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1.  The relationship between headache and religious attendance (the Nord-Trøndelag health study- HUNT) 
Background
Religious belief can be used as a pain coping strategy. Our purpose was to evaluate the relationship between headache and religious activity using prospective data from a large population-based study.
Methods
This longitudinal cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Survey (HUNT 2 and 3) performed in 1995–1997; and 2006–2008. Among the 51,383 participants aged ≥ 20 years who answered headache questions at baseline, 41,766 were eligible approximately 11 years later. Of these, 25,177 (60%) completed the question in HUNT 3 regarding religious activity. Frequent religious attendees (fRA) (used as a marker of stronger religious belief than average) were defined as those who had been to church/prayer house at least once monthly during the last six months.
Results
In the multivariate analyses, adjusting for known potential confounders, individuals with headache 1–14 days/month in HUNT 2 were more likely to be fRA 11 years later than headache-free individuals. Migraine at baseline predisposed more strongly to fRA at follow-up (OR = 1.25; 95% CI 1.19-1.40) than did non-migrainous headache (OR = 1.13; 95% 1.04-1.23). The odds of being fRA was 48% increased (OR 1.48; 95% 1.19-1.83) among those with migraine 7–14 days/month at baseline compared to subjects without headache. In contrast, headache status at baseline did not influence the odds of being frequent visitors of concerts, cinema and/or theatre at follow-up 11 years later.
Conclusions
In this prospective study, headache, in particular migraine, at baseline slightly increased the odds of being fRA 11 years later.
doi:10.1186/1129-2377-15-1
PMCID: PMC3880847  PMID: 24386923
Epidemiology; Religion; Spirituality; Headache; Migraine
2.  Acknowledgements to referees 2013 
Contributing reviewers
The quality of The Journal of Headache and Pain depends on the qualified and regular collaboration of renowned scientists, who devoted their time to constructively review the submitted articles.
We are indebted to the following experts who reviewed papers that completed the peer-reviewing process within 2013.
doi:10.1186/1129-2377-15-4
PMCID: PMC3904204  PMID: 24472416
3.  Gender differences of cognitive function in migraine patients: evidence from event-related potentials using the oddball paradigm 
Background
Migraine shows gender-specific incidence and has a higher prevalence in females. Gender plays an important role in the prevalence of migraine, but few studies have investigated the effect of gender on the cognitive functions of migraine patients. This study investigated gender differences in the cognitive function of migraine patients without aura.
Methods
We recruited 29 migraine patients (15 females; mean age 25.4 y) during the interictal period and 28 healthy age-matched participants (14 females; mean age 24.8 y). We used an auditory oddball paradigm to analyze target processing using event-related potentials.
Results
We investigated the N2 and P3 components. The P3 amplitude was decreased in patients compared with the control, and this reduction was not modulated by gender. These results of the P3 provided a new evidence for the dysfunction of cognitive function in migraine patients. The N2 amplitude was larger for male than female migraine patients, and this gender effect was not found in the control group.
Conclusions
These results of the P3 provided a new evidence for the dysfunction of cognitive function in migraine patients. And those of N2 may explain that male patients have the super-sensitivity of cerebral function relevant to the early target-selection and response preparation. Our findings emphasize the importance of considering gender when researching the cognitive function of migraine patients.
doi:10.1186/1129-2377-15-6
PMCID: PMC3904684  PMID: 24467625
Migraine; ERPs; P3; N2; Gender difference
5.  Diagnosis, prevalence estimation and burden measurement in population surveys of headache: presenting the HARDSHIP questionnaire 
The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. The Global Campaign against Headache is undertaking initiatives to improve and standardize methods in use for cross-sectional studies. One requirement is for a survey instrument with proven cross-cultural validity. This report describes the development of such an instrument. Two of the authors developed the initial version, which was used with adaptations in population-based studies in China, Ethiopia, India, Nepal, Pakistan, Russia, Saudi Arabia, Zambia and 10 countries in the European Union. The resultant evolution of this instrument was reviewed by an expert consensus group drawn from all world regions. The final output was the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, designed for application by trained lay interviewers. HARDSHIP is a modular instrument incorporating demographic enquiry, diagnostic questions based on ICHD-3 beta criteria, and enquiries into each of the following as components of headache-attributed burden: symptom burden; health-care utilization; disability and productive time losses; impact on education, career and earnings; perception of control; interictal burden; overall individual burden; effects on relationships and family dynamics; effects on others, including household partner and children; quality of life; wellbeing; obesity as a comorbidity. HARDSHIP already has demonstrated validity and acceptability in multiple languages and cultures. Modules may be included or not, and others (eg, on additional comorbidities) added, according to the purpose of the study and resources (especially time) available.
