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1.  Headache in epilepsy: prevalence and clinical features 
Background
Headache and epilepsy are two relatively common neurological disorders and their relationship is still a matter of debate. Our aim was to estimate the prevalence and clinical features of inter-ictal (inter-IH) and peri-ictal headache (peri-IH) in patients with epilepsy.
Methods
All patients aged ≥ 17 years referring to our tertiary Epilepsy Centre were consecutively recruited from March to May 2011 and from March to July 2012. They underwent a semi-structured interview including the International Classification Headache Disorders (ICHD-II) criteria to diagnose the lifetime occurrence of headache.χ2-test, t-test and Mann–Whitney test were used to compare clinical variables in patients with and without inter-IH and peri-IH.
Results
Out of 388 enrolled patients 48.5 % had inter-IH: migraine in 26.3 %, tension-type headache (TTH) in 19.1 %, other primary headaches in 3.1 %. Peri-IH was observed in 23.7 %: pre-ictally in 6.7 %, ictally in 0.8 % and post-ictally in 19.1 %. Comparing patients with inter-ictal migraine (102), inter-ictal TTH (74) and without inter-IH (200), we found that pre-ictal headache (pre-IH) was significantly represented only in migraineurs (OR 3.54, 95 % CI 1.88-6.66, P < 0.001). Post-ictal headache (post-IH) was significantly associated with both migraineurs (OR 2.60, 95 % CI 1.85-3.64, P < 0.001) and TTH patients (OR 2.05, 95 % CI 1.41-2.98, P < 0.001). Moreover, post-IH was significantly associated with antiepileptic polytherapy (P < 0.001), high seizure frequency (P = 0.002) and tonic-clonic seizures (P = 0.043).
Conclusions
Migraine was the most represented type of headache in patients with epilepsy. Migraineurs are more prone to develop pre-IH, while patients with any inter-IH (migraine or TTH) are predisposed to manifest a post-IH after seizures.
doi:10.1186/s10194-015-0556-y
PMCID: PMC4540713  PMID: 26245188
Headache; Epilepsy; Migraine; Pre-ictal headache; Post-ictal headache
2.  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
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.  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
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.  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
7.  Results from a pharmacy-based patient survey on the use of a fixed combination analgesic containing acetylsalicylic acid, paracetamol and caffeine by self-diagnosing and self-treating patients 
SpringerPlus  2016;5(1):721.
Background
Patients suffering from migraine or tension-type headache (TTH) often treat their complaints with over-the-counter (OTC) medications. Fixed dose combinations of acetylsalicylic acid, paracetamol and caffeine (APC) are among the most commonly used analgesics, and their efficacy for treating acute headache pain has been well demonstrated. This investigation was run to better characterize patients who treat their headache with OTC APC combinations, as well as treatment effects.
Methods
A pharmacy-based patient survey in 164 German pharmacies was performed. Patients (age ≥18 years) who purchased APC analgesics (of the brand Thomapyrin®) were handed a questionnaire, which had to be filled out at patients own discretion after taking the medication. Demographics, pain characteristics and perceived efficacy and tolerability data were analysed with descriptive statistics.
Results
Questionnaires from 1298 patients were analysed, of whom 71.9 % were females and 28.1 % were males. Headache patients were assigned to TTH or migraine according to diagnosis criteria of the International Headache Classification-II (ICHD-II), with 828 patients for TTH and 206 for migraine. About one third of patients in the subgroup migraine did not report their pain as migraine. Nausea, photophobia/phonophobia turned out to be the most distinguishing feature between migraine and TTH. The main reasons for purchasing the product were recommendation by the pharmacists (40.5 %) and/or friends or relatives (24.4 %). 74 % of TTH and 55 % of migraine patients reported onset of pain relief within the first 30 min. More than 90 % rated efficacy as well as tolerability to be “good” or “very good”.
