Major differences in the dynamics of primary and secondary progressive multiple sclerosis

Abstract

In patients with primary and secondary progressive multiple sclerosis (MS), major differences in the pattern and extent of abnormality on cerebral magnetic resonance imaging (MRI) between the two groups have recently been demonstrated. In the present study, 24 patients, matched for age, sex, duration of disease, and disability, had serial gadolinium diethylenetriaminepentaacetic acid-enhanced MRI over a 6-month period. The 12 patients in the secondary progressive group had a total of 109 new lesions over this time (18.2 lesions per patient per year) and 87% of these enhanced. Enhancement also occurred within and at the edge of preexisting lesions. In contrast, only 20 new lesions were seen in the primary progressive group (3.3 lesions per patient per year) and only one of these enhanced. There was no difference in the degree of clinical deterioration between the two groups over the 6-month period. These findings may indicate a difference in the dynamics of disease activity between the two forms of progressive MS, particularly in relation to the inflammatory component of the lesions, and have important implications for the selection of patients and the monitoring of disease activity in therapeutic trials.

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

“…Some patients, especially with primary progressive MS, have experienced few or no relapses and have little evidence on MRI scans for the past or present occurrence of inflammatory lesions. 3 On the other hand, pathological and quantitative MR imaging (MRI) evidence has emerged that shows that the disease involves "normal appearing" white matter (NAWM) and normal appearing gray matter (NAGM). In NAWM, there is evidence of astrocytosis, microglial activation, perivascular inflammation and axonal loss.…”

“…The same cannot be said of more advanced disease and primary progressive MS, in which there is evidence that at least some of the T2 abnormalities develop independently of BBB breakdown. 3 Whereas Gd enhancing and T2 lesions can be related to relapses they correlate poorly, if at all, with the evolution of disability. 19 It is notable, for example, that patients with primary progressive MS often have few Gd enhancing lesions and small T2 lesion loads.…”

“…19 It is notable, for example, that patients with primary progressive MS often have few Gd enhancing lesions and small T2 lesion loads. 3 One exception to this rule is that the accumulation of inflammatory lesions during the first 5 years of relapse-onset MS (measured as total T2 volume) is partly related to current and future disability. 21 These imaging observations fit broadly with the observation that relapse rate in the early years of relapsing remitting MS has an influence on the time-to-develop of moderate disability (EDSS 4) 22 but not the subsequent evolution to more severe disability.…”

The pathogenesis of primary progressive multiple sclerosis: antibody-mediated attack and no repair?

“…2,5,6 Irreversible disability occurs sooner after clinical onset in primary progressive MS than in patients with an initial relapsing-remitting course. 7 In contrast, once irreversible disability occurs, the time course of progressive disability is similar in primary progressive and secondary progressive MS. 7 Primary progressive MS is more difficult to diagnose than relapsing-remitting MS for the following reasons: (1) in contrast to the relapsing-remitting pattern which occurs in few neurological diseases other than MS, the progressive neurological deterioration over months and years that occurs in primary progressive MS is also typical of many other neurological diseases; (2) the variety of neurological symptoms and signs occurring in primary progressive MS tends to be more limited than in relapsingremitting MS, and this also reduces the distinctiveness of the clinical features; (3) there are fewer MRI focal brain lesions 8,9 and less frequent gadolinium-enhancing brain lesions 10 in primary progressive MS than in relapsing-remitting / secondary progressive MS; and (4) oligoclonal immunoglobulin (Ig) bands restricted to the cerebrospinal fluid (CSF) occur less frequently in male patients with a later onset and progressive myelopathy, 11 that is the type of patient likely to have primary progressive MS. New diagnostic criteria have recently been proposed for definite primary progressive MS; 12,13 however, the absolute requirement for evidence of intrathecal IgG synthesis will significantly reduce the diagnostic sensitivity.…”

A Controlled Trial of Mitoxantrone in Multiple Sclerosis: Serial MRI Evaluation at One Year

“…The duration of enhancement in relapsing-remitting patients is extremely variable ranging from less than 1 month to greater than 2 months; 30 generally, however the enhancing phase disappears within 4 weeks in about 2/3 of lesions. 8 - 10 In our placebo group, we detected a mean rate of 0.33 Gd-DTPA enhancing lesions/patient every two months, whereas the mean number of enhancing lesions/month observed in previous reports on untreated relapsing-remitting patients, ranges between 1.33 to 3 25.8.10.H Therefore, we might miss an enhancement in at least 50% of lesions with a bimonthly scan interval.…”