Diagnostic and prognostic magnetic resonance studies in patients with clinically isolated syndromes
Multiple Sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS) which usually presents as a Clinically Isolated Syndrome (CIS). Longitudinal clinical and MRI studies of patients with CIS give insight into the clinical prognostic factors for the development of Relapsing Remitting (RR) and Secondary Progressive (SP) MS. In this MD thesis, I have discussed the clinical and MRI correlations in a group of 65 patients recruited between 1995 and 1999 and who have been followed for approximately 3 years. In Chapters 3.2 and 3.3, I evaluated baseline MRI brain and spinal cord findings as predictive tests for MS at 3 years. In 2001, the International Panel on MS diagnosis published revised criteria on the diagnosis of MS. For the first time a diagnosis of MS could be made in patients with CIS suggestive of MS using MRI for evidence of Dissemination in Space (DIS) and Dissemination in Time (DIT). The accuracy of both the new MRI and clinical criteria was evaluated at one and 3 years, in Chapter 4.1. Although the new diagnostic criteria were found to specific for MS, their sensitivity was lower. While, high specificity was achieved by the requirement of new Gadolinium enhancing lesions at a 3 month follow up scan in patients imaged initially within 3 months of the onset of symptoms, the same requirement reduced sensitivity. New T2 lesions are seen more often on the 3 month follow up scan than new Gadolinium enhancing lesions. Our next project in chapter 4.2, was to evaluate inclusion of new T2 lesions as a predictive test for MS at 3 years. Interestingly, new T2 lesions used as evidence for DIT were sensitive for a diagnosis of MS at 3 years without a loss in specificity. Finally, as an exploratory exercise in this section, we evaluated new T2 lesions, regardless of evidence of MRI DIS. New T2 lesions were both sensitive and specific for a diagnosis of MS at 3 years. Further evaluation of a new T2 lesion at 3 months together with optimum MRI evidence for DIS is therefore warranted. Brain atrophy has been evaluated as a surrogate marker in MS. The cause and timing of atrophy and its association with inflammatory MRI lesions are not clear. In chapter 5.1, Ventricular Volume (VV) was analyzed as an atrophy marker in a cohort of 55 patients followed for one year. In Chapter 5.2, Grey Matter (GM), White Matter (WM), Brain Parenchymal Fractions (BPF) and (VV) were analyzed as atrophy markers in 58 patients followed for 3 years. Significant GM atrophy and an increase in VV were seen in those who developed MS. There were moderate correlations between lesions and increase in VV and reduction in GMF and BPF. In conclusion, although imaging of the brain is extremely helpful in patients with optic neuritis in order to assign risk of MS, imaging of the spinal cord is less useful. The new diagnostic criteria for the diagnosis of MS in patients with CIS are specific. Sensitivity of the diagnostic criteria may be improved by the inclusion of new T2 lesions after 3 months as evidence of DIT. Regional atrophy affecting both GM and VV size was noted in patients with CIS, who went on to develop MS. Pathogenic process including lesions and atrophy occur in the earliest clinical stages of MS and are only partially related. It is appropriate to measure both processes in future disease modifying treatment trials in patients with CIS or early MS.