John-Anker Zwart

Epidemiology of headache in Europe

The present review of epidemiologic studies on migraine and headache in Europe is part of a larger initiative by the European Brain Council to estimate the costs incurred because of brain disorders. Summarizing the data on 1‐year prevalence, the proportion of adults in Europe reporting headache was 51%, migraine 14%, and ‘chronic headache’ (i.e. ≥15 days/month or ‘daily’) 4%. Generally, migraine, and to a lesser degree headache, are most prevalent during the most productive years of adulthood, from age 20 to 50 years. Several European studies document the negative influence of headache disorders on the quality of life, and health‐economic studies indicate that 15% of adults were absent from work during the last year because of headache. Very few studies have been performed in Eastern Europe, and there are also surprisingly little data on tension‐type headache from any country. Although the methodology and the quality of the published studies vary considerably, making direct comparisons between different countries difficult, the present review clearly demonstrates that headache disorders are extremely prevalent and have a vast impact on public health. The data collected should be used as arguments to increase resources to headache research and care for headache patients all over the continent.

Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10−9, odds ratio = 1.23, 95% CI 1.150–1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10−11 (odds ratio = 1.18, 95% CI 1.127–1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10−5, permuted threshold for genome-wide significance 7.7 × 10−5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

Genome-wide meta-analysis identifies new susceptibility loci for migraine

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 × 10−8). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

Genome-wide association analysis identifies susceptibility loci for migraine without aura

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10−5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10−4; combined P = 7.06 × 10−11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10−4; combined P = 1.17 × 10−9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10−8 and P = 0.02; combined P = 3.86 × 10−8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

The prevalence of migraine and tension-type headaches among adolescents in Norway. The Nord-Trøndelag Health Study (Head-HUNT-Youth), a large population-based epidemiological study

The aim of this study was to examine the prevalence of headache and primary headache disorders like migraine and tension-type headaches among adolescents, and to explore the differences in headache prevalence and frequency by gender and age. This cross-sectional study was conducted in Nord-Trøndelag county, Norway, during the years 1995-97. In total, 8984 (88%) out of 10 202 invited adolescents aged 12-19 years participated in the youth part of the Nord-Trøndelag Health Study [Helseundersøkelsen i Nord-Trøndelag (HUNT)]. The total study population in this study consisted of 8255 individuals after exclusion of invalid questionnaires and students outside the target range of 13-18 years of age. The students completed a comprehensive questionnaire, and one of the questions was whether the students had experienced any headaches during the last 12 months. In addition, 5847 of these students were also subject to an interview in which they were asked whether they had experienced recurring headaches during the last year and, if so, were they classified as migraine (MI), tension-type headache (TTH) or non-classifiable headache. In the total questionnaire-based population, 76.8% reported having had headaches during the last 12 months (69.4% boys and 84.2% girls). Among those who also were interviewed, 29.1% reported having recurrent headaches (21.0% boys and 36.5% girls). The overall 1-year prevalence of migraine was 7%, of tension-type headache 18%, and of non-classifiable headache 4.8%. Higher prevalence rates were found for girls in all age groups and for all headache categories. The overall frequency of recurrent headaches did not vary significantly with age, but girls had significantly more frequent headaches than boys. We concluded that headache in general, and recurrent primary headache disorders like migraine and tension-type headaches, are common somatic complaints among Norwegian adolescents, especially among girls.

Analgesic use: A predictor of chronic pain and medication overuse headache The Head–HUNT Study

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Analgesic overuse among subjects with headache, neck, and low-back pain

Objectives: To examine the prevalence of chronic headache (≥15 days/month) associated with analgesic overuse in relation to age and gender and the association between analgesic overuse and chronic pain (i.e., migraine, nonmigrainous headache, neck and low-back pain). Methods: In the Nord–Trøndelag Health Study 1995 to 1997 (HUNT-2), a total of 51,383 subjects responded to headache questions (Head-HUNT), of which 51,050 completed questions related to musculoskeletal symptoms and 49,064 questions regarding the use of analgesics. Results: The prevalence of chronic headache associated with analgesic use daily or almost daily for ≥1 month was 1% (1.3% for women and 0.7% for men) and for analgesic overuse duration of ≥3 months 0.9% (1.2% for women and 0.6% for men). Chronic headache was more than seven times more likely among those with analgesic overuse (≥1 month) than those without (odds ratio [OR] = 7.5, 95% CI: 6.6 to 8.5). Upon analysis of the different chronic pain subgroups separately, the association with analgesic overuse was strongest for chronic migraine (OR = 10.3, 95% CI: 8.1 to 13.0), intermediate for chronic nonmigrainous headache (OR = 6.2, 95% CI: 5.3 to 7.2), and weakest for chronic neck (OR = 2.6, 95% CI: 2.3 to 2.9) and chronic low-back (OR = 3.0, 95% CI: 2.7 to 3.3) pain. The association became stronger with increasing duration of analgesic use for all groups and was most evident among those with headache, especially those with migraine. Conclusions: Chronic headache associated with analgesic overuse is prevalent and especially chronic migraine is more strongly associated with frequent intake of analgesics than other common pain conditions like chronic neck and chronic low-back pain.

