PB1400 - Neurologically asymptomatic patients with pure obstetric antiphospholipid syndrome cumulate progressive microstructural brain damages, mild functional abnormalities, and subtle cognitive impairments

Background: Despite being asymptomatic, women with pure obstetric antiphospholipid syndrome (oAPS) hold microstructural brain damage not observed in conventional neuroradiological exams (PMID: 26201292). It is unclear whether the subtle cerebral injuries are progressive or affecting brain function.

Aims: To examine the evolution of the microstructure cerebral injuries, the extension of the functional brain states, and the respective cognitive performance in pure oAPS with a low-dose aspirin (LDA) primary thromboprophylaxis.

Methods: 6-year noninvasive neuroimaging-informed follow-up in 66 women with oAPS and 17 controls sharing the same medical history. oAPS were categorized as positive for lupus anticoagulant (LA) and/or aβ2GPI-IgG (LA/aβ2GPI-G-positive) or negative (LA/aβ2GPI-G-negative). White-matter (WM) integrity along three time-points using longitudinal diffusion-tensor imaging (DTI) and gray-matter (GM) damages (cortical thickness and subcortical volume) were assessed. Brain network analyzes were conducted using functional MRI. The mini-mental state examination (MMSE) before the first and second MRI sessions and a comprehensive 1-hour battery of neuropsychological tests were performed. Correlations were built between scores related to the verbal fluency and complex attention and abnormal neurobiological markers in neuroimaging.

Results: DTI indices changed significantly over time in both APS groups, but not in controls, LA/aβ2GPI-G-positive women demonstrating stronger changes, with progressive WM impairments. Some focused decrease in cortical thickness and subcortical volume, i.e. on GM, were detected. No clinical neurologic nor mental health manifestations were observed. Evidences of progressive modifications in brain networks, and finally in functional connectivity, were demonstrated.

Conclusion(s): oAPS women taking LDA studied over a 6 years period showed evidence of subtle progressive microstructural brain damage despite absence of any perceptible clinical symptoms and of detectable lesions using conventional imaging. LA or aβ2GPI-G positive women developed more significant alterations than the other oAPS women. The long-term clinical significance deserves to be investigated.