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1.  Comparison of oxidative stress among migraineurs, tension-type headache subjects, and a control group 
Background:
A primary headache, particularly migraine, is associated with oxidative stress during the attack. However, data regarding the interictal state in migraineurs and in those with tension-type headache (TTH) is limited.
Objectives:
(1) To assess the oxidative stress in migraineurs and TTH subjects in between the episodes and (2) to see if there is a difference in the degree of oxidative stress in the different subtypes of migraine and TTH.
Materials and Methods:
Fifty migraineurs, 50 patients with TTH, and 50 control subjects were included in this study after screening for the exclusion criteria. Diagnosis of headache was made according to the International Classification of Headache Disorders (ICHD)-2 criteria. A venous blood sample was collected from the antecubital vein at least 3 days after the last attack of headache. The sample was centrifuged immediately and the plasma was stored at –70°C. The ferric reducing activity of plasma (FRAP) and the malondialdehyde (MDA) levels were assessed using colorimetric methods. Statistical analysis was done with the help of SPSS for Windows, v 11.0. One way ANOVA with post hoc Tukey test, independent sample t test, univariate regression, and multivariate regression analysis were done as indicated.
Results:
Migraineurs had higher values of MDA and FRAP than the subjects in the other two groups (P<0.001). No difference was observed between the TTH group and the control group. FRAP levels were significantly higher in subjects who had mixed migraine (migraine with aura and without aura) as compared to those with only migraine without aura (mean difference 196.1; 95% CI = 27.3 to 364.9; P = 0.01). Similarly, oxidative stress was significantly higher in patients with episodic TTH as compared to those with chronic TTH (FRAP t = 3.16; P = 0.003 and MDA t = 2.75; P = 0.008).
Conclusions:
This study suggests that oxidative stress continues even between headache episodes in migraineurs but not in those with TTH. This could probably be consequent to the different pathophysiological mechanisms of TTH and migraine.
doi:10.4103/0972-2327.56316
PMCID: PMC2824933  PMID: 20174497
Migraine; tension type headache; oxidative stress; ferric reducing activity of plasma; malondialdehyde
2.  Field testing the alternative criteria for tension-type headache proposed in the third beta edition of the international classification of headache disorders: results from the Korean headache-sleep study 
Background
According to the third beta edition of the International Classification of Headache Disorder (ICHD-3 beta), the diagnostic criteria for tension-type headache (TTH) might lead to the inclusion of individuals with headaches showing migrainous features. To better define TTH, the alternative diagnostic criteria were proposed in the appendix of ICHD-3 beta. This study attempted to test the alternative criteria for diagnosis of TTH proposed in ICHD-3 beta in a population-based sample from Korea.
Methods
We selected participants from the Korean population aged 19–69 years using stratified random sampling and evaluated them by interview using a questionnaire designed to identify headache type, headache characteristics, and psychiatric comorbidities.
Results
Of the 2,762 participants, 586 (21.3%) were diagnosed as having TTH using the standard criteria. Among these, 238 (40.6%) were also classified as having TTH using the alternative criteria. All 238 TTH subjects first diagnosed as having TTH by the alternative criteria were also classified as having TTH by the standard criteria. If the standard criteria were not applied, the remaining 348 patients were subclassified as having probable migraine (115, 19.6%) and unclassified headache (233, 39.7%). Compared with subjects diagnosed with TTH using the standard criteria, those diagnosed using the alternative criteria were less likely to demonstrate unilateral, pulsating headache, which is aggravated by movement, photophobia, phonophobia, and osmophobia.
Conclusion
Using the alternative criteria, less than half of the subjects with TTH according to the standard criteria were classified as having TTH. All the subjects with TTH by the alternative criteria were classified as having TTH by the standard criteria. This study also demonstrated that subjects diagnosed with TTH using the standard criteria could include people with headaches showing migrainous features.
