Lars Jacob Stovner

Epidemiology and comorbidity of headache

The burden associated with headache is a major public health problem, the true magnitude of which has not been fully acknowledged until now. Globally, the percentage of the adult population with an active headache disorder is 47% for headache in general, 10% for migraine, 38% for tension-type headache, and 3% for chronic headache that lasts for more than 15 days per month. The large costs of headache to society, which are mostly indirect through loss of work time, have been reported. On the individual level, headaches cause disability, suffering, and loss of quality of life that is on a par with other chronic disorders. Most of the burden of headache is carried by a minority who have substantial and complicating comorbidities. Renewed recognition of the burden of headache and increased scientific interest have led to a better understanding of the risk factors and greater insight into the pathogenic mechanisms, which might lead to improved prevention strategies and the early identification of patients who are at risk.

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.

Global prevalence of chronic migraine: A systematic review

The aim of this review was to summarize population-based studies reporting prevalence and/or incidence of chronic migraine (CM) and to explore variation across studies. A systematic literature search was conducted. Relevant data were abstracted and estimates were subdivided based on the criteria used in each study. Sixteen publications representing 12 studies were accepted. None presented data on CM incidence. The prevalence of CM was 0–5.1%, with estimates typically in the range of 1.4–2.2%. Seven studies used Silberstein–Lipton criteria (or equivalent), with prevalence ranging from 0.9% to 5.1%. Three estimates used migraine that occurred ≥ 15 days per month, with prevalence ranging from 0 to 0.7%. Prevalence varied by World Health Organization region and gender. This review identified population-based studies of CM prevalence, although heterogeneity across studies and lack of data from certain regions leaves an incomplete picture. Future studies on CM would benefit from an International Classification of Headache Disorders consensus diagnosis that is clinically appropriate and operational in epidemiological studies.

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.

Depression and anxiety disorders associated with headache frequency. The Nord-Trøndelag Health Study.

The aim of this large cross‐sectional population‐based study was to examine the association between migraine, non‐migrainous headache and headache frequency with depression, and anxiety disorders. From 1995 to 1997, all 92 566 inhabitants aged 20 years and above in Nord‐Trøndelag County in Norway were invited to participate in the Nord‐Trøndelag Health Study (‘Helseundersøkelsen i Nord‐Trøndelag’ = HUNT‐2). A total of 64 560 participated, whereof 51 383 subjects (80%) completed a headache questionnaire that was included. Of these 51 383 individuals, 47 257 (92%) completed the depression subscale items and 43 478 (85%), the anxiety subscale items of the Hospital Anxiety and Depression Scale (HADS). Associations were assessed in multivariate analyses, estimating prevalence odds ratios (OR) with 95% confidence intervals (CI). Depression and anxiety disorders as measured by HADS, were significantly associated with migraine (OR = 2.7, 95% CI 2.3–3.2; OR = 3.2, 95% CI 2.8–3.6) and non‐migrainous headache (OR = 2.2, 95% CI 2.0–2.5; OR = 2.7, 95% CI 2.4–3.0) when compared with headache‐free individuals. The association was stronger for anxiety disorders than for depression. The ORs for depression and anxiety disorders amongst both migraine and non‐migrainous sufferers increased with increasing headache frequency. Depression and anxiety disorders are associated with both migraine and non‐migrainous headache, and this association seems more dependent on headache frequency than diagnostic category.

The cost of headache disorders in Europe: the Eurolight project.

Background and purpose:  Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe.

Prevalence of migraine and non‐migrainous headache—head‐HUNT, a large population‐based study

The objective of this study was to estimate the 1-year prevalence of the following categories of headache; migraine, non-migrainous headache, frequent headache (> 6 days/month), and chronic headache (> 14 days/month). Between 1995 and 1997, all 92 566 inhabitants 20 years and older in Nord-Trøndelag county in Norway were invited to a comprehensive health study. Out of 64 560 participants, a total of 51 383 subjects (80%) completed a headache questionnaire. The overall age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men). The prevalence of migraine was 12% (16% in women and 8% in men), and for non-migrainous headache 26% (30% in women and 22% in men). For frequent headache (> 6 days per month) and for chronic headache (> 14 days per month), the prevalence was 8% and 2%, respectively. Women had a higher prevalence than men in all age groups and for all headache categories. Prevalence peaked in the fourth decade of life for both men and women, except for ‘frequent non-migrainous headache’, which was nearly constant across all age groups in both genders. In accordance with findings in other western countries, we found that headache suffering, including migraine, was highly prevalent, especially in younger women.

Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study

Abstract Objective: To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine. Design: Double blind, placebo controlled, crossover study. Setting: Neurological outpatient clinic. Participants: Sixty patients aged 19-59 years with migraine with two to six episodes a month. Interventions: Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for one week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a two week wash out period. Second treatment period of one placebo tablet once daily for one week and then two placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril. Main outcome measures: Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment. Results: In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment versus placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment versus placebo. Intention to treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points. Conclusion: The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine.

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.

Posterior cranial fossa dimensions in the Chiari I malformation: relation to pathogenesis and clinical presentation.

SummarySkull dimensions were measured on lateral skull radiographs in 33 adult patients with MRI-verified Chiari I malformations and in 40 controls. The posterior cranial fossa was significantly smaller and shallower in patients than in controls. In the patients, there was a positive correlation between posterior fossa size and the degree of the cerebellar ectopia, which might indicate that a posterior cranial fossa which was originally too small had been expanded by the herniation of hindbrain structures at an early stage. Pyramidal signs and cerebellar symptoms and signs, which may be due to compression of neural structures, were associated with a large degree of ectopia and a relatively large posterior cranial fossa. Syringomyelia and headache, which may be due to the valve action of the herniated cerebellar tissue, were not associated with a particularly large posterior fossa or herniation. No special clinical presentation was associated with a very small posterior cranial fossa, which may indicate that a small posterior cranial fossa per se has little or no clinical significance, although it may be the primary developmental anomaly.