To characterize the systemic neurologic manifestations and outcomes associated with immune checkpoint inhibitors (ICI).

ICI therapy is associated with a wide spectrum of neurologic adverse events (nAEs), of which may be life threatening prompting emergent diagnostic and therapeutic intervention. The optimal approach to management of ICI-related nAEs has yet to be established.

We conducted a retrospective review of patients who developed ICI-related nAEs between January 2014 through June 2018. Information on demographics, comorbidities, clinical presentation, diagnostics and therapeutic interventions of ICI-related nAEs were recorded. 

Eighteen patients with ICI-related nAEs were identified, with a higher incidence in those with ICI combination therapy (median 2 cycles, range 1-36). ICI-related nAEs were more frequently found within the central nervous system, of which central demyelinating disorders were the most common. Treatment was initiated after a median of 7.5 days (range 0 - 168) from nAE onset. In response, ICI therapy was discontinued in all patients and immunosuppressive therapy was instituted. Sixteen patients were steroid-responsive. Nine patients received steroid sparing agents such as intravenous immunoglobulin or alternatively hormonal replacement therapy depending on neurologic symptomatology. Five patients showed complete neurologic recovery, 11 patients obtained partial recovery and 2 patients had persistence of symptoms. 

The clinical phenotype of ICI-related nAEs is heterogenous. Given the expanding indications of ICIs in the treatment of systemic malignancies, clinicians need to be aware of potential nAEs as these therapies are anticipated to become more prevalent. Early Neurologic consultation should be entertained in order to effectively diagnose and initiate treatment while subsequently preventing long-term morbidity and mortality.