Progressive Multiple Cranial Neuropathies as a Manifestation of CAR-T Neurotoxicity

Abstract

To describe a case of delayed onset multiple cranial neuropathies as a manifestation of neurotoxicity after chimeric antigen receptor T-cell (CAR-T) therapy for multiple myeloma. While ICANS following CAR-T is a well-reported complication, it classically presents with encephalopathy, seizures, dysphasia, tremors, headache, and cerebral edema. Isolated unilateral facial neuropathies secondary to CAR-T neurotoxicity have been described, but progressive multiple cranial neuropathies have not. Herein, a 75-year-old male presented with left facial nerve palsy 19 days after initiating CAR-T therapy for multiple myeloma. Contrasted brain MRI showed contralateral right facial nerve enhancement, and his left facial palsy was treated with steroids and valacyclovir for 7 days. The facial palsy persisted and progressed to involve bilateral facial nerves and left cranial nerve VI by 31 days post-CAR-T. Specifically, his exam showed impaired abduction of left eye and nearly absent facial movement. Repeat contrasted MRI brain showed mild enhancement of bilateral facial nerves. Extensive serum and CSF testing was unremarkable. Initial treatment with oral steroids for 7 days was ineffective. Concern regarding the impact of steroids on CAR-T efficacy influenced treatment dose and duration. Anakinra was considered but not given. Subsequent treatment with intravenous high dose steroids, followed by a prolonged prednisone taper, led to resolution of CN VI palsy at 2.5 months from onset (2 weeks after completed therapy), and moderate improvement of bilateral facial palsy 5.5 months from onset (3.5 months after completed therapy). CAR-T neurotoxicity can present with progressive multiple cranial neuropathies. The best treatment of these cases is unknown; however, this patient improved in the context of corticosteroids and facial rehabilitation over a prolonged period of follow-up.