A Case of Pembrolizumab (Anti-PD-1) Induced Encephalitis

Objective N/A. Background PD-1 Immune checkpoint inhibitors (ICI) have been associated with neurologic immune-related adverse events including meningoencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of suspected pembrolizumab (anti PD-1) induced limbic encephalitis presenting as episodic aphasia. Design/Methods N/A. Results A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases post thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation surgery presented with recurrence of brain metastases one year after the diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region causing right homonymous hemianopsia. The metastases initially improved in size and number with radiation and serial brain MRIs were stable. Biopsy of the mets revealed a poorly differentiated carcinoma. He was subsequently treated with pembrolizumab for six months. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia concerning for seizures. Continuous EEG monitoring revealed a left-sided focus without seizures, and the episodes persisted despite levetiracetam and clobazam. Four lumbar punctures revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48–68 mg/dl), negative cytology, flow cytometry and viral studies including JC virus. Paraneoplastic panels in serum and cerebrospinal fluid were negative. Repeat MRIs findings were most consistent with radionecrosis and noted improvement of the metastatic lesions. Suspicion was raised for pembrolizumab-induced encephalitis and he received high-dose steroids with minimal response however, clinical improvement noted with reduced episode frequency after intravenous immunoglobulin induction therapy and rituximab maintenance therapy. Conclusions PD-1 ICI-related encephalitis is a diagnosis of exclusion that should be considered in patients with encephalopathy or other neurological deficits following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences are reported in males. Early recognition is crucial to prevent long-term neurologic damage. Outcomes are depend on patient characteristics and clinical presentation.