Valeria De Giuli1, Mario Grassi2, Corrado Lodigiani3, Rosalba Patella4, Marialuisa Zedde5, Carlo Gandolfo6, Andrea Zini7, Maria Luisa DeLodovici8, Maurizio Paciaroni9, Massimo Del Sette10, Cristiano Azzini11, Antonella Toriello12, Rossella Musolino13, Rocco Salvatore Calabrò14, Paolo Bovi15, Maria Sessa16, Alessandro Adami17, Giorgio Silvestrelli18, Anna Cavallini19, Simona Marcheselli20, Domenico Marco Bonifati21, Nicoletta Checcarelli22, Lucia Tancredi23, Alberto Chiti24, Enrico Maria Lotti25, Elisabetta Del Zotto26, Giampaolo Tomelleri15, Alessandra Spalloni4, Elisa Giorli27, Paolo Costa1, Loris Poli1, Andrea Morotti1, Filomena Caria1, Alessia Lanari18, Giacomo Giacalone28, Paola Ferrazzi3, Alessia Giossi16, Valeria Piras29, Davide Massucco6, Cataldo D'Amore9, Filomena Di Lisi4, Ilaria Casetta11, Laura Cucurachi30, Masina Cotroneo13, Alessandro De Vito11, Elisa Coloberti20, Maurizia Rasura4, Anna Maria Simone7, Massimo Gamba31, Paolo Cerrato32, Giuseppe Micieli33, Giovanni Malferrari5, Maurizio Melis29, Licia Iacoviello34, Alessandro Padovani1, Alessandro Pezzini1. 1. Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia. 2. Dipartimento di Scienze del Sistema Nervoso e del Comportamento, Unità di Statistica Medica e Genomica, Università di Pavia, Pavia, Italia. 3. Centro Trombosi, Istituto di Ricerca e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano-Milano, Italia. 4. Stroke Unit, Azienda Ospedaliera Sant'Andrea, Università "La Sapienza," Roma, Italia. 5. Unità di Neurologia, Arcispedale Santa Maria Nuova-Istituto di Ricerca e Cura a Carattere Scientifico, Reggio Emilia, Italia. 6. Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Genova, Italia. 7. Stroke Unit, Clinica Neurologica, Nuovo Ospedale Civile "S. Agostino Estense," Azienda Unità Sanitaria Locale, Modena, Italia. 8. Unità di Neurologia, Ospedale di Circolo, Università dell'Insubria, Varese, Italia. 9. Stroke Unit, Divisione di Medicina Cardiovascolare, Università di Perugia, Perugia, Italia. 10. Unità Operativa di Neurologia, Ospedale Galliera, Genova, Italia. 11. Stroke Unit, Divisione di Neurologia, Dipartimento di Neuroscienze e Riabilitazione, Azienda Ospedaliero-Universitaria di Ferrara, Italia. 12. Unità Operativa Complessa Neurologia, Azienda Ospedaliera Universitaria "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italia. 13. Dipartimento di Neuroscienze, Scienze Psichiatriche e Anestesiologiche, Clinica Neurologica, Università di Messina, Messina, Italia. 14. Istituto di Ricerca e Cura a Carattere Scientifico, Centro Neurolesi Bonino-Pulejo, Policlinico Universitario, Messina, Italia. 15. Unità Operativa Neurologia, Azienda Ospedaliera-Universitaria Borgo Trento, Verona, Italia. 16. Unità Operativa Neurologia, Istituti Ospitalieri, Cremona, Italia. 17. Stroke Center, Dipartimento di Neurologia, Ospedale Sacro Cuore Negrar, Verona, Italia. 18. Stroke Unit, Unità Operativa Neurologia, Azienda Ospedaliera "Carlo Poma," Mantova, Italia. 19. Stroke Unit, Istituto di Ricerca e Cura a Carattere Scientifico Fondazione Istituto "C. Mondino," Pavia, Italia. 20. Neurologia d'Urgenza e Stroke Unit, Istituto di Ricerca e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano-Milano, Italia. 21. Unità Operativa Complessa Neurologia, Ospedale Cà Foncello, Unità Locale Socio Sanitaria 9, Treviso, Italia. 22. Unità Operativa Complessa Neurologia, Ospedale Valduce, Como, Italia. 23. Unità Operativa Neurologia, Azienda Ospedaliera Ospedale Sant'Anna, Como, Italia. 24. Neurologia, Azienda Ospedaliera Universitaria Pisana, Pisa, Italia. 25. Unità Operativa Complessa Neurologia, AUSL Romagna, Ravenna, Italia. 26. Unità Operativa Recupero e Rieducazione Funzionale, Istituto di Ricerca e Cura a Carattere Scientifico Fondazione Don Gnocchi, Rovato, Italia. 27. Unità di Neurologia, Ospedale S. Andrea, La Spezia, Italia. 28. Stroke Unit, Unità Operativa Clinica Neurologia, Istituto di Ricerca e Cura a Carattere Scientifico S. Raffaele, Milano, Italia. 29. Stroke Unit, Azienda Ospedaliera "G. Brotzu," Cagliari, Italia. 30. Stroke Unit, Unità Operativa Neurologia, Ospedale "S. Chiara," Trento, Italia. 31. Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italia. 32. Dipartimento di Neuroscienze, Stroke Unit, Università di Torino, Torino, Italia. 33. Neurologia d'Urgenza, Istituto di Ricerca e Cura a Carattere Scientifico Fondazione Istituto "C. Mondino," Pavia, Italia. 34. Laboratorio di Epidemiologia Molecolare e Nutrizionale, Dipartimento di Epidemiologia e Prevenzione, Istituto di Ricerca e Cura a Carattere Scientifico Istituto Neurologico Mediterraneo, Neuromed, Pozzilli, Italia.
Abstract
Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS). Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD. Design, Setting, and Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine. Main Outcomes and Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS. Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99). Conclusions and Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.
Importance: Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS). Objective: To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD. Design, Setting, and Participants: A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine. Main Outcomes and Measures: Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS. Results: Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P < .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainouspatients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P > .99). Conclusions and Relevance: In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.
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