Sleep quality, arousal and pain thresholds in tension-type headache: a blinded controlled polysomnographic study.

INTRODUCTION: We aimed to compare subjective and objective sleep quality in tension-type headache (TTH) patients and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls and TTH patients. METHODS: A blinded cross-sectional study where polysomnography (PSG) and PT (to pressure, heat and cold) measurements were done in 20 patients with TTH (eight episodic (ETTH) and twelve chronic (CTTH) TTH) and 29 healthy controls. Sleep diaries and questionnaires were applied. RESULTS: TTH patients had more anxiety ( P = 0.001), insomnia ( P < 0.0005), daytime tiredness ( P < 0.0005) and reduced subjective sleep quality ( P < 0.0005) compared to healthy controls. Sleep diaries revealed more long awakenings in TTH ( P = 0.01) but no total sleep-time differences. TTH patients had more slow-wave sleep ( P = 0.002) and less fast arousals ( P = 0.004) in their PSGs. CTTH subjects had lower pressure PT ( P = 0.048) and more daytime sleepiness than the controls ( P = 0.039). Among TTH lower cold PT (CPT) correlated inversely with light sleep (N1) ( R = -0.49, P = 0.003) while slow arousals correlated inversely with headache-frequency ( R = -0.64, P = 0.003). CONCLUSIONS: We hypothesize that TTH patients need more sleep than healthy controls and might be relatively sleep deprived. Inadequate sleep may also contribute to increased pain sensitivity and headache frequency in TTH.

No increase in headache after previous intracranial infections: a historical cohort study (HUNT).

BACKGROUND AND PURPOSE: Despite the absence of robust scientific evidence, it is today generally accepted that the acute headache typical for intracranial infections can develop into permanent headache complaints. This widespread concept was explored in the first, large, longitudinal, population-based study. METHODS: Data on confirmed exposure to intracranial infections amongst all adult inhabitants in a geographical area during a 20-year period were assembled from hospital records. Surviving individuals were later invited to the third Nord-Trøndelag Health Survey (HUNT 3), where 39,690 (42%) of 94,194 invited inhabitants aged ≥20 years responded to a validated headache questionnaire. Using logistic regression, the 1-year prevalence of headache and its subtypes according to the diagnostic criteria of the International Headache Society was assessed and compared between those with and without previous confirmed intracranial infection. Age and sex were used as covariates. RESULTS: Overall, 43 participants were identified with earlier intracranial infection, whereof three had more than one infection: bacterial meningitis (n=19), lymphocytic meningitis (n=18), encephalitis (n=9), and brain abscess (n=1).The mean interval from infection to participation in HUNT 3 was 11.2 (range 1.5-19.7) years. There was no significant increase in the prevalence of headache (OR 1.10, 95% CI 0.58-2.07), its subtypes (migraine, or tension-type headache), or chronic daily headache (OR 1.85, 95% CI 0.45-7.68) amongst participants with previous intracranial infection compared with the surrounding population. CONCLUSIONS: This study challenges the existence of chronic post-bacterial meningitis headache and does not indicate the presence of other long-term headaches induced by intracranial infection.

The bidirectional relationship between headache and chronic musculoskeletal complaints: an 11-year follow-up in the Nord-Trøndelag Health Study (HUNT).

BACKGROUND AND PURPOSE: Chronic daily headache (CDH) and chronic musculoskeletal complaints (CMSCs) are associated disorders, but whether there is a causal relationship between them is unclear. OBJECTIVE: To determine whether CMSCs are associated with the subsequent development of CDH and vice versa. METHODS: This longitudinal population-based cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Study (HUNT 2 and 3) performed in 1995-1997 and 2006-2008. Amongst the 51 383 participants aged ≥ 20 years at baseline, 41 766 were eligible approximately 11 years later. Of these, 26 197 (63%) completed the questions regarding headache and CMSCs in HUNT 3. RESULTS: A bidirectional relationship was found between headache and CMSCs. In the multivariate analyses adjusting for known potential confounders, a nearly two fold risk (OR 1.8; 95% CI 1.5-2.3) for developing CDH was found for those with CMSCs at baseline. Vice versa, a similarly elevated risk of CMSCs (OR 1.8; 95% CI 1.2-2.6), and even higher risk of chronic widespread MSCs (OR 2.7; 95% CI 1.6-4.7), was found at follow-up amongst those with CDH at baseline. CONCLUSION: CMSCs predispose to CDH and CDH predisposes to CMSCs 11 years later. This may have relevance to understanding the pathophysiology of these disorders. CMSCs should be treated not only to relieve them but also to prevent the development of CDH, and vice versa.