doi:10.1186/1129-2377-15-3
PMCID: PMC3906903  PMID: 24400999
Epidemiology; Burden of headache; Methodology; Diagnostic instrument; Global Campaign against Headache
6.  The methodology of population surveys of headache prevalence, burden and cost: Principles and recommendations from the Global Campaign against Headache 
The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. Among the initiatives of the Global Campaign against Headache to improve and standardize methods in use for cross-sectional studies, the most important is the production of consensus-based methodological guidelines. This report describes the development of detailed principles and recommendations. For this purpose we brought together an expert consensus group to include experience and competence in headache epidemiology and/or epidemiology in general and drawn from all six WHO world regions. The recommendations presented are for anyone, of whatever background, with interests in designing, performing, understanding or assessing studies that measure or describe the burden of headache in populations. While aimed principally at researchers whose main interests are in the field of headache, they should also be useful, at least in parts, to those who are expert in public health or epidemiology and wish to extend their interest into the field of headache disorders. Most of all, these recommendations seek to encourage collaborations between specialists in headache disorders and epidemiologists. The focus is on migraine, tension-type headache and medication-overuse headache, but they are not intended to be exclusive to these. The burdens arising from secondary headaches are, in the majority of cases, more correctly attributed to the underlying disorders. Nevertheless, the principles outlined here are relevant for epidemiological studies on secondary headaches, provided that adequate definitions can be not only given but also applied in questionnaires or other survey instruments.
doi:10.1186/1129-2377-15-5
PMCID: PMC3907133  PMID: 24467862
Burden of headache; Epidemiology; Guidelines; Methodology; Global Campaign against Headache
7.  Release of CGRP from mouse brainstem slices indicates central inhibitory effect of triptans and kynurenate 
Background
CGRP is contained in a substantial proportion of unmyelinated trigeminal neurons innervating intracranial tissues. Previously, we have described a hemisected rodent scull preparation and later the intact trigeminal ganglion to measure stimulated CGRP release from trigeminal afferents.
Methods
Here, we establish a preparation for examining CGRP release from central trigeminal terminals using single fresh slices of the mouse medullary brainstem.
Results
Basal and stimulated amount of CGRP substantially exceeded the detection level. Experiments were designed as matched pairs of at least six brainstem slices per animal. Stimulation with high potassium induced calcium-dependent and reversible CGRP release. Capsaicin stimulation of TRPV1 provoked concentration-dependent CGRP release. The anti-migraine drug naratriptan did not inhibit capsaicin-induced CGRP release from peripheral terminals but inhibited the release from brainstem slices. The glutamate antagonist kynurenate showed a similar pattern of site-specific inhibition of CGRP release.
Conclusions
As observed earlier for other drugs used in the treatment of migraine this indicates that the central terminals in the spinal trigeminal nucleus may be the main site of action. The preparation allows evaluating the trigeminal brainstem as a pharmacological site of action.
doi:10.1186/1129-2377-15-7
PMCID: PMC3922191  PMID: 24506953
Headache; Migraine; Neuropeptide; Nociception; 5-HT receptor
8.  Hemicrania continua: towards a new classification? 
Hemicrania continua (HC) was described and coined in 1984 by Sjaastad and Spierings. Later cases, carrying this appellation, should conform to the original description. The proposed classification criteria (ICHD 3rd edition beta version) for HC focus e.g. on localized, autonomic and “vascular” features. Such features do, however, not belong to the core symptomatology of HC and should accordingly be removed. The genuine, original HC will then re-appear.The headache that the new criteria refer to, has in an unfair and unjustified manner been given the designation HC. A revision of the proposed criteria seems mandatory.
