Migraine is associated with transient and at times, permanent neurologic deficits. Of the 15% of the general population with migraine, approximately 40% or 15 million people in the United States suffer from these neurological deficits. The neurologic symptoms can be as or more disabling as the headache of migraine. There has been a link, noted over the past decade, of migraine and migrainous neurological deficits with antibodies that bind phospholipids. These antibodies are also linked to an increased risk for thrombosis, including stroke. Our preliminary studies suggest a significant link between {migraine with aura} and the presence of these antiphospholipid antibodies (aPL). We now propose to further investigate the significance of the transient focal neurologic events (TFNE) in clinic-based and population-based cohorts of migraine with aPL. Specifically, we aim to: (1) Estimate and compare the prevalence of aPL in 3 clinic-based cohorts (migraine with aura, migraine without aura, and matched controls), (2) To describe differences among migraine subsets and controls based on aPL status in a clinic population, (3) To estimate and compare the prevalence of aPL in population-based cohorts, and (4) To use a population-based sample to validate and refine a model for predicting aPL positivity in migraineurs derived from a clinic-based sample. METHODS: Subjects between the ages of {25} and 55 years old with {migraine with aura, and migraine without aura} according to 1988 IHS criteria will be recruited from the neurology inpatient and outpatient services and matched on race, sex and age with subjects without evidence of central neurologic disease. All eligible subjects will be assessed in face to face interviews in the clinic and hospital using a structured interview to detail the clinical features of headache, TFNE, vascular risk factors, thrombo-occlusive events, and family history of migraine and stroke. Blood for anticardiolipin antibody (aCL) determination will be drawn on conclusion of the interview. A large scale telephone survey by random digit dialing will use a newly validated instrument to identify active migraine cases and controls matched on age, sex, race and education who will be further assessed in face-to-face interviews in subjects' homes using a structured diagnostic interview to assess history of vascular risk factors, thrombo-occlusive events, and family history of migraine and stroke. Blood for aPL determination will be drawn on conclusion of the interview. Both the telephone and face-to-face interviews are with the same subjects as those studied in Project 1. LONG-TERM OBJECTS INCLUDE: To establish aPL as a marker for migrainous cephalgia and/or transient focal neurologic deficits and to define clinical features which allow prediction of aPL positivity. We would ultimately like to determine if aPL positive migraineurs are at increased risk of stroke, and other thrombo-occlusive events.
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