Farooq H. Maniyar

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.

The Relation Between Migraine, Typical Migraine Aura and “Visual Snow”

To assess the relationship between the phenotype of the “visual snow” syndrome, comorbid migraine, and typical migraine aura on a clinical basis and using functional brain imaging.

The origin of nausea in migraine–A PET study

BackgroundNausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea.MethodsWe performed positron emission tomography scans with H215O PET in premonitory phase of nitroglycerin-induced migraine and compared patients with and without nausea.ResultsThe results showed activation in rostral dorsal medulla and periaqueductal grey (PAG) in the nausea group, which was absent in the no nausea group. The rostral dorsal medullary area included the nucleus tractus solitarius, dorsal motor nucleus of the vagus nerve and the nucleus ambiguus, all of which are thought to be involved in brain circuits mediating nausea.ConclusionsThe results demonstrate that nausea can occur as a premonitory symptom in migraine, independent of pain and trigeminal activation. This is associated with activation of brain structures known to be involved in nausea. We conclude that nausea is a centrally driven symptom in migraine.

Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.

See Dreier (doi: 10.1093/aww112 ) for a scientific commentary on this article. Breakdown of the blood–brain barrier has long been postulated to occur in migraine. Schankin et al. explore this possibility using PET with [ 11 C]-dihydroergotamine. The radioligand does not bind to the brain parenchyma at rest or during migraine attacks, suggesting that the blood–brain barrier remains intact during attacks.

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.

Paroxysmal sneezing after hypothalamic deep brain stimulation for cluster headache

Background: Cluster headache (CH) is the most common of the trigeminal autonomic cephalalgias (TAC), presenting with excruciatingly severe, short-lasting, unilateral headache accompanied by cranial autonomic symptoms. Chronic CH occurs in 10–15% of patients. Deep brain stimulation in the posterior hypothalamic region (hDBS) is successful in treating about 60% of patients otherwise refractory to medical treatment. Case: A 28-year-old man had hDBS for medically refractory left-sided chronic CH, with a resultant reduction in frequency and severity of his attacks. He developed recurrent paroxysms of sneezing soon after the stimulation was started that have reduced after increasing the pulse width from 60 to 90 µs. Discussion: Stimulation of the brain in the region of the posterior hypothalamus could produce sneezing from activation of facial nerve parasympathetic or trigeminal afferent pathway activation through the trigeminohypothalamic tract, or through other central mechanisms. DBS in general offers the opportunity to illuminate our understanding of brain function and for CH offers particular opportunities to understand a devastating primary headache syndrome.

Functional imaging in chronic migraine

Chronic migraine is a relatively common disorder in neurological terms that causes very significant disability at a high cost. The precise mechanisms behind the progression of episodic migraine to chronic migraine are not well understood. Functional neuro-imaging works on the basis that neuronal activations are associated with changes in regional cerebral blood flow, and it can help us answer some of these questions. In this review, we discuss important recent studies in chronic migraine or studies relating to increasing frequency of migraine attacks. The findings show that increasing frequency of migraine attacks is associated with changes in key brainstem areas, basal ganglia and various cortical areas involved in pain.

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.

Clinical characterization of "visual snow" (Positive Persistent Visual Disturbance)

Results The survey-data of 120 patients with self-reported visual snow was reviewed to generate preliminary criteria. These were re-tested by interviewing 115 patients. The main criterion (black and white visual snow) was met by 57 patients. Additional visual symptoms were excessive floaters (84%), persistent after-images (83%), “hard time seeing at night” (65%), “little cells that travel on a wiggly path” (77%), photophobia (70%), “moving objects leave trails” (56%), “swirls, clouds or waves with eyes closed” (51%), and bright flashes (51%). Requiring at least one or three of these additional criteria reduced the sensitivity by 2% and 7%. No patient described the visual symptoms consistent with persistent visual aura in migraine. A history of migraine was seen in 54%, with 35% having typical migraine with aura. None of the patients noted intake of illicit drugs prior the onset of visual snow. All ophthalmology tests were non-contributory. Conclusions (i) Visual snow is a unique clinical syndrome. The main criterion (visual snow) is almost always associated with at least three additional criteria. (ii) The visual symptoms are distinct from migraine with aura. (iii) The high prevalence of history of migraine (with aura) points to a susceptibility for visual snow in patients with migraine. (iv) Intake of illicit drugs and ophthalmological diseases may not be of pathophysiological relevance.