Conclusions
The main reason for purchasing APC products in the pharmacy are TTH or migraine. About a third of patients fulfilling the IHCD-II criteria for migraine failed to recognize their headache as migraine. This could be explained e.g. by patients’ misconceptions about their pain. Patients’ assessments of efficacy and tolerability showed that the investigated APC combinations are valuable for the treatment of TTH and migraine headache. These data complement those of randomized clinical studies on such preparations.
doi:10.1186/s40064-016-2369-0
PMCID: PMC4908082  PMID: 27375990
Acetylsalicylic acid; Paracetamol; Caffeine; Headache; Migraine
8.  Interictal burden attributable to episodic headache: findings from the Eurolight project 
Background
Most primary headaches are episodic, and most estimates of the heavy disability burden attributed to headache derive from epidemiological data focused on the episodic subtypes of migraine and tension-type headache (TTH). These disorders give rise directly but intermittently to symptom burden. Nevertheless, people with these disorders may not be symptom-free between attacks. We analysed the Eurolight dataset for interictal burden.
Methods
Eurolight was a cross-sectional survey using modified cluster sampling from the adult population (18–65 years) in 10 countries of the European Union. We used data from nine. The questionnaire included headache-diagnostic questions based on ICHD-II and several question sets addressing impact, including interictal and cumulative burdens.
Results
There were 6455 participants with headache (male 2444 [37.9 %]). Interictal symptoms were reported by 26.0 % of those with migraine and 18.9 % with TTH: interictal anxiety by 10.6 % with migraine and avoidance (lifestyle compromise) by 14.8 %, both much more common than in TTH (3.1 % [OR 3.8] and 4.7 % [OR 3.5] respectively). Mean time spent in the interictal state was 317 days/year for migraine, 331 days/year for TTH. Those who were “rarely” or “never” in control of their headaches (migraine 15.2 %, TTH 9.6 %) had significantly raised odds of interictal anxiety, avoidance and other interictal symptoms. Among those with migraine, interictal anxiety increased markedly with headache intensity and frequency, avoidance less so but still significantly. Lost productive time was associated with high ORs (up to 5.3) of anxiety and avoidance.
A third (32.9 %) with migraine and a quarter (26.7 %) with TTH (difference: p < 0.0001) were reluctant to tell others of their headaches. About 10 % with each disorder felt families and friends did not understand their headaches. Nearly 12 % with migraine reported their employers and colleagues did not.
Regarding cumulative burden, 11.8 % reported they had done less well in education because of headache, 5.9 % reported reduced earnings and 7.4 % that their careers had suffered.
Conclusions
Interictal burden in those with episodic headache is common, more so in migraine than TTH. Some elements have the potential to be profoundly consequential. New methodology is needed to measure interictal burden if descriptions of headache burden are to be complete.
doi:10.1186/s10194-016-0599-8
PMCID: PMC4754227  PMID: 26879832
Headache; Migraine; Tension-type headache; Interictal burden; Public health; Europe; Eurolight project; Global Campaign against Headache
9.  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
10.  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
11.  Grey zones in the diagnosis of adult migraine without aura based on the International Classification of Headache Disorders-III beta: Exploring the covariates of possible migraine without aura 
An update to the International Classification of Headache Disorders is being developed, which may alter the diagnosis of disorders such as migraine headaches. Patients often report some, but not all, of the criteria for migraine without aura (MWoA), leading to several ‘grey zones’ that include patients who are not formally diagnosed with MWoA. The authors of this article assessed, in a total of 1365 patients diagnosed with MWoA, these ‘grey zones’ and possible implications for the update to the International Classification of Headache Disorders.
BACKGROUND:
Exploring clinical characteristics and migraine covariates may be useful in the diagnosis of migraine without aura.
OBJECTIVE:
To evaluate the diagnostic value of the International Classification of Headache Disorders (ICHD)-III beta-based diagnosis of migraine without aura; to explore the covariates of possible migraine without aura using an analysis of grey zones in this area; and, finally, to make suggestions for the final version of the ICHD-III.
