Published online before print October 20, 2005, doi: 10.1161/01.STR.0000185694.52347.6e
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(Stroke. 2005;36:2342.)
© 2005 American Heart Association, Inc.
Letters to the Editor |
Should We Distinguish Between Periventricular and Deep White Matter Hyperintensities?
School of Psychiatry, University of New South Wales and Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia
To the Editor:
The recent article by DeCarli et al1 addresses a somewhat neglected aspect of white matter hyperintensities (WMH), the significance of their anatomical location. The authors argue that the commonly accepted categorization into deep (DWMH) and periventricular (PVWMH) WMH is arbitrary, because the 2 are very highly correlated, and a spatial analysis does not reveal distinct populations. We think that this conclusion is premature, because the categorization depends on a number of factors. The first limitation of their analysis is that they examined individuals in their 70s who presented to a specialty clinic, suggesting that the white matter lesions in their sample were at an advanced stage. If an analogy is drawn from cerebral atrophy in dementia, regional differences in atrophy that are present in the different subtypes of dementia become less prominent in the later stages. In our study of WMH in middle age (60 to 64 years), the correlation of DWMH and PVWMH was much lower (r=0.621; P<0.001; n=477), accounting for <40% of the variance.2 It is possible that the 2 subtypes of WMH have different but converging trajectories, possibly because of overlapping but not identical risk factors and pathogenesis. Neuropathological differences between DWMH and PVWMH have been reported,3 which suggest that whereas cerebral ischemia is a common etiological factor, other mechanisms may be differentially involved. In our study, hypertension was a risk factor for both, but diastolic blood pressure (BP) correlated significantly with DWMH, whereas both systolic and diastolic BP were correlated with PVWMH.4 Homocysteine was a determinant of DWMH but not PVWMH,5 but lung capacity was more strongly related to PVWMH.6
The functional significance of the 2 subtypes is also likely to be different. In an earlier study involving stroke patients,7 we showed that although DWMH accounted for only one third of the total WMH volume, with the other two thirds being PVWMH, it had a stronger relationship with cortical perfusion. Our recent analysis of data from 397 community-based middle-aged individuals suggests that DWMH have a significant relationship with cortical atrophy (r=0.15; P=0.003) and ventricular dilatation (r=0.18, P<0.0005), but PVWMH do not (r=0.06, P=0.21; r=–0.03, P=0.56 respectively.8 There are also demonstrated differences in the effect of DWMH or PVWMH on cognitive function, motor function,9 and emotions.10
Therefore, we support the continuing distinction between DWMH and PVWMH, at least for research. In fact, additional anatomical categorization into lobar and arterial territorial regions may be relevant for some purposes. To lump all of the WMH into 1 category will hamper our understanding of their pathogenesis and functional relevance.
References
- DeCarli C, Fletcher E, Ramey V, Harvey D, Jagust WJ. Anatomical mapping of white matter hyperintensities (WMH). Stroke. 2005; 36: 50–55.
[Abstract/Free Full Text] - Wen W, Sachdev P. The topography of white matter hyperintensities on brain MRI in middle-aged individuals. NeuroImage. 2004; 22: 144–154.[CrossRef][Medline] [Order article via Infotrieve]
- Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, Radner H, Lechner H. Pathological correlates of incidental MRI white matter signal hyperintensities. Neurology. 1993; 43: 1683–1689.
[Abstract/Free Full Text] - Wen W, Sachdev PS. Extent and distribution of white matter hyperintensities in stroke patients: the Sydney Stroke Study. Stroke. 2004; 35: 2813–2819.
[Abstract/Free Full Text] - Sachdev PS, Parslow R, Salonikas C, Lux O, Wen W, Kumar R, Naidoo D, Christensen H, Jorm A. Homocysteine and the brain in mid-adult life: evidence for an increased risk of leukoaraiosis in men. Arch Neurol. 2004; 61: 1369–1376.
