References for this Review were identified through searches of PubMed with the search terms “small vessel disease(s)”, “white matter lesions”, “white matter changes”, “lacunar infarcts”, “subcortical vascular dementia”, “vascular cognitive impairment”, “neuroimaging”, “pathology”, and “therapy” from 1966 to January, 2010. Articles were also identified through searches of the author's own files. Only papers published in English were reviewed.
ReviewCerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges
Introduction
Small vessel disease is a term used with various meanings and in different contexts (ie, pathological, clinical, and neuroimaging aspects). These diseases are thought to be the most frequent pathological neurological processes1 and have a crucial role in at least three fields: stroke, dementia, and ageing. In this Review, the definition of small vessel disease is critically reassessed and an overview of recently described clinical consequences of cerebral forms of the disease is provided. Clarification of some of these concepts is needed because the term small vessel disease is likely to be used (or otherwise misused) more frequently in the near future as risk of developing these diseases increases with the ageing population and as increased use of MRI will identify more people with these diseases. Developing lines of research into the treatment of small vessel disease are outlined, and suggestions on the role of neuroimaging as a possible surrogate marker in therapeutic trials are provided. The aim of this Review is to provide clinicians and researchers with some basic concepts with a modern overview of small vessel disease to enable understanding of recent progress and future directions in the field.
Section snippets
Definitions
The term small vessel disease encompasses all the pathological processes that affect the small vessels of the brain, including small arteries and arterioles but also capillaries and small veins. However, the definition of a small vessel is not uniform: the results from a survey showed that there was less than 50% agreement among leading neuropathological centres on its definition.2 Most often, small vessel disease is used to refer only to the arterial vessels and little attention has been paid
Pathological features
Most of the topics dealt with in this Review are linked to the first two types of small vessel diseases and, therefore, only the pathological characteristics of these diseases are described.
Neuroimaging correlates of small vessel disease
As mentioned earlier, the consequences of small vessel disease on the brain parenchyma are heterogeneous, encompassing ischaemic and haemorrhagic manifestations (Figure 1, Figure 2). However, in neuroimaging, the term small vessel disease is often used misleadingly to describe the ischaemic consequences (ie, white matter lesions and lacunar lesions). Haemorrhagic lesions can be further distinguished as macrolesions and microlesions. Although major haemorrhages are easily recognised by
Small vessel disease and acute ischaemic stroke
Small vessel disease is the cause of about a quarter of all acute ischaemic strokes.104, 105 Overall, strokes caused by small vessel disease are less severe than other types of stroke in terms of the clinical picture during the acute phase and short-term prognosis.106, 107 However, the long-term outcome of these patients cannot be thought of as benign in terms of mortality and functional impairment.108 No specific treatment for strokes caused by small vessel disease in the acute phase has yet
Conclusions and future directions
Small vessel disease is an important cause of stroke, cognitive decline, and age-related disability. More attention and targeted efforts are needed to better understand the pathogenesis of vascular injury to the brain caused by small vessel disease and to thoroughly define the clinical consequences of these diseases. Given the frequent coexistence of different forms of small vessel disease (ie, white matter lesions, lacunar infarcts, and microbleeds), all relevant lesion types need to be taken
Search strategy and selection criteria
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