METHODS:
A total of 1365 patients (mean [± SD] age 38.5±10.4 years, 82.8% female) diagnosed with migraine without aura according to the criteria of the ICHD-III beta were included in the present tertiary care-based retrospective study. Patients meeting all of the criteria of the ICHD-III beta were classified as having full migraine without aura, while those who did not meet one, two or ≥3 of the diagnostic criteria were classified as zones I, II and III, respectively. The diagnostic value of the clinical characteristics and covariates of migraine were determined.
RESULTS:
Full migraine without aura was evident in 25.7% of the migraineurs. A higher likelihood of zone I classification was shown for an attack lasting 4 h to 72 h (OR 1.560; P=0.002), with pulsating quality (OR 4.096; P<0.001), concomitant nausea/vomiting (OR 2.300; P<0.001) and photophobia/phonophobia (OR 4.865; P<0.001). The first-rank determinants for full migraine without aura were sleep irregularities (OR 1.596; P=0.005) and periodic vomiting (OR 1.464; P=0.026). However, even if not mentioned in ICHD-III beta, the authors determined that motion sickness, abdominal pain or infantile colic attacks in childhood, associated dizziness and osmophobia have important diagnostic value.
CONCLUSIONS:
In cases that do not fulfill all of the diagnostic criteria although they are largely consistent with the characteristics of migraine in clinical terms, the authors believe that a history of infantile colic; periodic vomiting (but not periodic vomiting syndrome); recurrent abdominal pain; the presence of motion sickness or vertigo, dizziness or osmophobia accompanying the pain; and comorbid atopic disorder are characteristics that should to be discussed and considered as additional diagnostic criteria (covariates) in the preparation of the final version of ICHD-III.
PMCID: PMC4325894  PMID: 25493966
Covariates; Diagnostic criteria; Grey zones; ICHD-III; Migraine without aura
12.  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
13.  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
14.  Headache, depression and anxiety: associations in the Eurolight project 
Background
Headache disorders and psychiatric disorders are both common, while evidence, mostly pertaining to migraine, suggests they are comorbid more often than might be expected by chance. There are good reasons for establishing whether they are: symptoms of comorbid illnesses may summate synergistically; comorbidities hinder management, negatively influencing outcomes; high-level comorbidity indicates that, where one disease occurs, the other should be looked for. The Eurolight project gathered population-based data on these disorders from 6624 participants.
Methods
Eurolight was a cross-sectional survey sampling from the adult populations (18–65 years) of 10 EU countries. We used data from six. The questionnaire included headache-diagnostic questions based on ICHD-II, the Headache-Attributed Lost Time (HALT) questionnaire, and HADS for depression and anxiety. We estimated odds ratios (ORs) to show associations between migraine, tension-type headache (TTH) or probable medication-overuse headache (pMOH) and depression or anxiety.
Results
pMOH was most strongly associated with both psychiatric disorders: for depression, ORs (vs no headache) were 5.5 [2.2–13.5] (p < 0.0001) in males, 5.5 [2.9–10.5] (p < 0.0001) in females; for anxiety, ORs were 10.4 [4.9–21.8] (p < 0.0001) and 7.1 [4.5–11.2] (p < 0.0001). Migraine was also associated with both: for depression, ORs were 2.1 [1.3–3.4] (p = 0.002) and 1.8 [1.1–3.1] (p = 0.030); for anxiety 4.2 [2.8–6.3] (p < 0.0001) and 2.4 [1.7–3.4] (p < 0.0001). TTH showed associations only with anxiety: ORs 2.5 [1.7–3.7] (p < 0.0001) for males, 1.5 [1.1–2.1] (p = 0.021) for females. Participants with migraine carried 19.1 % probability of comorbid anxiety, 6.9 % of depression and 5.1 % of both, higher than the representative general-population sample (14.3, 5.6 and 3.8 %). Probabilities in those with MOH were 38.8, 16.9 and 14.4 %; in TTH, they did not exceed those of the whole sample. Comorbid psychiatric disorder did not add to headache-attributed productive time losses, but weak associations existed (R2 = 0.020–0.082) for all headache types between lost productive time and probabilities of depression and, less so, anxiety.
