Aetiology

Ischaemic stroke is a syndrome, not a disease. It is caused by a transient or permanent critical reduction in cerebral blood flow due to arterial occlusion or stenosis. Identification of the underlying mechanisms and aetiologies is important so that appropriate therapy can be initiated to decrease the risk of recurrent stroke.

A classification scheme for ischaemic stroke developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST) provides a framework for determining the stroke mechanism, with implications for identifying the underlying aetiology:[3]

  • Large artery atherosclerosis affects the extracranial carotid or vertebral arteries, or less commonly the major intracranial arteries. It is a site for thrombus formation that then embolises to distal sites and/or occludes the vessel.

  • Small vessel (lacunar) stroke is caused by thrombotic occlusion of a small penetrating artery affected by lipohyalinosis (lipid accumulation due to ageing and hypertension), resulting in a <1.5-cm infarct in the perfusion territory of the affected small vessel.

  • Cardioembolism results from thrombus formation in the heart, which then embolises to the intracranial circulation, and is associated with cardiac disease such as atrial fibrillation. Accumulating evidence suggests that aortic atherosclerotic plaque is another potential source of thrombus formation with embolism.

  • Strokes of other determined aetiology may be caused by various diseases of the intracranial or extracranial vessels (e.g., dissection, vasculitis, venous thrombosis) or haematological system (e.g., sickle cell anaemia, antiphospholipid antibody syndrome, and other hypercoagulable states).

  • Strokes of indeterminate aetiology, despite complete work-up, are not uncommon. In the Northern Manhattan Stroke Study, 32% of strokes had no identifiable aetiology.[20]

Pathophysiology

Regardless of the aetiology, ischaemic stroke occurs when blood supply in a cerebral vascular territory is critically reduced due to occlusion or critical stenosis of a cerebral artery. A minority of ischaemic strokes are caused by cerebral sinus or cortical vein thrombosis. These are frequently associated with a prothrombotic (hypercoagulable or hyperaggregable) state, with resulting venous insufficiency and reduced blood flow.

Pathophysiologically, ischaemic stroke can be broadly classified as:

  • Primary vascular pathologies (e.g., atherosclerosis, aortic arch atherosclerosis, arterial dissection, migraine, or vasculitis) that directly reduce cerebral perfusion and/or result in artery-to-artery embolism (i.e., stenosis or occlusion of a distal artery by an embolus originating in a proximal artery)

  • Cardiac pathologies (e.g., atrial fibrillation, myocardial ischaemia/infarction, patent foramen ovale) that lead to cerebral arterial occlusion due to embolism

  • Haematological pathologies (e.g., prothrombotic hypercoagulable or hyperaggregable states) that directly precipitate cerebrovascular thrombosis (particularly venous), or facilitate systemic venous or intracardiac thrombus formation and cardioembolism.

Classification

Oxford Community Stroke Project classification system (also known as the Bamford or Oxford classification)[2]

Classifies ischaemic stroke based on the initial presenting symptoms and clinical signs. This system does not require imaging to classify the stroke, instead, it is a purely clinical diagnosis.

  • Total anterior circulation stroke

  • Partial anterior circulation stroke

  • Posterior circulation stroke

  • Lacunar syndrome

Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria[3]

Classifies ischaemic stroke according to pathophysiology:

Large artery atherosclerosis

  • Infarction in the perfusion territory of an extracranial or intracranial artery with >50% stenosis, and no other likely cause of stroke.

Cardioembolism

  • Infarction in the presence of at least 1 cardiac condition strongly associated with stroke, such as atrial fibrillation.

Small vessel occlusion

  • Infarction <1.5 cm in diameter in the perfusion territory of a small penetrating blood vessel.

Stroke of other determined aetiology

  • Examples include cerebral infarction caused by vasculitis, arterial dissection, and hypercoagulable states.

Stroke of indeterminate aetiology

  • Infarction in the setting of 2 or more different potential aetiologies, no potential aetiology despite complete diagnostic evaluation, or an incomplete evaluation.

Causative classification of stroke modified TOAST criteria[4]

This web-based validated classification algorithm sub-types ischaemic stroke according to pathophysiological mechanism. Categories are:

  • Large artery atherosclerosis

  • Cardio-aortic embolism

  • Small artery occlusion

  • Other causes

  • Indeterminate causes.

Indeterminate causes are divided into:

  • Unknown - embolic stroke of undetermined source

  • Unknown - multiple causes

  • Unknown - incomplete evaluation.

Each sub-type except for the indeterminate group is sub-divided based on the weight of evidence as:

  • Evident

  • Probable

  • Possible.

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