MRI and DTI Characteristics of Natalizumab Associated PML during a Novel Treatment Protocol (P07.061)

Objective: To describe clinical and MRI features of natalizumab associated PML. Background Natalizumab is an effective therapy but is associated with risk of PML. PML is treated by removing natalizumab from blood by plasma exchange (PLEX). However, more active restoration of the immune cell migration may be associated with better outcome. Design/Methods: 26-year-old male developed PML after receiving 40 doses of natalizumab. PML produced new onset of nystagmus and left sided ataxia. MRI showed a non-enhancing left MCP lesion extending into the cerebellum. Treatment included PLEX, mefloquine 250mg daily, and mirtazapine 45mg daily; 1 week after PLEX: filgrastim 300mcg x 5 days, maraviroc 150 twice daily, zonisamide 100mg daily. Results: PML lesion volume on FLAIR MRI before PLEX was 9.8cc, but increased to 15.2 cc post PLEX and filgrastim. T1 volume increased from 5.6cc to 9.9cc. This was not associated with any gadolinium enhancement. After immune reconstitution inflammatory syndrome (IRIS) and post IV steroids, the T2 FLAIR volume increased to 18.1 cc and T1 volume to 16.3 cc with little contrast enhancement. MS lesion activity did not change. DTI of the PML lesion showed decreased in FA and axial diffusivity but increase in radial diffusivity compared to non-lesion side. Prior to PML, patient had an EDSS of 4.5. At the time of PML, EDSS increased to 6.5. Three months after treatment for PML, the EDSS decreased to 5.5. Conclusions: Using this protocol, our patient had a favorable outcome. The enlargement of T2 FLAIR and T1 signal without much contrast enhancement may represent unmasking of a greater area of PML lesion. The clinical worsening during PML therapy may be due to a combination of unmasking of a greater PML lesion and IRIS. DTI imaging suggests both an axonal and myelin loss within the PML lesion. Disclosure: Dr. Javed has received personal compensation for activities with Teva Neuroscience, Bayer Pharmaceuticals, Serono, Inc., Novartis, Questcor and Biogen Idec as a consultant and/or speaker. Dr. Ko has received personal compensation for activities with Biogen Idec, Serono, Inc., and Teva Neuroscience for consulting services. Dr. Balabanov has received personal compensation for activities with Biogen Idec, Teva Neuroscience and Genzyme as a consultant, and speaker bureau honoraria from Biogen Idec and Teva Neuroscience.Dr. Balabanov has received research support from Biogen Idec. Dr. Stefoski has received personal compensation for activities with Biogen Idec, Acorda, Serono, Elan, and Teva Neuroscience. Dr. Stefoski has received royalty payments from Acorda Therapeutics. Dr. Stefoski has received research support from Biogen Idec, Novartis, Serono, and Pfizer.