A 63-year-old man with stage IV metastatic melanoma presented with progressively worsening generalized weakness and fatigue after a single dose of ipilimumab/nivolumab. Prior to immunotherapy, he noted a 3-year gradual onset of generalized weakness and dyscoordination, treated under the surmise of paraneoplastic Parkinsonism. After immunotherapy, symptoms dramatically worsened, requiring multiple hospital admissions. Exam revealed upward gaze diplopia, impaired single-breath count, fatigability, lingual fasciculations, and brisk reflexes. Lumbar puncture, MRI brain, and myasthenia panel were non-diagnostic; nonetheless, patient demonstrated clinical improvement after high-dose steroids, only to worsen after dosage tapering. An EMG revealed axonal neuropathy and diffuse denervation and reinnervation, raising suspicion for underlying ALS. He was treated with PLEX/IVIG due to suspicion for superimposed myasthenic-like syndrome, but unfortunately expired from acute hypoxic respiratory failure secondary to aspiration pneumonia.

The case report suggests pre-existing neurological deficits could be a risk factor for NIRS, and more specific neurological screening may serve to risk-stratify patients prior to treatment with ICIs. Further research regarding the safety of ICI use in patients with underlying neurological deficits may guide future therapeutic decision-making.