doi:10.1186/1129-2377-15-8
PMCID: PMC3936800  PMID: 24524413
Hemicrania continua; Headache classification
9.  Should we educate about the risks of medication overuse headache? 
Background
Medication-overuse headache (MOH) is caused by the regular use of medications to treat headache. There has been a lack of research into awareness of MOH. We distributed an electronic survey to undergraduate students and their contacts via social networking sites. Analgesic use, awareness of MOH, perceived change in behaviour following educational intervention about the risks of MOH and preferred terminology for MOH was evaluated.
Findings
485 respondents completed the questionnaire (41% having received healthcare training). 77% were unaware of the possibility of MOH resulting from regular analgesic use for headache. Following education about MOH, 80% stated they would reduce analgesic consumption or seek medical advice. 83% indicated that over the counter analgesia should carry a warning of MOH. The preferred terminology for MOH was painkiller-induced headache.
Conclusions
This study highlights the lack of awareness of MOH. Improved education about MOH and informative packaging of analgesics, highlighting the risks in preferred lay terminology (i.e. painkiller-induced headache), may reduce this iatrogenic morbidity and warrants further evaluation.
doi:10.1186/1129-2377-15-10
PMCID: PMC3942071  PMID: 24524380
Medication-overuse headache; Analgesia; Headache; Prevention; Education
10.  Short lasting activity-related headaches with sudden onset in children: a case-based reasoning on classification and diagnosis 
Background
Short lasting headaches related to activity or cough are rare, particularly in childhood, and can be difficult to diagnose, especially in young children who are not able to describe their symptoms. In the literature there are few data on this topic in adults and the paediatric cases reported are even more rare.
Findings
We present the clinical history of a 7-year-old child and a 3-year-old child both diagnosed as having activity-related headaches, characterized by sudden onset of short lasting (few seconds) attacks, that were triggered by cough or exercise. There were no accompanying symptoms and the neurological examination was normal in both cases. Brain magnetic resonance imaging showed, in the first case, a cerebellar pilocytic astrocytoma and, in the second case, a Chiari 1 malformation. Both cases received an early diagnosis, were surgically treated and had a good prognosis at follow-up.
Conclusions
When headache has a recent onset, it presents suddenly, and it is triggered by strain, even with normal neurological examination, neuroimaging is mandatory in order to exclude secondary headaches, especially in children.
doi:10.1186/1129-2377-14-3
PMCID: PMC3606961  PMID: 23565626
Children; Cough headache; Exertional headache; Secondary headaches; Chiari 1 malformation
11.  Headache and mechanical sensitization of human pericranial muscles after repeated intake of monosodium glutamate (MSG) 
Background
A single intake of monosodium glutamate (MSG) may cause headache and increased muscle sensitivity. We conducted a double-blinded, placebo-controlled, crossover study to examine the effect of repeated MSG intake on spontaneous pain, mechanical sensitivity of masticatory muscles, side effects, and blood pressure.
Methods
Fourteen healthy subjects participated in 5 daily sessions for one week of MSG intake (150 mg/kg) or placebo (24 mg/kg NaCl) (randomized, double-blinded). Spontaneous pain, pressure pain thresholds and tolerance levels for the masseter and temporalis muscles, side effects, and blood pressure were evaluated before and 15, 30, and 50 min after MSG intake. Whole saliva samples were taken before and 30 min after MSG intake to assess glutamate concentrations.
Results
Headache occurred in 8/14 subjects during MSG and 2/14 during placebo (P = 0.041). Salivary glutamate concentrations on Day 5 were elevated significantly (P < 0.05). Pressure pain thresholds in masseter muscle were reduced by MSG on Day 2 and 5 (P < 0.05). Blood pressure was significantly elevated after MSG (P < 0.040).
Conclusion
In conclusion, MSG induced mechanical sensitization in masseter muscle and adverse effects such as headache and short-lasting blood pressure elevation for which tolerance did not develop over 5 days of MSG intake.
doi:10.1186/1129-2377-14-2
PMCID: PMC3606962  PMID: 23565943
Monosodium glutamate; Craniofacial sensitivity; Pain; Accumulation; Headache
12.  Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache 
Background
Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls).
