Paradoxical Tumefactive Worsening of Multiple Sclerosis After Natalizumab Initiation: A Case Report

Background: Natalizumab is a widely used anti-α4 integrin inhibitor for treating highly active multiple sclerosis. Although clinical and radiological relapses were observed in the pivotal natalizumab trials, severe disease activity after initiation of the drug is a rare phenomenon and has been reported only in isolated cases. Objective: To present a case of a patient who experienced a paradoxical increase in disease activity after the second dose of natalizumab. Methods: We describe the case, review the literature concerning similar cases and suggest possible mechanisms for this phenomenon. Results: Our case involves a patient who developed extensive tumefactive demyelinating lesions and multiple gadolinium-enhancing lesions detected on magnetic resonance imaging after receiving the second dose of natalizumab. A brain biopsy confirmed the presence of demyelination, and the patient’s condition improved after treatment with intravenous methylprednisolone, intravenous immunoglobulin and plasma exchange. Tests for anti-natalizumab antibodies were negative. Conclusions: Paradoxical worsening can occur in the setting of natalizumab treatment, which warrants careful attention and should prompt anti-natalizumab antibody testing. We discuss potential mechanisms. Further research is needed to better understand the mechanisms and risk factors for paradoxical worsening and to develop strategies for mitigating this adverse effect with significant patient impact.