Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients
Introduction
The presence of characteristic hyperintense white matter lesions on T2WI is useful in diagnosing MS [1], [2] and can assist in the longitudinal assessment of pathologic alterations in treatment trials [3]. However, bright T2WI lesions are nonspecific and reflect a wide spectrum extending from mild reversible changes to severe irreversible damage in white matter [4]. Furthermore, T2 hyperintensities may be inadequate to detect important microscopic disease [5]. Contrast enhancement on T1WI is transient, variable, and may not predict permanent injury or disease progression [6]. Both hyperintense and enhancing lesion loads have shown poor correlations with clinical findings in MS and appear to provide incomplete assessments of therapies [7].
MS has been recognized as a global disease process including brain atrophy [8], [9]. Cortical and subcortical gray matter involvement has been shown by pathologic examination [10], MRI fluid-attenuated inversion recovery (FLAIR) [11], and functional PET imaging [12]. Gray matter hypometabolism in MS may worsen over time [13] and predict cognitive disability [14]. Recently, we showed that hypointensity on T2-weighted images (probably pathologic iron deposition) occurred commonly in the cortical and subcortical gray matter of MS patients and correlated with certain clinical parameters [15], [16]. As we have previously reported in these 114 MS patients [15], abnormal T2 hypointensity was present in the thalamus in 57% (n=65) and in the putamen in 42% (n=48) of patients. T2 hypointensity was also present in the caudate in 24% (n=27) and in the rolandic cortex in 8% (n=9) of patients. T2 hypointensity was significantly related to longer disease duration and advancing neurologic disability. Secondary progressive patients had significantly worse BT2 in thalamus, putamen, and caudate than relapsing-remitting patients. No abnormality in these structures was appreciated on T1WI, PDWI, or FLAIR images, consistent with iron deposition. In a follow-up study of the same patient group, we evaluated whether T2 hypointensity correlated with other established MRI markers of disease involvement including brain atrophy and white matter T1 and T2 plaques.
Section snippets
Subjects and methods
Of 154 clinically definite [17] MS patients ages 18–60 screened during a 2-year period, excluded were those with poor quality MR images, other major illnesses, exacerbations in the previous 4 weeks, or primary progressive disease course [18]. Primary progressive patients were excluded because only two such patients were identified and this subgroup is being accumulated for a separate publication. Subsequently, 114 patients (89 women) were included in the study (age mean±SEM: 43±0.9 years; range
Results
T2 hypointensity was correlated positively and significantly with several MRI variables (see Fig. 1 for correlation coefficients and their 95% confidence intervals). In the multiple regression model, T2 hypointensity was predicted by the following regional MRI abnormalities: third ventricular enlargement, parietal atrophy, frontal T1 lesions, and cerebellar T2 lesions (all p<0.01; Table 1). Robust regression analysis showed that third ventricular enlargement (p<0.01), and parietal atrophy (p
Discussion
We found associations between gray matter T2 hypointensity (“black T2”—BT2) and other MRI markers of tissue damage in MS patients. The most common site of BT2 was the thalamus, followed by the putamen, caudate and sometimes the cerebral cortex that was associated with physical disability, disease duration, and clinical course [15]. This is the first study to suggest a relationship between BT2 and atrophy and between BT2 and T1 hypointensities in MS patients. The present study extends previous
Acknowledgements
This study was supported by National Institutes of Health NINDS 1 K23 NS42379-01 (R. Bakshi). We thank Dr. Jack H. Simon for helpful suggestions and for critically reviewing the manuscript. This work was presented in part at the 1999 Annual Meeting of the American Neurological Association, Seattle, WA, USA. We thank Dr. Brydon Grant (University at Buffalo) for statistical computations using the MARS package.
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