Browsing by Subject "Migraine"

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  • Pyykko, Ilmari; Manchaiah, Vinaya; Farkkila, Markus; Kentala, Erna; Zou, Jing (2019)
    Objective: The aim of the present study was to evaluate complaints in people with Meniere's disease (MD) with and without migraine and headache to study the association between MD and Vestibular Migraine (VM). We believe this will help us understand if these two disorders represent a disease continuum in that they may share a common aetiology. Methods: The study used a retrospective design and included data of 911 patients with MD from the Finnish Meniere Federation database. The study participants had a mean age of 60.2 years, mean duration of disease of 12.6 years, and 78.7% of the participants were females. The questionnaire data comprised of both disease specific and impact related questions. The data were analyzed using the Mann-Whitney U test, the Kruskal Wallis H test, logistic regression analyses, and decision tree analysis. Results: Migraine and headache was reported by 190 subjects (20.9%) and 391 subjects (42.9%) respectively. We found that patients that could be classified as VM in the study (i.e., those with frequent vertigo spells associated with migraine) more often reported complaints of severe MD symptoms, had reduced health-related quality of life, suffered more from anxiety, had more neurological complaints, and experienced a reduced sense of coherence than the non-migraneous patients with MD. However, neither the decision tree analysis nor the logistic regression analysis could reliably discriminate VM from MD patients. Conclusion: Our study results confirm that MD is frequently associated with headache and migraine. In addition, results also indicate that migraine provokes the severity of MD. We suggest that MD and VM may share similar pathophysiological mechanisms. Hence, the future MD classification systems should include a category referred to as 'MD with migraine' that will include patients with VM. (C) 2019 Elsevier B.V. All rights reserved.
  • Siewert, Katherine M.; Klarin, Derek; Damrauer, Scott M.; Chang, Kyong Mi; Tsao, Philip S.; Assimes, Themistocles L.; Smith, George Davey; Voight, Benjamin F.; Anttila, Verneri; Palta, Priit; Muona, Mikko; Kallela, Kaarlo Mikko; Koiranen, Markku; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Kurki, Mitja Ilari; Hämäläinen, Eija Inkeri; Eriksson, Johan G.; Salomaa, Veikko; Heikkilä, Kauko; Männikkö, Minna; Hiekkala, Marjo; Kajanne, Risto; Kaprio, Jaakko; Aromaa, Arpo J.; Raitakari, Olli; Järvelin, Marjo-Riitta; Wessman, Maija; Palotie, Aarno (2021)
    Background: Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods: To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results: We report multiple phenotypes with genetic correlation (P < 1.06 × 10-3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions: This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
  • Stevenson, Nathan J.; Vanhatalo, Sampsa (2018)
    Neonatal seizures are widely considered a neurological emergency with a need for prompt treatment, yet they are known to present a highly elusive target for bedside clinicians. Recent studies have suggested that the design of a neonatal seizure treatment trial will profoundly influence the sample size, which may readily increase to hundreds or even thousands as the achieved effect size diminishes to clinical irrelevance. The self-limiting and rapidly resolving nature of neonatal seizures diminishes the measurable treatment effect every hour after seizure onset and any effect may potentially be confused with spontaneous resolution, precluding the value of many observational studies. The large individual variability in seizure occurrence over time and between etiologies challenges group comparisons, while the absence of clinical signs mandates quantification of seizure occurrence with continuous multi-channel EEG monitoring. A biologically sound approach that views neonatal seizures as a functional cot-side biomarker rather than an object to treat can overcome these challenges. (C) 2018 Elsevier Ltd. All rights reserved.
  • Zhao, Huiying; Eising, Else; de Vries, Boukje; Vijfhuizen, Lisanne S.; Anttila, Verneri; Winsvold, Bendik S.; Kurth, Tobias; Stefansson, Hreinn; Kallela, Kaarlo Mikko; Malik, Rainer; Stam, Anine H.; Ikram, M. Arfan; Ligthart, Lannie; Freilinger, Tobias; Alexander, Michael; Mueller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Aromas, Arpo; Eriksson, Johan G.; Boomsma, Dorret I.; van Duijn, Cornelia M.; Zwart, John-Anker; Quaye, Lydia; Kubisch, Christian; Dichgans, Martin; Wessman, Maija; Stefansson, Kari; Chasman, Daniel I.; Palotie, Aarno; Martin, Nicholas G.; Montgomery, Grant W.; Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.; Nyholt, Dale R.; Int Headache Genetics Consortium (2016)
    Introduction It 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. Aim Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods Gene-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. Results We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (p(gene-based)0.05) in the MA subgroup, 107 also produced p(gene-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) (p(binomial-test) = 1.5x10(-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 259bp 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. Conclusions Our 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.
