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Case Report: Longitudinal Extensive Transverse Myelitis With Novel Autoantibodies Following Two Rounds of Pembrolizumab

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A 63-year-old male with metastatic non-small cell lung cancer developed longitudinal extensive transverse myelitis (LETM) following two cycles of Pembrolizumab, an immune checkpoint inhibitor (ICI) targeting the programmed cell death receptor 1 (PD-1). Magnetic resonance imaging (MRI) showed centromedullary contrast enhancement at several levels, cerebrospinal fluid (CSF) cytology showed lymphocytic pleocytosis, and indirect immunofluorescence assay (IFA) on the primate cerebellum, pancreas, and intestine revealed strong binding of neuronal autoantibodies to unknown antigens. CSF C–X–C motif ligand 13 (CXCL13) was elevated. The patient was treated with plasma exchange (PEX) and intravenous (i.v.) methylprednisolone (MP) 1 g/day for 5 days followed by oral (p.o.) MP 100 mg/day for 10 days with clinical and radiological response. However, after discontinuation of MP, LETM relapsed and the patient developed paralytic ileus presumably due to autoimmune enteropathy and suffered a fatal gastrointestinal sepsis. Findings of novel neuronal autoantibodies and highly elevated CXCL13 in CSF suggest that the severe neurological immune-related adverse event (nirAE) was B-cell mediated contrary to the commonly assumed ICI-induced T-cell toxicity. An individual evaluation of the underlying pathophysiology behind rare nirAEs is essential for choosing treatment regimens and securing optimal outcome.

OriginalsprogEngelsk
Artikelnummer655283
TidsskriftFrontiers in Neurology
Vol/bind12
ISSN1664-2295
DOI
StatusUdgivet - 30 apr. 2021

Bibliografisk note

Publisher Copyright:
© Copyright © 2021 Charabi, Engell-Noerregaard, Nilsson and Stenör.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

ID: 66269796