Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine–enhancing magnetic resonance imaging lesions

Abstract

It is now well established that clinically stable patients with relapsing-remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] < 3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients.

Surges of Increased T Cell Reactivity to an Encephalitogenic Region of Myelin Proteolipid Protein Occur More Often in Patients with Multiple Sclerosis Than in Healthy Subjects

“…However, some of the surges of T cell reactivity to PLP 184 -209 were not associated with either a clinical relapse or the development of gadoliniumenhancing MRI brain lesions. The lack of a constant association with clinical relapse is not surprising, given that clinical relapses are insensitive indicators of disease activity compared with gadolinium-enhanced MRI (30). Even with the use of gadolinium-enhanced brain MRI as in the present study, new lesions would have been missed if they occurred in the spinal cord or optic nerve, if they were small brain lesions, or if they developed without preceding gadolinium enhancement.…”

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

“…Nevertheless, their presence increases the risk of continuous disease activity 48 and the short-term appearance of clinical relapses. 46,48,49 All of the disease-modifying agents that are approved by the FDA for the treatment of MS show a significant effect on limiting Gd enhancement as recently reviewed. 1 Furthermore, a drug that exacerbates MS may be detected early by observing worsening Gd enhancement.…”

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

“…In chronic relapsing experimental autoimmune encephalomyelitis (EAE), an animal model of MS, relapses are characterized by inflammatory cell infiltration and primary demyelination, whereas remissions are characterized by resolution of inflammation and by remyelination. 20 Clinical relapses of MS are associated with an increase in the number and extent of gadolinium-enhancing lesions, 21 which correlate with perivascular inflammation. 22 Patients with relapsing-remitting MS have surges of increased numbers of circulating myelin-reactive T lymphocytes which partly correlate with the number of gadolinium-enhancing brain lesions.…”

“…Gadolinium-enhancing MRI brain lesions occur much less frequently in primary progressive MS than in secondary progressive MS10 and relapsing-remitting MS, 21 indicating that there is less inflammation in the brain in primary progressive MS. Histological studies have shown less perivascular lymphocytic cuffing and parenchymal inflammatory cell infiltration in the CNS in primary progressive MS than in secondary progressive MS. 28 Immunological studies have shown increased blood T-cell reactivity to the 184-209 region of myelin proteolipid protein in relapsing-remitting MS and secondary progressive MS, but not in primary progressive MS, 29 although T-cell reactivity to the gangliosides GM3 and GQ1b is increased in primary progressive MS. 30 Furthermore, blood leukocyte expression of adhesion molecules, which have a role in the trafficking of circulating leukocytes into the CNS, is different between primary progressive MS and relapsing-remitting/secondary progressive MS.…”