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).

Conclusion: 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.

Fig 1

Power spectra of the oxygenated hemoglobin oscillations at the 3 stages of glyceryl trinitrate infusion (pre-infusion, 15 minutes, and 40 minutes postinfusion) averaged over all subjects in each group: healthy controls (top), patients with pure familial hemiplegic migraine (FHM) group (middle), and FHM patients with coexisting migraine with aura (MA)/migraine without aura (MO, bottom). LFO frequency was defined as the frequency within the 0.09-0.11 Hz range.

Fig 2

Boxplots during baseline, 15 minutes from infusion start, and 40 minutes after infusion start for familial hemiplegic migraine (FHM) + migraine with aura (MA)/migraine without aura (MO, gray boxes), pure FHM (striped boxes), and healthy controls (dotted boxes). Band near the middle is the median value. The bottom and top of the boxes is the 25th and 75th percentile. The ends of the whiskers represent the maximum and minimum of the data. y-axis units are in micromoles (μM). Outliers are shown except 1 extreme outlier in FHM + MA/MO patients (15 minutes: 233 μM) and 2 extreme outliers in healthy subjects (15 minutes: 216 μM; 40 minutes: 130 μM).