title: Nitric oxide modulation of low-frequency oscillations in cortical vessels in FHM--a NIRS study.
abstract: BACKGROUND
  The pathophysiological alterations in patients with familial hemiplegic migraine (FHM) are not yet fully known. The headache characteristics in patients with FHM mutations have been examined in a series of glyceryl trinitrate (GTN) provocation studies in FHM patients, but the cortical vascular response to GTN in FHM patients has never been investigated before.
  
  
  OBJECTIVE
  To investigate changes in spontaneous low-frequency oscillations (LFO) of cortical vessels in response to the nitric oxide donor GTN by near-infrared spectroscopy in FHM patients.
  
  
  METHODS
  Twenty-three FHM patients without known mutations and 9 healthy controls received a continuous intravenous infusion of GTN 0.5 µg/kg/minute over 20 minutes. Using near-infrared spectroscopy, we recorded oxygenated hemoglobin (oxyHb) LFO amplitude bilateral at the frontal cortex at baseline and 15 minutes and 40 minutes after start of the GTN infusion.
  
  
  RESULTS
  GTN changed oxyHb LFO amplitude in FHM patients (P = .002), but not in healthy controls (P = .121). Only in FHM patients with coexisting common migraine types did GTN infusion induced changes in LFO amplitudes (P < .001), where post-hoc analysis revealed an increase in LFO amplitude 15 minutes (P = .003) and 40 (P = .013) minutes after start of infusion compared with baseline. Interestingly, GTN infusion induced no changes in LFO amplitude in patients with a pure FHM phenotype (P = .695).
  
  
  CONCLUSIONS
  FHM patients with a mixed phenotype (coexisting common type of migraine) showed an increase in oxyHb LFO amplitude during GTN infusion, whereas FHM patients with pure phenotype showed no changes. These data suggest possible differences in frontal cortical nitric oxide vascular sensitivity between FHM patients with a mixed phenotype and patients with pure FHM.
authors.affiliation: Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik W
authors.initials: HW
authors.lastname: Schytz
authors.forename: Jakob M
authors.initials: JM
authors.lastname: Hansen
authors.forename: Dorte
authors.initials: D
authors.lastname: Phillip
authors.forename: Juliette
authors.initials: J
authors.lastname: Selb
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D000368:Aged; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000098:blood supply*; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010641:Phenotype; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D005996:Nitroglycerin