Thursday, August 30, 2007

Possible New MRI Marker for Multiple Sclerosis Progression

By Crystal Phend, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.

BOSTON, Aug. 28 -- Bright spots commonly seen on T1 magnetic resonance imaging brain scans of multiple sclerosis patients may help predict risk of disease progression, researchers here said.

The number of these hyperintense lesions was also significantly correlated with physical disability (P=0.04) and brain atrophy (P≤0.001), found Rohit Bakshi, M.D., of Harvard and Brigham and Women's Hospital, and colleagues.

The findings of their retrospective study suggest that these lesions could be a new clinically relevant biomarker for multiple sclerosis, they wrote in the September issue of the journal Radiology.

Hyperintense lesions on T2-weighted MRI have been used for diagnosis and monitoring of multiple sclerosis, but the clinical correlations have seemed weak, they noted.

"Clearly, there is a need for better MRI markers of disease activity and tissue damage," they wrote.

So, the researchers retrospectively reviewed a database of 145 consecutive multiple sclerosis patients referred to a community-based comprehensive MS center from 1995 to 1999.

The majority of patients were women (77%) and had relapsing-remitting multiple sclerosis (63%). The remaining 34% had secondary-progressive disease. Those with primary-progressive disease were excluded. The mean disease duration was 9.6 years.

Two researchers blinded to patients' clinical details reviewed MRIs from each patient and found that 78% had T1 hyperintense lesions with a mean of 2.3 lesions per patient.

The lesions were typically seen in the supratentorial regions of the brain, particularly the superior and inferior frontal lobes and the superior parietal lobe.

More than a third of the lesions showed up with uniform hyperintensity (38%), but the majority showed hyperintensity only around the rim of the lesion (62%). The average diameter was 0.8 cm.

Patients with more advanced clinical disease were significantly more likely to have multiple than single T1 hyperintense lesions (P<0.001). The findings were:

71% of patients with secondary progressive disease had multiple lesions whereas only 8% had single lesions.
46% of patients with relapsing-remitting disease had multiple lesions whereas 30% had single lesions.

Total number of T1 hyperintense lesions was also significantly correlated with more advanced disease (P=0.003), although the number of T2 hyperintense lesions was not (P=0.059).

"Thus, only the T1 hyperintense lesion subtype was associated with advancing clinical disease course," the researchers noted.

The same pattern was seen for physical disability and brain atrophy, in which T1 lesions were weak-to-moderate predictors but significant whereas T2 lesions were not.

The researchers found that the total number of T1 hyperintense lesions was significantly correlated with physical disability score on the Expanded Disability Status Scale (P=0.04), whereas the total number of T2 hyperintense lesions was not (P=0.14).

Total cortical brain atrophy was significantly associated with the total number of T1 hyperintense lesions on univariate analysis (P<0.001) and after adjusting for disease course (P=0.001).

Another measure of brain atrophy, third ventricular width, was also associated with the total number of T1 hyperintense lesions on univariate analysis (P<0.001) and after controlling for disease course (P=0.001).

The researchers noted that the findings were limited by the use of various MRI protocols across the retrospectively examined cohort, including inconsistent use of contrast-material enhanced imaging, the cross-sectional design that did not allow study of the evolution of T1 hyperintense lesions, and the lack of a quantitative analysis of T1 hyperintensity or relaxation time.

Prospective studies are needed to evaluate multiple T1 protocols, "to see whether the effect is technically dependent;" to incorporate newer techniques, such as diffusion-tensor imaging and MR spectroscopy; and to assess prediction of clinical progression, they said.

"On the basis of these limitations, we urge caution that the results and conclusion of this study should be treated as exploratory and require confirmation in a larger prospective study," they wrote.

Meanwhile, they suggested that physicians should look for hyperintense lesions on nonenhanced T1-weighted MR images "as these may provide useful diagnostic information."

"For the proper evaluation of the presence of gadolinium-based contrast agent enhancement on contrast-enhanced images," they added, "nonenhanced images should be examined concurrently to determine whether hyperintensity on contrast-enhanced images is related to enhancement or to intrinsic T1 shortening in lesions."

Dr. Bakshi reported support in part by grants from the National Institute of Neurological Disorders and Stroke, the National Multiple Sclerosis Society, and the National Science Foundation. The researchers reported no conflicts of interest.
Additional Multiple Sclerosis Coverage

Primary source: Radiology
Source reference:
Janardhan V, et al "Multiple Sclerosis: Hyperintense Lesions in the Brain on Nonenhanced T1-weighted MR Images Evidenced as Areas of T1 Shortening" Radiology 2007;244:823-831.