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 strokes and TOAST 4 prevail at a younger age
- cardioembolic strokes predominate at an older age (increased occurrence of AFib and cardiac diseases), as well as arteriolopathy

→ ischemic stroke diagnosis and classification

TOAST 1 – Large Artery Atherosclerosis (macroangiopathy)

significant stenosis (> 50%) or occlusion of relevant extra- or intracranial artery due to atherosclerosis
cortical lesion on brain CT/MRI
subcortical lesion on brain CT/MRI > 1.5 cm

a specific and probably underdiagnosed etiology is thromboembolism from an unstable (complicated) non-stenosing (< 50%) artery plaques in CCA, ICA, and aorta [Harloff, 2010]
there is growing recognition of the importance of atherosclerotic plaque composition and morphology
- 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 2 – Cardioembolism

at least one potential cardioembolic source must be identified
- cardiac sources are divided into high-risk and medium-risk groups based on their propensities for embolism
an example of some high-risk sources:
- atrial fibrillation
- mechanical valve
- thrombus in the left atrium/ventricle
- atrial myxoma
- endocarditis
clinical and brain imaging findings are similar to TOAST 1
cardioembolic etiology is supported by infarcts/TIAs in different vascular territories (including silent lesions on CT/MRI)
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)

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

→ see here

dissection
vasospasm
- primary (idiopathic)
- secondary (a consequence of complicated migraine, VSP provoked during angiography or by drugs, etc.)
reversible vasoconstriction syndrome (RCVS)
moya-moya
metabolic diseases
- Fabry disease
- homocystinuria
cerebral amyloid angiopathy (CAA)
embolization from (pseudo) aneurysm (extra-/intracranial)
migraine (probably due to vasospasm)
genetically linked diseases of the connective tissue
- Marfan syndrome
- Ehlers-Danlos syndrome
- fibromuscular dysplasia (FMD)
Sneddon syndrome
- non-inflammatory thrombotic angiopathy affecting small to medium-sized arteries, clinically CMP + livedo racemosa
carotid artery web

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
CARASIL
Fabry
MELAS
HANAC (Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps)
HERNS (Hereditary endotheliopathy with retinopathy, nephropathy, and stroke) → more

Susac syndrome
- retinocochleocerebral vasculopathy
- rare microangiopathy of cochlea, retina, and brain with unknown etiology

COVID-19
- often in younger patients, in up to 1/3 of cases asymptomatic) [Shahjouei, 2021] [Fridman, 2020]
  - 36% in age <55 yrs, 46% < 65 yrs [Shahjouei, 2021]
- predominantly embolic mechanism with large artery occlusion (LVO) due to a hypercoagulable state [Shahjouei, 2021] [Yaghi, 2020]
- more severe course
- ↑ D-dimers

angiography (including cardiac catheterization) → complications of endovascular procedures
carotid surgery
surgery with ECC (Extra Corporeal Circulation)
air and fat embolisms (see below)

fat embolism
- typically following trauma (long bone fractures) and surgical procedures (including plastic surgery with fat extraction)
air embolism (microscopic x macroscopic)
- 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 i.v. 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 or border zone (watershed) infarcts
etiology
- systemic hypotension
  - cardiac failure
  - surgery with extracorporeal circulation (ECC)
- hypoperfusion in carotid occlusion/stenosis (⇒ TOAST 1! )

variety of mechanisms ( e.g., vasospasms, cardioembolism in endocarditis)
oral contraceptives (usually in combination with a hypercoagulable state and/or smoking)
cocaine, crack, amphetamine, LSD, heroin (often leading to 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 are detected (like AFib in a patient with carotid stenosis > 50%, carotid stenosis + microangiopathy, etc.)
- cryptogenic stroke (CS) – no etiology is determined despite extensive evaluation
- incomplete diagnostic evaluation