Endothelial injury to cognitive decline: a 12-month follow-up using computed tomography perfusion and diffusion magnetic resonance imaging in immune-mediated thrombotic thrombocytopenic purpura

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare blood disorder that leads to microvessel clots and brain injury. While modern treatments have improved survival during initial disease onset, long-term complications such as cognitive decline are now a prominent concern for reasons that are not yet fully understood. OBJECTIVES: This prospective study aimed to investigate the effects of iTTP on the brain in the postremission phase to address a critical gap in our understanding of iTTP-brain pathophysiology. METHODS: We followed 22 iTTP survivors over 1 year. Participants underwent advanced brain magnetic resonance imaging (MRI) to assess white matter integrity, computed tomography perfusion to evaluate cerebral blood perfusion and blood-brain barrier (BBB) integrity, and cognitive testing. RESULTS: At baseline, most patients (82%) showed brain abnormalities on MRI, and all presented with compromised BBB integrity (mean permeability surface product, 0.43 ± 0.13 mL/min/100 g). After 12 months, BBB function improved (0.37 ± 0.10 mL/min/100 g; P = .04) but remained compromised. Over this period, MRI revealed progressive brain volume loss, and diffusion imaging showed reduced white matter integrity in tracts related to memory and verbal processing. Cognitive scores remained lower than those of controls, especially in the memory and verbal domains. CONCLUSION: These findings suggest that brain injury and cognitive dysfunction in patients with iTTP are not limited to the acute phase but continue to progress after remission. This progression may be underpinned by persistent vascular injury, including BBB dysfunction and reduced perfusion. Long-term brain monitoring and early neuroprotective strategies may be needed to improve the quality of life of iTTP survivors.