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Calcitonin gene–related peptide does not cause the familial hemiplegic migraine phenotype

From the Danish Headache Center and Department of Neurology (J.M.H., J.O., M.A.) and Department of Pediatrics (L.L.T.), Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark.

Address correspondence and reprint requests to Dr. Jakob Møller Hansen, Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Nordre Ringvej 57, Bolig 23-24, DK-2600 Glostrup, Copenhagen, Denmark jmh{at}dadlnet.dk

Objective: The neuropeptide calcitonin gene–related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype.

Methods: We included 9 FHM patients with known mutations in the CACNA1A and ATP1A2 genes and 10 healthy controls. All subjects received IV infusion of CGRP (1.5 µg/min). We recorded headache intensity on a verbal rating scale and vascular changes in the middle cerebral artery and the superficial temporal artery.

Results: CGRP infusion did not induce an aura in any of the participants. The incidences of reported migraine and migraine-like headache were not different in the two groups, with 22% (2 of 9) reporting migraine in the patient group and 10% (1 of 10) reporting migraine-like headache in the control group (95% CI –0.31 to 0.55; p = 0.58). Headache severity and intensity were not different between the groups.

Conclusions: Familial hemiplegic migraine (FHM) patients do not show hypersensitivity of the calcitonin gene–related peptide (CGRP)–cyclic adenosine 3',5'-monophosphate pathway, as characteristically seen in migraine patients without aura. This indicates that the pathophysiologic pathways underlying migraine headache in FHM may be different from the common types of migraine and questions whether CGRP antagonists would be effective in the treatment of FHM patients.

Abbreviations: AUC = area under the curve; CGRP = calcitonin gene–related peptide; CSD = cortical spreading depression; FHM = familial hemiplegic migraine; GTN = glyceryl trinitrate; ICHD = International Classification of Headache Disorders; IHS = International Headache Society; HR = heart rate; MA = migraine with aura; MAP = mean arterial pressure; MO = migraine without aura; STA = superficial temporal artery; V_meanMCA = mean velocity of blood flow in the middle cerebral artery; VRS = verbal rating scale.

This study was part of the EUROHEAD project (www.eurohead.org) and supported by grants from the University of Copenhagen, The Danish Medical Association Research Fund, Danish Headache Society, The Lundbeck Foundation through the Center for Neurovascular Signaling, and the European Community (EUROHEAD [LSHM-CT-2004-504837]).

Disclosure: The authors report no disclosures.

Received February 20, 2008. Accepted in final form June 5, 2008.