Immune-checkpoint inhibitors (ICIs) constitute one of the greatest advances in cancer therapeutics. However, immune-related adverse events (irAEs) are potentially life-threatening toxicities of these treatments. Incidence of fatal (irAEs) ranges from 0.3% to 1.3%, and frequency of neurologic-irAEs (n-irAEs) is 1%. 

Anti-Neurochondrin antibodies have been identified in patients with rapidly progressive cerebellar ataxias and brainstem syndromes. Rarely, they have been associated with myelopathy or malignancy. To our knowledge, this is the first case of anti-neurochondrin positive immune-checkpoint inhibitors n-irAE.

A 61 year-old-male with epithelioid pleural mesothelioma presented with fatigue, dyspnea, paresthesias and left foot drop that occurred three weeks after his first cycle of ipilimumab/nivolimumab. MRI of the spine revealed increased T2 signal in the thoracic cord and conus medullaris. CSF showed lymphocytic pleocytosis, elevated protein and negative oligoclonal bands. He was treated with high-dose corticosteroids and was discharged on a steroid taper, but his symptoms did not improve. Three weeks later, he presented with confusion, lower extremity weakness, inability to ambulate and urinary retention. Repeat MRI showed increased T2 signal and enhancement in basal ganglia, hippocampi and extension of the previous spinal cord lesion involving cervical, thoracic and conus medullaris sections. Repeat CSF was positive for anti-neurochondrin antibodies. His hospital course was complicated by generalized seizures, dysautonomia, quadriplegia and respiratory failure. He received 5 sessions of plasmapheresis, 2g/kg of IVIg and 1000 mg of rituximab without improvement. He required tracheostomy and percutaneous gastrostomy placement and was discharged to a long-term facility with minimal improvement of his mental status and no changes in motor weakness.  Honoring his wishes, he was later transitioned to comfort care and he passed away.

N-irAEs can be devastating with high morbidity and mortality. Further  research is need to identify possible antibodies that could be associated to them and potentially represent a therapeutic target.