[Abstract/Free Full Text] - Sachdev PS, Anstey KJ, Parslow RA, Wen W, Maller J, Kumar R, Christenson H, Jorm AF. Pulmonary function, cognitive impairment and brain atrophy in a middle aged community sample. Dement Geriatr Cogn Disord. 2005; in press.
- Wen W, Sachdev P, Shnier R, Brodaty H. Effect of white matter hyperintensities on cortical cerebral blood volume using perfusion MRI. NeuroImage. 2004; 21: 1350–1356.[Medline] [Order article via Infotrieve]
- Wen W, Sachdev PS, Chen X. Gray matter reduction is correlated with white matter hyperintensity volume: a voxel-based morphometric study in a large epidemiological sample. Neuroimage. 2005; in press.
- Sachdev PS, Wen W, Christensen H, Jorm AF. White matter hyperintensities are related to physical disability and poor motor function. J Neurol Neurosurg Psych. 2005; 76: 362–367.
[Abstract/Free Full Text] - Steffens DC, Krishnan RR, Crump C, Burke GL. Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. Stroke. 2002; 33: 1636–1644.
[Abstract/Free Full Text]
Response:
Department of Neurology and Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California at Davis, Davis, California
Division of Biostatistics, Department of Epidemiology and Preventive Medicine, University of California at Davis, Davis, California
We appreciate the keen observations of Drs Sachdev and Wen regarding the importance of anatomical distributions of abnormal white matter hyperintensities (WMH) as seen on MRI. In fact, we agree with Drs Sachdev and Wen that the location of WMH is important, but we continue to believe that current categorical definitions of subcortical versus deep white matter are probably inadequate, because they do not have clear biological correlates. For example, the superior longitudinal fasciculus, an anatomically discrete white matter bundle, traverses both periventricular and deep white matter locations. Evolving image mapping methods such as our own1 and that of Drs Sachdev and Wen2 offer the unique opportunities for an "unbiased" analysis of the anatomical distribution of WMH throughout the brain, offering the potential for better correlation with anatomically valid white matter structures. Unfortunately, appropriate statistical methods have yet to be developed for this approach. In this regard, we are developing new statistical methods that will take into account the location of WMH relative to important biological and anatomical structures and enable more sophisticated spatial analysis.
The authors raised a second issue related to study differences in subject selection. We have previously shown that total WMH volume is strongly associated with age, and age-related differences increase more dramatically with age after 60 years.3 As Drs Sachdev and Wen2 note, the distribution of WMH may also vary with subject age. For example, younger individuals are more likely to have limited WMH abutting the ventricular system with scattered, punctate WMH throughout subcortical white matter. As we suggest, WMH may "coalesce" or merge with periventricular WMH as total WMH burden increases,1 which could explain differences in relationships shown by Drs Sachdev and Wen2 and ourselves. Underlying disease will also affect the distribution of WMH. For example, WMH may be more common in the frontal areas of individuals with depression4 or involve gray matter structures in stroke. Whereas age-related or disease-related differences among various studies may explain some of the differences in reported relationships between WMH location and behavior, we continue to believe that advances in our understanding of the etiology and seminology of WMH will be best served by developing new methods that enable accurate anatomical representation of white matter tracts.
References
- DeCarli C, Fletcher E, Ramey V, Harvey D, Jagust WJ. Anatomical mapping of white matter hyperintensities (WMH): exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke. 2005; 36: 50–55.
[Abstract/Free Full Text] - Wen W, Sachdev P. The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals. NeuroImage. 2004; 22: 144–154.[CrossRef][Medline] [Order article via Infotrieve]
- Decarli C, Massaro J, Harvey D, Hald J, Tullberg M, Au R, Beiser A, D’Agostino R, Wolf PA. Measures of brain morphology and infarction in the Framingham Heart Study: establishing what is normal. Neurobiol Aging. 2005; 26: 491–510.[CrossRef][Medline] [Order article via Infotrieve]
- Thomas AJ, Perry R, Kalaria RN, Oakley A, McMeekin W, O’Brien JT. Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depression. Int J Geriatr Psychiatry. 2003; 18: 7–13.[CrossRef][Medline] [Order article via Infotrieve]
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