Nanna Arngrim

Migraine induced by hypoxia: an MRI spectroscopy and angiography study

Migraine with aura is prevalent in high-altitude populations suggesting an association between migraine aura and hypoxia. We investigated whether experimental hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura. We also investigated the metabolic and vascular response to hypoxia. In a randomized double-blind crossover study design, 15 migraine with aura patients were exposed to 180 min of normobaric hypoxia (capillary oxygen saturation 70-75%) or sham on two separate days and 14 healthy controls were exposed to hypoxia. Glutamate and lactate concentrations in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P < 0.05). We found no difference in the metabolic or vascular responses to hypoxia between migraine patients and controls. In conclusion, hypoxia induced migraine-like attacks with and without aura and dilated the cranial arteries in patients with migraine with aura. Hypoxia-induced attacks were not associated with altered concentration of glutamate or other metabolites. The present study suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated.

Measurement precision and biological variation of cranial arteries using automated analysis of 3 T magnetic resonance angiography

BackgroundNon-invasive magnetic resonance angiography (MRA) has facilitated repeated measurements of human cranial arteries in several headache and migraine studies. To ensure comparability across studies the same automated analysis software has been used, but the intra- and interobserver, day-to-day and side-to-side variations have not yet been published. We hypothesised that the observer related, side-to-side, and day-to-day variations would be less than 10%.MethodsTen female participants were studied using high-resolution MRA on two study days separated by at least one week. Using the automated LKEB-MRA vessel wall analysis software arterial circumferences were measured by blinded observers. Each artery was analysed twice by each of the two different observers. The primary endpoints were to determine the intraclass correlation coefficient (ICC) and intra- an inter-observer, the day-to-day, and side-to-side variations of the circumference of the middle meningeal (MMA) and middle cerebral (MCA) arteries.ResultsWe found an excellent intra- and interobserver agreement for the MMA (ICC: 0.909-0.987) and for the MCA (ICC: 0.876-0.949). The coefficient of variance within observers was ≤1.8% for MMA and ≤3.1% for MCA; between observers ≤3.4% (MMA) and ≤4.1% (MCA); between days ≤6.0% (MMA) and ≤8.0% (MCA); between sides ≤9.4% (MMA) and ≤6.5% (MCA).ConclusionThe present study demonstrates a low (<5%) inter- and intraobserver variation using the automated LKEB-MRA vessel wall analysis software. Furthermore, the study also suggests that the day-to-day and side-to-side variations of the MMA and MCA circumferences are less than 10%.

Sensory migraine aura is not associated with structural grey matter abnormalities.

Migraine with aura (MA) is characterized by cortical dysfunction. Frequent aura attacks may alter cerebral cortical structure in patients, or structural grey matter abnormalities may predispose MA patients to aura attacks. In the present study we aimed to investigate cerebral grey matter structure in a large group of MA patients with and without sensory aura (i.e. gradually developing, transient unilateral sensory disturbances). We included 60 patients suffering from migraine with typical visual aura and 60 individually age and sex-matched controls. Twenty-nine of the patients additionally experienced sensory aura regularly. We analysed high-resolution structural MR images using two complimentary approaches and compared patients with and without sensory aura. Patients were also compared to controls. We found no differences of grey matter density or cortical thickness between patients with and without sensory aura and no differences for the cortical visual areas between patients and controls. The somatosensory cortex was thinner in patients (1.92 mm vs. 1.96 mm, P = 0.043) and the anterior cingulate cortex of patients had a decreased grey matter density (P = 0.039) compared to controls. These differences were not correlated to the clinical characteristics. Our results suggest that sensory migraine aura is not associated with altered grey matter structure and that patients with visual aura have normal cortical structure of areas involved in visual processing. The observed decreased grey matter volume of the cingulate gyrus in patients compared to controls have previously been reported in migraine with and without aura, but also in a wide range of other neurologic and psychiatric disorders. Most likely, this finding reflects general bias between patients and healthy controls.

Association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers

Summary Acetazolamide caused headache and dilatation of intracranial arteries. Acetazolamide‐induced extracellular acidosis may cause sensitization of perivascular nociceptors, which, in combination with vasodilation, may induce headache. ABSTRACT The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double‐blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We recorded headache on a verbal rating scale from 0 to 10 during an immediate phase (0–90 minutes) and a delayed phase (2–12 hours). The circumference of cranial arteries was measured using 3T high‐resolution magnetic resonance angiography 30 and 60 minutes after injection. Acetazolamide provoked immediate headache in 9 participants compared to 3 participants after placebo (P = .031). Eleven participants reported headache in the delayed phase after acetazolamide, compared with 4 after placebo (P = .016). The area under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2–12 h) (P = .005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P = .002) as well as the cerebral (P = .003), cavernous (P = .002), and cervical (P = .005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache.

