Stroke—by definition a loss of brain function due to disturbance in blood supply to the brain—has been classified based on the duration of symptoms, clinical presentation, etiology, vascular or anatomical area of the brain affected, and by syndrome. About 80–85 % of strokes are ischemic and 15–20 % are hemorrhagic. The causative mechanism may be related to local intracranial vascular pathologies such as atherosclerosis, a more distant source of pathology such as emboli from extracranial artery disease or the heart, or reduced cerebral perfusion in the setting of circulatory failure. These categories are further subdivided based on the causative process (Fig. 1.2).

Ischemic stroke may be caused by large artery thrombosis, cardio-embolism, small vessel occlusion, venous infarction, or other determined or undetermined causes. Hemorrhagic stroke may be caused by hypertension, vascular malformations, amyloid angiopathy, an infarct with secondary hemorrhage, spontaneous subarachnoid hemorrhage usually due to aneurysm rupture, anticoagulants or antiplatelet drugs, coagulation and platelet disorders, and a small proportion of them are of undetermined etiologies.

Large vessel disease encompasses pathology involving the extracranial carotid vessels and the intracranial arteries including the proximal branches of the Circle of Willis. Pathological processes affecting large arteries include atherosclerosis, arterial dissection, inflammatory arteritis, vasculitis, fibromuscular dysplasia, Moyamoya disease, and cerebral angiographic vasospasm after subarachnoid hemorrhage. Atherosclerosis is the predominant cause of large vessel disease. Thrombi can form on atherosclerotic plaques or spontaneously in the setting of an underlying coagulopathy. Identification of the specific underlying vascular pathology and its extent is integral to determining the potential value of subsequent surgical and medical interventions.

Transient ischemic attacks (TIAs) are “a falsely benign form of brain attack” [14] with about 1 in 20 suffering a stroke within the subsequent 48 h, presenting a golden opportunity for prevention of further brain ischemia [15]. The 2009 American Heart Association (AHA) scientific statement on the definition and evaluation of TIA adopted an imaging-based definition [16]; a change from the prior temporal-based definition. The statement formally defines TIA as “a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.” The change in the definition was required because up to 50 % of TIAs diagnosed by the former definition have evidence of infarction on magnetic resonance imaging (MRI) (diffusion-weighted). TIA Class 1 recommendations of the AHA include imaging within 24 h, either MRI with diffusion weighting or computed tomography (CT)—though MRI is preferred. The proposed change in definition from time-based to imaging-based has implications for international clinical trials involving countries in which urgent MRI is not routinely available. Noninvasive imaging of the extracranial carotid arteries and intracranial cerebral vessels is also recommended.

Silent brain infarcts are a category of stroke in which stroke is evident on imaging studies in the absence of a history of TIA or stroke. The reported prevalence of silent brain infarcts is 8–28 % of patients in eight population-based studies [17]. Despite the lack of a history of TIA or stroke, these patients have been found to have neurological deficits including cognitive impairment, depression, visual field deficits, limb dysfunction, frailty, and physical decline. Thus, it has been suggested that they be referred to as “covert strokes.” Their prevalence is up to 5 times that of stroke and increases with age [17]. Covert brain infarcts detected by imaging are thus not necessarily asymptomatic. They are also not benign. Once detected, management implications are unclear and they are an important issue for ongoing stroke prevention research. Subclinical brain ischemia is potentially preventable, though there are no proven interventions to date. Definitive randomized controlled trials of current secondary preventive treatments are required to demonstrate the benefit of treatment in this patient population.

Clinically recognized strokes therefore represent the tip of the iceberg of vascular-mediated injury to the brain. A recently published prospective cohort study of the timing of onset of cognitive decline followed 10,308 British civil servants, performing tests of memory, reasoning, vocabulary, and semantic fluency; assessed 3 times over 10 years and found cognitive decline evident at ages 45–49 [18]. The Honolulu-Asia Aging study of 3,735 Japanese-American men showed that every 10 mmHg increase in midlife systolic pressure increased cognitive impairment by 7 % [19]. Whilst blood pressure lowering has not been shown to reduce vascular cognitive decline, there may be several reasons why this may be the case, including outcome measures that lack the sensitivity to detect appreciable differences when they are present.

Cardio-embolic stroke constitutes approximately 20 % of ischemic stroke and this proportion has remained relatively stable over the past few decades. This subtype of stroke is diagnosed when the probable cause of the stroke is presumed to be a consequence of embolism arising from the heart. The clinical diagnosis of cardio-embolic stroke can be made using the criteria outlined in Table 1.2.

Examples of major-risk sources include atrial fibrillation, intracardiac thrombus, atrial myxomas, and infective endocarditis. Minor-risk sources include calcific aortic stenosis, patent foramen ovale, mitral valve prolapse with myxomatous valves, and left ventricular systolic dysfunction with no associated thrombus (Figs. 1.3 and 1.4; Table 1.3).