Premonitory Phase Of Migraine Research Articles

Recent advances in the elucidation of migraine pathophysiology

Three hypotheses have been proposed so far regarding the pathophysiology of migraine: one is the "vascular theory", which posits cerebral vascular dysfunction as the etiological factor. The second is the "neuronal theory", which suggests that migraine is triggered by cortical spreading depression. The third is the "trigemino-vascular theory", which postulates that migraine is triggered by inflammation of trigeminal nerves and vessels around trigeminal ganglion cells. Nowadays, the "trigemino-vascular theory" is widely accepted. However, recent advances in imaging analysis indicate that the origin of migraine lies in a premonitory phase which precedes the aura phase. Modern imaging techniques such as functional MRI and PET reveal high activity of the hypothalamic area during the premonitory phase of migraine. These findings suggest that hypothalamic activation might be a generator of a migraine attack. On the other hand, current analyses show that the photosensitivity of migraine (photophobia) could be caused by dysfunction of the newly discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). In the absence of visual signaling from rods and cones, light activation of ipRGCs expressing melanopsin photopigment is sufficient to produce photophobia during migraine. The ipRGCs project to the hypothalamus; their activation might be the trigger for migraine attacks. Significant advances in molecular biology and imaging in recent years have clarified the previous hypotheses of migraine pathophysiology.

The Migraine Premonitory Phase

The premonitory phase of migraine is defined as the presence of nonpainful symptomatology occurring hours to days before the onset of headache. Symptoms can include neck stiffness, yawning, thirst, and increased frequency of micturition. Clinical recognition of these symptoms is important to ensure early and effective attack management. Further understanding of the clinical phenotype and neurobiological mediation of these symptoms is important in the advancement of therapeutics research in both acute and preventive treatments of migraine. Since 2014, functional imaging studies have been conducted during the premonitory stage of migraine and have provided novel insights into the early neurobiology and anatomy of the earliest stage of the migraine attack. These studies have shown early involvement of subcortical brain areas including the hypothalamus, substantia nigra, dorsal pons, and various limbic cortical areas, including the anterior cingulate cortex during the premonitory phase. More recent work has revealed altered hypothalamic-brainstem functional connectivity during migraine, which starts before the onset of pain. These exciting findings have provided functional correlation of the symptoms experienced by patients and changes seen on functional brain imaging. This article focuses on the prevalence, phenotype, and proposed neurobiology of premonitory symptomatology in migraineurs as well as the scope of future research.

The Premonitory Phase of Migraine

The Premonitory Phase of Migraine

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.

Photic hypersensitivity in the premonitory phase of migraine--a positron emission tomography study.

Sensitivity to light (photophobia) is a common ill-understood symptom of migraine, whose neurobiology is important in understanding the disorder. Patients reporting premonitory symptoms before migraine headache were infused with nitroglycerin (GTN) at a first visit. Patients who responded with premonitory symptoms followed by a delayed headache resembling their migraine had positron emission tomography (PET) scans at least 1 week later, during which GTN infusion was repeated. H2 (15) O PET scans were performed during baseline (pain free), premonitory phase (pain free) and migraine headache. Patients were divided into two groups, with and without photophobia in the premonitory phase. The differences between the premonitory and baseline scans were analysed within groups and between groups using statistical parametric mapping. Thirteen patients participated in the PET study, 10 of whom had at least one PET scan during the premonitory phase in the absence of pain. Data from these 10 patients were included in the final analysis. Five patients had photophobia and five patients did not have photophobia in the premonitory phase. Comparing the premonitory scans to baseline scans, there was activation of extrastriate visual cortex (BA18) in patients with photophobia. This activation was significantly greater than in the patients without photophobia. Our findings indicate that photic hypersensitivity is linked to activation of the visual cortex during the premonitory phase of migraine in the absence of headache.

Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks

Our aim was identify brain areas involved in the premonitory phase of migraine using functional neuroimaging. To this end, we performed positron emission tomography scans with H2(15)O to measure cerebral blood flow as a marker of neuronal activity. We conducted positron emission tomography scans at baseline, in the premonitory phase without pain and during migraine headache in eight patients. We used glyceryl trinitrate (nitroglycerin) to trigger premonitory symptoms and migraine headache in patients with episodic migraine without aura who habitually experienced premonitory symptoms during spontaneous attacks. The main outcome was comparing the first premonitory scans in all patients to baseline scans in all patients. We found activations in the posterolateral hypothalamus, midbrain tegmental area, periaqueductal grey, dorsal pons and various cortical areas including occipital, temporal and prefrontal cortex. Brain activations, in particular of the hypothalamus, seen in the premonitory phase of glyceryl trinitrate-triggered migraine attacks can explain many of the premonitory symptoms and may provide some insight into why migraine is commonly activated by a change in homeostasis.

Imaging the premonitory phase of migraine - new insights into generation of the migraine attack

When questioned closely the majority of migraineurs report premonitory symptoms before headache that represent the earliest clinical manifestations of the attack [1]. The premonitory phase has not been hitherto imaged and offers an opportunity to understand fundamental aspects of the disorder.

The premonitory phase of migraine and migraine management

The objective was to determine, through a literature review, whether treatment during the premonitory phase of migraine is a potentially useful migraine management strategy. A general literature review was done with regard to the nature of migraine premonitory symptoms, their frequency, their reliability in predicting migraine attacks, and the effectiveness of medication treatment when given during the premonitory phase. Many different symptoms have been reported as premonitory symptoms that occur before migraine attacks. Up to 87% of patients with migraine may experience premonitory symptoms, although some studies have provided estimates as low as 33%. In selected patients, premonitory symptoms may be relatively reliable predictors of a migraine attack to follow. Both naratriptan (open-label study) and domperidone (double-blind, randomized, placebo-controlled study) have been reported to be effective when given during the premonitory phase. More research is needed, but there is some evidence that medication treatment during the premonitory phase has the potential to be helpful in selected patients with migraine.