Methods
In the present work we employed specialized proteomic techniques, namely two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS), and the innovative Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS), to discover characteristic proteomic profiles associated with MOH condition.
Results
By 2-DE and MS analysis we identified 21 over-excreted proteins in MOH patients, particularly in NSAIDs abusers, and the majority of these proteins were involved in a variety of renal impairments, as resulted from a literature search. Urine protein profiles generated by SELDI-TOF-MS analysis showed different spectra among groups. Moreover, significantly higher number of total protein spots and protein peaks were detected in NSAIDs and mixtures abusers.
Conclusions
These findings confirm the presence of alterations in proteins excretion in MOH patients. Analysis of urinary proteins by powerful proteomic technologies could lead to the discovery of early candidate biomarkers, that might allow to identify MOH patients prone to develop potential drug overuse-induced nephrotoxicity.
doi:10.1186/1129-2377-14-6
PMCID: PMC3606963  PMID: 23565828
Medication-overuse headache; Proteomics; NSAIDs; Nephrotoxicity; SELDI-TOF-MS; Two-dimensional gel electrophoresis
13.  Prevalence of medication overuse headache in an interdisciplinary pain clinic 
Background
Medication overuse headache (MOH) has been recognized as an important problem in headache patients although the pathophysiological mechanisms remain unclear. The diagnosis of MOH is based on clinical characteristics defined by the International Headache Society. The aim was the evaluation of the diagnostic criteria of MOH in a mixed population of chronic pain patients to gain information about the prevalence and possible associations with MOH.
Methods
Data of all patients referred to the interdisciplinary pain clinic at the University Hospital of Zurich between September 2005 and December 2007 were retrospectively analyzed. Demographic data (age, sex, history of migration), as well as data about duration of pain disease, category of pain disease (neurological, psychiatric, rheumatologic, other), use of medication, history of trauma, and comorbidity of depression and anxiety have been collected.
Results
Totally 178 of 187 consecutive chronic pain patients were included in the study. A total of 138 patients (78%) used analgesics on 15 or more days per month. Chronic headache was more prevalent among patients with analgesic overuse (39.8%) than without analgesic overuse (18%). The prevalence of MOH was 29%. The odds ratio (OR) for a patient with medication overuse to have chronic headache was 13.1 if he had a history of primary headache, compared to a patient without a primary headache syndrome. Furthermore, history of headache (OR 2.5, CI [1.13;5.44]), history of migration (OR 2.9, CI [1.31;6.32]) and comorbid depression (OR 3.5, CI [1.46;8.52]) were associated with overuse of acute medication, in general.
Conclusions
Primary headaches have a high risk for chronification in patients overusing analgesics for other pain disorders. Whereas history of headache, history of migration and comorbidity of depression are independentely associated with analgesic overuse in this group of patients.
doi:10.1186/1129-2377-14-4
PMCID: PMC3606964  PMID: 23565761
Medication overuse; Headache; Interdisciplinary pain management; Chronic pain
14.  Management of secondary chronic headache in the general population: the Akershus study of chronic headache 
Background
The prevalence of secondary chronic headache in our population is 0.5%. Data is sparse on these types of headache and information about utilisation of health care and medication is missing. Our aim was to evaluate utility of health service services and medication use in secondary chronic headache in the general population.
Methods
An age and gender stratified cross-sectional epidemiological survey included 30,000 persons 30–44 years old. Diagnoses were interview-based. The International Classification of Headache Disorders 2nd ed. was applied along with supplementary definitions for chronic rhinosinusitis and cervicogenic headache. Secondary chronic headache exclusively due to medication overuse was excluded.
Results
One hundred and thirteen participants had secondary chronic headache. Thirty % had never consulted a physician, 70% had consulted their GP, 35% had consulted a neurologist and 5% had been hospitalised due to their secondary chronic headache. Co-occurrence of migraine or medication overuse increased the physician contact. Acute headache medication was taken by 84% and 11% used prophylactic medication. Complementary and alternative medicine was used by 73% with the higher frequency among those with than without physician contact.