doi:10.1186/1129-2377-15-28
PMCID: PMC4030019  PMID: 24884333
Classification; Criteria; Headache; Migraine; Probable migraine; Tension-type headache
3.  Headache-related work disability in young men 
Based on the knowledge that migraine and tension-type headache (TTH) are associated with reduced effectiveness at work and impairment of function in social roles, we studied the different influences that these primary headaches have on work in a specialized and homogeneous population. We studied 140 consecutive male patients, aged 18–35 years, attending an outpatient headache clinic at the Neurology Department of an Army General Hospital. Using International Headache Society (IHS) criteria, 60 patients were diagnosed with migraine and 80 patients with TTH. The impact of headache on work during the preceding 2 months was assessed using a selfadministered questionnaire, based on MIDAS. Two parameters of work disability were derived: the lost work days (LWD) and the days with reduced effectiveness while being at work (REWD). Of 142 LWD due to headaches, 95 (66.9%) were attributable to migraine and 47 (33.1%) to TTH (plt;0.001). Of 490 REWD, 120 (24.4%) were reported by migraineurs and 370 (75.5%) by TTH patients (p<0.001). The number of LWD in migraine was significantly higher (p<0.001) than in TTH group; the number of REWD in TTH group was significantly higher (p<0.001) than in migraine group. Pain intensity was the main factor contributing to disability at work in migraine group (plt;0.001), in contrast with TTH group in which there was no statistical difference (p>0.05) between pain intensity and duration of pain. Patients with migraine were much more likely to report actual lost workdays because of headache whereas TTH was responsible for the largest proportion of decreased work effectiveness. Assessing headache severity with an objective method (i.e. questionnaire) may improve headache care and lead to proper treatment decisions. Special attention must be given to particular populations.
doi:10.1007/s101940200023
PMCID: PMC3613233
Key words Migraine; Tension-type headache; Worn effectiveness
4.  One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults 
The Journal of Headache and Pain  2012;13(2):147-157.
Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0414-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0414-5
PMCID: PMC3274583  PMID: 22246025
Prevalence of migraine; Prevalence of tension-type headache; Migraine; Tension-type headache; Headache
5.  One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults 
The Journal of Headache and Pain  2012;13(2):147-157.
Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0414-5) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0414-5
PMCID: PMC3274583  PMID: 22246025
Prevalence of migraine; Prevalence of tension-type headache; Migraine; Tension-type headache; Headache
6.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
7.  Classification and clinical features of headache patients: an outpatient clinic study from China 
The Journal of Headache and Pain  2011;12(5):561-567.
This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.
doi:10.1007/s10194-011-0360-2
PMCID: PMC3173628  PMID: 21744226
Outpatient; Headache; Cross-sectional study; Clinical feature; Migraine
8.  Interactions between migraine and tension-type headache and alcohol drinking, alcohol flushing, and hangover in Japanese 
The Journal of Headache and Pain  2012;13(2):137-145.
The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) Tokyo health checkup examinees. We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%. Based on ICHD-II criteria migraine was diagnosed in 419 (75/344) subjects, and tension-type headache (TTH) in 613 (249/364). We classified the headaches of the remaining 1,545 (694/851) of headaches sufferers into the category “other headaches (OH)”. The migraineurs drank alcohol less frequently than the subjects with TTH among current/past alcohol flushers and than the subjects with OH regardless of flushing category. No such difference in drinking frequency was observed between TTH and OH. Current/past flushers drank alcohol less frequently than never flushers, and the likelihood that male migraineurs would avoid alcohol drinking than men with TTH or OH was stronger among current/past flushers than among never flushers. Flushers and women were more susceptible to hangover than never flushers and men, respectively, regardless of headache type. Among never flushers, women with migraine were more susceptible to hangover than women with OH. The difference in alcohol sensitivity may partly explain less alcohol consumption by migraineurs.
doi:10.1007/s10194-011-0413-6
PMCID: PMC3274580  PMID: 22234728
Alcohol; Alcohol flushing; Aldehyde dehydrogenase-2; Hangover; Migraine; Tension-type headache
9.  Interactions between migraine and tension-type headache and alcohol drinking, alcohol flushing, and hangover in Japanese 
The Journal of Headache and Pain  2012;13(2):137-145.
The aim of the study was to investigate associations between headache types and alcohol drinking, alcohol flushing, and hangover. Alcohol consumption is inhibited by the presence of inactive aldehyde dehydrogenase-2 (ALDH2) whose carriers are susceptible to alcohol flushing and hangovers. We conducted a cross-sectional study of the 2,577 subjects (men/women: 1,018/1,559) who reported having ever experienced headaches unrelated to common colds and alcohol hangovers among 5,408 (2,778/2,630) Tokyo health checkup examinees. We used a questionnaire inquiring about current and past facial flushing after drinking a glass of beer which identifies the presence of inactive ALDH2 with a sensitivity and specificity of approximately 90%. Based on ICHD-II criteria migraine was diagnosed in 419 (75/344) subjects, and tension-type headache (TTH) in 613 (249/364). We classified the headaches of the remaining 1,545 (694/851) of headaches sufferers into the category “other headaches (OH)”. The migraineurs drank alcohol less frequently than the subjects with TTH among current/past alcohol flushers and than the subjects with OH regardless of flushing category. No such difference in drinking frequency was observed between TTH and OH. Current/past flushers drank alcohol less frequently than never flushers, and the likelihood that male migraineurs would avoid alcohol drinking than men with TTH or OH was stronger among current/past flushers than among never flushers. Flushers and women were more susceptible to hangover than never flushers and men, respectively, regardless of headache type. Among never flushers, women with migraine were more susceptible to hangover than women with OH. The difference in alcohol sensitivity may partly explain less alcohol consumption by migraineurs.
