Silent cerebral infarction during immune TTP remission - prevalence, predictors, and impact on cognition

Abstract

Immune TTP (iTTP) survivors have increased risk of cardiovascular disease including stroke, and report persistent cognitive difficulties during remission. We conducted this prospective study of iTTP survivors in clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neuro-deficits, during clinical remission. We also tested the hypothesis that SCI is associated with cognitive impairment assessed using the NIH ToolBox cognition battery. We used fully corrected T scores adjusted for age, sex, race, and education. Based on DSM-5 criteria, we defined mild and major cognitive impairment as T-scores that are 1-2 SD and > 2 SD below the mean on at least one test, respectively. Forty-two patients have been enrolled, with 36 completing MRI.SCI was present in 50% (18) , of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs. 27.7%, P=0.026) including major cognitive impairment (50% vs. 5.6%, P=0.010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment [OR 10.5 (95% CI 1.45 - 76.63); P = 0.020] and major cognitive impairment [OR 7.98 (95% CI 1.11 - 57.27); P = 0.039] after adjusting for history of stroke and Beck depression inventory scores. In summary, MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these 'silent' infarcts are neither silent nor innocuous.