Conclusion
The pattern of health care utilisation indicates that there is room for improving management of secondary chronic headache.
doi:10.1186/1129-2377-14-5
PMCID: PMC3606965  PMID: 23565808
Secondary chronic headache; Chronic migraine; Medication-overuse headache; Health care utilisation; General population
15.  Migraine: the seventh disabler 
doi:10.1186/1129-2377-14-1
PMCID: PMC3606966  PMID: 23566305
16.  Clinical profile of cluster headaches in China – a clinic-based study 
Background
The clinical profile of cluster headache in Chinese patients have not been fully studied.
Methods
The classification and clinical features of 120 consecutive patients with cluster headache (105 males, 15 females; mean age, 34.9 ± 10.5 years) visiting at International Headache Center from May 2010 to August 2012 were analyzed.
Results
Patients came from 16 different regions of China. Mean age at onset of cluster headache was 26.7 ± 10.9 years. Only 13 patients (10.8%) had previously been diagnosed with cluster headache. Mean time to diagnosis from first symptoms was 8.2 ± 7.1 years (range, 0–35 years). Chronic cluster headache was observed in only 9 patients (7.5%). The most commonly reported location of cluster headache was temporal region (75.0%), followed by retro-orbital region (68.3%), forehead (32.5%), vertex (32.5%) and occipital (22.5%). Lacrimation was the most consistently reported autonomic feature (72.5%). During acute attacks, 60.0% of patients experienced nausea, and 41.7% experienced photophobia and 40.8% experienced phonophobia. In addition, 38.3% reported restless behavior and 45.8% reported that physical activity exacerbated the pain. None of patients experienced visual or other kinds of aura symptoms before cluster attacks. We found that 38.3% of patients had <1 cluster period and 35.8% for 1–2 cluster periods per year with these periods occurring less frequently during the summer than during other seasons. Cluster duration was 1–2 months in 32.5% of patients. During cluster periods, 73.3% of patients had 1–2 attacks per day, and 39.2% experienced cluster attacks ranging in duration from 1 h to less than 2 h. The duration of attacks were 1.5 (1–2.25) hours for males and 1.5 (1-3) for females respectively. The World Health Organization quality of life-8 questionnaire showed that cluster headache reduced life quality.
Conclusions
Compared to Western patients, Chinese patients showed a relatively low prevalence of chronic cluster headaches, pain sites mainly focused on areas distributed by the first division of the trigeminal nerve, a low frequency of restlessness and absent aura. These clinical features may be more common in Eastern populations, including mainland Chinese, Japanese and Taiwanese patients, than in Western patients.
doi:10.1186/1129-2377-14-27
PMCID: PMC3620490  PMID: 23574884
Cluster headache; Chinese; Features; Sense of restlessness
18.  Peripheral endothelial function and arterial stiffness in patients with chronic migraine: a case–control study 
Background
Migraine is a complex and disabilitating neurovascular disorder predominantly affecting women. There is strong evidence that nitric oxide is critically involved in migraine pathophysiology. The aim of the present study was to test the hypothesis that chronic migraine is associated with ultrasonographic endothelial dysfunction and increase in arterial stiffness. These parameters were assessed using a novel plethysmograph by peripheral arterial tonometry.
Methods
Twenty-one patients with chronic migraine and twenty-one healthy controls matched by sex and gender were recruited. Measurement of the ultrasonographic endothelial function and augmentation index were made according to manufacturer’s protocol.
Results
The mean of patient’s peripheral arterial tonometry ratios was 1.93 ± 0.39 and for healthy control 2.21 ± 0.44 (p = 0.040). The median of patients’ augmentation index was −6,0 (IQR: 6.5 to −15) in healthy controls and 9.0 (IQR: 4 to 12) in chronic migraine, (p = 0.002).
