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MIGRAINE COMORBIDITY

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Messé SR, Silverman IE, Kizer JR, Homma S, Zahn C, Gronseth G, Kasner SE. Practice Parameter: Recurrent stroke with patent foramen ovale and atrial septal aneurysm: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;62:1042-1050.

Objectives: (1) To evaluate the risk of subsequent stroke or death in patients with a cryptogenic stroke and a patent foramen ovale (PFO), atrial septal aneurysm (ASA), or both. (2) To establish the optimal method of stroke prevention in this population of patients.

Methods: MEDLINE, the Cochrane database of systematic reviews, key meeting abstracts from 1997 to 2002, and relevant reference lists were searched to select studies that prospectively collected outcome data in cryptogenic stroke patients with and without interatrial septal abnormalities. Studies were also selected that prospectively compared at least two treatment options. The quality of each study was graded (class I to IV) using a standard classification-of-evidence scheme for each question. Risk analyses were performed and data were pooled when appropriate.

Results: The literature search generated 129 articles of which only four fulfilled the inclusion and exclusion criteria. Two studies were graded class I, one study was graded class II, and one study was graded class IV for prognosis. Pooled results of the two class I and one class II studies demonstrated no increased risk of subsequent stroke or death in patients with PFO compared to those without (RR: 0.95; 95% CI: 0.62 to 1.44). One class I study found increased risk of recurrent stroke in patients with PFO and ASA (annual rate = 3.8% vs. 1.05%; RR: 2.98, 95% CI: 1.17 to 7.58) but not increased risk of a composite of stroke and death (annual rate = 3.8% vs. 1.8%; RR: 2.10; 95% CI: 0.86 to 5.06). Regarding therapy, one study was graded class II, one study was graded class III, and two studies were graded class IV. Among patients with cryptogenic stroke and PFO or ASA, there was no significant difference in stroke or death rate in warfarin-treated patients relative to aspirin-treated patients and the confidence intervals were unable to rule out a benefit of one drug over the other (annual rate = 4.7% vs. 8.9%, RR: 0.53; 95% CI: 0.18 to 1.58). Minor bleeding rates were higher in the cohort of patients who received warfarin (22.9/100 patient-years vs. 8.66/100 patient-years; rate ratio = 2.64; P < .001). No studies compared medical therapy with surgical or endovascular closure.

Conclusion: PFO is not associated with increased risk of subsequent stroke or death among medically treated patients with cryptogenic stroke. However, both PFO and ASA possibly increase the risk of subsequent stroke (but not death) in medically treated patients younger than 55 years. In patients with a cryptogenic stroke and an atrial septal abnormality the evidence is insufficient to determine if warfarin or aspirin is superior in preventing recurrent stroke or death, but minor bleeding is more frequent with warfarin. There is insufficient evidence to evaluate the efficacy of surgical or endovascular closure.

Comment: Yet more on the issue of PFO and stroke, which is of relevance in the migraine with aura literature. The comorbidity of PFO and migraine with aura is established; the clinical implication is not. —Stewart J. Tepper
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Document Type: Research Article

Publication date: September 1, 2004

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