PML and IRIS: Between a Rock and a Hard Place

Background: Progressive multifocal leukoencephalopathy (PML) is a known complication of natalizumab and a number of other MS treatments. The clinical course of PML is frequently complicated by the occurrence of immune reconstitution inflammatory syndrome (IRIS). Distinguishing between PML and IRIS is challenging and treatment of these two conditions potentially opposes one another. While there are no established treatment protocols for PML or IRIS various medication regimens have been tried. Because PML and IRIS are relatively rare complications their clinical course and radiologic features remain incompletely characterized.

Objectives: To describe the clinical course, radiologic findings, treatment, and outcomes of 6 patients with natalizumab associated PML and IRIS. 

Methods: We describe 6 patients with natalizumab-associated PML and IRIS treated at The Elliot Lewis Center from 2012 to 2016, and review their clinical course, radiologic findings, and treatment. 

Results: Of the 6 patients, 4 patients had JCV titers prior to diagnosis: 2 had titers persistently above 2.0 and 2 had titers between 0.4 and 0.7.  3 patients received plasma exchange (PLEX) shortly after diagnosis. Other treatments included various combinations of solumedrol, IVIG, cidofivir, maraviroc, and mertizapine. IRIS developed in all patients, presenting as clinical deterioration and enhancing MRI lesions with onset averaging 2 months after diagnosis. 

Conclusions: PML presented with vague, non specific symptoms or was clinically silent prior to being detected on MRI. Clinical deterioration typically began 5 weeks after diagnosis and was accompanied by MRI progression. Steroids almost always halted or reversed clinical progression, suggesting IRIS as the cause for clinical deterioration rather than PML. PLEX may precipitate aggressive IRIS and it’s utility in natalizumab related PML should be evaluated. Treatment with cidofivir, maraviroc, mirtazapine, and IVIG are unproven but have potential benefits that need further investigation.