Clinical and MRI features of primary progressive multiple sclerosis
In approximately 10-15% of cases Multiple Sclerosis follows a progressive rather than a relapsing course and this is known as Primary Progressive Multiple Sclerosis (PPMS). In this thesis previous clinical, pathological and Magnetic Resonance Imaging (MRI) studies of PPMS are reviewed and new studies using two cohorts of patients with PPMS are presented. In the first of these studies an existing cohort of patients with PPMS are re-examined at first two, and then five years, clinically and with MRI, to provide the longest period of MRI follow up in the condition to date. Changes in clinical and MRI measures over this time, and their correlation, are described. Over this extended period, some limited correlation can be found between clinical and MRI measures in PPMS. It is also seen that there is great variability in the rate of MRI and clinical progression between individuals with PPMS, although for a given individual progression is relatively constant. The possible implications of this observation for the nature of the underlying disease process are discussed. The second part of this thesis describes the clinical and MRI features of a second cohort of patients with clinically early PPMS, examined within five years of the first onset of symptoms, the first study to examine this stage of the condition. It is seen that much of the MRI variation seen in established PPMS is already present at this time and that the degree of MRI abnormality, even at this early stage, can be substantial. The specific question as to whether a distinct, early, inflammatory phase occurs in the condition (on the model of the more fully studied relapsing MS subtype) is addressed by the use of triple dose Gadolinium in a subgroup of this cohort examined over six months and evidence for the possible existence of such a phase in some patients with PPMS is found.