Conclusions
Patients with chronic migraine have ultrasonographic endothelial dysfunction and increase in the arterial stiffness. An improved understanding of the role in the endothelial system of migraine may provide a basis for preventive drugs in migraine and restore the endothelial function.
doi:10.1186/1129-2377-14-8
PMCID: PMC3619990  PMID: 23565915
Chronic migraine; Endothelial dysfunction; Case control study; EndoPAT device arterial stiffness
19.  Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): a prospective, randomized, open-label trial 
Background
The aim of this study was to compare the effectiveness of an educational strategy (advice to withdraw the overused medication/s) with that of two structured pharmacological detoxification programmes in patients with complicated medication overuse headache (MOH) plus migraine.
Methods
One hundred and thirty-seven complicated MOH patients participated in the study. MOH was defined as complicated in patients presenting at least one of the following: a) a diagnosis of co-existent and complicating medical illnesses; b) a current diagnosis of mood disorder, anxiety disorder, eating disorder, or substance addiction disorder; c) relapse after previous detoxification treatment; d) social and environmental problems; e) daily use of multiple doses of symptomatic medications. Group A (46 patients) received only intensive advice to withdraw the overused medication/s. Group B (46 patients) underwent a standard detoxification programme as outpatients (advice + steroids + preventive treatment). Group C (45 patients) underwent a standard inpatient withdrawal programme (advice + steroids + fluid replacement and antiemetics preventive treatment). Withdrawal therapy was considered successful if, after two months, the patient had reverted to an intake of NSAIDs lower than 15 days/month or to an intake of other symptomatic medication/s lower than 10 days/month.
Results
Twenty-two patients failed to attend follow-up visits (11 in Group A, 9 in Group B, 2 in Group C, p < 0.03). Overall, we detoxified 70% of the whole cohort, 60.1% of the patients in Group A and in Group B, and 88.8% of those in Group C (p < 0.01).
Conclusions
Inpatient withdrawal is significantly more effective than advice alone or an outpatient strategy in complicated MOH patients.
doi:10.1186/1129-2377-14-10
PMCID: PMC3620000  PMID: 23565591
Medication overuse headache; Management; Migraine; Treatment
20.  Triptans in prevention of menstrual migraine: a systematic review with meta-analysis 
Randomized clinical trials (RCT) assessing the efficacy and tolerability of triptans compared with placebo as short-term prophylaxis of menstrual migraine (MM) were systematically reviewed in this study. Triptans, which interfere with the pathogenesis of migraine and are effective in relieving associated neurovegetative symptoms, have been extensively proposed for prevention of menstrual migraine attacks. We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized, double-blind, placebo-controlled trials on triptans for MM until 1 Oct, 2012. A total of six RCTs were identified. Two authors independently assessed trial’s quality and extracted data. Numbers of participants free from MM per perimenstrual period (PMP), requiring rescue medication, suffering from headache-associated symptoms and experiencing adverse events in treatment and control groups were used to calculate relative risk (RR) and number needed to treat (NNT) with their corresponding 95% confidence interval (CI). A total of 633 participants received frovatriptan 2.5 mg QD, 584 received frovatriptan 2.5 mg BID, 392 received naratriptan 1 mg BID, 70 received naratriptan 2.5 mg BID, 80 received zolmitriptan 2.5 mg BID, 83 received zolmitriptan 2.5 mg TID and 1104 received placebo. Overall, triptans is an effective, short-term, prophylactic treatment of choice for MM. Considering MM frequency, severity and adverse events, frovatriptan 2.5 mg BID and zolmitriptan 2.5 mg TID tend to be the preferred regimens.
doi:10.1186/1129-2377-14-7
PMCID: PMC3620011  PMID: 23565873
Meta-analysis; Systematic review; Frovatriptan; Naratriptan; Zolmitriptan; Menstruation; Migraine; Prophylaxis
21.  New insights into the cardiovascular risk of migraine and the role of white matter hyperintensities: is gold all that glitters? 
