Cerebral hemodynamics in the different phases of migraine and cluster headache

Abstract

Headache is one of the most common ailments; migraine is one of the most prevalent and disabling neurological disorders and cluster headache presents as one of the most excruciating pain disorders. Both are complex disorder characterized by recurrent episodes of headache. A key feature is that various triggers can set off an attack providing the opportunity to explore disease mechanisms by experimentally inducing attacks. This review summarizes neuroimaging and hemodynamic studies in human in provoked and spontaneous attacks of migraine and cluster headache. Cerebral hemodynamics during different phases of the migraine attack demonstrate alterations in cerebral blood flow and perfusion, vessel caliber, cortical and sub-cortical function, underscoring that migraine pathophysiology is highly complex. Migraine attacks might begin in diencephalic and brainstem areas, whereas migraine aura is a cortical phenomenon. In cluster headache pathophysiology, the hypothalamus might also play a pivotal role, whereas the pattern of cerebral blood flood differs from migraine. For both disorders, alterations of arterial blood vessel diameter might be more an epiphenomenon of the attack than a causative trigger. Studying cerebral hemodynamics in provocation models are important in the search for specific biomarkers in the hope to discover future targets for more specific and effective mechanism-based anti-headache treatment.

Keywords: Brain imaging; cerebral hemodynamics; cluster headache; headache provocation; migraine.

Figures

Figure 1.

The symptoms and signs during a migraine attack, arbitrarily divided into five distinct phases. In one prospective study, the most common premonitory symptoms are tiredness (72%), followed by difficulty with concentration (51%), neck stiffness (30%) and sensitivity to light (49%). Similar data were found retrospectively by Schoonman et al. with fatigue (46%), phonophobia (36%), yawning (36%) and prospectively by Quintela et al. with anxiety (46%), phonophobia (44%), irritability (42%), yawning (40%) and by Kelman with fatigue (26%), mood change (23%) and gastrointestinal symptoms (22%). Figure adapted from Blau.

Figure 2.

Areas of hyperperfusion during the premonitory phase of the migraine attack. In this earliest phase, patients realize symptoms prior to headache suggesting a dysfunction of the hypothalamus, periaqueductal grey as well as the dorsal pons in congruence with the symptoms reported (a). Patients with photophobia in the premonitory phase similary show hyperperfusion in the occipital lobe (b), patients with nausea in the dorsal medulla as well as the periaqueductal grey (c).

Figure 3.

The BOLD response of the trigeminal nucleus to noxious trigeminal stimulation is reduced in interictal migraineurs (insert). In the days prior to the next migraine attack, this response increases substantially suggesting almost a predictability of the so far unpredictable headache attacks, modified from Stankewitz et al.

Figure 4.

Typical propagation pattern of a visual migraine aura. The figure depicts the right visual hemifield and the travelling visual migraine aura, with the numbers indicating the time passed (in min) since first occurrence (a). Here, the visual disturbance is projected onto a flat model of the primary visual cortex by reversed retinotopic mapping (b). Used with permission and adapted from Dahlem and Hadjikhani.

Figure 5.

Schematic illustration in migraine with aura of the temporal relation between angiography (time 0 h), hypoperfusion, aura, headache, hyperperfusion, disappearance of headache, and disappearance of hyperperfusion. Note the discrepancy between the headache and cerebral blood flow changes, adapted from Olesen et al.

Figure 6.

The experimental set-up of a human migraine study, modified from Olesen et al. Headache intensity is recorded on a verbal rating scale from 0 to 10 (0, no headache; 1, a very mild headache (including a feeling of pressing or throbbing); 5, moderate headache; 10, worst imaginable headache). At baseline, and then at fixed and predefined intervals, the hemodynamic effects of the infusion are recorded, and may include recordings of the intra- and extracranial arteries. Vital signs such as heart rate and blood pressure are measured continuously throughout the study. The studies can be tailored to assess certain aspects. If the focus is to address imaging or plasma levels of a given substances, scans and blood samples are conducted at baseline, and when the effects are expected as well as after treatment of the attack.