The premonitory phase of migraine--what can we learn from it?

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7-88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.