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White matter change and stroke risk
  1. P M Matthews
  1. Centre for Functional MRI of the Brain, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; paul{at}fmrib.ox.ac.uk

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    Large cohort studies have defined an increasing range of therapeutic interventions that can be applied to reduce stroke risk. However, application of these in a specialist practice is complicated by the problem of interindividual variation. A major practical issue is to differentiate those patients who will do well on standard treatment from those for whom a specifically targeted, more aggressive approach is needed. Ideally, it would be possible to profile patients at presentation to identify those at highest risk. If such a strategy could be made reliable, it would help simultaneously to balance a commitment to provide the best care available for each patient and to reassure government and other funders that potentially expensive therapeutic interventions are being employed in the most cost-effective fashion.

    MRI provides an attractive tool for stratifying risk in a stroke population. It offers a good definition of brain injury and promises to deliver increasingly quantitative markers of specific pathological changes.1 With growing access to MRI scanners and routine imaging of stroke cases, even this relatively expensive “screening test” would be of potential value as a marker of risk if it can be shown to be both sensitive and prognostically useful. A fundamental problem that has thus far limited enthusiasm for the use of MRI in establishing prognosis (as opposed to establishing clinical-pathological correlations) has been the non-specificity of T2 hyperintensity—the most sensitive marker—on conventional MRI. T2 hyperintensity in white matter, for example, can arise from enlarged perivascular spaces, increased tissue fluid, inflammation, or gliosis.

    In the paper by Yamauchi et al2 (this issue pp576–82) there are important new observations suggesting that conventional T2 weighted MRI may provide clinically useful information for risk stratification in an older stroke population. This paper follows a series of communications from several groups showing correlations between recognised risk factors such as hypertension3 and clinical syndromes such as cognitive impairment.4

    Yamauchi et al2 followed prospectively 89 patients who either had symptomatic lacunar infarcts or who were neurologically normal and presented for other reasons. Subjects with large vessel disease were specifically excluded. White matter lesions were graded using a simple scoring system based on the extent and distribution of changes. Clinical monitoring and serial MRI studies were performed over a period of around four years to test the predictive value of white matter lesion changes at baseline and over time.

    Seven patients had ischaemic or haemorrhagic strokes. These occurred only in patients with white matter lesions at baseline, and the proportion of patients who had stroke was greater in those with more severe white matter lesion changes than in those with milder white matter lesions. A Cox proportional hazards model identified both the expected risk factors for stroke (hypertension, uncontrolled diabetes mellitus, and smoking) and also the extent of white matter lesion changes. However, in a multiparametric model, the only independent predictors of stroke were the extent of the white matter lesions and uncontrolled diabetes mellitus. When patients with lacunar infarcts were considered separately, only the extent of white matter lesion changes was an independent predictor of later stroke.

    Over the follow up period none of the patients showed regression of white matter lesions, suggesting irreversible pathology. Extending the association of white matter lesion extent with stroke risk found in the cross sectional studies, patients showing increases in white matter lesion load during the period of observation had a greater risk of later stroke.

    The risk of stroke increases substantially after an initial cerebrovascular event. However, it has been less clear whether white matter changes can be interpreted as “silent strokes” that similarly contribute to risk. This study persuasively supports the notion that the extent of white matter lesion changes is an independent predictor and may provide prognostic information. Further work is needed to confirm these findings. Potential areas for such further work include the application of objective criteria for evaluation, the use of whole brain imaging, and thinner slices to improve the definition of changes. Nonetheless, Yamauchi et al offer the gratifying prospect of better targeting of aggressive management, although clearly a substantial therapeutic challenge remains—a disappointing observation in their study was that the severe white matter lesion group continued to have a higher risk of stroke despite apparently appropriate conventional management of vascular factors during the follow up period. Greater future effort might be directed towards developing therapeutic strategies directed at high risk populations, defined jointly by clinical and imaging measures.

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