Conclusion
In this large study we confirmed that depression and especially anxiety are comorbid more than by chance with migraine, and showed the same is true, but more strongly, with MOH. Arguably, migraine patients and, more certainly, MOH patients should be screened with HADS in pursuit of best outcomes.
doi:10.1186/s10194-016-0649-2
PMCID: PMC4887397  PMID: 27245683
Headache; Migraine; Tension-type headache; Medication-overuse headache; Depression; Anxiety; Comorbidity; Associations; Public health; Europe; Eurolight project; Global Campaign against Headache
15.  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
16.  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
17.  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
18.  Melatonin 4 mg as prophylactic therapy for primary headaches: a pilot study 
Functional Neurology  2016;31(1):33-37.
Summary
There is growing evidence that headaches are connected to melatonin secretion. Our aim was to assess the potential effectiveness of melatonin for primary headache prevention.
Forty-nine patients (37 with migraine and 12 with chronic tension-type headache, TTH) were prescribed oral melatonin, 4 mg, 30 minutes before bedtime for six months. Forty-one (83.6%) of the 49 patients completed the study, while eight dropped out for personal reasons.
A statistically significant reduction in headache frequency was found between baseline and final follow-up after six months of treatment (p=0.033 for TTH patients and p<0.001 for migraineurs). The Headache Impact Test score was significantly reduced in both groups of headache patients (p=0.002 and p<0.001, respectively).
At baseline, melatonin levels, measured both during a headache attack and a pain-free period, did not differ between patients with TTH and migraineurs (p=0.539 and p=0.693, respectively), and no statistically significant differences in Hamilton Depression Rating Scale scores were found between the two groups.
This pilot study shows promising results, in terms of headache frequency reduction and daily quality of life improvement, in both groups.
doi:10.11138/FNeur/2016.31.1.033
PMCID: PMC4819816  PMID: 27027892
Hamilton Depression Rating Scale; Headache Impact Test (HIT-6); melatonin; primary headaches; prevention
19.  Short-term diagnostic stability of probable headache disorders based on the International Classification of Headache Disorders, 3rd edition beta version, in first-visit patients: a multicenter follow-up study 
Background
A “Probable headache disorder” is diagnosed when a patient’s headache fulfills all but one criterion of a headache disorder in the 3rd beta edition of the International Classification of Headache Disorder (ICHD-3β). We investigated diagnostic changes in probable headache disorders in first-visit patients after at least 3 months of follow-up.
Methods
This was a longitudinal study using a prospective headache registry from nine headache clinics of referral hospitals. The diagnostic change of probable headache disorders at baseline was assessed at least 3 months after the initial visit using ICHD-3β.
Results
Of 216 patients with probable headache disorders at baseline, the initial probable diagnosis remained unchanged for 162 (75.0 %) patients, while it progressed to a definite diagnosis within the same headache subtype for 45 (20.8 %) by fulfilling the criteria during a median follow-up period of 6.5 months. Significant difference on the proportions of constant diagnosis was not found between headache subtypes (P < 0.935): 75.9 % for probable migraine, 73.7 % for probable tension-type headache (TTH), and 76.0 % for probable other primary headache disorders (OPHD). Among patients with headache recurrence, the proportion of constant diagnosis was higher for probable migraine than for probable TTH plus probable OPHD (59.2 vs. 23.1 %; P < 0.001). The proportions of constant diagnosis did not significantly differ by follow-up duration (>3 and ≤ 6 months vs. > 6 and ≤ 10 months) in probable migraine, probable TTH, and probable OPHD, respectively.
