Progressive silent cerebral infarction is associated with stroke and persistent cognitive impairment in survivors of iTTP

Survivors of immune thrombotic thrombocytopenic purpura (iTTP) face an increased risk of cerebrovascular disease, including silent cerebral infarction (SCI), cognitive impairment, and stroke. The prospective Neurologic Sequelae of iTTP study evaluated the natural history of SCI (by brain magnetic resonance imaging) during clinical remission and its association with stroke risk and cognitive impairment, measured by the National Institutes of Health 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 8 of 28 patients (28.6%), with the median ARWMC score increasing from 4 to 5 (P = .002). SCI progression was associated with a higher baseline ARWMC score (median, 7 vs 1; P = .011) but not with age, hypertension, diabetes, or average remission ADAMTS13 activity. Over a median follow-up of 32 months, 6 of 42 participants (14.3%) developed stroke, with significantly higher stroke risk among those with a higher baseline ARWMC score (hazard ratio, 1.36; 95% confidence interval, 1.01-1.83; P = .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 end points for clinical trials aimed at mitigating stroke risk and improving cognitive outcomes after iTTP.