Do White Matter Brain Lesions Indicate Cardiac Shunt in a Migraineur?
Do White Matter Brain Lesions Indicate Cardiac Shunt in a Migraineur?
Abstract & Commentary
By Dara G. Jamieson, MD Associate Professor of Clinical Neurology, Department of Neurology and Neuroscience, Weill Medical College, Cornell University. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil; and is on the speaker's bureau for Boehringer Ingelheim and Merck.
Synopsis: While about one-half of patients with migraine with aura have a patent foramen ovale, their right-to-left cardiac shunt does not increase the risk of white matter lesions on MRI scan of the brain.
Sources: Adami A, et al; SAM Study Group. Right-to-left shunt does not increase white matter lesion load in migraine with aura patients. Neurology 2008;71:101-107; Del Sette M, et al. White matter lesions in migraine and right-to-left shunt: a conventional and diffusion MRI study. Cephalalgia 2008;28:376-382; Anzola GP, et al; SAM Study Group. Is migraine associated with right-to-left shunt a separate disease? Results of the SAM study. Cephalalgia 2008;28:360-366.
Neurologists who order brain MRIs for their patients with migraine often need to explain to them the clinical significance of incidentally noted white matter lesions (WMLs). These WMLs are scattered areas of presumed myelin loss, gliosis, or ischemia that appear as hyperintense signals on standard and fluid-attenuated inversion recovery (FLAIR) T2-weighted sequences. WMLs can be found on the brain MRI of normal individuals, but they are associated with migraine with aura (MA+), cerebral ischemia, and demyelinating disorders. The clinical significance of WMLs in patients with MA+ is poorly understood but the lesion burden increases with increased severity of disease. These three papers are from the Shunt Associated Migraine (SAM) study, which examines the correlation between MA+, right-to-left shunt (RLS) due to a patent foramen ovale (PFO), and WMLs. The SAM study, a prospective, Italian multicenter, observational study of consecutive MA+ patients, tested the hypothesis that MA+ associated with RLS is a specific migraine syndrome differentiated from MA+ without RLS.
In the paper by Adami et al, 185 patients (77% women) underwent a standardized headache and vascular risk factors questionnaire, a contrast-enhanced transcranial Doppler to assess RLS, blood coagulation tests, and a brain MRI with standard and FLAIR T2-weighted sequences to assess deep and periventricular WMLs. WML load was correlated between patients with and without RLS. Only increased age was associated with WMLs (p<0.001). Deep WMLs were increased in patients with longer MA+ history. Del Sette et al enrolled 87 MA+ subjects, diagnosing RLS in 45% of patients and WMLs in 61% of patients. No DWI hyperintense lesions were detected. The presence of WMLs did not correlate with any migraine clinical feature, whereas the presence, number, and volume of WMLs were increased in older migraineurs. Both papers found no significant difference in the total volume and number of WMLs between the groups with and without RLS. The presence of RLS did not increase the white matter lesion load in patients with MA+.
About 50% of patients with MA+ have a PFO, an unexplained correlation. The intriguing suggestion that PFO closure may decrease migraine attack hints that the PFO could play a role in triggering migraine attacks. The SAM study compared the clinical and radiological characteristics between MA+ patients with shunt-unrelated migraine (SUM) and shunt-associated migraine (SAM), as reported by Anzola et al. SAM patients (42% of the total 460 patients) were significantly younger (34.1 ± 10 vs. 37.1 ± 11 years), had a more frequent family history of migraine (76% vs. 66%), and a higher frequency of sensory symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of SAM with other cardiac abnormalities and with coagulation disorders. The higher family history of migraine in SAM suggested a possible genetic linkage between migraine and RLS. The SAM study confirmed the association between MA+ and RLS, but the presence of a RLS did not differentiate a separate clinical entity.
Commentary
The incidence of both WMLs and PFOs are increased in patients with MA+ but their pathophysiologic correlation is unclear. The pathology of the WMLs is poorly characterized and the theory that they may represent cardioembolic ischemic lesions is intriguing. However, the SAM study showed no correlation between the presence of WMLs and PFO, and no specific headache characteristics are associated with cardiac shunting. These SAM results, as well as the unproven clinical benefit of PFO closure, add weight to the theory of genetic co-localization of MA+ and PFO, as opposed to a direct causative link. Until the results of clinical trials of PFO closure in migraine patients are analyzed, the SAM study dictates caution in ascribing a causative relationship between brain lesions, cardiac shunting, and clinical characteristics in migraine patients. Neurologists can reassure their patients with MA+ that incidental deep WMLs are common and do not represent any known cardiac or brain risk.
While about one-half of patients with migraine with aura have a patent foramen ovale, their right-to-left cardiac shunt does not increase the risk of white matter lesions on MRI scan of the brain.Subscribe Now for Access
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