(3) SCLC is one of the most strongly associated tumors with PNS [7C12]. treatment options for patients with malignancies, including small-cell lung cancer (SCLC) [3]. However, ICIs cause inflammatory side effects by increasing the activity of the immune system [4]. Therefore, ICIs are presumed to be a risk factor for PNS [5, 6]. In fact, cases of PNS induced by ICIs have recently increased [7C12]. Herein, we report a case of ICI-induced limbic encephalitis developed in a patient with SCLC. The present report suggests that clinicians should consider the possibility of PNS when patients develop neurological symptoms after ICI initiation. 2. Case Report A 66-year-old man with a history of smoking for 40 years was referred to our hospital for abnormal chest radiograph findings. The patient had a history of bronchial asthma, with no history of autoimmune diseases. Computed tomography (CT) and positron emission tomography with 18F-fluorodeoxyglucose revealed a tumor mass in the right hilum, hilar and mediastinal lymph node swelling, and multiple lung metastases. Brain magnetic resonance imaging (MRI) showed no abnormal finding (Figure 1). Pathological findings of bronchoscopy of the primary tumor revealed SCLC. Therefore, the patient was diagnosed with extensive disease SCLC (ED-SCLC) and was treated with carboplatin and etoposide, and atezolizumab was initiated as first-line chemotherapy. Treatment led to a complete response. Open in a separate window Figure 1 Fluid-attenuated inversion Caldaret recovery (FLAIR) image of brain magnetic resonance imaging (MRI) before initiation of treatment with immune checkpoint inhibitor reveals no abnormal finding. The patient developed disorientation after three courses of chemotherapy over 2 months. Although follow-up without any treatment was continued, the disorientation worsened with coma. Dysphagia and gait disturbances due to muscle weakness also developed; however, we could not perform detailed neurological examination owing to the state of his consciousness. Fluid-attenuated inversion recovery (FLAIR) imaging of brain MRI after coma development showed a high-intensity area in the bilateral temporal lobes (Figure 2). Caldaret Furthermore, anti-Hu and anti-Zic4 antibodies were highly detected in Caldaret the blood test. The cerebrospinal fluid examination showed no evidence of tumor cells or infection, including herpes simplex virus and varicella-zoster virus (Table 1). Based on these results, anti-Hu and anti-Zic4 antibodies-positive limbic encephalitis as PNS was given as the final diagnosis. As steroid pulse therapy was initiated, the disturbance of consciousness improved. However, dysphagia and gait disturbance showed no improvement. Due to this, intravenous immunoglobulin (IVIG) therapy was also initiated Caldaret leading to improvement of dysphagia, but not with gait disturbance. Brain MRI findings at 3 months after initiation of steroid treatment also improved slightly (Figure 3), and Rabbit polyclonal to Fyn.Fyn a tyrosine kinase of the Src family.Implicated in the control of cell growth.Plays a role in the regulation of intracellular calcium levels.Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension.Blocks axon outgrowth and attraction induced by NTN1 by phosphorylating its receptor DDC.Associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein.Three alternatively spliced isoforms have been described.Isoform 2 shows a greater ability to mobilize cytoplasmic calcium than isoform 1.Induced expression aids in cellular transformation and xenograft metastasis. blood test at that time showed anti-Zic4 antibody negativity with anti-Hu antibody persistence. Open in a separate window Figure 2 FLAIR image of brain MRI after development of neurological symptoms reveals high-intensity area in bilateral temporal lobes (red arrowheads). Open in a separate window Figure 3 FLAIR image of brain MRI after development of neurological symptoms reveals slight improvement of high-intensity area in bilateral temporal lobes (red arrowheads). Table 1 Laboratory findings at the onset of PNS.
AmphiphysinNegativeAppearanceClear?CV2NegativeCell count5/lPNMA2NegativePoly0%RiNegativeMono100%YoNegativeProtein94mg/dlHu3+Glucose72mg/dlRecoverinNegativeADAQ1U/lSOX1NegativeHSV-PCRNegative?TitinNegativeVZV-PCRNegative?Zic43+???GAD65NegativeCytologyClass I?TrNegativeCultureNegative? Open in a separate window ADA, adenosine deaminase; HSV, herpes simplex virus; VZV, varicella-zoster virus. At the time of writing, 6 months have passed since the development of limbic encephalitis, and the neurological symptoms did not worsen. Furthermore, a complete response was observed. 3. Discussion In the present case, limbic encephalitis as PNS was diagnosed due to the following reasons. (1) Anti-Hu and anti-Zic4 antibodies were detected in the serum at the onset of neurological symptoms. (2) SCLC was presented at the onset of neurological symptoms. (3) SCLC is one of the most strongly associated tumors with PNS [7C12]. (4) MRI revealed a high-intensity area in the bilateral temporal lobes, which was consistent with limbic encephalitis. (5) No other possible cause was found.