Objective: In contrast to patients with migraine with aura (MA) and migraine without aura (MO), most patients with familial hemiplegic migraine (FHM) do not report migraine-like attacks after pharmacologic provocation with glyceryl trinitrate (GTN), a donor of nitric oxide. In the present study, we examined patients with FHM without known gene mutations and hypothesized that 1) GTN would cause more migraine-like attacks in patients with FHM compared to controls, and 2) GTN would cause more migraine attacks in patients with FHM with coexisting MA or MO compared to the pure FHM phenotype.
Methods: The study design was a balanced provocation study. Twenty-three patients with FHM and 11 healthy controls received a continuous IV infusion of 0.5 mug/kg/min GTN over 20 minutes.
Results: We found no difference in the incidence of migraine-like attacks comparing all patients with FHM (30%) to controls (9%) (p = 0.15). Patients with FHM with coexisting MA or MO reported more migraine attacks after GTN (55%) than patients with the pure FHM phenotype (8.3%) (p = 0.02). Compared to healthy controls, more patients with FHM with coexisting MA or MO reported migraine-like attacks than controls (p = 0.03), whereas the FHM group with the pure FHM phenotype did not (p > 0.05).
Conclusions: Compared to patients with migraine with aura (MA) and migraine without aura (MO), patients with familial hemiplegic migraine (FHM) without known gene mutations display a reduced sensitivity to nitric oxide. A subset of patients with FHM with coexisting nonhemiplegic migraine is more sensitive than controls. These data extend our previous findings that pathophysiologic pathways in FHM may differ from those of MO and MA.