The impact of body mass index on the prevalence of low back pain: the HUNT study.

Study Design. A cross-sectional population-based study. Objective. To examine the association between body mass index and chronic low back pain, with adjustment for potential confounders. Summary of Background Data. Although many studies have investigated this association, it is still unclear whether there is a general relationship between body mass index and low back pain which applies to all populations. Methods. This study is based on data collected in the HUNT 2 study in the county of Nord-Trøndelag in Norway between 1995 and 1997. Among a total of 92,936 persons eligible for participation, 30,102 men and 33,866 women gave information on body mass index and indicated whether they suffered from chronic low back pain (69% participation rate). A total of 6293 men (20.9%) and 8923 women (26.3%) experienced chronic low back pain. Relations were assessed by logistic regression of low back pain with respect to body mass index and other variables. Results. In both sexes, a high body mass index was significantly associated with an increased prevalence of low back pain. In men the estimated OR per 5 kg/m2 increase in body mass index was 1.07 (95% CI: 1.03–1.12) and in women 1.17 (95% CI: 1.14–1.21), after adjustment for age, with a significantly stronger association in women. Additional adjustment for education, smoking status, leisure time physical activity, employment status, and activity at work hardly affected these associations. No interactions were found with most other factors. Conclusion. This large population-based study indicates that obesity is associated with a high prevalence of low back pain. Further studies are needed to determine if the association is causal.

Neck mobility in different headache disorders

The main purpose of this study was to assess neck mobility (by Cybex equipment) in different headache disordered and, in particular, cervicogenic headache, and to compare; these findings with those in controls. A total of 51 control subjects and 90 headache patients were investigated, whereof 28 patients suffered from common migraine (migraine without aura), 34 from tension‐type headache (H episodic and 25 chronic), and 28 patients from cervicogenic headache. One‐way ANOVA and post hoc Bonferroni analysis showed significant differences between those with cervicogenic headache and the other groups for rotation ( P <0.001) and flexion/extension ( P <0.001), but not for lateral neck movement ( P =NS). There were no significant differences between migraine patients, tension‐type headache patients, and controls. In all four groups, there was a significant positive correlation between active and passive neck movement for rotation ( P <0.001), flexion/extension ( P <0.001), and lateral neck movement ( P <0.001). Repeated measures analysis of variance (ANOVA) showed no significant day‐to‐day differences in 10 control subjects. In the control group (n=51), there was a significant negative correlation between age and neck movement. For rotation. Pearsons correlation coefficient was: r =‐0.71 ( P <0.001), for flexion/extension r =‐0.71 ( P <0.001), and for lateral neck movement r =‐0.67 ( P <0.001). No significant sex difference was found as for any of the neck movements. Pain at the time of investigation did not seem to influence neck mobility. Cervicogenic headache has been recognized as a pair syndrome by the International Association for the Study of Pain (IASP). Since reduced neck mobility is one of the major criteria for this diagnosis, it emphasizes the need for systematic, objective neck mobility measurements in the individual patient to substantiate the diagnosis. The technique is simple and proved reliable.

Headache prevalence related to smoking and alcohol use. The Head‐HUNT Study

The aim of this study was to examine a possible association between smoking, alcohol and headache in a large population‐based cross‐sectional study. A total of 51 383 subjects completed a headache questionnaire and constituted the ‘Head‐HUNT’ Study. Questionnaire‐based information on smoking was available in 95% and on alcohol in 89% of the individuals. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI). Prevalence rates for headache were higher amongst smokers compared with never smokers, most evident for those under 40 years smoking more than 10 cigarettes per day (OR 1.5, 95% CI 1.3–1.6). Passive smoking was also associated with higher headache prevalence. For alcohol use, there was a tendency of decreasing prevalence of migraine with increasing amounts of alcohol consumption compared with alcohol abstinence. Only with regard to symptoms indicating alcohol overuse, a positive association with frequent headache was found. The association between headache and smoking found in the present study raises questions about a causal relationship, e.g. that smoking causes headache or that it allays stress induced by headache. The observed negative association between migraine and alcohol consumption is probably explained by the headache precipitating properties of alcohol.