Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days-19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.

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Background Treatment with immune checkpoint inhibitors (ICI) has greatly improved survival for patients with a number of malignant diseases in recent years. Neurological immune-related adverse events (n-irAE) of varying severity have been reported in the literature. We aimed to identify the incidence of n-irAE, focusing on immune-related encephalitis (IRE), in patients treated with ICI for multiple non-hematological malignancies in our institution. Methods All patients with histologically verified cancer that received treatment with ICI at the Sheba Medical Center between January 2017 and August 2019 were surveyed. Medical records for each patient were reviewed and information regarding n-irAE was recorded. Results In total, 1993 patients were included. Eleven cases of IRE were recorded, affecting 0.55% of patients overall, eight had non-melanoma cancer. Eight patients had made a full recovery. Conclusions IRE is a n-irAE more frequent than previously reported, particularly in non-melanoma patients. The diagnostic criteria and optimal treatment needs to be determined. ICI re-challenge after IRE can be considered for selected patients.