title: Familial hemiplegic migraine type 2 does not share hypersensitivity to nitric oxide with common types of migraine.
abstract: Familial hemiplegic migraine type 2 (FHM-2) and common types of migraine show phenotypic similarities which may indicate a common neurobiological background. The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that ATP1A2 mutations in patients with FHM-2 are associated with hypersensitivity to NO-cGMP pathway. Eight FHM-2 patients with R202Q, R763C, V138A and L764P mutations and nine healthy controls received intravenous infusions of 0.5 mug kg(-1) min(-1) glyceryl trinitrate (GTN) over 20 min. We recorded the following variables: headache intensity on a verbal rating scale; mean flow velocity in the middle cerebral artery (V(meanMCA)) by transcranial Doppler; diameter of the superficial temporal artery (STA) by ultrasound. The primary end-points were differences in incidence of migraine headache and area under the curve (AUC) for headache score during an immediate phase (0-120 min) and a delayed phase (2-14 h) after start of infusion. We found no difference in the incidence of reported migraine between FHM-2 patients, 25% (two out of eight), and controls, 0% (0 out of nine) (95% confidence interval -0.06, 0.56) (P = 0.21). The AUC(headache) in the immediate (P = 0.37) and delayed (P = 0.09) phase was not different between patients and controls. The GTN infusion resulted in a biphasic response in patients. During the immediate phase, the median peak headache occurred at 30 min and tended to be higher in patients, 1 (0, 3.8), than in controls, 0 (0, 1) (P = 0.056). During the delayed phase, the median peak headache occurred 4 h after the start of the infusion and was significantly higher in patients, 2.5 (0, 3), than in controls, 0 (0, 0) (P = 0.046). We found no difference in the AUC(VmeanMCA) (P = 0.77) or AUC(STA) (P = 0.53) between FHM-2 patients and controls. GTN infusion failed to induce more migraine in FHM-2 patients than in controls. The pathophysiological pathways underlying migraine headache in FHM-2 may be different from the common types of migraine.
authors.affiliation: Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. jamoha01@glo.regionh.dk
authors.forename: J M
authors.initials: JM
authors.lastname: Hansen
authors.forename: L L
authors.initials: LL
authors.lastname: Thomsen
authors.forename: R
authors.initials: R
authors.lastname: Marconi
authors.forename: G
authors.initials: G
authors.lastname: Casari
authors.forename: J
authors.initials: J
authors.lastname: Olesen
authors.forename: M
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002560:Cerebrovascular Circulation; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000502:physiology; D020325:Migraine with Aura / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D013699:Temporal Arteries / Q000502:physiology; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D005996:Nitroglycerin; D006152:Cyclic GMP