ATEZOLIZUMAB RELATED ENCEPHALOPATHY

Case presentation A 70-year old woman presented with acute confusional state. She had been receiving atezolizumab for locally invasive lung adenocarcinoma. Laboratory workup showed no significant abnormalities. Electroencephalogram (EEG) was negative for epileptiform discharges. Brain MRI showed a solitary left occipital brain lesion compatible with brain metastasis, which had been submitted to stereotactic radiation therapy in previous months. There were no signs of vascular abnormalities or meningeal enhancements. Cerebral spinal fluid (CSF) was not compatible with inflammatory or infectious findings (leukocytes 0; red blood cells 50; protein 56mg/dl; glucose 80mg/dl). CSF cultures and quantitative tests were negative. Serological paraneoplastic antibodies were also negative. Neurological examination revealed no focal neurological deficits. The patient was alert, disoriented to time and place. Language assessment revealed a moderate receptive aphasia. She was submitted to high doses corticosteroid therapy and symptoms resolved within a week. Discussion: Atezolizumab is a humanized IgG1 monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand (PD-L1). This antibody has become a new treatment option of patients with non-small cell lung cancer (NSCLC) after failure of cisplatin based chemotherapy. Treatment with checkpoint inhibitors can induce adverse effects related to an exacerbated immune response. Autoimmune neurotoxicity such as encephalitis and encephalopathy are rare events that have been described associated with atezolizumab treatment. Our patients presented with encephalopathy that could not be attributed to any other cause and she had an effective response to corticosteroid therapy. Final Remarks: Although rare, neurological autoimmune induced events should be promptly recognized in patients receiving checkpoint inhibitors therapy in order to improve patient care and avoid poor outcomes.