Immune Checkpoint Inhibitor-Induced Encephalitis: Hu Done It?

Le résumé fourni par la source

Abstract Paraneoplastic syndromes (PNS) encompass a group of immune-mediated disorders with heterogeneous clinical manifestations. Although PNS are traditionally associated with malignancy, they have also recently been reported in fewer than 100 patients with Immune Checkpoint Inhibitor-induced Encephalitis (ICE).1,2 We describe a case of anti-Hu associated ICE, a challenging diagnosis in which prompt recognition is critical as delayed diagnosis can result in irreversible neurologic injury and mortality. An 82-year-old man with metastatic prostate cancer presented with fatigue and weakness in the setting of initiating a new chemotherapeutic regimen with cabozantinib and nivolumab a week prior. While admitted, a stroke code was activated for acute non-responsiveness and he was intubated for hypercapnic respiratory failure. MRI demonstrated edema and hyper-perfusion of the right medial temporal lobe. EEG found focal non-convulsive status epilepticus. CSF studies demonstrated a normal opening pressure, lymphocytic pleocytosis, and negative meningoencephalitis PCR. In the absence of evidence for acute infection with radiographic evidence of a limbic encephalitis, ICE was suspected and the patient was treated with methylprednisolone 1g daily. The patient's encephalopathy rapidly improved and he was extubated three days later. A CSF autoimmune encephalitis panel subsequently returned positive for Anti-Neuronal Nuclear Antibody-type 1 (Anti-ANNA1) (Anti-Hu; 1:3840). Despite initial improvement, the patient experienced recurrent respiratory failure, declined re-intubation, and expired. Serious immune-related neurological complications are seen in <1% of patients receiving immune checkpoint inhibitor (ICI) therapy.3,5 ICE can present with or without autoantibodies, and patients with detectable levels of autoantibodies have been reported to have poorer prognosis.1,2 Though the exact mechanism remains unclear, it is hypothesized that ICI therapy can precipitate anti-Hu mediated PNS. In patients with pre-existing anti-Hu antibodies, initiation of ICI therapy has also been reported to both exacerbate or unmask PNS.3,5 Anti-Hu mediated ICE is not well described and its clinical manifestation is pleomorphic, making diagnosis challenging. Radiographic studies, EEG and lumbar puncture should be obtained to secure a diagnosis and rule out potential infection. In the absence of infection, ICE patients may benefit from holding their ICI and initiating immunosuppressive therapy, which may include steroids, intravenous immunoglobulin, plasmapheresis, rituximab, and tocilizumab.5 Although our patient experienced a poor outcome, early recognition is key as timely administration of these therapies can result in significant neurologic improvement and recovery.

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