The clinical utility of magnetic resonance imaging in multiple sclerosis and the “clinico-radiological paradox”

Magnetic Resonance Imaging (MRI) is central to the diagnosis of Multiple Sclerosis (MS). Íew diagnostic criteria, established in 2001, reflect its increasingly important role. MRI is also central to the investigation of the clinically isolated syndrome (CIS), in order to determine the likelihood of conversion to clinically definite MS. However, over the last decade it has become increasingly clear that the correlation of conventional MRI with disease severity and disability in MS, as measured by EDSS, is limited. This limitation has been referred to as the "clinico-radiological paradox". As a result of this paradox the role of MRI in monitoring progression of disease, as well as its prognostic value, have remained less clear. Over the last few years, non-conventional MRI techniques have been developed in order to monitor the progression of the disease more faithfully and, if possible, resolve the "clinico-radiological paradox".

The present review first looks at the clinical utility of conventional MRI in MS. The findings on T2-weighted imaging, T1-weighted imaging, proton-density-weighted imaging. FLAIR imaging and Gadolinium enhanced T1-weighted imaging are briefly discussed. The use of conventional MRI within four different clinical contexts of MS is then described. Firstly, the central role of conventional MRI in the diagnosis of MS, as arrived at with the new McDonald diagnostic criteria, is looked at. Secondly, the importance of conventional MRI in the investigation of CIS and the likelihood of conversion to clinically definite MS is discussed. Thirdly, the role of conventional MRI in the monitoring of disease progression is dealt with, along with the possible pitfalls of over relying on it. Finally, the limited ability of convertional MRI to predict future disability is discussed.

The relatively poor association between severity of disease and radiological extent of involvement on conventional MRI, also known as the "clinico-radiological paradox" is then delineated, along with the resulting limitations that follow on the clinical use of MRI in MS. The three aspects of the paradox are described in more detail: a) the relatively dissapointing correlation between T2 lesion load and disability as measured by EDSS, b) the large proportrion of gadolinium enhancing lesions which are not associated with clinical relapses, and c) the low lesion load on conventional MRI of patients with primary progressive MS, despite their relatively higher disability.

The second part of the present paper briefly reviews the new non-conventional MRI techniques currently emerging in an effort to monitor the disease more faithfully. Magnetization transfer imaging (MTI), is first described and the results of studies correlating findings on MTI with disability are briefly mentioned. Magnetic resonance spectroscopy is then looked at, focusing on its ability to measure axonal loss and thus investigate one of the most important aspects of the disease. Thirdly, diffusion weighted imaging is briefly discussed, as a further emerging tool in the monitoring of MS. The significance of abnormalities detected within the normal appearing white matter with the above-mentioned techniques is particularly emphasized. Measures of brain and spinal cord atrophy are then briefly looked at and their better correlation with clinical disability as measured by EDSS is noted. Finally, the use of functional MRI is discussed as well as its possible role in explaining patients with low EDSS scores and high lesion load on conventional MRI.

The present review ends with a brief mention of some of the limitations associated with the use of EDSS as a scale of disability in MS, leading to the development of new measures of disability, like the MS Functional Composite. These limitations could also be contributing to the "clinico-radiological paradox".

Key words: Multiple Sclerosis, magnetic resonance imaging, clinoco-radiological paradox, EDSS, non-conventional MRI.