The role of migraine as an independent risk factor for cardiovascular events has been debated for several years, while it is more established for ischemic stroke. Recently, new studies have examined the likelihood of migraine to determine cardiovascular events, supporting the hypothesis of a predominant role in patients with migraine with aura, the risk including both sexes. In the literature, multiple pathophysiological mechanisms are described to explain this association, and are here discussed. Furthermore, the emerging evidence that a higher headache frequency and long-term migraine may worsen the cardio-metabolic profile in migraineurs (e.g. with a higher Framingham risk score and risk of developing atherosclerosis, insulin resistance and metabolic syndrome) makes it increasingly necessary to reduce the number and severity of attacks, not only to alleviate the painful symptoms, but also to improve the prognosis in these patients.
doi:10.1186/1129-2377-14-9
PMCID: PMC3620371  PMID: 23565964
Migraine; Cardiovascular events; Risk factors
22.  The cross- ethnic variations in the prevalence of headache and other somatic complaints among adolescents in Northern Israel 
Background
Headache is the most common cause for chronic or recurrent pain in childhood and adolescence. Chronic pain may have a long-term effect on adolescents. It might contribute to functional limitations, such as poor school attendance, and it may adversely affect development of healthy social relationships. The aim of our study was to examine the cross- ethnic variation in the prevalence of headache in a non- clinical sample of adolescents in Northern Israel and to learn about its association to other somatic complaints.
Methods
A self-administered, anonymous questionnaire was presented to 2,088 tenth grade students attending 19 high-schools in Northern Israel (all the public high schools within two districts). Participants were Jews and Arabs, the latter including Muslim, Christians, and Druze, aged 15 to 16. Parental and student consent was obtained from all participants. The study was approved by the IRB of our institution.
Results
All 2088 questionnaires were returned although only 2019 were usable and analyzed. Arab adolescents comprised 55% (1117) of the analyzed sample and Jews 45% (902), 56% of participants were girls. Of the Arab participants, 18.6% reported having frequent headaches (girls 25.3%, boys 9.1%, P<0.0001) much less than their Jewish peers (P<0.0001) among whom 27.9% reported having frequent headaches (girls 35.6%, boys 19% P<0.0001). Other somatic complaints such as abdominal pain, palpitations, disordered sleep and fatigue were more frequent in adolescents (Jews and Arabs, girls and boys) who suffered from headaches than in their peers who did not report having headaches (P<0.0001), the same pattern observed in the Jewish and the Arab group.
Conclusions
Headache is a frequent complaint among adolescents in Northern Israel. Jewish adolescents reported having headaches more frequently than their Arab peers. Those who suffered from frequent headaches also reported having significantly more other somatic complaints than adolescents without headaches. Girls had more somatic complaints then boys in the two ethnic groups.
doi:10.1186/1129-2377-14-21
PMCID: PMC3620373  PMID: 23566020
Headache; Somatic complains; Adolescents; Ethnicity
23.  Prevalence and burden of primary headache disorders among a local community in Addis Ababa, Ethiopia 
Background
Headache disorders are the most common complaints worldwide. Migraine, tension type and cluster headaches account for majority of primary headaches and improvise a substantial burden on the individual, family or society at large. There is a scanty data on the prevalence of primary headaches in sub-Saharan Africa in general and Ethiopia in particular. Moreover there is no population based urban study in Ethiopia. The purpose of this study is to determine the prevalence and burden of primary headaches in local community in Addis Ababa, Ethiopia.
Methods
Cross-sectional sample survey was carried out in Addis Ketema sub city, Kebele 16/17/18 (local smallest administrative unit). Using systematic random sampling, data were collected by previously used headache questionnaire, over a period of 20 days.
Results
The study subjects were 231 of which 51.5% were males and 48.5% were females. The overall one year prevalence of primary headache disorders was 21.6% and that for migraine was 10%, migraine without aura 6.5% migraine with aura was 2.6% and probable migraine was 0.9%. The prevalence of tension type of headache was found to be 10.4%, frequent episodic tension type headache was 8.2% followed by infrequent tension type headache of 2.2%. The prevalence of cluster headache was 1.3%. The burden of primary headache disorders in terms of missing working, school or social activities was 68.0%. This was 78.3% for migraineurs and 66.7% for tension type headache. Majority 92.0% of primary headache cases were not using health services and 66.0% did not use any drug or medications during the acute attacks and none were using preventive therapy.
