ISCHEMIC STROKE / CLASSIFICATION AND ETIOLOGY
Etiologic classification of ischemic stroke
David Goldemund M.D.
Updated on 30/12/2023, published on 19/04/2023
- individualized stroke prevention is based on the presumed underlying etiology (CEA in patients with symptomatic high-grade carotid stenosis, anticoagulation in patients with cardioembolic infarcts due to AFib)
- the use of standardized diagnostic algorithms and established classifications (such as TOAST and CISS) is recommended
Evaluation of ischemic stroke etiology
Brain imaging
- assess the nature, size, and location of the lesion on brain CT/MRI scans; note any pathological findings
- both CT and MRI are used in the acute stroke setting
- for patients with suspected acute stroke and a negative baseline CT/MRI, adding follow-up imaging to confirm the diagnosis is reasonable (AHA/ASA 2021 2a/B-NR)
- for patients with TIA and negative imaging, adding a follow-up MRI is reasonable (AHA/ASA 2021 2a/B-NR)
- follow-up CT/MRI is advisable before initiating anticoagulation to assess the extent of ischemia and exclude possible hemorrhagic transformation (best visualized on GRE/SWI) (AHA/ASA 2021 2b/B-NR)
Vascular imaging
- vascular imaging is used to detect stenosis or occlusion and to assess probable etiology (atherosclerosis, dissection, FMD, etc.)
- in acute stroke patients, standard baseline imaging in most centers consists of brain CT+CT angiography (alternatively, MRI+MRA)
- patients with mRS 0-3, who are not candidates for recanalization therapy, should have vascular imaging within 24 h of admission (in the non-acute setting, neurosonology is the most commonly used method)
- both extra- and intracranial arteries should be evaluated (CTA from the aortic arch to the vertex is recommended)
- in acute stroke patients, standard baseline imaging in most centers consists of brain CT+CT angiography (alternatively, MRI+MRA)
- methods:
- CT angiography (see an in-depth tutorial on vascular assessment of stroke patients)
- MR angiography
- neurosonology
- in the acute stroke setting, TIBI may be used to detect and monitor intracranial occlusion (the method became less useful with the availability of CTA and the advent of mechanical recanalization)
- DSA (most commonly used for endovascular procedures)
Arrhythmias detection
Markers associated with a higher incidence of AFib |
Electrophysiological |
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Biochemical |
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Morphological |
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Comorbidities |
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Cardiac imaging
Laboratory tests
- assess vascular risk factors (AHA/ASA 2021 1/N-BR)
- consider testing for hypercoagulable states in selected cases
- screening is not beneficial due to the low detection rate and high cost
- autoantibodies testing if vasculitis is suspected
- screening is not recommended due to the low detection rate and high cost
- cardiac enzyme testing (CK, CKMB, LD, high-sensitivity cardiac troponin)
- to exclude concomitant myocardial infarction (MI), which may be a source of cardioembolism
- troponin elevation is often attributed to a brain lesion rather than MI
- other tests
- toxicology (drugs)
- CSF analysis (vasculitis, DDx of neuroinfection)
- biopsy for conditions like vasculitis (brain and meninges), CADASIL (skin), etc.
- genetic testing (e.g., CARASIL, CADASIL, ACTA2, Grange syndrome, hypercoagulable states, and other genetic small vessel diseases
- consider screening for obstructive sleep apnea (OSA) (AHA/ASA 2021 2b/B-R)
Classification of ischemic stroke
- stroke is a highly heterogeneous disease in terms of etiology and clinical course
- numerous classifications and subdivisions exist, many of them combining different elements (e.g., etiopathogenetic mechanism with risk factors or clinical presentation ), which can potentially lead to confusion
- TOAST classification is widely recognized and seems to be most useful for clinical practice
Classification based on etiology and pathophysiology
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Classification based on the appearance and location of ischemia (which may indicate etiology)
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Classification based on duration (in conjunction with brain imaging)
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Pathophysiologic classification
- the diagram provides a simplified representation of complex etiopathogenesis, where multiple mechanisms may coexist (e.g., arteriolopathy may have a thrombotic or atherothrombotic component, etc.)
