Natalizumab (NTZ) is a humanized monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Discontinuation of natalizumab can result in a rebound of multiple sclerosis activity, sometimes severe.

Reasons for discontinuation: risk for progressive multifocal leukoencephalopathy (PML) with presence of JK virus, adverse side effect, noncompliance


Mechanism: natalizumab targets integrin and blocks the entry of chronic inflammatory cells into the brain; somewhat analogous to immune reconstitution inflammatory syndrome (IRIS)


Patient selection: multiple sclerosis with discontinuation of NTZ


Clinical and imaging features of discontinuation syndrome:

(1) discontinuation of NTZ, usually within the past 3 to 6 months

(2) neurological deterioration

(3) cognitive impairment

(4) worsening of the Expanded Disability Status Scale (EDSS), with significant clinical worsening associated with a two-step EDSS increase

(5) large increase in T2 and gandolinium-enhanced lesions on brain MRI

(6) exclusion of alternative diagnosis (such as PML)

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