  • Jacobsen, Kaya K.; Nievergelt, Caroline M.; Zayats, Tetyana; Greenwood, Tiffany A.; Anttila, Verneri; Akiskal, Hagop S.; Haavik, Jan; Fasmer, Ole Bernt; Kelsoe, John R.; Johansson, Stefan; Oedegaard, Ketil J.; BiGs Consortium IHG Consortium; Liu, Chengyu; Wedenoja, Juho Olavi; Kaunisto, Mari Anneli; Heikkilä, Kauko Veli; Kaprio, Jaakko Arthur; Wessman, Maija; Kallela, Mikko; Färkkilä, Markus; Artto, Ville; Eriksson, Johan; Palotie, Aarno Veikko; Daly, Mark (2015)
  • Chaudhry, Shafqat R.; Lendvai, Ilana S.; Muhammad, Sajjad; Westhofen, Philipp; Kruppenbacher, Johannes; Scheef, Lukas; Boecker, Henning; Scheele, Dirk; Hurlemann, Rene; Kinfe, Thomas M. (2019)
    Objective: To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs. Methods: This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls. Results: No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1 beta was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p <0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-alpha (TNF-alpha), leptin, adiponectin, ghrelin remained unchanged [p > 0.05]. No severe device-/stimulation-related adverse events occurred. Conclusion: 2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1 beta plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-alpha, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. (C) 2019 Elsevier Inc. All rights reserved.
  • Eising, Else; de Leeuw, Christiaan; Min, Josine L.; Anttila, Verneri; Verheijen, Mark H. G.; Terwindt, Gisela M.; Dichgans, Martin; Freilinger, Tobias; Kubisch, Christian; Ferrari, Michel D.; Smit, August B.; de Vries, Boukje; Palotie, Aarno; van den Maagdenberg, Arn M. J. M.; Posthuma, Danielle; Int Headache Genetics Consortium (2016)
    Background Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.
  • IHGC; Häppölä, Paavo; Gormley, Padhraig; Nuottamo, Marjo E.; Artto, Ville; Sumelahti, Marja-Liisa; Nissilä, Markku; Keski-Santti, Petra; Ilmavirta, Matti; Kaunisto, Mari A.; Hämäläinen, Eija I.; Ripatti, Samuli; Pirinen, Matti; Wessman, Maija; Palotie, Aarno; Kallela, Mikko (2022)
    Background Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. Methods We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. Results Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02-0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08-0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14-0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26-0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31-0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. Conclusions The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.
  • Bostroem, Azize; Scheele, Dirk; Stoffel-Wagner, Birgit; Hönig, Frigga; Chaudhry, Shafqat R.; Muhammad, Sajjad; Hurlemann, Rene; Krauss, Joachim K.; Lendvai, Ilana S.; Chakravarthy, Krishnan V.; Kinfe, Thomas M. (2019)
    BackgroundRising evidence indicate that oxytocin and IL-1 impact trigemino-nociceptive signaling. Current perspectives on migraine physiopathology emphasize a cytokine bias towards a pro-inflammatory status. The anti-nociceptive impact of oxytocin has been reported in preclinical and human trials. Cervical non-invasive vagus nerve stimulation (nVNS) emerges as an add-on treatment for the preventive and abortive use in migraine. Less is known about its potential to modulate saliva inflammatory signaling in migraine patients. The rationale was to perform inter-ictal saliva measures of oxytocin and IL-1 ss along with headache assessment in migraine patients with 10weeks adjunctive nVNS compared to healthy controls.Methods12 migraineurs and 12 suitably matched healthy control were studied with inter-ictal saliva assay of pro- and anti-neuroinflammatory cytokines using enzyme-linked immuno assay techniques along with assessment of headache severity/frequency and associated functional capacity at baseline and after 10weeks adjunctive cervical nVNS.ResultsnVNS significantly reduced headache severity (VAS), frequency (headache days and total number of attacks) and significantly improved sleep quality compared to baseline (p
  • de Vries, Boukje; Anttila, Verneri; Freilinger, Tobias; Wessman, Maija; Kaunisto, Mari A.; Kallela, Kaarlo Mikko; Artto, Ville; Vijfhuizen, Lisanne S.; Goebel, Hartmut; Dichgans, Martin; Kubisch, Christian; Ferrari, Michel D.; Palotie, Aarno; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.; Int Headache Genetics Consortium (2016)
    BackgroundBefore the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set. MethodsWe selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls. ResultsNone of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately. ConclusionThe available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine.
  • Fuglsang, Cecilia H.; Johansen, Troels; Kaila, Kai; Kasch, Helge; Bach, Flemming W. (2018)
    Background Impaired brain oxygen delivery can trigger and exacerbate migraine attacks. Normoxic hypercapnia increases brain oxygen delivery markedly by vasodilation of the cerebral vasculature, and hypercapnia has been shown to abort migraine attacks. Stable normoxic hypercapnia can be induced by a compact partial rebreathing device. This pilot study aimed to provide initial data on the device's efficacy and safety. Methods Using a double-blinded, randomized, cross-over study design, adult migraine-with-aura patients self-administered the partial rebreathing device or a sham device for 20 minutes at the onset of aura symptoms. Results Eleven participants (mean age 35.5, three men) self-treated 41 migraine attacks (20 with the partial rebreathing device, 21 with sham). The partial rebreathing device increased mean End Tidal CO2 by 24%, while retaining mean oxygen saturation above 97%. The primary end point (headache intensity difference between first aura symptoms and two hours after treatment (0-3 scale) - active/sham difference) did not reach statistical significance (-0.55 (95% CI: -1.13-0.04), p=0.096), whereas the difference in percentage of attacks with pain relief at two hours was significant (p=0.043), as was user satisfaction (p=0.022). A marked efficacy increase was seen from first to second time use of the partial rebreathing device. No adverse events occurred, and side effects were absent or mild. Conclusion Normoxic hypercapnia shows promise as an adjunctive/alternative migraine treatment, meriting further investigation in a larger population. Clinical study registered at with identifier NCT03472417