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. METHODS: From November 2008 to August 2009, a cross-sectional survey was conducted in eight countries representing 55% of the adult EU population. Participation rates varied between 11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using bottom-up methodology, we estimated direct (medications, outpatient health care, hospitalization and investigations) and indirect (work absenteeism and reduced productivity at work) annual per-person costs. Prevalence data, simultaneously collected and, for migraine, also derived from a systematic review, were used to impute national costs. RESULTS: Mean per-person annual costs were €1222 for migraine (95% CI 1055-1389; indirect costs 93%), €303 for tension-type headache (TTH, 95% CI 230-376; indirect costs 92%), €3561 for medication-overuse headache (MOH, 95% CI 2487-4635; indirect costs 92%), and €253 for other headaches (95% CI 99-407; indirect costs 82%). In the EU, the total annual cost of headache amongst adults aged 18-65 years was calculated, according to our prevalence estimates, at €173 billion, apportioned to migraine (€111 billion; 64%), TTH (€21 billion; 12%), MOH (€37 billion; 21%) and other headaches (€3 billion; 2%). Using the 15% systematic review prevalence of migraine, calculated costs were somewhat lower (migraine €50 billion, all headache €112 billion annually). CONCLUSIONS: Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

[Doubtful nosological validity of the chronic whiplash syndrome]. / Fragliche nosologische Validität des chronischen Halswirbelschleudertraumasyndroms.

BACKGROUND: Since the 1980s, victims of traffic accidents in western countries increasingly report chronic symptoms which they attribute to a whiplash injury of the cervical spine. In an extensive review article published in 1996, it was, however, concluded that this so-called chronic whiplash syndrome has little nosological validity. It was now investigated whether this conclusion could be upheld by the results of later published studies. METHODS: Extensive evaluation was carried out of all the whiplash literature listed in Pubmed since 1996 with the question whether research over the last 15 years has achieved a better validation of this syndrome. RESULTS: Of the over 1,600 publications about whiplash since 1996, no study could be identified which confirmed the nosological validity of the chronic whiplash syndrome. CONCLUSION: As a positive consequence of the results of this study, accident victims suffering whiplash can be informed about the very good prognosis after whiplash in a more trustworthy way. Many iatrogenic injuries can thus be avoided. The expert opinion after whiplash without radiologically documented and/or neurologically confirmed significant acute traumatic injury which can cause chronic symptoms, should generally not be in favor of insurance benefits. The authors propose that all of a set of minimal criteria should be fulfilled if in exceptional cases a probable relationship between the trauma and chronic symptoms can be assumed.

Increased headache prevalence in female adolescents and adult women with early menarche. The Head-HUNT Studies.

BACKGROUND: Age at menarche is associated with cardiovascular events and lifestyle factors such as body mass index (BMI), certain women's diseases like breast cancer and endometriosis and with occurrence of certain physical symptoms during puberty. It is unclear whether age at menarche is an independent determinant of headache. OBJECTIVES: The aim of the study was to explore age of menarche in relation to headache prevalence in a large population-based study of both adolescents and adult women (HUNT). METHODS: In the Nord-Trøndelag Health Study in Norway 1995-97 (HUNT 2), a total of 26,636 (57%) of 46,506 invited women responded to questions regarding menarche and headache (Head-HUNT). In the youth part of HUNT 2, 3196 female students were interviewed about their headache complaints and 2766 (87%) responded to questions regarding menarche. All the final analyses were adjusted for age, use of oral contraceptives and BMI, and for adults also for educational level. RESULTS: Headache was more prevalent amongst females with menarche ≤ 12 years, both amongst adolescents (OR=1.3, 95% CI=1.1-1.5) and adults (OR=1.1, 95% CI=1.1-1.2), evident for migraine and non-migrainous headache. CONCLUSION: Headache, both migraine and non-migrainous headache, was more prevalent amongst both adolescents and adult females with early menarche. Early menarche may increase headache susceptibility, or be a consequence of a common pathogenetic factor, e.g., sensitivity to estrogens.

Headache, migraine and cardiovascular risk factors: the HUNT study.