doi:10.1007/s10194-011-0413-6
PMCID: PMC3274580  PMID: 22234728
Alcohol; Alcohol flushing; Aldehyde dehydrogenase-2; Hangover; Migraine; Tension-type headache
10.  Migraine may be a risk factor for the development of complex regional pain syndrome 
The aim was to assess the relative frequency of migraine and the headache characteristics of complex regional pain syndrome (CRPS) sufferers. CRPS and migraine are chronic, often disabling pain syndromes. Recent studies suggest that headache is associated with the development of CRPS. Consecutive adults fulfilling International Association for the Study of Pain criteria for CRPS at a pain clinic were included. Demographics, medical history, and pain characteristics were obtained. Headache diagnoses were made using International Classification of Headache Disorders, 2nd edn criteria. Migraine and pain characteristics were compared in those with migraine with those without. ANOVA with Tukey post hoc tests was used to determine the significance of continuous variables and Fisher’s exact or χ2 tests for categorical variables. The expected prevalence of migraine and chronic daily headache (CDH) was calculated based on age- and gender-stratified general population estimates. Standardized morbidity ratios (SMR) were calculated by dividing the observed prevalence of migraine by the expected prevalence from the general population. The sample consisted of 124 CRPS participants. The mean age was 45.5 ± 12.0 years. Age-and gender-adjusted SMRs showed that those with CRPS were 3.6 times more likely to have migraine and nearly twice as likely to have CDH as the general population. Aura was reported in 59.7% (74/124) of participants. Of those CRPS sufferers with migraine, 61.2% (41/67) reported the onset of severe headaches before the onset of CRPS symptoms Mean age of onset of CRPS was earlier in those with migraine (34.9 ± 11.1 years) and CDH (32.5 ± 13.4 years) compared with those with no headaches (46.8 ± 14.9 years) and those with tension-type headache (TTH) (39.9 ± 9.9 years), P < 0.05. More extremities were affected by CRPS in participants with migraine (median of four extremities) compared with the combined group of those CRPS sufferers with no headaches or TTH (median 2.0 extremities), P < 0.05. The presence of static, dynamic and deep joint mechanoallodynia together was reported by more CRPS participants with migraine (72.2%) than those with no headaches or TTH (46.2%), P ≤ 0.05. Migraine may be a risk factor for CRPS and the presence of migraine may be associated with a more severe form of CRPS. Specifically: (i) migraine occurs in a greater percentage of CRPS sufferers than expected in the general population; (ii) the onset of CRPS is reported earlier in those with migraine than in those without; and (iii) CRPS symptoms are present in more extremities in those CRPS sufferers with migraine compared with those without. In addition, as we also found that the presence of aura is reported in a higher percentage of those CRPS sufferers with migraine than reported in migraineurs in the general population, further evaluation of the cardiovascular risk profile of CRPS sufferers is warranted.
doi:10.1111/j.1468-2982.2009.01916.x
PMCID: PMC3979276  PMID: 19614690
Migraine; chronic daily headache; complex regional pain syndrome; allodynia; aura
11.  Associations between sleep disturbance and primary headaches: the third Nord-Trøndelag Health Study 
The Journal of Headache and Pain  2010;11(3):197-206.