Etiologic classification
- TOAST classification of stroke remains the most widely utilized system for categorizing stroke
- only a summary is presented below
- other improved classification systems include:
- the variability in the reported proportions of individual stroke subtypes is due to the age composition of the cohort and the diagnostic methods used).
- the proportional representation of stroke subtypes may change with the development of new diagnostic methods (e.g., long-term ECG monitoring increases the detection of paroxysmal AFib, thus decreasing the percentage of cryptogenic strokes, etc.)
- significant stenosis (> 50%) or occlusion of a relevant extra- or intracranial artery due to atherosclerosis
- evidence of plaque hemorrhage, thrombus, plaque cap rupture, or angiogenesis indicates a high-risk plaque, irrespective of the degree of stenosis
- → assessement of atherosclerotic plaques
- search for aortic arch atherosclerosis, which is categorized as large artery atherosclerosis in both TOAST and CISS classifications
- brain imaging (CT/MRI)
- cortical lesion
- subcortical lesion > 1.5 cm (originally published)
- it is known, however, that even smaller lesions may be caused by branch artery atherosclerosis (see the CISS classification)
- common mechanisms of stroke in the TOAST 1 category:
- thromboembolism, atheroma embolization, or both (artery-to-artery embolization)
- the composition of the embolus may vary, ranging from a fragile fresh fibrin thrombus that easily fragments to a compact, tightly organized thrombus with solid plaque masses
- thrombosis or intraplaque bleeding leading to arterial occlusion
- occlusion of perforators caused by large plaques
- hypoperfusion due to severe stenosis (⇒ border zone infarcts)
- thromboembolism, atheroma embolization, or both (artery-to-artery embolization)
- cardioembolic stroke accounts for ~ 20-45% of all ischemic strokes (the proportion increases with advanced cardiac imaging and prolonged ECG monitoring)
- thromboembolism from the left atrium or ventricle is the most common; hypoperfusion is less frequent (⇒ typically resulting in border zone infarcts, as seen in conditions like cardiomyopathy)
- clinical syndromes and infarct features on brain imaging are usually indistinguishable from TOAST 1
- detection of left atrial thrombus on baseline CTA can help establish the correct etiological diagnosis
- arteriolopathy (primarily affecting arteries 0.4-0.5 mm in diameter) may lead to cerebral infarction or hemorrhages in deep brain structures
- the primary etiology of arteriolopathy is lipohyalinosis
- especially prevalent in patients with hypertension
- lipohyalinosis is characterized by arterial wall thickening, leading to vessel stenosis or occlusion
- brainstem or subcortical lacunar infarcts on CT/MRI (diameter < 1.5 cm) or subcortical ischemic leukoencephalopathy (→ FAZEKAS scale, ARWMC scale)
- clinical presentation
- asymptomatic cases
- lacunar syndromes
- encephalopathy with cognitive impairment +/- pseudobulbar syndrome (attributable to the status lacunaris)
- + the presence of traditional vascular risk factors (hypertension, dyslipidemia, diabetes, etc.)
- distinguish non-arteriolopathic occlusion of perforating arteries
- 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 and are more common in younger patients [Zhou, 2018]
- high-resolution MRI can be used for diagnosis [Petrone, 2016]
- embolization (originating from proximal arterial segments or cardioembolism)
- atherosclerosis of the parent artery near the perforator origin – Branch Artery Disease (BAD) / Branch Occlusive Disease (BOD)
- vasculitis
- non-inflammatory vasculopathies
- genetic microangiopathies
- hematologic disorders
- iatrogenic insults, etc.
- cause of stroke remains undetermined due to insufficient diagnostic certainty
- ≥2 potential causes of stroke were identified (e.g., atrial fibrillation + carotid stenosis > 50%, significant carotid stenosis + microangiopathy, etc.)
- cryptogenic stroke (CS) – no etiology identified despite extensive evaluation [Bang, 2014]
- incomplete diagnostic evaluation