BACKGROUND: Migraine with aura (MA) has been found to be a risk factor for cardiovascular disease including ischaemic stroke and myocardial infarction. Studies have also reported a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting as to whether this is restricted to MA or also holds true for migraine without aura (MO). This study aims to examine the relation between headache and cardiovascular risk factors in a large cross-sectional population-based study. METHODS: A total of 48,713 subjects (age ≥ 20 years) completed a headache questionnaire and were classified according to the headache status in the Nord-Trøndelag Health Study in Norway 1995-1997 (HUNT 2). Framingham 10-year risk for myocardial infarction and coronary death could be calculated for 44,098 (90.5%) of these. Parameters measured were blood pressure, body mass index, serum total and high-density lipoprotein cholesterol. RESULTS: Compared to controls, Framingham risk score was elevated in non-migraine headache sufferers (OR 1.17, 95% CI 1.10-1.26), migraineurs without aura (OR 1.17, 95% CI 1.04-1.32) and most pronounced amongst migraineurs with aura (OR 1.54, 95% CI 1.21-1.95). Framingham risk score consistently increased with headache frequency. For non-migrainous headache and MO, the increased risk was accounted for by the lifestyle factors smoking, high BMI and low physical activity, whilst such factors did not explain the elevated risk associated with MA. CONCLUSIONS: Both MA, MO and non-migrainous headache are associated with an unfavourable cardiovascular risk profile, but different mechanisms seem to underlie the elevated risk in MA than in the other headache types.

The Eurolight project: the impact of primary headache disorders in Europe. Description of methods.

The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients' organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients' organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe.

Prevalence of cluster headache in the Republic of Georgia: results of a population-based study and methodological considerations.

We present a study of the general-population prevalence of cluster headache in the Republic of Georgia and discuss the advantages and challenges of different methodological approaches. In a community-based survey, specially trained medical residents visited 500 adjacent households in the capital city, Tbilisi, and 300 households in the eastern rural area of Kakheti. They interviewed all (n = 1145) biologically unrelated adult occupants using a previously validated questionnaire. The household responses rates were 92% in Tbilisi and 100% in Kakheti. The survey identified 32 persons with possible cluster headache, who were then personally interviewed by one of two headache-experienced neurologists. Cluster headache was confirmed in one subject. The prevalence of cluster headache was therefore estimated to be 87/100,000 (95% confidence interval < 258/100,000). We used a conservative approach, which has an obvious advantage of high-quality data collection, but is very demanding of manpower and time.

Cerebrospinal fluid cytokine levels in migraine, tension-type headache and cervicogenic headache.

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1beta, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines [IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-beta1 (TGF-beta1)] were included. There were significant group differences in IL-1ra, TGF-beta1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-beta1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.

Management of medication overuse headache: 1-year randomized multicentre open-label trial.

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month x headache intensity x headache hours) at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had > or = 50% reduction in monthly headache days compared with 25% in the withdrawal group (P = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).

Headache after concussion.

BACKGROUND AND PURPOSE: Chronic post-traumatic headache attributed to mild head injury is a somewhat disputed headache diagnosis. A main object of this study was to assess the validity of this diagnosis by studying the headache pattern of concussed patients that participated in one historic (n = 131) and one prospective cohort (n = 217) study. METHODS: Head injury patients were recruited from two hospitals in Kaunas, Lithuania. Controls were recruited amongst patients with minor orthopaedic traumas not involving the head and neck. RESULTS: When data from the two studies were pooled, no difference in any headache category (diagnosis, attack frequency, symptoms) was found one or more years after the trauma, except that photophobia was somewhat more prevalent amongst the concussed patients. In both injury groups, the existence of pre-traumatic headache was a predictor of post-traumatic headache, although pre-traumatic headache seems to have been underreported amongst the concussed patients. There was a significant negative correlation between the duration of unconsciousness and the headache. CONCLUSIONS: This negative correlation, and the lack of specificity indicates that headache occurring 3 months or more after concussion is not caused by the head or brain injury. Rather it may represent an episode of one of the primary headaches, possibly induced by the stress of the situation.

Increased baroreflex sensitivity and heart rate variability in migraine patients.

OBJECTIVES: We investigated whether spontaneous baroreflex sensitivity and heart rate variability (HRV) are different in migraine patients compared to healthy controls. MATERIAL AND METHODS: Sixteen female migraine patients without aura aged 18-30 years and 14 age-matched healthy female controls were included. Continuous finger blood pressure and ECG were measured supine during paced breathing in the laboratory. Continuous finger blood pressure was measured the following 24-h period. Spontaneous baroreflex sensitivity (time-domain cross correlation baroreflex sensitivity) as well as HRV parameters were calculated. RESULTS: Spontaneous baroreflex sensitivity measured in the 24-h period was increased in patients (20.6 ms/mmHg) compared to controls (15.7 ms/mmHg, P = 0.031). HRV parameters were increased during paced breathing in patients (P < 0.045). CONCLUSIONS: The results suggest that central hypersensitivity in migraine also includes cardiovascular reactivity and may be important for the understanding of the mechanisms for the effect of antihypertensive drugs for migraine prophylaxis.

