How does SLE cause CNS manifestations?
Despite autopsy findings, the pathogenesis of NPSLE remains unknown. However, it is unlikely that a single pathogenic mechanism is responsible for the myriad of clinical manifestations observed in NPSLE (see Question #12). Diffuse cerebral manifestations that are often transient, reversible on therapy, and not consistently associated with brain pathologic abnormalities, most likely have a different pathogenesis from the focal symptoms, which are usually acute in onset, permanent even with therapy, and frequently associated with pathologic lesions at autopsy. Many investigators believe that cerebrovascular endothelial dysfunction plays a pivotal role. Primary NPSLE events tend to occur during active lupus, supporting complement activation as an important contributor to this endothelial dysfunction. Endothelial dysfunction and its associated microvasculopathy can disrupt the blood-brain barrier, allowing an influx of cells, autoantibodies, and cytokines into the CNS, which can cause diffuse neuropsychiatric manifestations. Additionally, procoagulant factors (e.g., antiphospholipid antibodies and others) can augment endothelial cell activation by further predisposing the patient to thrombosis and emboli, leading to strokes and other focal manifestations. In any single patient with NPSLE, a combination of these mechanisms likely contributes to clinical manifestations. Notably, cerebral vasculitis is rarely the cause of NPSLE.