Conclusions
In this study, a probable headache diagnosis, based on ICHD-3β, remained in approximately three-quarters of the outpatients; however, diagnostic stability could differ by headache recurrence and subtype. Probable headache management might have to consider these differences.
doi:10.1186/s10194-016-0605-1
PMCID: PMC4759261  PMID: 26892842
Headache; Migraine; Tension-type headache; Tracking; Stability; Probable diagnosis
20.  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
21.  Anxiety and Depression in Tension-Type Headache: A Population-Based Study 
PLoS ONE  2016;11(10):e0165316.
Although tension-type headache (TTH) is a frequent type of headache disorder and imposes a significant burden, there is scant information about the prevalence and impact of comorbid anxiety and depression among individuals with TTH. We investigated the prevalence and clinical impact of anxiety and depression among patients with TTH in the general population. We recruited Korean participants aged 19–69 years using a two-stage clustered random sampling method. To identify the presence of headache type, anxiety, and depression, we used a semi-structured interview using certain questionnaires. To assess the level of anxiety and depression, we used the Goldberg Anxiety Scale and Patient Health Questionnaire-9, respectively. Among 2,695 participants, 570 people (21.2%) had TTH during previous 1 year. In participants with TTH, the prevalence of anxiety (9.5% vs. 5.3%, p = 0.001) and depression (4.2% vs. 1.8%, p = 0.001) was significantly higher than that of non-headache participants. The prevalence of anxiety among TTH participants with >15 attacks per month [21.4%, odds ratio (OR): 4.0] and 1–14 attacks per month (13.1%, OR: 2.2) was higher than that in those with <1 attack per month (6.4%), however this tendency was not observed in participants with depression. Visual Analogue Scale (VAS) score [median 5.0 vs. 4.0, p = 0.010] and Headache Impact Test-6 (HIT-6) score [median 45.5 vs. 42.0, p < 0.001] were significantly higher among those with anxiety. Furthermore, VAS scores [median 5.0 vs. 4.0, p = 0.010] and HIT-6 scores [median 45.5 vs. 42.0, p = 0.027] were also significantly higher among TTH patients with depression than among those without depression. In conclusion, anxiety and depression were more prevalent in participants with TTH than in non-headache participants. These two conditions were associated with an exacerbation of headache symptoms in individuals with TTH.
doi:10.1371/journal.pone.0165316
PMCID: PMC5082613  PMID: 27783660
22.  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
23.  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
24.  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
25.  Association of the Apolipoprotein E polymorphism with migraine: a meta-analysis 
BMC Neurology  2015;15:138.
Background
Apolipoprotein E (ApoE) gene has been reported to be associated with migraine and tension-type headache (TTH), but the results are conflicting. This study aimed to evaluate the association of ApoE with migraine by a meta-analysis.
Methods
MEDLINE, ISI Web of Knowledge, The Cochrane Central Register of Controlled Trials, and EMBASE databases were searched to identify eligible studies published in English from 2000 to 2014. Data were extracted using standardized forms. The association was assessed by relative risk (RR) with 95 % confidence intervals (CIs) using a fixed or random effects model.
Results
Four studies, comprising 649 migraineurs, 229 TTH subjects and 975 controls, met all the criteria and were included in the meta-analysis. No significant difference was found comparing genotypic and allelic frequencies in the case of migraineurs versus controls and TTH subjects versus controls. Only when migraineurs and TTH subjects were considered as a whole group, ApoE4 was found to increase the relative risk of headache by 1.48 (95 % CI 1.16, 1.90; P = 0.002), compared to controls.
Conclusions
ApoE ε4 allele is not associated with migraine susceptibility, but is positively related to headache (including migraine and TTH).
doi:10.1186/s12883-015-0385-2
PMCID: PMC4534059  PMID: 26264634

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