Pembrolizumab (anti-pd-1) induced limbic encephalitis presenting as episodic aphasia

Abstract PD-1 immune checkpoint inhibitors (ICI) have been associated with neurological immune-related adverse events including meningioencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of pembrolizumab (Anti-PD-1) induced limbic encephalitis presenting as episodic aphasia. A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases, post total-thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation presented with recurrence of brain metastasis 1 year after diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region. The metastases had initially improved in size and number with radiation, followed on serial MRI Brain - that were stable. Biopsy of recurrence revealed a poorly differentiated cancer. He was subsequently treated with pembrolizumab for 6 months for refractory carcinoma. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia, initially concerning for seizures. Continuous EEG monitoring revealed non-epileptogenic left-sided foci and no seizures were captured. Patient empirically started on levetiracetam and clobazam - however, episodes persisted. Lumbar puncture revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48-68 mg/dL), negative cytology, flow cytometry, and viral studies including JC virus. Paraneoplastic panel in serum and cerebrospinal fluid were negative. Repeat MRI findings were most consistent with radionecrosis and on contrary improvement of the previous metastatic lesions. This rose suspicion for pembrolizumab-induced encephalitis and he received high dose steroids with minimal response but great clinical improvement with IVIG and induction/maintenance therapy with rituximab. Marked reduction in aphasic episodes were noticed thereafter. PD-1 ICI-related encephalitis is diagnosis of exclusion that should be considered in patients with encephalopathy or neurological deficit following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences reported in males. Early recognition is crucial to prevent long-term neurological damage. Outcomes depend on patient characteristics and timeline of presentation.