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Massive CNS monocytic infiltration at autopsy in an alemtuzumab-treated patient with NMO
Published Web Locationhttps://doi.org/10.1212/nxi.0000000000000034
ObjectivesTo describe the clinical course and neuropathology at autopsy of a patient with neuromyelitis optica (NMO) treated with alemtuzumab.
ResultsA 61-year-old woman with aquaporin-4 immunoglobulin G antibody seropositive NMO had 10 clinical relapses in 4 years despite treatment with multiple immunosuppressive therapies. Alemtuzumab was administered and was redosed 15 months later. For the first 19 months after the initial alemtuzumab infusion, the patient did not experience discrete clinical relapses or have evidence of abnormally enhancing lesions on brain or spinal cord MRI. However, she experienced insidiously progressive nausea, vomiting, and vision loss, and her brain MRI revealed marked extension of cortical, subcortical, and brainstem T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. She died 20 months after the initial alemtuzumab infusion. Acute, subacute, and chronic demyelinating lesions were found at autopsy. Many of the lesions showed marked macrophage infiltration with a paucity of lymphocytes.
ConclusionsFollowing alemtuzumab treatment, there appeared to be ongoing innate immune activation associated with tissue destruction that correlated with nonenhancing T2/FLAIR hyperintensities on MRI. We interpret the cessation of clinical relapses, absence of contrast-enhancing lesions, and scarcity of lymphocytes at autopsy to be indicative of suppression of adaptive immunity by alemtuzumab. This case illustrates that progressive worsening in NMO can occur as a consequence of tissue injury associated with monocytic infiltration. This observation may be relevant to multiple sclerosis (MS) as well as NMO and might explain why in previous studies of secondary progressive MS alemtuzumab did not seem to inhibit disability progression despite a dramatic decline in contrast-enhancing lesions.
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