Chinese Ischemic Stroke Subclassification (CISS)

Created 12/04/2022, last revision 01/12/2022

  • classification of an acute ischemic stroke has a substantial impact on patient care, secondary stroke prevention, and stroke research
  • the most popular and commonly used stroke classification system is the TOAST
  • other established systems:
  • Chinese ischemic stroke subclassification (CISS) attempts to improve TOAST by sub-classifying strokes with greater accuracy; CISS has the following notable differences  (Gao, 2011) :
    • aortic arch atherosclerosis belongs to LAA
    • CISS distinguishes underlying mechanisms related to LAA
    • CISS applies a new concept of penetrating artery disease – atheromatosis in the junction of parent vessel and penetrating arteries (branch artery disease) vs. fibrohyalinosis
      • intracranial atheromatous branch artery disease (BAD) affecting penetrating arteries is classified into large artery atherosclerosis (LAA)
  • new imaging technologies allow visualization of the previously non-visible underlying pathologies and ambiguous lesions
Chinese Ischemic Stroke Subclassification (CISS)

Large artery atherosclerosis

Aortic arch atherosclerosis

  • acute multiple infarcts, especially involving bilateral anterior and/or anterior and posterior circulations
  • evidence of significant aortic arch atherosclerosis – aortic plaques >4 mm and/or aortic thrombi (detected by HR-MRI/MRA and/or TEE)
  • no evidence of atherosclerosis of relevant intracranial or extracranial large arteries (vulnerable plaques or stenosis ≥50% or occlusion)
  • no evidence of the potential cause of cardiogenic stroke (CS) or other etiologies that can cause multifocal acute ischemic lesions
Aortic arch atherosclerosis on CTA

Intra- and extracranial LAA

  • any distribution of acute infarct (except isolated infarct in the territory of one penetrating artery), with evidence of atherosclerosis involving intracranial or extracranial large arteries (vulnerable plaque or stenosis ≥50%) that supply the infarcted area
  • penetrating artery territory infarct can be included if atherosclerotic plaque in the parent artery is detected (by HR-MRI)
  • no evidence of potential cardiac embolic cause or other causes of stroke
Large artery atherosclerosis (LAA)

The underlying mechanisms of ischemic stroke caused by intra- or extracranial LAA are further defined as:

  • artery-to-artery embolism:
    • small cortical infarcts or a single territory infarct in the area supplied by the relevant intra-/extracranial artery affected by atherosclerosis
    • no border-zone infarct (BZI) related to this artery
    • diagnosis is confirmed if the infarcts are multiple or if the single infarct is accompanied by MES on TCD
      • however, a single cortical or territorial infarct without obtaining MES can also be diagnosed as an artery-to-artery embolism
  • hypoperfusion/impaired emboli clearance
    • infarcts occur in the border-zone area
    • no acute cortical or territory infarcts related to the diseased artery
    • stenosis of the clinically relevant intracranial or extracranial artery is usually >70%, with or without evidence of hypoperfusion or poor collateral compensation in the related region of perfusion
    • perfusion may be compromised because of a sudden drop in blood pressure or other systemic hypoperfusion events
  • parent artery plaque/thrombus stenosing/occluding the penetrating artery  (branch artery disease)
    • isolated acute infarct in penetrating artery territory, evidence of plaque/any degree of stenosis in the junction of parent and penetrating artery
      • an isolated acute infarct in the basal ganglia, and no other acute infarct in the territory supplied by the ipsilateral MCA
      • an isolated acute infarct in the pons, and no other acute infarct in the territory supplied by the basilar artery
  • multiple mechanisms: ≥ 2 underlying mechanisms mentioned above are present
Penetrating artery disease with a parent artery atherosclerosis
Border zone infarcts (BZI)
  • severe stenosis leads to border-zone infarction (BZI) because of hypoperfusion (hemodynamic effect) with/without impaired emboli clearance
  • it is difficult to separate these two mechanisms
    • impaired emboli clearance is probable if TCD detects micro-embolizations (MES)
    • however, the absence of MES doesn´t exclude the existence of an impaired emboli clearance mechanism

Cardioembolic stroke

  • multiple infarcts, especially involving bilateral anterior and/or anterior and posterior circulations (including cortical infarcts) that have occurred close in time
  • evidence of cardiac disease that has a potential for embolism
  • no evidence of atherosclerosis on relevant intracranial or extracranial large arteries (vulnerable plaques or stenosis ≥50% or occlusion)
  • no evidence of other etiologies that can cause multifocal acute ischemic infarcts such as vasculitides, hemostatic disturbances, and tumorous embolism
  • if the possibility of aortic arch atherosclerosis has been excluded, CS is definite. Otherwise, the category should be possible CS
  • any documented history of permanent or transient atrial fibrillation/flutter with or without spontaneous echo contrast or left atrial thrombus, sick sinus syndrome
  • prosthetic heart valve
  • myocardial infarction within the past 4 weeks
  • mural thrombus in the left cavities, left ventricular aneurysm
  • dilated cardiomyopathy
  • ejection fraction <35%
  • endocarditis
  • intracardiac mass
  • PFO plus in situ thrombosis, PFO plus concomitant PE, or DVT preceding the brain infarction

Penetrating artery disease

  • acute isolated infarct in the clinically relevant territory of one penetrating artery
  • such infarct can be caused by atherosclerosis at the junction of the parent and penetrating artery (also called branch artery disease, which belongs to LAA) or lipohyalinotic degeneration of arterioles (arteriolopathy)
    • atherosclerotic lesions and fibrohyalinosis usually coexist – it is difficult or even impossible to distinguish between the two (both clinically and radiologically)
    • high-resolution MRI (not used as a standard imaging technique) can detect atherosclerotic lesions in proximal segments of penetrating arteries ⇒ lacunar infarctions are not equivalent to intrinsic small vessel disease (fibrohyalinosis)
  • no evidence of atherosclerotic plaque (detected by HR-MRI) or stenosis in the parent artery
  • with evidence of vulnerable plaques or stenosis ≥50% in ipsilateral proximal intracranial or extracranial large arteries, the isolated penetrating infarct is classified as undetermined etiology – multiple etiology
  • with evidence of cardiac disease that has a potential for embolism, the isolated penetrating infarct is classified as UE (multiple etiology)
  • chronic penetrating artery disease leads to leukoaraiosis (→ Binswanger disease)
Lacunar infarct in thalamus (DWI)
Binswanger's disease
Extensive leukoencephalopathy in Binswanger´s disease (FLAIR)

Other etiology

  • evidence of other specific diseases (e.g., vascular-related disease, infective disorder, inherited disease, hematological system disorder, vasculitis) that are relevant to the index stroke and can be demonstrated by blood tests, cerebrospinal fluid (CSF) tests, and vascular imaging  (see TOAST 4)
  • the possibility of LAA or CS has been excluded

Undetermined etiology

  • multiple: evidence of ≥ 1 potential cause; it is difficult to determine which was the relevant cause of the index stroke
  • unknown: no evidence of any specific potential etiology that is clinically relevant to the index stroke
  • inadequate evaluation: routine assessments are not completed, which makes the etiology undetermined

 → cryptogenic stroke

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