{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzn4sd\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzn4sd\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;11\\\/1\\\/24\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;11\\\/1\\\/24\u0022}],\u0022ac\u0022:{\u0022spmdc;11\\\/1\\\/24\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;11\\\/1\\\/24\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe following summary discusses several presentations concerning the relationship between migraines and stroke, including epidemiology, genetics, and mechanisms, in an effort to explain the link between migraines with aura and stroke.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECerebrovascular Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEpisodic \u0026amp; Paroxysmal Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe following summary discusses several presentations concerning the relationship between migraines and stroke, including epidemiology, genetics, and mechanisms, in an effort to explain the link between migraines with aura and stroke.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMigraine and Stroke: Epidemiological Evidence\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EMigraines are relatively common, occurring in about 12% of the population. Migraines that are associated with aura, a more serious form of migraine, occur in 20% to 40% of migraineurs [Lipton et al. \u003Cem\u003EHeadache\u003C\/em\u003E 2001]. Gretchen E. Tietjen, MD, University of Toledo, Toledo, Ohio, presented epidemiological evidence for the relationship between migraine with aura and stroke. Results from meta-analyses indicate that migraine with aura is associated with a 2-fold increased risk of stroke (RR, 2.16; 95% CI, 1.53 to 3.03) compared with those without migraine, whereas migraine without aura is not associated with risk of stroke (RR, 1.23; 95% CI, 0.90 to 1.69). Stroke risk is doubled in women with migraine. Age \u0026lt;45 years, smoking, and oral contraceptive use further increased the risk [Schurks et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2009]. In persons with migraine with aura, frequency of migraines has also been found to be related to stroke risk, with those experiencing \u0026gt;12\/year at higher risk (OR, 10.4; 95% CI, 2.18 to 49.4) [Donaghy et al. \u003Cem\u003EJ Neurol Neurosurg Psychiatry\u003C\/em\u003E 2002]. Several studies have shown that migraine is associated with cardiovascular (CV) risk factors [Bigal et al. \u003Cem\u003ENeurology\u003C\/em\u003E 2010; Bushnell et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2009; Scher et al. \u003Cem\u003ENeurology\u003C\/em\u003E 2005), but the migraine-with-aura-related stroke risk is highest in those with the most favorable CV risk profiles [Kurth et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2008]. Results from a recent study that investigated the predictive value of major CV factors in young adults with ischemic stroke showed the risk of migraine with aura increased with decreasing number of CV risk factors (OR, 0.50; 95% CI, 0.24 to 0.99 for 2 factors or more), increasing number of thrombophilic variants (OR, 2.21; 95% CI, 1.05 to 4.68 for carriers of at least 1 of the 2), and the presence of right-to-left atrial shunt (OR, 2.41; 95% CI, 1.37 to 3.45), as compared with patients without migraine. None of these factors affected the risk of migraine without aura [Pezzini A et al. \u003Cem\u003EStroke\u003C\/em\u003E 2011].\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMigraine and Stroke: Genetic Evidence\u003C\/h2\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EArn van den Maagdenberg, PhD, Leiden University Medical Center, The Netherlands, presented data that showed the genetic link between migraine and ischemic stroke. Bolay and colleagues [Bolay et al. \u003Cem\u003ENat Med\u003C\/em\u003E 2002] suggested that cortical spreading depression (CSD), which underlies the migraine aura, may also cause headache itself by activating the trigeminovascular system). Prof. van den Maagdenberg believes genetic mutations that affect these mechanisms can help explain the pathophysiology of migraines.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EGenetic studies of monogenic subtypes of migraine, such as familial hemiplegic migraine (FHM), revealed gene mutations in components of ion transport systems, including the voltage-gated Ca\u003Csup\u003E2+\u003C\/sup\u003E channel gene CACNA1A; the ATP1A2 gene, which encodes the alpha2 subunit of the Na\u003Csup\u003E+\u003C\/sup\u003E\/K\u003Csup\u003E+\u003C\/sup\u003E pump; and the gene SCN1A, which encodes a subunit of voltage-gated Na\u003Csup\u003E+\u003C\/sup\u003E channels that is essential for the generation and propagation of action potentials. Mutations in these ion transporter genes, in addition to hemiplegic migraine, may also cause cerebral ataxia, seizures, fatal mild head trauma-induced edema, and recurrent stroke.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EMigraine and stroke (or small vessel disease) are linked by at least two other monogenic disorders: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and retinal vasculopathy with cerebral leukodystrophy (RVCL). CADASIL is the most common form of hereditary stroke and is characterized by progressive white matter degeneration and smooth muscle cell abnormalities. About 30% of CADASIL patients also have migraine with aura, often as the presenting clinical symptom. RVCL is a lesser-known disease in which migraine can be prominent in certain families.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ETransgenic mouse models with monogenic migraine gene mutations were generated (Eikermann-Haerter et al. \u003Cem\u003EAnn Neurol\u003C\/em\u003E 2009; van den Maagdenberg et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2004), of which the S218L missense mutation in the CACNA1A gene causes a particularly dramatic hemiplegic migraine syndrome that is associated with cerebellar ataxia, seizures, and severe, sometimes fatal, brain edema triggered by only mild head trauma. S218L mutant mice display an exquisite sensitivity to CSD, with a vastly reduced triggering threshold, an increased propagation velocity, and frequent multiple CSD events after a single stimulus. In contrast, mice that bear the R192Q missense CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus [van den Maagdenberg et al. \u003Cem\u003EAnn Neurol\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003ECellular and transgenic mouse studies suggest that neuronal hyperexcitability and increased susceptibility to CSD, the correlate of migraine aura, are important molecular mechanisms in migraine. Normalizing glutamatergic neurotransmission in R192Q mutant mice in cortical slice preparations also normalized CSD susceptibility, showing a causative link between enhanced glutamate release and CSD facilitation [Tottene et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2009]. A key role for glutamate in migraine pathophysiology is also shown by increased levels in CSF and plasma of migraine patients. Using genetically modified animal models may help delineate the link between the migraines and stroke, Prof. van den Maagdenber concluded.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMigraine and Stroke: Experimental Insights into Mechanisms\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ECenk Ayata, MD, Massachusetts General Hospital, Boston, Massachusetts, presented data from animal models of migraine and stroke that may help explain the mechanism(s) that links these two highly prevalent disorders. In one animal model that used CSD as a surrogate for migraine with aura, Nozari and colleagues demonstrated that particulate or air-induced microemboli triggered CSD, often without causing microinfarction, suggesting that a subset of migraine auras may belong to a spectrum of hypoperfusion disorders, along with transient ischemic attacks and silent infarcts [Nozari et al. \u003Cem\u003EAnn Neurol\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EDr. Ayata also showed data suggesting that transgenic mice that expressed CACNA1A migraine gene mutations exhibit an increased susceptibility to not only CSD but also anoxic depolarization and peri-infarct depolarizations, thereby hastening the growth of the ischemic core. As a result, mutant mice develop considerably larger infarctions and worse neurological outcomes, including high mortality. This mechanism is a result of tissue hyperexcitability, independent of vascular factors. Because hyperexcitability is a phenotype that is shared between rare monogenic forms of migraine with aura and more common but genetically complex forms, Dr. Ayata suggested that brain hyperexcitability may be a common mechanism that worsens ischemic outcome in migraineurs.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EDr. Ayata cautioned, however, that these two mechanisms are not the only mechanisms that explain the link between migraine and stroke and that they may be operational in only a subset of migraineurs.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/1\/24.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn4sd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}