Cerebral reactivity in migraine patients measured with functional near-infrared spectroscopy

Abstract

Background: There are two major theories describing the pathophysiology of migraines. Vascular theory explains that migraines resulted from vasodilation of meningeal vessels irritating the trigeminal nerves and causing pain. More recently, a neural theory of migraine has been proposed, which suggests that cortical hyperexcitability leads to cortical spreading depression (CSD) causing migraine-like symptoms. Chronic migraine requires prophylactic therapy. When oral agents fail, there are several intravenous agents that can be used. Understanding underlying causes of migraine pain would help to improve efficacy of migraine medications by changing their mechanism of action. Yet to date no study has been made to investigate the link between vascular changes in response to medications for migraine versus pain improvements. Functional near-infrared spectroscopy (NIRS) has been used as an inexpensive, rapid, non-invasive and safe technique to monitor cerebrovascular dynamics.

Method: In this study, a multi-distance near-infrared spectroscopy device has been used to investigate the cortical vascular reactivity of migraine patients in response to drug infusions and its possible correlation with changes in pain experienced. We used the NIRS on 41 chronic migraine patients receiving three medications: magnesium sulfate, valproate sodium, and dihydroergotamine (DHE). Patients rated their pain on a 1-10 numerical scale before and after the infusion.

Results: No significant differences were observed between the medication effects on vascular activity from near channels measuring skin vascularity. However, far channels--indicating cortical vascular activity--showed significant differences in both oxyhemoglobin and total hemoglobin between medications. DHE is a vasoconstrictor and decreased cortical blood volume in our experiment. Magnesium sulfate has a short-lived vasodilatory effect and increased cortical blood volume in our experiment. Valproate sodium had no significant effect on blood volume. Nonetheless, all three reduced patients' pain based on self-report and no significant link was observed between changes in cortical vascular reactivity and improvement in migraine pain as predicted by the vascular theory of migraine.

Conclusion: NIRS showed the potential to be a useful tool in the clinical setting for monitoring the vascular reactivity of individual patients to various migraine and headache medications.

Fig. 1

Volume of tissue sampled by an NIRS measurement: the highly scattered photons are reflected back to the tissue’s surface, mostly within a banana-shaped optical pathway. As a result, a photodetector placed on the skin (on the same surface as the source) can measure the reflected light [19]

Fig. 2

Configuration of NIRS probe: each probe has one LED source, one detector 1 cm from the source (near channel) and two detectors at 2.8 cm from the source (far channels)

Fig. 3

) NIRS probes placement: two NIRS probes are located on both sides of the forehead

Fig. 4

) Experimental Protocol: NIRS data recorded for 2 mins before and 4 min after start of infusion. Whole infusion takes 15–30 min

Fig. 5

Self-reported pain scores by medication: subjects reported their pain based on a 1–10 numeric scale before and after the infusion. Changes between initial and final reported pain (Δ Pain) is considered as self-reported pain improvement

Fig. 6

Sample of recorded NIRS data during medication infusion (DHE for this subject) on a migraine patient: near channel (on left) measures oxyhemoglobin (HbO₂) and total hemoglobin (THb) changes during the infusion on the skin while far channels (on right) measure both skin and cortical activities. Blue line infusion time