Conclusion
Prevalence and burden of primary headache disorders was substantial in this community. Health service utilization of the community for headache treatment was poor.
doi:10.1186/1129-2377-14-30
PMCID: PMC3620379  PMID: 23574933
Prevalence; Primary headaches; Burden; Addis Ababa; Ethiopia
24.  Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study 
Background
Our aim was to compare subjective and objective sleep quality and arousal in migraine and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls, interictal, preictal and postictal migraine.
Methods
Polysomnography and PT (to pressure, heat and cold) measurements were done in 34 healthy controls and 50 migraineurs. Subjective sleep quality was assessed by sleep diaries, Epworth sleepiness scale, Karolinska sleep questionnaire and Pittsburgh sleep quality index. Migraineurs who had their sleep registration more than 48 h from an attack were classified as interictal while those who were less than 48 h from an attack were classified as either preictal or postictal.
Results
Migraineurs reported more insomnia and other sleep-related symptoms than controls, but the objective sleep differences were smaller and we found no differences in daytime sleepiness. Interictal migraineurs had more awakenings (p=0.048), a strong tendency for more slow-wave sleep (p=0.050), lower thermal pain thresholds (TPT) (heat pain thresholds p=0.043 and cold pain thresholds p=0.031) than controls. Migraineurs in the preictal phase had shorter latency to sleep onset than controls (p=0.003). Slow-wave sleep correlated negatively with pressure PT and slow bursts correlated negatively with TPT.
Conclusion
Lower PT in interictal migraineurs seems related to increased sleep pressure. We hypothesize that migraineurs on the average suffer from a relative sleep deprivation and need more sleep than healthy controls. Lack of adequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.
doi:10.1186/1129-2377-14-12
PMCID: PMC3620398  PMID: 23565669
Migraine phase; Sleep; Arousal; Pain thresholds
25.  HURT (Headache Under-Response to Treatment) questionnaire in the management of primary headache disorders: reliability, validity and clinical utility of the Arabic version 
Background
To support better headache management in primary care, the Global Campaign against Headache developed an 8-question outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire. HURT was designed by an expert consensus group with patient-input. It assesses the need for and response to treatment, and provides guidance on actions to optimize therapy. It has proven content validity.
We aim to evaluate the Arabic version of HURT for clinical utility in primary care in Saudi Arabia.
Methods
HURT was translated according to the Global Campaign’s translation protocol. We assessed test-retest reliability in consecutive patients of four primary-care centres, who completed HURT at two visits 4-6 weeks apart while receiving usual care. We then provided training in headache management to the GPs practising in these centres, which were randomized in pairs to control (standard care) or intervention (care guided by implementation of HURT). We assessed responsiveness of HURT to clinical change by comparing base-line responses to HURT questions 1-6 with those at follow up. We assessed clinical utility by comparing outcomes between control and intervention pairs after 3 months, using locally-developed 5-point verbal-rating scales: the patient-satisfaction scale (PSS) and doctor-satisfaction scale (DSS).
Results
For test-retest reliability in 40 patients, intra-class correlation coefficients were 0.66-0.78 for questions 1-4 and 0.90-0.93 for questions 5-7 (all P ≤ 0.001). For the dichotomous response to question 8, Kappa coefficient = 1 (P < 0.0001). Internal consistency was good (Cronbach’s alpha = 0.74). In 342 patients, HURT signalled clinical improvement over 3 months through statistically significant changes in responses to questions 1-6. PSS scores were higher among those in whom HURT recorded improvement, and also higher among those with less severe headache at baseline. Patients treated with guidance from HURT (n = 207) were more satisfied than controls (n = 135), but this did not quite reach statistical significance (P = 0.06).
Conclusion
The Arabic HURT Questionnaire is reliable and responsive to clinical change in Arabic-speaking headache patients in primary care. HURT showed clinical utility in this first assessment, conducted in parallel with studies elsewhere in other languages, but this needs further study. Other Arabic instruments are not available as standards for comparison.
doi:10.1186/1129-2377-14-16
PMCID: PMC3620405  PMID: 23565801
Headache; Management; HURT questionnaire; Primary care; Reliability; Validation; Global campaign against headache

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