CNS dysfunction in the antiphospholipid syndrome

Abstract

Though many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in this disease. We review clinical data obtained from a large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white matter disease and behavioral changes in APS or linked to laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta2-glycoprotein I, a central autoantigen in APS, which induces persistent high levels of aPL. These mice develop hyperactive behavior after a period of four to five months as well as deficits in learning and memory and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. Another model we have developed, in which IgG from APS patients induce depolarization of brain synaptoneurosomes, may serve as a model for the pathogenesis of epilepsy in APS.

Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study

“…The most direct evidence supporting the hypothesis of autoantibody involvement in NPSLE is derived from studies of animal models (13)(14)(15)(16)(17), whereas evidence from human studies is frequently conflicting or inconclusive (18)(19)(20)(21)(22). This may be due in part to methodologic difficulties involving, for example, selection of patients for study, lack of rigor in the characterization of NP events, and differences between laboratories in assay techniques.…”

“…The latter include antiphospholipid antibodies (aPL), antiribosomal P antibodies (anti-P), and autoantibodies that bind to neuronal antigens such as the recently described antibodies to the NR2 glutamate receptor (13). Although there is biologic plausibility and data from in vitro studies and animal studies to implicate these autoantibodies in the causality of nervous system disease (13)(14)(15)(16)(17), studies of humans with SLE have yielded inconsistent findings (18)(19)(20)(21)(22). Previous investigations have been limited by their cross-sectional study design, heterogeneity of study patients in terms of disease duration, and lack of standardization in both the classification of NP events and the methodology used for autoantibody detection.…”

Neonatal Lupus Erythematosus

“…The known connection between autoantibodies, in the setting of SLE, Sjögren syndrome, and APL syndrome, with adult human CNS diseases like CNS vasculitis, white matter lesions, chorea, seizures, and cognitive dysfunction supports the association between neonatal CNS injury and maternal autoantibodies. Additionally, animal studies show that APL, anti-SSA/Ro, and antidsDNA antibodies mediate neurologic dysfunction, potentiate seizures, and lead to excitotoxic injury to the animal brain [67][68][69][70][71][72][73].…”

Central Nervous System Manifestations in Rheumatic Diseases

“…Neurologic disorders are among the most prominent clinical manifestations associated with the antiphospholipid syndrome. Such neurologic disorders are predominantly related to focal central nervous system thrombo-occlusive events (12,13). Antiphospholipid antibodies have been associated with a variety of neurologic manifestations.…”