Carbon monoxide may be an important molecule in migraine and other headaches

Introduction Carbon monoxide was previously considered to just be a toxic gas. A wealth of recent information has, however, shown that it is also an important endogenously produced signalling molecule involved in multiple biological processes. Endogenously produced carbon monoxide may thus play an important role in nociceptive processing and in regulation of cerebral arterial tone. Discussion Carbon monoxide-induced headache shares many characteristics with migraine and other headaches. The mechanisms whereby carbon monoxide causes headache may include hypoxia, nitric oxide signalling and activation of cyclic guanosine monophosphate pathways. Here, we review the literature about carbon monoxide-induced headache and its possible mechanisms. Conclusion We suggest, for the first time, that carbon monoxide may play an important role in the mechanisms of migraine and other headaches.

Hypoxic mechanisms in primary headaches

Background Hypoxia causes secondary headaches such as high-altitude headache (HAH) and headache due to acute mountain sickness. These secondary headaches mimic primary headaches such as migraine, which suggests a common link. We review and discuss the possible role of hypoxia in migraine and cluster headache. Methods This narrative review investigates the current level of knowledge on the relation of hypoxia in migraine and cluster headache based on epidemiological and experimental studies. Findings Epidemiological studies suggest that living in high-altitude areas increases the risk of migraine and especially migraine with aura. Human provocation models show that hypoxia provokes migraine with and without aura, whereas cluster headache has not been reliably induced by hypoxia. Possible pathophysiological mechanisms include hypoxia-induced release of nitric oxide and calcitonin gene-related peptide, cortical spreading depression and leakage of the blood-brain barrier. Conclusion There is a possible link between hypoxia and migraine and maybe cluster headache, but the exact mechanism is currently unknown. Provocation models of hypoxia have yielded interesting results suggesting a novel approach to study in depth the mechanism underlying hypoxia and primary headaches.

Heterogenous migraine aura symptoms correlate with visual cortex functional magnetic resonance imaging responses: Functional MRI during Aura

Migraine aura is sparsely studied due to the highly challenging task of capturing patients during aura. Cortical spreading depression (CSD) is likely the underlying phenomenon of aura. The possible correlation between the multifaceted phenomenology of aura symptoms and the effects of CSD on the brain has not been ascertained.

Heterogenous migraine aura symptoms correlate with visual cortex fMRI responses

Migraine aura is sparsely studied due to the highly challenging task of capturing patients during aura. Cortical spreading depression (CSD) is likely the underlying phenomenon of aura. The possible correlation between the multifaceted phenomenology of aura symptoms and the effects of CSD on the brain has not been ascertained.

Migraine without aura is not associated with incomplete circle of Willis: a case-control study using high-resolution magnetic resonance angiography

BackgroundThe circle of Willis is an important source of collateral blood flow to maintain adequate cerebral perfusion, particularly in the posterior circulation. Some studies report a relationship between incomplete circle of Willis and migraine, whereas other studies show no difference between the prevalence of incomplete circle of Willis in migraineurs and controls. In the present study we compared the prevalence of incomplete circle of Willis in female migraine patients without aura to female healthy non-migraine controls.Using 3-Tesla magnetic resonance angiography we recorded three-dimensional time-of-flight angiograms in 85 female participants (48 migraine patients without aura [median age 28 years] and 37 healthy controls [median age 25 years]). The images were subsequently analysed blindly by a neuroradiologist to detect incomplete circle of Willis.FindingsWe found no difference between the prevalence of incomplete circle of Willis in patients, 20/47 (43%), and controls, 15/37 (41%), p = 0.252. Post hoc analysis showed a significant relationship between age and prevalence of incomplete circle of Willis, p = 0.003.ConclusionWe found no relationship between migraine without aura and incomplete circle of Willis.

Evidence of a Christmas spirit network in the brain: functional MRI study.

Objective To detect and localise the Christmas spirit in the human brain. Design Single blinded, cross cultural group study with functional magnetic resonance imaging (fMRI). Setting Functional imaging unit and department of clinical physiology, nuclear medicine and PET in Denmark. Participants 10 healthy people from the Copenhagen area who routinely celebrate Christmas and 10 healthy people living in the same area who have no Christmas traditions. Main outcome measures Brain activation unique to the group with Christmas traditions during visual stimulation with images with a Christmas theme. Methods Functional brain scans optimised for detection of the blood oxygen level dependent (BOLD) response were performed while participants viewed a series of images with Christmas themes interleaved with neutral images having similar characteristics but containing nothing that symbolises Christmas. After scanning, participants answered a questionnaire about their Christmas traditions and the associations they have with Christmas. Brain activation maps from scanning were analysed for Christmas related activation in the “Christmas” and “non-Christmas” groups individually. Subsequently, differences between the two groups were calculated to determine Christmas specific brain activation. Results Significant clusters of increased BOLD activation in the sensory motor cortex, the premotor and primary motor cortex, and the parietal lobule (inferior and superior) were found in scans of people who celebrate Christmas with positive associations compared with scans in a group having no Christmas traditions and neutral associations. These cerebral areas have been associated with spirituality, somatic senses, and recognition of facial emotion among many other functions. Conclusions There is a “Christmas spirit network” in the human brain comprising several cortical areas. This network had a significantly higher activation in a people who celebrate Christmas with positive associations as opposed to a people who have no Christmas traditions and neutral associations. Further research is necessary to understand this and other potential holiday circuits in the brain. Although merry and intriguing, these findings should be interpreted with caution.