The aim of the study was to evaluate the association between sleep disturbance and headache type and frequency, in a random sample of participants in the third Nord-Trøndelag Health Survey. The headache diagnoses were set by neurologists using the ICHD-2 criteria performing a semi structured face-to-face interview. Sleep problems were measured by the two validated instruments Karolinska Sleep Questionnaire (KSQ) and Epworth Sleepiness Scale (ESS). Among 297 participants, 77 subjects were headache-free, whereas 135 were diagnosed with tension-type headache (TTH), 51 with migraine, and 34 with other headache diagnoses. In the multivariate analyses, using logistic regression, excessive daytime sleepiness, defined as ESS ≥ 10, was three times more likely among migraineurs compared with headache-free individuals (OR = 3.3, 95% CI 1.0–10.2). Severe sleep disturbances, defined as KSQ score in the upper quartile, was five times more likely among migraineurs (OR = 5.4, 95% CI 2.0–15.5), and three times more likely for subjects with TTH (OR = 3.3, 1.4–7.3) compared with headache-free individuals. Subjects with chronic headache were 17 times more likely to have severe sleep disturbances (OR = 17.4, 95% CI 5.1–59.8), and the association was somewhat stronger for chronic migraine (OR = 38.9, 95% CI 3.1–485.3) than for chronic TTH (OR = 18.3, 95% CI 3.6–93.0). In conclusion, there was a significant association between severe sleep disturbances and primary headache disorders, most pronounced for those with chronic headache. Even though one cannot address causality in the present study design, the results indicate an increased awareness of sleep problems among patients with headache.
doi:10.1007/s10194-010-0201-8
PMCID: PMC3451918  PMID: 20224943
Chronic headache; Migraine; Tension-type headache; Karolinska Sleep Questionnaire; Daytime sleepiness
12.  Is There a Relation between Tension-Type Headache, Temporomandibular Disorders and Sleep? 
Pain Research and Treatment  2013;2013:845684.
Introduction. Tension-Type Headache (TTH) is the most prevalent headache often associated with impaired function and quality of life. Temporomandibular Disorders (TMD) and TTH frequently coexist; characterized by pericranial tenderness and impact on daily life. We aim to apply a standardized questionnaire for TMD to characterize and analyse an eventual relation between sleep and oral health in TTH in a controlled design. Material and Methods. 58 consecutive TTH patients and 58 healthy controls were included. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) questionnaire, Oral Health Impact profile (OHIP) and questionnaires for sleep were applied. Results. TTH-patients had significantly higher pain scores (P < 0.001), decreased quality of life (P < 0.001), and higher total sleep scores (P < 0.001) compared to controls. Conclusion. For the first time we have identified a clear relation between TTH and TMD symptoms, depression, anxiety, poor sleep, and impairments of oral function in carefully classified patients. These findings indicate a close, but incomplete, overlap between TTH and TMD. Their underlying pathophysiological mechanisms need further research.
doi:10.1155/2013/845684
PMCID: PMC3856154  PMID: 24349777
13.  Patent foramen ovale in patients with tension headache: is it as common as in migraineurs? An age- and sex-matched comparative study 
The Journal of Headache and Pain  2009;10(6):431-434.
The association of patent foramen ovale (PFO) and atrial septal aneurysm (ASA) with migraine headache attack (MHA) has been clearly shown. The same findings have been recently demonstrated also in cluster headache. Although tension-type headaches (TTH) are the most common kind of headache, their association with these atrial septal abnormalities has never been studied before. The study was conducted to clarify whether there was a significant association between the presence of such atrial septal abnormalities and tension headache, when compared with migraineurs. One hundred consecutive patients with migraine and 100 age- and sex-matched subjects with TTH and 50 healthy volunteers with no headache were enrolled in the study and underwent a complete transesophageal echocardiographic study with contrast injections at rest and with the Valsalva maneuver. There was no significant difference between the age and the sex of the participants of the three groups. The overall prevalence of PFO was 23% in patients with TTH and that of large PFOs was only 11%. The 23% prevalence of PFO in patients with TTH was not statistically different from 16% found in our normal control group. Furthermore, we found a significantly higher prevalence of PFO in migraineurs (50%) when compared with patients with tension headache (p < 0.001). This was also true for the collective presence of large PFOs and ASAs (35%) (p < 0.001). Although atrial septal anomalies have an association with MHA, they do not have a significant association with TTH.
doi:10.1007/s10194-009-0154-y
PMCID: PMC3476217  PMID: 19756944
Tension-type headache; Migraine headache; Patent foramen ovale; Atrial septal aneurysm
14.  Headaches in Multiple Sclerosis Patients Might Imply an Inflammatorial Process 
PLoS ONE  2013;8(8):e69570.
