Cold Ziehl-Neelsen stain for Campylobacter in gastric biopsy specimens.

Abstract

<h3>Objective:</h3> To understand the role of immune checkpoint inhibitors (ICI) particularly anti-PD1 inhibitor in anti-Hu associated paraneoplastic neurological syndrome (PNS). <h3>Background:</h3> While ICI enhance anti-tumor immune reactivity resulting in tumor regression they also reduce immune tolerance towards self-antigen and predispose to the development of autoimmunity. <h3>Design/Methods:</h3> We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of preexisting anti-Hu antibody associated sensorimotor polyneuropathy after treatment with programmed cell death 1(PD-1) inhibitor, nivolumab. We review the literature to understand the clinical outcomes of patients with anti-Hu PNS treated with anti-PD1 treatment. <h3>Results:</h3> Our series identified 6 previously reported cases of anti-Hu PNS treated with anti-PD1 inhibitors. These included 4 men and 2 women (median age, 48 years). The patients were receiving nivolumab (n=3), cemiplimab (n=1), pembrolizumab (n=1) and combination treatment of nivolumab and iplimumab (n=1) for treatment of neoplasm of lung (n=3), merkel cell carcinoma in breast (n=1) and thigh (n=1), and extraskeletal chondrosarcoma (n=1). The clinical spectrum of PNS comprised of encephalitis (n=3), a combination of sensory neuronopathy and anti-NMDAR encephalitis (n=1), isolated sensory neuronopathy (n=1), and encephalomyelitis (n=1). Median time to onset of PNS after anti-PD-1 treatment was 117 days. Three of the 6 (50%) patients had a fatal outcome. One of the two patients which improved was treated with Natalizumab. All patient had MRI abnormalities in the form of increased T2/Fluid Attenuated Inversion Recovery (FLAIR) hyperintenisty in medial temporal (n=4), multifocal cortical and subcortical (n=1) and spinal cord (n=2). All but one (n=4) had elevated cells on cerebrospinal fluid analysis with rest (n=5) having elevated protein. <h3>Conclusions:</h3> ICI have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS. Timely identification of PNS with close monitoring for potential worsening is recommended in all patients with PNS who receive ICI. <b>Disclosure:</b> Dr. Raibagkar has nothing to disclose. Dr. Ho has nothing to disclose. Dr. Gunturu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi, Genzyme, and Eli Lilly. Dr. Srinivasan has nothing to disclose.