Antiphospholipid Syndromes and the Nervous System Clinical Features, Mechanisms, and Treatment

Antiphospholipid antibodies (aPL) are predominantly acquired, circulating immunoglobulins (IgG, IgM, IgA isotypes) with affinity for anionic and neutral phospholipid-containing moieties. They are now recognized as a risk factor for thrombosis. Currently, the two most clinically studied and relevant aPL are the lupus anticoagulant (LA) and anticardiolipin antibodies (aCL). They can also be inherited, with families reported to have aPL in consecutive generations. Although aPL have been recognized since 1906' with the discovery of the Wassermann test for syphilis (syphilitic sera contain aPL), it has been only 10 years since the characterization of a syndrome associated with these antibodies. Cardiolipin, a specific serologically active phospholipid, was isolated from beef heart by Pangborn2 35 years following Wassermann's detection of aPL. Antibodies to cardiolipin bind to cause a positive or false-positive Venereal Disease Research Laboratory (VDRL) test for syphilis because cardiolipin is an antigen in the VDRL test. Eleven years after Pangborn's report, two importance observations were published. Moore and Mohr3 found that patients with a long-standing false-positive VDRL had a high prevalence of autoimmune diseases, including systemic lupus erythematosus (SLE) and hemolytic anemia. Conley and Hartmann4 reported two people with SLE, a false-positive VDRL, and abnormal coagulation studies that suggested these patients should have a bleeding dyscrasia. These authors determined that the coagulopathy was due to a circulating serum "anticoagulant," and this in vitro phenomenon was subsequently called the "lupus anticoagulant." The possibility of a relationship between the LA and the presence of a falsepositive VDRL arose. In retrospect, Aggeler et a15 were probably the first group to document a thrombotic complication in a patient with thrombocytopenic purpura and a "circulating anticoagulant." Eleven years after Conley and Hartmann's report, Bowie et aI6 insightfully recognized that in patients with SLE, stroke and other thrombotic events were associated with the LA. Several groups confirmed this association in SLE and drew attention to other seemingly unrelated features such as thrombocytopenia, miscarriages, and a false-positive VDRL.