Recent studies on Multiple Sclerosis (MS) pathology mention the involvement of “tertiary B cell follicles” in MS pathogenesis. This inflammatory process, which occurs with interindividually great variance, might be a link between MS pathology and headaches. The aim of this study was to detect the prevalence of headaches and of subtypes of headaches (migraine, cluster, tension-type headache [TTH]) in an unselected MS collective and to compile possibly influencing factors. Unselected MS patients (n = 180) with and without headache were examined by a semi-structured interview using a questionnaire about headache, depression and the health status. Additionally clinical MS data (expanded disability state score [EDSS], MS course, medication, disease duration) were gathered. N = 98 MS patients (55.4%) reported headaches in the previous 4 weeks. We subsequently grouped headache patients according to the IHS criteria and detected 16 (16.3%) MS patients suffering from migraine (migraine with aura: 2 [2%]; migraine without aura: 14 [14.3%]), 23 (23.5%) suffering from TTH and none with a cluster headache. Thus, headaches of 59 (60.2%) MS patients remained unclassified. When comparing MS patients with and without headaches significant differences in age, gender, MS course, physical functioning, pain and social functioning occurred. MS patients with headaches were significantly younger of age (p = 0.001), female (p = 0.001) and reported more often of a clinically isolated syndrome (CIS) and relapsing/remitting MS (RRMS) instead of secondary chronic progressive MS (SCP). EDSS was significantly lower in MS patients suffering from headaches compared to the MS patients without headaches (p = 0.001). In conclusion headache in MS patients is a relevant symptom, especially in early stages of the MS disease. Especially unclassified headache seems to represent an important symptom in MS course and requires increased attention.
doi:10.1371/journal.pone.0069570
PMCID: PMC3734145  PMID: 23940524
15.  Health-care utilization for primary headache disorders in China: a population-based door-to-door survey 
Background
In order to know the status quo of health care for primary headache disorders in China, questions about headache consultation and diagnosis were included in a nationwide population-based survey initiated by Lifting The Burden: the Global Campaign against Headache.
Methods
Throughout China, 5,041 unrelated respondents aged 18–65 years were randomly sampled from the general population and visited unannounced at their homes. After basic sociodemographic and headache diagnostic questions, respondents with headache answered further questions about health-care utilization in the previous year.
Results
Significantly higher proportions of respondents with migraine (239/452; 52.9%) or headache on ≥15 days per month (23/48; 47.9%) had consulted a physician for headache than of those with tension-type headache (TTH) (218/531; 41.1%; P < 0.05). Multivariate analysis showed associations between disability and probability of consultation in those with migraine (mild vs. minimal: AOR 3.4, 95% CI: 1.6–7.4; moderate vs. minimal: 2.5, 1.2–5.4; severe vs. minimal: 3.9, 1.9–8.1) and between rural habitation and probability of consulting in those with TTH (AOR: 3.5; 95% CI: 1.9–6.3, P < 0.001). Married respondents with TTH were less likely than unmarried to have consulted (AOR: 0.26; 95% CI: 0.07–0.93; P = 0.038). About half of consultations (47.8–56.5%) for each of the headache disorders were at clinic level in the health system. Consultations in level-3 hospitals were relatively few for migraine (5.9%) but more likely for headache on ≥15 days/month (8.7%) and, surprisingly, for TTH (13.3%). Under-diagnosis and misdiagnosis were common in consulters. More than half with migraine (52.7%) or headache on ≥15 days/month (51.2%), and almost two thirds (63.7%) with TTH, reported no previous diagnosis. Consulters with migraine were as likely (13.8%) to have been diagnosed with “nervous headache” as with migraine. “Nervous headache” (9.8%) and “vascular headache” (7.6%) were the most likely diagnoses in those with TTH, of whom only 5.6% had previously been correctly diagnosed. These were also the most likely diagnoses (14.0% each) in consulters with headache on ≥15 days/month.
Conclusions
This picture of the status quo shows limited reach of headache services in China, and high rates of under-diagnosis and misdiagnosis in those who achieve access to them. This is not a picture of an efficient or cost-effective response to major causes of public ill-health and disability.
doi:10.1186/1129-2377-14-47
PMCID: PMC3673891  PMID: 23731663
China; Headache disorders; Migraine; Tension-type headache; Health-care utilization; Global campaign against headache
16.  Application of ICHD-II Criteria in a Headache Clinic of China 
PLoS ONE  2012;7(12):e50898.
Background
China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People's Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II).
Methods and Results
Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2nd decade for females and the 1st decade for males.
