Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy.

B-cell maturation antigen (BCMA) is a prominent tumor-associated target for chimeric antigen receptor (CAR)-T cell therapy in multiple myeloma (MM). Here, we describe the case of a patient with MM who was enrolled in the CARTITUDE-1 trial ( NCT03548207 ) and who developed a progressive movement disorder with features of parkinsonism approximately 3 months after ciltacabtagene autoleucel BCMA-targeted CAR-T cell infusion, associated with CAR-T cell persistence in the blood and cerebrospinal fluid, and basal ganglia lymphocytic infiltration. We show BCMA expression on neurons and astrocytes in the patient's basal ganglia. Public transcriptomic datasets further confirm BCMA RNA expression in the caudate of normal human brains, suggesting that this might be an on-target effect of anti-BCMA therapy. Given reports of three patients with grade 3 or higher parkinsonism on the phase 2 ciltacabtagene autoleucel trial and of grade 3 parkinsonism in the idecabtagene vicleucel package insert, our findings support close neurological monitoring of patients on BCMA-targeted T cell therapies.

Recurrent orthostatic global amnesia in a patient with postoperative hyperfibrinogenemia.

Transient global amnesia (TGA) is characterized by sudden, temporary dysfunction of antegrade and recent retrograde memory without other neurologic deficits. Although there is sometimes a precipitating event, the origin of TGA remains controversial. We encountered a patient who developed recurrent TGA when upright, in whom the symptom promptly and regularly resolved when supine. Symptoms began about a week after cardiac surgery concurrent with marked hyperfibrinogenemia and acceleration of the erythrocyte sedimentation rate, and abated without recurrence when these laboratory abnormalities were ameliorated by anticoagulant and corticosteroid therapy. Diagnostic studies, including temporal artery biopsy and cerebral angiography, disclosed no anatomic vascular pathology. This is the first report of TGA associated with postoperative inflammation in which amnesia was provoked by orthostatic positioning. In conclusion, these observations implicate ischemia caused by hemodynamic vascular insufficiency as a possible cause of TGA.