“Restlessness” After Cancer Diagnosis and Treatment

A 76-year-old woman sought care for unintentional weight loss, hematuria, and fatigue. She was diagnosed with plurimetastatic renal cell carcinoma. After resection of the primary tumor and metastases, she was treated with pembrolizumab, an immune checkpoint inhibitor. The patient experienced involuntary tongue and face movements with dysphagia and weight loss. She was also described as “restless.” At that point, the patient was in cancer remission with ongoing immune checkpoint inhibitor treatment. Blood testing was unremarkable. Brain magnetic resonance imaging showed basal ganglia T2/fluid-attenuated inversion recovery hyperintensities without gadolinium enhancement. Cerebrospinal fluid testing showed slightly increased protein concentration and 8 cerebrospinal fluid-restricted oligoclonal bands. Serum and cerebrospinal fluid testing for neural autoantibodies showed immunoglobulin G immunoreactivity in a mouse tissue indirect immunofluorescence assay, predominantly staining the basal ganglia. The immunoglobulin G was subsequently identified to bind to phosphodiesterase 10A. The patient was diagnosed with paraneoplastic phosphodiesterase 10A-immunoglobulin G autoimmunity manifesting as hyperkinetic movement disorder triggered by immune checkpoint inhibitor treatment. Given the patient’s cancer remission, the immune checkpoint inhibitor treatment was discontinued. She was treated with high-dose intravenous corticosteroids, with improvement of her hyperkinetic movement disorder but persistence of some dystonic movements. Further treatment with oral prednisone did not produce further improvement. The patient was treated symptomatically with onabotulinumtoxinA injections and tetrabenazine, which ameliorated her dystonic movements. Three years after her cancer diagnosis, she was alive and in cancer remission with minimal residual movements. Immune checkpoint inhibitors are monoclonal antibodies targeting “stop signs” of the immune response, which lead to enhanced endogenous responses, including those against cancer. Autoimmune complications are consequences of the enhanced immunity and can affect all organs, including the nervous system.