Nocebo as headache trigger: evidence from a sham-controlled provocation study with RF fields.

BACKGROUND: A large proportion of the population in Norway has experienced headache in connection with mobile phone use, but several double-blind provocation studies with radiofrequency (RF) and sham exposures have shown no relation between headache and mobile phone RF fields. AIMS: To investigate the type and location of headache experienced by participants in one provocation study in order to gain insight into possible causes and mechanisms of the headaches. METHOD: Questionnaire about headache, indication on figure of location of headache after exposure, interview with neurologist about headache features to make headache diagnoses. RESULTS: The 17 participants went through 130 trials (sham or RF exposure). No significant difference existed in headache type, laterality or location between the headaches experienced with the two exposures types. In most participants, the headache was compatible with tension-type headache. DISCUSSION: As participants experienced their typical 'mobile phone headache' both with and without RF exposure, and since the experiment did not involve the stress or the arm/head position of mobile phone use, the most likely explanation is that the headache in this situation is caused by negative expectations (nocebo). CONCLUSION: This and other similar studies indicate that headache occurring in connection with mobile phone use is not related to RF fields, and that a nocebo effect is important for this and possibly other headache triggers.

Whiplash headache is transitory worsening of a pre-existing primary headache.

Acute and chronic whiplash headache are new diagnostic entities in the ICHD-2 (5.3, 5.4). In a prospective cohort study, 210 rear-end collision victims were identified consecutively from police records and asked about head and neck pain in questionnaires after 2 weeks, 3 months and 1 year. The results were compared with those of matched controls who were also followed for 1 year. Of 210 accident victims, 75 developed headache within 7 days. Of these, 37 had also neck pain and complied with the criteria for acute whiplash headache. These 37 had the same headache diagnoses, headache features, accompanying symptoms and long-term prognosis as the 38 without initial neck pain who therefore did not comply with the acute whiplash headache diagnosis. Previous headache was a major risk factor for headache both in the acute and chronic stage. Compared with the non-traumatized controls, headache in the whiplash group had the same prevalence, the same diagnoses and characteristic features, and the same prognosis. Both acute and chronic whiplash headache lack specificity compared with the headache in a control group, and have the same long-term prognosis, indicating that such headaches are primary headaches, probably elicited by the stress of the situation.

Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study.

Associations between headache, including migraine, and gastrointestinal (GI) symptoms were studied in a large questionnaire-based cross-sectional study (the Head-HUNT Study). The headache questionnaire was completed by 43,782 individuals, who answered all the questions concerning nausea, reflux symptoms, diarrhoea and constipation. In the multivariate analyses, adjusting for age, sex, educational level, medication use, depression and anxiety, a higher prevalence of headache was found in individuals with much reflux [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.2, 2.6], diarrhoea (OR 2.4, 95% CI 2.1, 2.8), constipation (OR 2.1, 95% CI 1.9, 2.4) and nausea (OR 3.2, 95% CI 2.6, 3.8) compared with those without such complaints. All the GI symptoms investigated seemed to be approximately as common among persons with non-migrainous headache as among migraine sufferers, but the association between headache and GI complaints increased markedly with increasing headache frequency. This may suggest that headache sufferers generally are predisposed to GI complaints.

Thermal pain thresholds are decreased in the migraine preattack phase.

BACKGROUND AND PURPOSE: Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls. METHODS: A thermode was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup of 11 migraine patients had been tested within 24 h before their next attack and in the interictal phase. RESULTS: In the preattack phase, HPT was lower compared with the paired interictal recording for the hand (44.8 degrees C vs. 45.9 degrees C, P = 0.009), neck (46.8 degrees C vs. 48.2 degrees C, P = 0.02), and forehead (45.1 degrees C vs. 46.3 degrees C, P = 0.02). Neck and hand CPT were higher in the preattack phase than interictally (10 degrees C vs. 7.3 degrees C, P = 0.01 and 11.6 degrees C vs. 9.4 degrees C, P = 0.06, respectively). Preattack forehead changes were most apparent on the headache side of the subsequent attack. DISCUSSION: Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack.

Headache prevalence related to diabetes mellitus. The Head-HUNT study.

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.