Background Natalizumab has been shown to be a cost-effective treatment for rapidly evolving severe relapsing–remitting multiple sclerosis (MS). However concern has arisen over the increased risk of PML with duration of therapy. The situation is complicated by recent evidence that stopping Natalizumab, in the absence of PML, may result in a rebound inflammatory response.

Case We describe a 34-year-old man with relapsing remitting MS diagnosed in 2000. He was initially treated with betaferon but due to continued frequent disabling relapses was treated with Mitoxantrone from 2003 to 2004 and became relapse free. He then had further severe relapses in 2008 that led to Natalizumab and by August 2010 he had 26 infusions. He decided to temporarily stop treatment due to the increased risk of PML. In March 2011 he presented with dysarthria, visual symptoms and cognitive impairment. His MRI showed multiple areas of periventricular signal increase in the frontal and parietal lobes, brainstem and cerebellum (areas previously affected) with variable contrast enhancement. JC virus DNA was not detected in the CSF. Subsequent STRATIFY-JCV assay was positive.

Conclusion Some clinicians recommend a temporary cessation of Natalizumab treatment after 2 years to reduce the risk of PML. JC virus antibody testing and previous immunosuppressant exposure is clarifying who is at risk. However the decision to discontinue treatment also carries significant risk of further deterioration due to rebound of underlying disease. These patients will require ongoing immune modulation to avoid rebound of their disease and further clinical deterioration in the absence of PML.