Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities

Abstract

Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes.

Neurological safety of fingolimod: An updated review

“…Clinical presentation is characterized by rapid worsening of previous neurological deficits as a result of an overwhelming immune response to JCV antigen, which leads to massive destruction of virus‐infected and non‐infected neuronal and glial tissues 76. Therefore, the onset of this syndrome is accelerated by PLEX, occurring in the majority of the patients within days to several weeks 65, 77…”

“…MRI shows an increase in size of pre‐existing T2/fluid‐attenuated inversion recovery lesions with either a patchy, punctate, irregular or ill‐defined appearance in the border of the PML lesion with contrast enhancement 76, 78. Contrast enhancement is the most common imaging sign suggestive of PML‐IRIS, seen in 92.3% of patients 78.…”

“…Contrast enhancement is the most common imaging sign suggestive of PML‐IRIS, seen in 92.3% of patients 78. This is accompanied by increasing edema, cerebral swelling and mass effect, which are not typical of PML 76. Differentiation between PML‐IRIS and rebound exacerbation of MS is usually possible by applying well‐defined MRI criteria 79…”

“…methylprednisolone (1 g per day) for 3–5 days,50, 65, 76, 77, 81 or intravenous immunoglobulin83 is currently being tried in an attempt to control the deleterious effects of an exuberant inflammatory cascade, although no controlled studies have been carried out to prove its effectiveness. As PML‐IRIS can persist for several months, long‐term oral steroid therapy might be necessary, together with close clinical and MRI monitoring 77.…”

MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

“…PML has a higher likelihood of being detected on DWI than are MS lesions; therefore, DWI is recommended as an additional sequence for the assessment of acute PML lesions as well as surveillance for subclinical disease. 106 Patients treated with natalizumab, despite a positive JC titer (antibody titer above 0.4), should undergo surveillance scans on a regular basis. It has been recommended that patients with a JC antibody positive titer of less than 1.5 should undergo the regular 12-month scan and then start surveillance scans every 6 months.…”