A trial of antithrombotic therapy in patients with refractory migraine and antiphospholipid antibodies: A retrospective study of 75 patients.

OBJECTIVE: It has been reported that patients with antiphospholipid antibodies (aPL) and refractory migraine may experience symptomatic improvement with antithrombotic therapy, but this phenomenon has not been well studied. This study was undertaken to detail the response to trials of antithrombotic therapy in these patients. METHODS: This is a retrospective study of 75 patients with refractory migraine and aPL who were given a 2-4 week trial of aspirin, clopidogrel and/or anticoagulation. Major response was defined as 50-100% improvement in frequency and/or severity of migraine; minor response: 25-49% improvement; no response: <25% improvement. RESULTS: 66 patients were given a trial of aspirin: 47% responded (21% major); 60 patients were given a trial of clopidogrel: 83% responded (67% major); and 34 patients were given a trial of anticoagulation (usually apixaban): 94% responded (85% major). The response rate to any anti-thrombotic therapy was 89% (83% major). Many patients also noted improvement in non-headache symptoms. No patient experienced stroke. There was no major bleeding during any 2-4 week treatment trial and only 3 of 69 patients maintained on an antithrombotic regimen for a median follow up of 29.9 months (5-100) experienced major bleeding. CONCLUSIONS: There was a high rate of symptomatic response to antithrombotic therapy in this context and long-term follow up suggested an individualized symptom-derived antithrombotic regimen may be associated with a low bleeding risk. Our data support consideration of a 2-4 week trial of antithrombotic therapy, usually starting with antiplatelet therapy, in aPL-positive patients with refractory migraine, particularly if other treatment options have been exhausted. As a retrospective study, our data provide only Class IV level of evidence, but they suggest randomized controlled trials are warranted to validate these encouraging findings.

Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid.

OBJECTIVE: Intrathecal IgG synthesis, persistence of bands of oligoclonal IgG, and memory B-cell clonal expansion are well-characterized features of the humoral response in multiple sclerosis (MS). Nevertheless, the target antigen of this response remains enigmatic. METHODS: We produced 53 different human IgG1 monoclonal recombinant antibodies (rAbs) by coexpressing paired heavy- and light-chain variable region sequences of 51 plasma cell clones and 2 B-lymphocyte clones from MS cerebrospinal fluid in human tissue culture cells. Chimeric control rAbs were generated from anti-myelin hybridomas in which murine variable region sequences were fused to human constant region sequences. Purified rAbs were exhaustively assayed for reactivity against myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein by immunostaining of transfected cells expressing individual myelin proteins, by protein immunoblotting, and by immunostaining of human brain tissue sections. RESULTS: Whereas humanized control rAbs derived from anti-myelin hybridomas and anti-myelin monoclonal antibodies readily detected myelin antigens in multiple immunoassays, none of the rAbs derived from MS cerebrospinal fluid displayed immunoreactivity to the three myelin antigens tested. Immunocytochemical analysis of tissue sections from MS and control brain demonstrated only weak staining with a few rAbs against nuclei or cytoplasmic granules in neurons, glia, and inflammatory cells. INTERPRETATION: The oligoclonal B-cell response in MS cerebrospinal fluid is not targeted to the well-characterized myelin antigens myelin basic protein, proteolipid protein, or myelin oligodendrocyte glycoprotein.