title: Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla.
abstract: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.
  
  
  CONCLUSIONS
  This multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling.
authors.affiliation: Department of Neurology and Medical Image Analysis Center, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Magon
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: May
authors.affiliation: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany, Department of Neurology, Klinikum rechts der Isar, Technische Universitaet Muenchen, 81675 Muenchen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Stankewitz
authors.affiliation: Department of Neurology, University of California-San Francisco, San Francisco, California 94143, NIHR-Wellcome Trust Clinical Research Facility, King's College London, London WC2R 2LS, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
authors.affiliation: Department of Neurology, University of California-San Francisco, San Francisco, California 94143.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Tso
authors.affiliation: Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, 1165 Copenhagen, Denmark.
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
authors.affiliation: Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, 1165 Copenhagen, Denmark.
authors.forename: Faisal Mohammad
authors.initials: FM
authors.lastname: Amin
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universitaet Muenchen, 81675 Muenchen, Germany.
authors.forename: Christian L
authors.initials: CL
authors.lastname: Seifert
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health University Institute, Verdun, Quebec H4H 1R3, Canada, Department of Psychiatry, McGill University, Montreal, Quebec H3A 0G4, Canada, and.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Department of Neurology and.
authors.forename: Jannis
authors.initials: J
authors.lastname: Müller
authors.affiliation: Department of Neurology and Department of Neurology, DKD Helios Klinik Wiesbaden, 65191 Wiesbaden, Germany till.sprenger@helios-kliniken.de.
authors.forename: Till
authors.identifier: http://orcid.org/0000-0002-5390-819X
authors.initials: T
authors.lastname: Sprenger
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008881:Migraine Disorders / Q000473:pathology*; D012720:Severity of Illness Index; D013787:Thalamic Nuclei / Q000473:pathology*; D055815:Young Adult
keywords: MRI; brain volumes; deep gray matter; migraine; thalamic nuclei; thalamus