Massive exacerbation of multiple sclerosis after withdrawal and early restart of treatment with natalizumab.

We present a 46-year-old woman with a relapse of multiple sclerosis (MS) that began 3 months after withdrawal from long-term treatment with natalizumab. Shortly after restart of a single dose of natalizumab she developed a fulminant MS rebound with stupor and tetraparesis. Cerebral MRI showed massive progression in the number of lesions and tumefactive lesions with ring gadolinium-enhancement. Stereotactic brain biopsy revealed acute demyelination and B-cell dominated inflammation. The patient improved during therapeutic plasma exchange. We speculate that early restart of natalizumab in the case of a relapse may worsen disease evolution possibly by modifying regulatory immune effector processes during an inflammatory rebound phase. A restart of natalizumab in MS patients suffering from a recent relapse or with signs of active inflammation should be considered with caution.