Clinical application of near-infrared spectrocospy in migraine patients

C. Hirth, G. Arnold, H. Obrig, T. Wolf, A. Villringer

Introduction

Migraine was previously considered as a cerebrovascular disease, that goes along with an initial hypoperfusion in the phase of the aura and followed by hyperperfusion in the phase of migraine headache. Recently, an alternative hypothesis of origination of the neurological symptoms of aura and migraine headache were put forward. It is suspected that the so called cortical spreading depression (CSD) an electrophysiological phenomenon which slowly moves over the cortex may be a correlate of the neurological symptoms occuring during migraine attack especialy the migraine aura. In animal experiments it has been shown that CSD which first had been described by Leao, is coupled to hemodynamic changes as well - an initial circumscribed hypoperfusion is followed by a hyperperfusion. Oxygenation changes associated with CSD induced hyperperfusion can be detected in animal experiments by means of Near-infrared spectroscopy (project Wolf). However the association between CSD and the activation of the trigeminovascular system propagated as a trigger of migraine headache by Moskowitz remains unclear. The activation of the trigeminovascular system goes along with extravasation of albumine (sterile inflammation, see project Arnold), wich can be blocked by common drugs used for migraine therapy namely ergotamin or sumatriptan. These drugs have a vasoconstrictive effect as well. Up to now informations about changes in microcirculation and cortical oxygenation during migraine aura and migraine headache in humans are not available.

The aims of this project are

1. Assessment of transient changes of brain tissue oxygenation during aura and headache phase of a migraine attack by means of NIRS
2. Monitoring of drug effects in migraine therapy

Method

A optical method - Near-infrared spectroscopy (NIRS) - seems to be particularly suitable for such measurements in migraine patients. NIRS permits the nonivasive assessment of changes of brain tissue oxygenation. Since oxygenated hemoglobin, deoxygenated hemoglobin and cytochrome oxidase have different absorption spectra in the near-infrared region concentration changes of those substances can be measured noninvasively. Total hemoglobin [tota-Hb] calculated as a sum of [oxy-Hb] and [deoxy-Hb] gives information about changes of blood volume under the assumption that hematocrit remains stable. The advantage of the method is that it is noninvasive, inexpensive and highly flexible in use so that it possible to performe bedside-monitoring.

In contrary to other functional neuroimaging methods wich are able to measure cerebral blood flow (for example PET) the good temporal resolution of NIRS makes it possible to carry out continuous and simultaneous monitoring of NIRS parameters. As mentioned above changes in regional cerebral oxygenation during CSD in animal experimets can be detected.

Experimental protocol

1. During migraine aura NIRS parameters are to be measured continuously over the presumed affected brain area. Special attention is directed to pronounced transient oxygenation changes in reflection of hemodynamic changes as seen in animal experiments during CSD
2. Drug effects in therapy of an acute migraine attack are to be monitored.
3. Behaviour of measurement parameters in both experimental protocols has to be determined and investigated in a number of patients and compared to a control group

Subsequently a first NIRS-measurement in a patient during migraine attack and treatment with sumatriptan is demonstrated.

Case

In the present early phase of application of NIRS in clinical settings the measurements carried out can give further information about applicability of this method as a tool for bedside monitoring of different neurologic diseases. Increasing experience with current methodological problems can contribute to optimization of measurement conditions for example optode positioning, measurement duration, and influencing effects.

We hope that in the future NIRS may also be used for monitoring of patients suffering from neurovascular diseases for example stroke and for monitoring of therapeutic procedures in the neurological intensive care unit. Simultaneous measurements in combination with other established examination methods such as Doppler sonography can help to clarify interrelation between macrocirculation and microcirculation and can lead to a better distinction between regional oxygenation changes caused by more global or more localized hemodynamic changes. These informations are important for a better understanding and interpretation of the NIRS signal.

Further investigations are concentrated on methodological problems and technical innovations. These are on the one hand determination of pathlength that is necessary to allow calculation of absolute values of NIRS parameters and on the other hand more exact determination of cytochrome oxidase signal as an important parameter of intracellular oxygenation state. These two points are of particular interest for measurements in pathological conditions. Another interesting point is to improve the poor spatial resolution of NIRS: NIRS imaging.

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