To describe the clinical, serological and neuroimaging features of an adult with hyperacute myelopathy in the context of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor (CAR)-T cell therapy for B cell acute lymphoblastic leukemia (B-ALL).

CAR-T cell therapies have revolutionized the treatment of hematological malignancies. There are increasing reports of rare neurological complications including acute myelopathies for which etiologies remain unclear, particularly following CAR-T for lymphoma in adults and B-ALL in children.

A 30-year-old female known for refractory B-ALL was administered brexucabtagene autoleucel (day 0). Complications  in the first 6 days included fever, hypotension with mean arterial pressure repeatedly <60mmHg and encephalopathy treated with anakinra, tocilizumab and dexamethasone. On day 8, she awoke with flaccid paraplegia, T8 sensory level, urinary retention and constipation. Brain MRI showed bilateral thalami diffusion restriction and bilateral superior cerebellar peduncles, pons and medulla FLAIR hyperintensity that resolved on 11-month follow-up. Thoracic spine MRI reported diffuse holocord T2/STIR hyperintensity. CSF showed no pleocytosis and pattern 4 oligoclonal bands. Serum aquaporin-4 and myelin oligodendrocyte glycoprotein immunoglobulins were negative. Treatments included additional intrathecal cytarabine, methotrexate, hydrocortisone and intravenous immunoglobulin. Two weeks later, sensory level improved to T10 and she developed autonomic dysreflexia. Spine MRI at 8 months showed marked myelomalacia and T6-T11 cord atrophy consistent with a preceding spinal cord stroke. There was no further recovery at 14-month follow-up.

We provide a novel description of severe thoracic myelopathy following CD19-directed CAR-T therapy in adult B-ALL complicated by CRS and ICANS. Based on the hyperacute temporal profile, absence of CNS-specific inflammatory biomarkers, clinical evolution with poor recovery despite immunotherapy and longitudinal MRI findings, we concluded  the patient experienced a spinal cord stroke in the context of hypoperfusion and hypercoagulability due to systemic inflammation.