The association of intrathecal immunoglobulin synthesis and cortical lesions predicts disease activity in clinically isolated syndrome and early relapsing-remitting multiple sclerosis

Background: The intrathecal production of immunoglobulin (Ig) is a major biological feature of multiple sclerosis (MS), and immunopathological studies have suggested a primary role of the humoral immune response in causing irreversible brain damage. Objective: To evaluate whether, in the early phases of MS, intrathecal Ig synthesis correlates with the presence of cortical lesions (CLs), and if their association could predict the clinical course of the disease. Methods: Eighty-six patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included magnetic resonance imaging and cerebrospinal fluid examination. The risk ratios (RR) for conversion to MS and for a new disease activity were calculated. Results: Patients with clinically isolated syndromes (CIS) having CLs and intrathecal synthesis of Ig had the highest risk of conversion to MS (RR = 3.4; Wald 95% CI = 1.7-7.0, p<0.001) whereas CIS patients without CLs and intrathecal synthesis of Ig had the lowest risk of conversion to MS (RR = 0.1, Wald 95% CI = 0.02-0.7, p<0.001). The highest risk of having disease-related activity during the follow-up was observed in CIS and relapsing-remitting MS patients showing CLs and intrathecal Ig synthesis (RR = 2.1; Wald 95% CI = 1.5-3.1, p < 0.001) while the lowest in CIS and relapsing-remitting MS patients without CLs and intrathecal Ig synthesis (RR = 0.3; Wald 95% CI = 0.1-0.7, p < 0.001). Conclusion: We observed that the association of intrathecal immunoglobulin synthesis and CLs was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity.