Dataset Information

Migraine with aura in women is not associated with structural thalamic abnormalities.

ABSTRACT: Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data analysis methods. Both studies found differences of thalamic nuclei volumes between patients and healthy controls, but the results of the studies were not consistent. Here, we investigated whether migraine with aura is associated with changes in thalamic volume by analysing MRI data obtained from a large, cross-sectional population-based study which specifically included women with migraine with aura (N = 156), unrelated migraine-free matched controls (N = 126), and migraine aura-free co-twins (N = 29) identified from the Danish Twin Registry. We used two advanced, validated analysis methods to assess the volume of the thalamus and its nuclei; the MAGeT Brain Algorithm and a recently developed FreeSurfer-based method based on a probabilistic atlas of the thalamic nuclei combining ex vivo MRI and histology. These approaches were very similar to the methods used in each of the two previous studies. Between-group comparisons were corrected for potential effects of age, educational level, BMI, smoking, alcohol, and hypertension using a linear mixed model. Further, we used linear mixed models and visual inspection of data to assess relations between migraine aura frequency and thalamic nuclei volumes in patients. In addition, we performed paired t-tests to compare volumes of twin pairs (N = 29) discordant for migraine with aura. None of our analyses showed any between-group differences in volume of the thalamus or of individual thalamic nuclei. Our results indicate that the pathophysiology of migraine with aura does not involve alteration of thalamic volume.

SUBMITTER: Hougaard A

PROVIDER: S-EPMC7404547 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Migraine with aura in women is not associated with structural thalamic abnormalities.

Hougaard Anders A Nielsen Silas Haahr SH Gaist David D Puonti Oula O Garde Ellen E Reislev Nina Linde NL Iversen Pernille P Madsen Camilla Gøbel CG Blaabjerg Morten M Nielsen Helle Hvilsted HH Krøigård Thomas T Østergaard Kamilla K Kyvik Kirsten Ohm KO Madsen Kristoffer Hougaard KH Siebner Hartwig Roman HR Ashina Messoud M

NeuroImage. Clinical 20200725

Migraine with aura is a highly prevalent disorder involving transient neurological disturbances associated with migraine headache. While the pathophysiology is incompletely understood, findings from clinical and basic science studies indicate a potential key role of the thalamus in the mechanisms underlying migraine with and without aura. Two recent, clinic-based MRI studies investigated the volumes of individual thalamic nuclei in migraine patients with and without aura using two different data ...[more]

PMID: 32763831

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Project description:IntroductionIt is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AimUsing a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.MethodsGene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.ResultsWe found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.ConclusionsOur results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

Project description:ImportanceMigraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear.ObjectiveTo estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors.Design, setting, and participantsFemale health professionals in the US (the Women's Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018.ExposuresSelf-reported migraine with aura compared with migraine without aura or no migraine at baseline.Main outcomes and measuresThe primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort.ResultsThe study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes.Conclusions and relevanceIn this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.

Project description:IntroductionMigraine is a common neurological disorder with a higher prevalence occurring in women. Migraine without aura (MwoA) is the most common type of migraine. In recent years, the safety and effectiveness of acupuncture for migraines have been internationally recognised. Contralateral acupuncture (CAT) (Jùcì) is an ancient classic acupuncture technique from Huang Di Nei Jing that refers to the acupoints on the right side (healthy side) selected for diseases on the left (affected side) and vice versa. Some studies have shown that efficacy of CAT on the painful disorder is even better than ipsilateral acupuncture (IAT), but there remains a lack of high-quality evidence to support it.Methods and analysisThis is a single-centre, randomised and sham-controlled clinical trial in China with three parallel groups that aim to evaluate the efficacy of CAT in women with unilateral MwoA. 243 participants will be randomly divided into the experimental group (CAT group), control group 1 (IAT group) and control group 2 (sham acupuncture group) (1:1:1 allocation ratio). Each group will be given 30-minute treatment sessions, once every other day, approximately three times per week, for a total of 24 treatments and follow-up visits two times. The primary outcome is the changes in days of migraine attacks. The secondary outcomes are frequency of migraine attacks, intensity of migraine, migraine duration, the dose of intake of acute medication, the Migraine-Specific Quality of Life Questionnaire, the Migraine Disability Assessment Score, the Headache Impact Test-6 and the Pittsburgh Sleep Quality Index. The data will be collected at the baseline time (week 0), end of treatment (week 4-8) and the follow-up time (week 12-16). Adverse events will be collected and recorded during each treatment.Ethics and disseminationEthics approval was obtained from the Ethics Committee of the Sports Trauma Specialist Hospital of Yunnan Province (2021-01). All participants will provide written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal and presented at conferences.Trial registration numberChinese Clinical Trial Registration Center (ChiCTR2100051479).

Project description:Status epilepticus (SE) is a life-threatening emergency that can result in de novo development or worsening of epilepsy. We tested the hypothesis that the aberrant cortical output during neocortical focal status epilepticus (FSE) would induce structural and functional changes in the thalamus that might contribute to hyperexcitability in the thalamocortical circuit. We induced neocortical FSE by unilateral epidural application of convulsant drugs to the somatosensory cortex of anesthetized mice of both sexes. The resulting focal EEG ictal episodes were associated with behavioral seizures consisting of contralateral focal myoclonic activity and persisted for 2-3 h. Ten and 30 days later, brains were processed for either immunohistochemistry (IHC) or in vitro slice recordings. Sections from the center of the thalamic reticular nucleus (nRT, see methods), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM) from the ventrobasal nucleus (VB) were used to measure density of NeuN-immunoreactive neurons, GFAP-reactive astrocytes, and colocalized areas for VGLUT1 + PSD95- and VGLUT2 + PSD95-IR, presumptive excitatory synapses of cortical and thalamic origins. Whole-cell voltage-clamp recordings were used to measure spontaneous EPSC frequency in these nuclei. We found that the nRT showed no decrease in numbers of neurons or evidence of reactive astrogliosis. In contrast, there were increases in GFAP-IR and decreased neuronal counts of NeuN positive cells in VB. Dual IHC for VGLUT1-PSD95 and VGLUT2-PSD95 in VB showed increased numbers of excitatory synapses, likely of both thalamic and cortical origins. The frequency, but not the amplitude of sEPSCs was increased in nRT and VB neurons. SIGNIFICANCE STATEMENT: Previous reports have shown that prolonged neocortical seizures can induce injury to downstream targets that might contribute to long-term consequences of FSE. Effects of FSE in thalamic structures may disrupt normal thalamo-cortical network functions and contribute to behavioral abnormalities and post-SE epileptogenesis. Our results show that a single episode of focal neocortical SE in vivo has chronic consequences including cell loss in VB nuclei and increased excitatory connectivity in intra-thalamic and cortico-thalamic networks. Additional experiments will assess the functional consequences of these alterations and approaches to mitigate cell loss and alterations in synaptic connectivity.

Dataset Information

Migraine with aura in women is not associated with structural thalamic abnormalities.

Publications

Migraine with aura in women is not associated with structural thalamic abnormalities.

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