Functional imaging reveals cerebral microvascular dysfunction in primary antiphospholipid syndrome: Pathophysiologic insights and translational implications

Mameli, A.

Writing - Original Draft Preparation

;Indovina, L.;Cocciolillo, F.;Serra, A.

Formal Analysis

;Marongiu, F.

Writing - Review & Editing

;Barcellona, D.

Writing - Review & Editing

2026-01-01

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Abstract

Primary antiphospholipid syndrome (PAPS) is an autoimmune thromboinflammatory disorder primarily characterized by recurrent arterial and venous thromboses and persistently elevated antiphospholipid antibodies (aPL). Beyond its classical vascular manifestations, an expanding spectrum of neuropsychiatric symptoms—including cognitive impairment, mood disturbances, and attention deficits—has been reported in PAPS, often in the absence of overt ischemic lesions on structural neuroimaging. In this study, we present original data from a cohort of 25 well-defined PAPS patients who underwent brain single-photon emission computed tomography (SPECT) imaging with Statistical Parametric Mapping (SPM) analysis. Compared to age- and sex-matched controls, PAPS patients demonstrated a consistent pattern of cerebral hypoperfusion involving bilateral frontoparietal cortices, independent of clinical neurological manifestations or MRI findings. These abnormalities suggest functional microvascular impairment potentially mediated by chronic endothelial dysfunction, complement activation, and aPL-induced neuroinflammatory cascades. Our findings support the hypothesis that cerebral involvement in PAPS extends beyond thrombotic injury to include immune-mediated microvascular and neuroglial dysregulation. This study highlights the value of functional imaging in uncovering subclinical cerebral dysfunction and proposes a neuroimmunological framework for understanding and managing cognitive and psychiatric symptoms in PAPS. Early identification of such changes may offer a window for therapeutic intervention before irreversible neuronal damage occurs.