Conclusions/Significance
This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.
doi:10.1371/journal.pone.0050898
PMCID: PMC3519829  PMID: 23239993
17.  Plasma calcitonin gene-related peptide concentration is comparable to control group among migraineurs and tension type headache subjects during inter-ictal period 
The Journal of Headache and Pain  2009;10(3):161-166.
Calcitonin gene-related peptide (CGRP) is known to increase during acute attack of migraine and tension type headache (TTH). However, its concentration during inter-ictal period is not known. This may help us to understand the pathophysiology of these headaches. The objectives of this study are to find out the concentration of CGRP in plasma during inter-ictal period among migraineurs and TTH and to compare it with control group through cross-sectional study from headache clinic of a tertiary centre. Study sample comprised of three groups: migraineurs, TTH subjects as well as a healthy control group. Fifty subjects in each group were included after screening for the respective inclusion criteria and exclusion criteria. None of the subjects was blood relatives of other subject. Their venous blood was drawn and plasma was separated to be kept at −70°C. CGRP was analysed with commercially available ELISA kit. Data were analysed with the help of SPSS V 11.0 for Windows. Chi-square, independent sample t test and one-way ANOVA with post hoc Tukey and univariate regression were performed. Plasma CGRP concentration was not different among three diagnostic groups (F = 0.78; P = 0.49). Similarly, plasma CGRP concentration was not different among episodic TTH and chronic TTH groups (t = 0.32; P = 0.97) and comparison of episodic and chronic migraine groups also revealed similar results in this study (1.14 vs. 0.94 ng/ml; P = 0.23). The presence of aura did not affect the inter-ictal CGRP levels among migraineurs (F = 0.16; P = 0.85). In conclusion, this study suggests that migraine and TTH could be episodic disorders and subjects have comparable CGRP levels during inter-ictal period.
doi:10.1007/s10194-009-0110-x
PMCID: PMC3451985  PMID: 19277835
Migraine; Tension type headache; CGRP; Inter-ictal period
18.  Negative Emotions in Migraineurs Dreams: The Increased Prevalence of Oneiric Fear and Anguish, Unrelated to Mood Disorders 
Behavioural Neurology  2014;2014:919627.
Background. Migraineurs brain has shown some functional peculiarities that reflect not only in phonophobia, and photophobia, but also in mood and sleep. Dreaming is a universal mental state characterized by hallucinatory features in which imagery, emotion, motor skills, and memory are created de novo. We evaluated dream contents and associated emotions in migraineurs. Materials and Methods. 412 subjects: 219 controls; and 148 migraineurs (66 with aura, MA; 82 without aura, MO), and 45 tension type headache patients (TTH). A semistructured retrospective self-reported questionnaire was used to evaluate dreams. The Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9) were administered to evaluate anxiety and depression. Results. Migraineurs showed increased levels of anxiety (P = 0.0002 for MA versus controls, P = 0.004 for MO versus controls). Fear and anguish during dreaming were more frequently reported by migraine patients compared to controls, independently by anxiety and depression scores. Discussion. The brain of migraineurs seems to dream with some peculiar features, all with a negative connotation, as fear and anguish. It may be due to the recorded negative sensations induced by recurrent migraine pain, but it may just reflect a peculiar attitude of the mesolimbic structures of migraineurs brain, activated in both dreaming and migraine attacks.
doi:10.1155/2014/919627
PMCID: PMC4094847  PMID: 25049452
19.  Cardiovascular responses to cognitive stress in patients with migraine and tension-type headache 
BMC Neurology  2007;7:23.
Background
The purpose of this study was to investigate the temporal relationship between autonomic changes and pain activation in migraine and tension-type headache induced by stress in a model relevant for everyday office-work.
Methods
We measured pain, blood pressure (BP), heart rate (HR) and skin blood flow (BF) during and after controlled low-grade cognitive stress in 22 migraineurs during headache-free periods, 18 patients with tension-type headache (TTH) and 44 healthy controls. The stress lasted for one hour and was followed by 30 minutes of relaxation.
Results
Cardiovascular responses to cognitive stress in migraine did not differ from those in control subjects. In TTH patients HR was maintained during stress, whereas it decreased for migraineurs and controls. A trend towards a delayed systolic BP response during stress was also observed in TTH. Finger BF recovery was delayed after stress and stress-induced pain was associated with less vasoconstriction in TTH during recovery.
Conclusion
It is hypothesized that TTH patients have different stress adaptive mechanisms than controls and migraineurs, involving delayed cardiovascular adaptation and reduced pain control system inhibition.
doi:10.1186/1471-2377-7-23
PMCID: PMC2048502  PMID: 17683636
20.  Pain sensitivity and pericranial tenderness in children with tension-type headache: a controlled study 
Journal of Pain Research  2013;6:425-434.
