Cerebral Small Vessel Disease in Immune-Mediated Thrombotic Thrombocytopenic Purpura Patients During the Acute Phase and Disease Remission.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by acute neurological manifestations and long-term sequelae related to microvascular brain injury. Cerebral small vessel disease (cSVD), detectable on MRI through lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, is a risk factor for stroke and cognitive decline, but its prevalence and evolution in iTTP are unknown. We conducted a prospective study of consecutive patients with acute iTTP and age-matched controls to assess the prevalence and one-year progression of cSVD. Brain MRI was performed at enrollment and repeated after 12-18 months in clinical remission. cSVD burden was quantified using a standardized 0-4 score based on four MRI markers. Twenty-five patients (median age 56 years; 60% women) were enrolled. Acute focal ischemic lesions were detected in 13 (52%). cSVD was present in 48% of patients versus 27% of controls, while moderate burden (score ≥ 2) occurred in 24% versus none. Ordinal logistic regression showed an association between iTTP and higher cSVD scores (OR 3.19, 95% CI 1.00-10.14), independent of traditional cardiovascular risk factors. Follow-up MRI was available in 22 patients (88%). In paired analyses, cSVD prevalence increased from 50% to 64%, moderate-to-high burden from 27% to 41%, and six patients (27%) showed score progression. At 1 year, patients had higher odds of greater cSVD burden than controls (age- and sex-adjusted ordinal OR 7.00, 95% CI 1.65-29.74). These findings indicate that cSVD is common during acute iTTP and progresses during the first year despite hematological remission.