Diagnosis and Management of Immune Checkpoint Inhibitor-Associated Neurologic Toxicity: Illustrative Case and Review of the Literature

Immune checkpoint inhibitors (ICIs) initiate antitumor immunity by blocking the action of immune inhibitor-signaled cytotoxic proteins, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, and programmed cell death ligand 1. However, in rare cases (approximate to 1%-12% of patients), ICI treatment causes neurologic immune-related adverse events (irAEs). These include, but are not limited to, headache, encephalitis, neuropathies, myasthenia gravis, and myositis. The symptoms associated with irAEs can range from mild (grade 1-2) to severe (grade 3-4); however, they are often challenging to diagnose because they may present as generalized symptoms, such as fatigue and weakness, that can also be caused by the cancer itself. Here, we present an illustrative case of a 67-year-old woman who presented with signs of a neurologic irAE, including progressive dysphagia and weakness leading to falls, which started during treatment with pembrolizumab and worsened following initiation of ipilimumab. Following neurological and pathological evaluation, she was diagnosed with myositis. She was treated with steroids and improved rapidly. In this article, we review previous literature to provide guidance to frequently asked questions concerning the diagnosis and management of neurologic irAEs in patients with advanced cancer. With prompt and effective treatment, most patients will achieve a complete recovery.