Brain MRI showed atrophy in the right medial temporal region and mild enlargement of the high signal lesions in the basal frontal regions (Fig.1). has rapidly increased after the introduction of BMS 299897 ICI therapy [1,3,4,5,6,7]. We report a case of anti-Ma2 limbic encephalitis developing 3 months after the termination of a 15-month course of nivolumab therapy for malignant pleural mesothelioma. == Case Report/Case Presentation == An 82-year-old male with biopsy-confirmed stage I malignant pleural mesothelioma underwent chemotherapy after pleurodesis treatment. After a 4-month course of cytotoxic chemotherapy with carboplatin and pemetrexed as first-line therapy, he received 31 courses of anti-programmed death-1 (PD-1) receptor monoclonal antibody nivolumab (240 mg/body) for 15 months as a second-line therapy. However, his malignant pleural mesothelioma was refractory with enlarged right axillary lymph nodes, and the chemotherapy regimen was switched to 3 courses of gemcitabine plus vinorelbine as third-line therapy. Eighteen months after the initial dose of nivolumab (3 months after the last dose), he presented with partial seizures of the right face, followed by memory deficits and speech difficulties. Upon presentation to the neurology clinic, the patient exhibited somnolence and cognitive impairment, as demonstrated by a Mini-Mental State Examination (MMSE) score of 14/30 points. On brain magnetic resonance imaging (MRI) and fluid-attenuated inversion recovery images demonstrated high-signal BMS 299897 lesions in the right mesial temporal and bilateral basal frontal regions (Fig.1). Diffusion-weighted images showed high signal lesions in the left basal frontal area without gadolinium enhancement on T1 images. Brain single-photon emission computed tomography with 99mTc showed decreased blood flow in the right mesial temporal and basal frontal areas. Upon analysis, the cerebrospinal fluid (CSF) was acellular with a mildly high protein level (63.3 mg/dL), and oligoclonal IgG bands. Neither the herpes simplex virus nor the varicella-zoster virus was detected in the CSF by the polymerase chain reaction test. The serum anti-Ma2 antibody was positive, but other onconeural antibodies (anti-amphiphysin, CV2, -Ri, -Yo, -Hu, -recoverin, -SOX1, -titin, -zic4, -GAD65, and -Tr), anti-NMDA receptor antibody, anti-LGI-1 antibody, anti-CASPR2 antibody, anti-AQP-4 antibody, and anti-MOG antibody were all negative. The CSF was not screened for anti-Ma2 antibodies. Although anti-Ma2 antibody is often associated with testicular tumors, a subsequent testicular ultrasound and tumor marker test results were negative. == Fig. 1. == aChest CT showing pleural thickening of the lower right lung lobe with calcified lesions.b, cFluid-attenuated inversion recovery images on brain MRI demonstrating high-signal lesions in the right mesial temporal and bilateral basal frontal regions.dChest CT exhibiting an enlargement of the right hilar lymph nodes.e, fBrain MRI showing atrophy in the right medial temporal region and mild enlargement of the high-signal lesions in the basal frontal regions. CT, computed tomography; MRI, magnetic resonance imaging. BMS 299897 We considered a diagnosis of anti-Ma2 limbic encephalitis related to nivolumab and he underwent 2 sessions of intravenous high-dose methylprednisolone therapy (1,000 mg/body, 3 days). His disorientation and memory subsequently improved as demonstrated by an improved MMSE score of 24/30 points and his speech spontaneity increased. MRI showed mild improvement in the left frontal lesion. Although he was additionally treated with intravenous immunoglobulin (0.4 g/kg, 5 days), no further improvement was observed. Levetiracetam was administered to treat the patient’s seizures, and there was no recurrence until he was discharged on hospital day 36. We then restarted third-line chemotherapy with BMS 299897 gemcitabine and vinorelbine, repeated this combination for 6 courses over 9 months, and then discontinued chemotherapy secondary to right hilar lymph node enlargement. Two months later, secondary seizures occurred and he was re-hospitalized. Brain MRI showed atrophy in the right medial temporal region and mild enlargement of the high signal lesions in the basal frontal regions (Fig.1). CSF examination demonstrated no elevated cell counts and negative oligoclonal bands, but the serum anti-Ma2 antibody remained positive. The chest computed tomography exhibited marked enlargement of the right hilar lymph nodes with no further pleural thickening (Fig.1). After 1 session of intravenous methylprednisolone therapy, there was no recurrence of seizures, and he was discharged with a modified Rankin Scale Mouse monoclonal to HK2 score of 3. == Discussion.