A 75-year-old Japanese man without any previous neurological illnesses was diagnosed with lung squamous cell carcinoma, stage IIIA, T3N1M0, in the upper right lobe. He underwent two cycles of platinum-based chemotherapy (carboplatin + nab-paclitaxel and carboplatin + docetaxel) as first-line chemotherapy. Thereafter, he was administered nivolumab (3 mg/kg) as second-line treatment. On the day of treatment with nivolumab, he had an infusion reaction as an adverse event. The cancer progressed after one cycle of nivolumab and chest computed tomography (CT) scan showed new lesions in the upper left lobe and an increase in right pleural effusion (Fig. 1) He underwent another round of platinum-based chemotherapy (cisplatin + pemetrexed + bevacizumab) as third-line treatment 3 weeks after the nivolumab treatment. However, he did not complete one cycle of the chemotherapy due to grade 3 constipation according to the Common Terminology Criteria for Adverse Events version 4.1.
Two months after treatment with nivolumab, he was hospitalized because of acute paralysis in the bilateral lower limbs, sensory loss below the Th10 level, and urinary retention. Spinal magnetic resonance imaging (MRI) showed T2 hyperintense lesions between C5-6 and Th12-L1 (Fig. 2). Analysis of the cerebrospinal fluid (CSF) showed an increased white cell count of 1195/μL (638 neutrophils and 557 mononuclear cells), protein concentration of 380.9 mg/dL, and a decreased glucose concentration of 40 mg/dL (blood glucose 139 mg/dL). CSF cytology was negative, and CSF cultures for bacteria, mycobacterium, and fungi were also negative. Polymerase chain reaction tests for herpesvirus 1–7 were negative. CSF tumor markers (carcinoembryonic antigen, squamous cell carcinoma, cytokeratin 19 fragment, and soluble interleukin-2 receptor) were all negative. Paraneoplastic autoantibodies (anti-Hu, Yo, Ri, amphiphysin, CV2, PNMA2, recoverin, SOX1, titin, zic4, GAD65 and Tr) were negative as well. An enzyme-linked immunosorbent assay (ELISA) and cell-based assay (CBA) for anti-aquaporin-4 (AQP4) antibody in the serum after hospitalization were positive, but these tests had been negative in the serum on the day of administration of nivolumab. CBA for anti-myelin-oligodendrocyte glycoprotein antibody in the serum was negative. Brain MRI and ophthalmologic examinations were normal. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD).
Two weeks later, after steroid pulse therapy, spinal MRI showed improvement in the rostral region, but a remnant lesion in the caudal region. Analysis of CSF showed improvement after treatment, but his symptoms of paralysis in the bilateral lower limbs and sensory loss improved only minimally. In this patient, steroid reactivity was poor. Plasmapheresis was performed, but his clinical symptoms did not improve. The patient’s paralysis in the bilateral lower limbs and sensory loss are gradually getting improved after plasmapheresis and continues rehabilitation for six months.