Clinically reversible ustekinumab-induced encephalopathy: case report and review of the literature.

Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23 approved for the treatment of Crohn's disease, has shown to be an effective therapy with a favourable safety profile. Clinical trials and real-world studies have reported very few neurological adverse events, including posterior reversible encephalopathy syndrome, idiopathic intracranial hypertension and headache. We describe the case of a 48-year-old man with Crohn's disease who initiated treatment with ustekinumab on top of ongoing treatment with methotrexate 25 mg/week who presented with an acute-onset encephalopathy that rapidly evolved to severe tetraparesis and akinetic mutism, associated with extensive leukoencephalopathy and restricted diffusion on brain magnetic resonance imaging (MRI), 1 month after the second dose of ustekinumab. Comprehensive in-patient diagnostic testing ruled out vascular, demyelinating, metabolic, tumoral and infectious etiologies. Brain biopsy showed patchy infiltrates of foamy histiocytes with perivascular distribution, associated with edema, diffuse astrocytic gliosis and focal perivascular axonal destruction without demyelination, and ustekinumab-induced neurotoxicity was suspected. After drug discontinuation, the patient presented a complete clinical recovery despite the persistence of leukoencephalopathy. In conclusion, in an era in which biological therapies are continually evolving and expanding, knowledge about the potential neurotoxicity of these new therapies and their management becomes crucial. Although ustekinumab-induced encephalopathy is uncommon, the recognition of this potentially serious side effect is important because prompt withdrawal is associated with a favourable outcome. Whether methotrexate played an additional contributing role is currently unknown, but it is a factor that should be considered.

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© The Author(s), 2022.

Déclaration de conflit d'intérêts

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: FG receives royalties from Euroimmun for the use of IgLON5 as an autoantibody test and honoraria for Assistant Editor of MedLink Neurology. AS has received compensation for consulting services from Sanofi, Merck, Alexion and Janssen, and speaking honoraria from Sanofi, Merck, Biogen-Idec, TEVA, Roche and Novartis. JP has received research support from AbbVie and Pfizer, and consultant fees from AbbVie, Arena, Athos, Boehringer Ingelheim, Celgene, Galapagos, Genentech, GSK, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Robarts, Protagonist, Takeda, Theravance and Wasserman.