title: Familial hemiplegic migraine type 1 shows no hypersensitivity to nitric oxide.
abstract: Familial hemiplegic migraine type 1 (FHM-1) is a dominantly inherited subtype of migraine with aura and transient hemiplegia associated with mutations in the CACNA1A gene. FHM-1 shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. Experimental studies have established that activation of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that CACNA1A mutations in patients with FHM-1 are associated with hypersensitivity to NO-cGMP pathway. We included eight FHM-1 patients with R583Q and C1369Y mutations and nine healthy controls, who received intravenous infusions of 0.5 microg kg(-1) min(-1) glyceryl trinitrate (GTN) over 20 min. We recorded: 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 Dermascan. One patient reported migraine without aura 5 h after start of the GTN infusion. No aura was reported. The AUC(headache) in the immediate phase was more pronounced in patients than in controls (P = 0.01). In the 14 h following GTN infusion, there was no difference in the AUC(headache) between patients and controls (P = 0.17). We found no difference in the AUC(VmeanMCA) (P = 0.12) or AUC(STA) (P = 0.71) between FHM-1 patients and controls. None of the control persons reported migraine-like headache. FHM-1 patients do not show hypersensitivity of the NO-cGMP pathway, as characteristically seen in migraine patients with and without aura. This indicates that the pathophysiological pathways underlying migraine headache in FHM-1 may be different from the common types of migraine.
authors.affiliation: Danish Headache Centre and Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup, 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: J
authors.initials: J
authors.lastname: Olesen
authors.forename: M
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D006152:Cyclic GMP