Objective:

To describe a rare presentation of immune-checkpoint inhibitor (ICI) associated limbic encephalitis with horizontal ocular flutter and dysautonomia in the setting of renal cell carcinoma.

Background:

ICIs can trigger or unmask paraneoplastic neurologic syndromes (PNS) through immune system activation, including anti-Ma2 encephalitis, a rare paraneoplastic syndrome that is most commonly associated with testicular and lung cancers. Typical clinical presentation involves limbic, diencephalic, and/or brainstem dysfunction, and rarely opsoclonus-myoclonus syndrome. Association with renal cancer, as well as presentation with either dysautonomia or ocular flutter, is rare.

Design/Methods:

NA

Results:

A 67-year-old woman with renal cell carcinoma developed 6 weeks of progressive cognitive decline beginning 3 weeks after initiation of ipilimumab/nivolumab. Examination revealed disorientation, impaired attention, and deficits in short- and long-term memory without focal motor findings. Initial brain MRI was unrevealing. Possible metabolic and infectious etiologies were treated without improvement.

During hospitalization, she developed facial twitching with EEG demonstrating bilateral temporal epileptiform discharges. She subsequently developed horizontal ocular flutter followed by autonomic instability including hypotension, hypothermia, bradycardia, and complete heart block requiring ICU transfer. Myocarditis was excluded.

CSF demonstrated pleocytosis (10 cells/µL) and elevated protein (68 mg/dL). Repeat MRI showed T2/FLAIR hyperintensities involving the amygdala, bilateral basal ganglia, and hypothalamus.

Given high suspicion for ICI-associated encephalitis, IV methylprednisolone and plasmapheresis were initiated empirically prior to antibody confirmation. CSF later returned positive for anti-Ma2 antibodies. She had resolution of autonomic instability and partial cognitive improvement (9/30 to 16/30 on MOCA). Care was ultimately transitioned to palliation, and she died from other complications of her disease shortly thereafter.

Conclusions:

This case represents a rare presentation of ICI-associated anti-Ma2 encephalitis in renal cell carcinoma, with unusual features including isolated horizontal ocular flutter without ataxia or myoclonus and severe dysautonomia. Early recognition of ICI-associated PNS and empiric immunotherapy are critical to avoid treatment delays.