Progressive Silent Cerebral Infarction is Associated with Stroke and Persistent Cognitive Impairment in iTTP Survivors Open Access

• Silent cerebral infarction is progressive during clinical remission of iTTP.

• Progressive silent cerebral infarction is associated with stroke and persistent cognitive impairment.

Immune thrombotic thrombocytopenic purpura (iTTP) survivors face an increased risk of cerebrovascular disease, including silent cerebral infarction (SCI), cognitive impairment, and stroke. The prospective Neurologic Sequelae of iTTP (NeST) study evaluated the natural history of SCI (by brain MRI) during clinical remission and its association with stroke risk and cognitive impairment, measured by the NIH Toolbox Cognition Battery. SCI burden was quantified using the modified Age-Related White Matter Changes (ARWMC) score. Among 42 patients who completed the baseline study visit, 28 completed a second assessment at a median interval of 12.5 months. New or progressive SCI were observed in 28.6% (8/28), with the median ARWMC score increasing from 4 to 5 (P = 0.002). SCI progression was associated with a higher baseline ARWMC score (median 7 vs. 1, P = 0.011) but not with age, hypertension, diabetes, or average remission ADAMTS13 activity. Over a median follow-up of 32 months, 14.3% (6/42) participants developed stroke, with significantly higher stroke risk among those with a higher baseline ARWMC score [hazard ratio (HR) 1.36 (95% CI 1.01-1.83), P = 0.043]. Cognitive function significantly improved in patients without SCI progression but not in those with progressive SCI. In summary, SCI is progressive during clinical remission in iTTP and associated with an increased risk of stroke and persistent cognitive impairment. SCI burden and progression may serve as shorter-term endpoints for clinical trials aimed at mitigating stroke risk and improving cognitive outcomes after iTTP.