Background

A 76-year-old woman with no prior medical history presented with weight loss, hematuria, and fatigue and was diagnosed with metastatic renal cell carcinoma. She underwent resection of the primary tumor and metastatic lesions and was subsequently treated with pembrolizumab (PD-1 inhibitor). Approximately three months after initiation of immunotherapy, she developed involuntary tongue and facial movements, dysphagia, and weight loss, and was described as “restless.” Nearly one year after symptom onset, neurological examination demonstrated a generalized hyperkinetic movement disorder with prominent oromandibular and cervical dystonia, dyskinesias, and some choreiform movements involving the proximal upper extremities; her cancer remained in remission with ongoing immunotherapy.

A brain MRI demonstrated bilateral basal ganglia FLAIR/T2 hyperintensities without gadolinium enhancement (Figure). Cerebrospinal fluid (CSF) revealed normal cell count, mildly elevated protein (44 mg/dL), and eight CSF-restricted oligoclonal bands. Serum and CSF neural autoantibody testing showed IgG reactivity against basal ganglia structures and was confirmed to be specific for phosphodiesterase 10A (PDE10A-IgG). The patient was diagnosed with PDE10A autoimmunity presenting as a hyperkinetic movement disorder triggered by immune checkpoint inhibitor therapy. Pembrolizumab was discontinued, and she was treated with high-dose steroids followed by plasma exchange and symptomatic therapies, with partial improvement. At a three-year follow-up, she remained in cancer remission, with minimal residual movement abnormalities.

Find out how our suite of autoimmune movement disorder testing can help diagnose PDE10A autoimmunity in patients who present with hyperkinetic movement disorders.