Purpose
To compare tenderness and pain sensitivity in children (aged 7–17 years) with tension-type headache (TTH) and healthy controls using total tenderness score (TTS), pressure pain threshold (PPT), and pain perceived at suprapressure pain threshold (supraPPT).
Patients and methods
Twenty-three children with frequent episodic TTH, 36 with chronic TTH, and 57 healthy controls were included. TTS was measured bilaterally at seven pericranial myofascial structures. PPT and supraPPT were assessed in the finger, m. temporalis, and m. trapezius by a Somedic® algometer. SupraPPT was defined as the pain perceived at a stimulus calculated as the individual site-specific PPT + 50%.
Statistics
The effect of group, sex, age, headache frequency, intensity, and years on TTS, PPT, and supraPPT was analyzed by general linear models. Confirmatory factor analysis was analyzed for mutual relations between measurements.
Results and conclusion
Tenderness increased uniformly in both frequent episodic TTH (median 14; interquartile range [IQR] 10–18; P < 0.001) and chronic TTH (median 13; IQR 9–20; P < 0.001) compared to controls (median 5, IQR 3–11). However, the children with frequent episodic TTH and chronic TTH did not show significantly increased sensitivity when measured by PPT or supraPPT. Factor analysis confirmed that the site-specific measurements depended on general latent variables. Consequently, the PPT and supraPPT tests can be assumed to measure central pain-processing levels.
doi:10.2147/JPR.S42869
PMCID: PMC3682848  PMID: 23785242
sensitization; pain measurement; total tenderness score; pressure pain threshold; pathophysiological mechanisms; suprathreshold stimulation
21.  Trigger factors of migraine and tension-type headache: experience and knowledge of the patients 
The Journal of Headache and Pain  2006;7(4):188-195.
The objective was to examine potential trigger factors of migraine and tension-type headache (TTH) in clinic patients and in subjects from the population and to compare the patients’ personal experience with their theoretical knowledge. A cross-sectional study was carried out in a headache centre. There were 120 subjects comprising 66 patients with migraine and 22 with TTH from a headache outpatient clinic and 32 persons with headache (migraine or TTH) from the population. A semistructured interview covering biographic data, lifestyle, medical history, headache characteristics and 25 potential trigger factors differentiating between the patients’ personal experience and their theoretical knowledge was used. The most common trigger factors experienced by the patients were weather (82.5%), stress (66.7%), menstruation (51.4%) and relaxation after stress (50%). The vast majority of triggers occurred occasionally and not consistently. The patients experienced 8.9±4.3 trigger factors (range 0–20) and they knew 13.2±6.0 (range 1–27). The number of experienced triggers was smallest in the population group (p=0.002), whereas the number of triggers known did not differ in the three study groups. Comparing theoretical knowledge with personal experience showed the largest differences for oral contraceptives (65.0 vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%, p>0.001) and cheese (52.5 vs. 8.4%, p<0.001). In conclusion, almost all trigger factors are experienced occasionally and not consistently by the majority of patients. Subjects from the population experience trigger factors less often than clinic patients. The difference between theoretical knowledge and personal experience is largest for oral contraceptives, chocolate and cheese.
doi:10.1007/s10194-006-0305-3
PMCID: PMC3476072  PMID: 16897622
Migraine; Tension-type headache; Weather; Stress; Menstruation
22.  Prevalence of primary headaches in Germany: results of the German Headache Consortium Study 
The Journal of Headache and Pain  2012;13(3):215-223.
We investigated the prevalence of migraine (MIG), tension-type headache (TTH), and chronic headache in a population-based sample in Germany. A total of 18,000 subjects aged between 18 and 65 years were screened from 2003 until 2005 using a validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age 43 ± 13.1 years, 52.7% women). Headache frequency <15 days/month was reported by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95% CI): 15.9–17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8–13.1) episodic TTH, and 1,150 (11.9%, [11.3–12.6]) episodic MIG + episodic TTH, 1,396 (14.5%, [13.8–15.2]) unclassifiable headache. In women, episodic MIG peaked between 36 and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between 56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years, episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable frequency between 36 and 66 years. Headache ≥15 days/month was reported by 2.6% (n = 255, [95% CI 2.3–3]). Chronic MIG was reported by 1.1% (n = 108, [0.91–1.33]), chronic TTH (n = 50, [95% CI 0.4–0.7]), chronic MIG + TTH 0.8% (n = 74, 95% CI 0.6–0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1–0.3]). Chronic headache was more frequent in women compared to men with the highest prevalence between 46 and 65 years. It is of note that the number of subjects with chronic headache is small in all age groups. The results of our large, population-based study provide reliable, age- and sex-specific estimates of the prevalence of primary headache disorders in Germany. The prevalence with respect to episodic and chronic primary headache disorders in Germany is comparable to other European countries and the USA.
