After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Migraine is a debilitating neurological disorder affecting around 1 in 7 people worldwide, but its molecular mechanisms remain poorly understood. Some debate exists over whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we performed the largest genetic study of migraine to date, comprising 59,674 cases and 316,078 controls from 22 GWA studies. We identified 44 independent single nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that map to 38 distinct genomic loci, including 28 loci not previously reported and the first locus identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants for this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch patients and 4,580 population-matched controls. We selected SNPs from 12 loci with two or more SNPs with P-values < 1 × 10 −5 for follow-up in 2,508 patients and 2,652 controls. Two loci, i.e. 1q22 (MEF2D) and 3p24 (near TGFBR2) replicated convincingly (P = 4.9 × 10 −4 , P = 1.0 × 10 −4 , respectively). Meta-analysis of the discovery and replication data yielded two additional genome-wide significant (P < 5 × 10 −8 ) loci in PHACTR1 and ASTN2. In addition, SNPs in two previously reported migraine loci in or near TRPM8 and LRP1 significantly replicated. This study reveals the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. Main textMigraine is a disabling episodic neurovascular brain disorder affecting 12% of the general population [1][2][3][4] . Migraine attacks are typically characterized by severe throbbing unilateral headache and nausea, vomiting and photo-and phonophobia (migraine without aura; MO). In up to one third of patients attacks may be associated with neurological aura symptoms (migraine with aura; MA). Previous genome-wide association studies (GWAS) identified a migraine susceptibility locus on chromosome 8q22, close to MTDH, in the clinic-based International Headache Genetics Consortium (IHGC) MA study 5 and three other loci in or near PRDM16, LRP1, and TRPM8 in the population-based migraine Women's Genome Health Study (WGHS) 6 . For TRPM8 there was suggestive association (P < 1 × 10 −5 ) also in the clinic-based IHGC MA GWAS 5 . Here we report the first GWAS in MO, the most common form of migraine. We analyzed two large samples from headache centres in Germany and the Netherlands including 2,326 MO patients and 4,580 population-matched controls (Supplementary Note and Supplementary Fig. 1). A quantile-quantile plot of the joint analysis ( Supplementary Fig. 2) and an overall inflation factor ( 1000) of 1.03 were used as final quality control measures. The discovery dataset identified one genome-wide significant (P < 5 × 10 −8 ) locus on chromosome 1q22 as well as eleven additional loci containing multiple SNPs with suggestive association (P < 1 × 10 −5 ) (Supplementary Table 1). Eighteen SNPs from these 12 loci were taken forward to the replication stage in four Fig. 1 and Supplementary Table 1). Eight SNPs in six loci showed P-values < 0.05 in the replication study, and five of these SNPs also showed P-values < 5 × 10 −8 in the meta-analysis combining the discovery and replication cohorts (Table 1, Fig. 1 and Supplementary Fig. 3). Four loci (1q22, 3p24, 6p24, 9q33) replicated, although replication was less convincing for loci on 6p24 and 9q33 with replication P-values of 0.012 and 0.018, respectively, although P-values were < 5 × ...

This study presents the first account of the prevalence of headache syndromes, defined according to the International Headache Society criteria, in a large representative sample of the German population; 5000 persons representative of the total population were selected from 30,000 households. Subjects were requested to answer a questionnaire about headache occurrence during their lifetime. The completion rate was 81.2%. Seventy-one point four percent (n = 2902) reported a history of headache. Twenty-seven point five percent fulfilled the criteria for migraine. Thirty-eight point three percent (n = 1557) met the criteria for tension-type headache and 5.6% (n = 229) did not fulfil criteria for either migraine or tension-type headache. Significant correlations were found between the prevalence of the different headache syndromes and sociodemographic variables such as sex, age and place of residence. The prevalence of headache did not exhibit any significant differences between the various länder (states or regions) of Germany. When extrapolated to the total population these results reveal that 54 million people in Germany suffer from headache at least occasionally or persistently. These findings suggest that the magnitude of the neurological disorders, migraine and tension-type headache, is seriously underestimated and thus constitutes a major contemporary health problem.

The headache associated with medication overuse is variable and often has a peculiar pattern with characteristics shifting, even within the same day, from migraine-like to those of tension-type headache.