Supplementary Material for: Unusual presentation of a rare case of immunotherapy combination induced encephalitis: A case report

Introduction Immune checkpoint inhibitors have revolutionized cancer treatment owing to their ability to activate cellular immune checkpoint pathways and mediate an anti-tumor activity. Due to their immunological actions, immune-related adverse events (irAEs) have become a concern. Neurological adverse events are rarely seen whether in the central or peripheral nervous system and can be potentially life-threatening. We present a rare case of occipital encephalitis following dual immunotherapy treatment in a patient with melanoma.
Case Report A 41 year old man diagnosed with nodular melanoma of the right torso with axillary lymphadenopathies was treated with dual immunotherapy: nivolumab and ipilimumab. After 24 weeks, patient developed right homolateral hemianopia, imaging findings correlated with occipital encephalitis. Auto-antibodies were not detected. The patient was treated with steroids and exhibited radiological improvement of his encephalitis but maintained his right hemianopia.
Conclusion Neurological side effects of immunotherapy are not very common and range from mild to severe life threatening symptoms. Previous analyses have shown that combination immunotherapy has a higher risk of side effects than monotherapy. Diagnosis of neurological manifestations is usually made by imaging, mainly brain magnetic resonance imaging (MRI), or detection of auto-antibodies in the CSF. The gold standard treatment is usually corticosteroids or rarely other molecules such as IVIg or monoclonal antibodies. The prognosis is usually favorable.

免疫检查点抑制剂因能激活细胞免疫检查点通路并介导抗肿瘤活性，已彻底改变癌症治疗。由于其免疫作用，免疫相关不良事件（irAEs）已成为关注焦点。无论中枢还是外周神经系统，神经系统不良事件均罕见，但可能危及生命。我们报告一例黑色素瘤患者接受双重免疫治疗后发生罕见枕叶脑炎的病例。

一名41岁男性，诊断为右侧躯干结节性黑色素瘤伴腋窝淋巴结病变，接受双重免疫治疗：纳武利尤单抗（nivolumab）和伊匹木单抗（ipilimumab）。24周后，患者出现右侧同侧偏盲，影像学表现与枕叶脑炎相符。未检测到自身抗体。患者接受类固醇治疗后，脑炎影像学改善，但右侧偏盲持续存在。

免疫治疗的神经系统副作用并不常见，症状从轻度到严重危及生命不等。既往分析表明，联合免疫治疗的副作用风险高于单药治疗。神经系统表现的诊断通常通过影像学（主要是脑磁共振成像MRI）或脑脊液（CSF）中自身抗体的检测。金标准治疗通常为皮质类固醇，少数情况下使用IVIg或单克隆抗体等其他分子。预后通常良好。