doi:10.1007/s10194-012-0425-x
PMCID: PMC3311829  PMID: 22395638
Migraine; Tension-type headache; Chronic daily headache; Prevalence
23.  Prevalence of primary headaches in Germany: results of the German Headache Consortium Study 
The Journal of Headache and Pain  2012;13(3):215-223.
We investigated the prevalence of migraine (MIG), tension-type headache (TTH), and chronic headache in a population-based sample in Germany. A total of 18,000 subjects aged between 18 and 65 years were screened from 2003 until 2005 using a validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age 43 ± 13.1 years, 52.7% women). Headache frequency <15 days/month was reported by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95% CI): 15.9–17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8–13.1) episodic TTH, and 1,150 (11.9%, [11.3–12.6]) episodic MIG + episodic TTH, 1,396 (14.5%, [13.8–15.2]) unclassifiable headache. In women, episodic MIG peaked between 36 and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between 56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years, episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable frequency between 36 and 66 years. Headache ≥15 days/month was reported by 2.6% (n = 255, [95% CI 2.3–3]). Chronic MIG was reported by 1.1% (n = 108, [0.91–1.33]), chronic TTH (n = 50, [95% CI 0.4–0.7]), chronic MIG + TTH 0.8% (n = 74, 95% CI 0.6–0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1–0.3]). Chronic headache was more frequent in women compared to men with the highest prevalence between 46 and 65 years. It is of note that the number of subjects with chronic headache is small in all age groups. The results of our large, population-based study provide reliable, age- and sex-specific estimates of the prevalence of primary headache disorders in Germany. The prevalence with respect to episodic and chronic primary headache disorders in Germany is comparable to other European countries and the USA.
doi:10.1007/s10194-012-0425-x
PMCID: PMC3311829  PMID: 22395638
Migraine; Tension-type headache; Chronic daily headache; Prevalence
24.  Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache 
The Journal of Headache and Pain  2007;8(3):157-166.
The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.
doi:10.1007/s10194-007-0384-9
PMCID: PMC3476146  PMID: 17568991
Catecholamines; Cortisol; Migraine; Tension-type headache; Stress
25.  Validation of a guideline-based decision support system for the diagnosis of primary headache disorders based on ICHD-3 beta 
Background
China may have the largest population of headache sufferers and therefore the most serious burden of disease worldwide. However, the rate of diagnosis for headache disorders is extremely low, possibly due to the relative complexity of headache subtypes and diagnostic criteria. The use of computerized clinical decision support systems (CDSS) seems to be a better choice to solve this problem.
Methods
We developed a headache CDSS based on ICHD-3 beta and validated it in a prospective study that included 543 headache patients from the International Headache Center at the Chinese PLA General hospital, Beijing, China.
Results
We found that the CDSS correctly recognized 159/160 (99.4%) of migraine without aura, 36/36 (100%) of migraine with aura, 20/21 (95.2%) of chronic migraine, and 37/59 (62.7%) of probable migraine. This system also correctly identified 157/180 (87.2%) of patients with tension-type headache (TTH), of which infrequent episodic TTH was diagnosed in 12/13 (92.3%), frequent episodic TTH was diagnosed in 99/101 (98.0%), chronic TTH in 18/20 (90.0%), and probable TTH in 28/46 (60.9%). The correct diagnostic rates of cluster headache and new daily persistent headache (NDPH) were 90.0% and 100%, respectively. In addition, the system recognized 32/32 (100%) of patients with medication overuse headache.
Conclusions
With high diagnostic accuracy for most of the primary and some types of secondary headaches, this system can be expected to help general practitioners at primary hospitals improve diagnostic accuracy and thereby reduce the burden of headache in China.
doi:10.1186/1129-2377-15-40
PMCID: PMC4074417  PMID: 24934331
Headache; Computer-assisted diagnosis; Clinical decision support; ICHD-3 beta; SAGE

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