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Background: Headache disorders are under-recognized and under-diagnosed. A principal factor in their suboptimal management is lack of headache-related training among health-care providers, especially in primary care. In Estonia, general practitioners (GPs) refer many headache patients to neurological specialist services, mostly unnecessarily. GPs request 'diagnostic' investigations, which are usually unhelpful and therefore wasteful. GP-made headache diagnoses are often arcane and non-specific, and treatments based on these are inappropriate. The aim of this study was to develop, implement and test an educational model intended to improve headache-related primary health care in Estonia. Methods: This was a controlled study consisting of baseline observation, intervention and follow-up observation using the same measures of effect. It involved six GPs in Põlva and the surrounding region in Southern Estonia, together with their future patients presenting consecutively with headache as their main complaint, all with their consent. The primary outcome measure was referral rate (RR) to neurological specialist services. Secondary measures included number of GP-requested investigations, GP-made headache diagnoses and how these conformed to standard terminology (ICD-10), and GP-recommended or initiated treatments. Results: RR at baseline ( n = 490) was 39.5 %, falling to 34.7 % in the post-intervention group ( n = 295) (overall reduction 4.8 %; p = 0.21). In the large subgroup of patients (88 %) for whom GPs made clearly headache-related ICD-10 diagnoses, RR fell by one fifth (from 40 to 32 %; p = 0.08), but the only diagnosis-related RR that showed a statistically significant reduction was (pericranial) myalgia (19 to 3 %; p = 0.03). There was a significant increase towards use of more specific diagnoses. Use of investigations in diagnosing headache reduced from 26 to 4 % ( p < 0.0001). Initiation of treatment by GPs increased from 58 to 81 % ( p < 0.0001). Conclusions: These were modest changes in GPs' entrenched behaviour. Nevertheless they were empirical evidence that GPs' practice in the field of headache could be improved by structured education. Furthermore, the changes were likely to be cost-saving. To our knowledge this study is the first to produce such evidence. [ABSTRACT FROM AUTHOR]

Background: Structural white matter abnormalities in pain-modulating, regions are present in migraine. Whether they are associated with pain chronification and with cognitive reserve is unclear. Methods: Prospective, cohort, six-month study of adult patients with episodic or chronic migraine, and controls. Cognitive reserve, quality of life, impact of pain on daily living, depression and anxiety were assessed. Participants underwent a diffusion-tensor MRI to establish the integrity of white matter tracts of three regions of interest (ROIs) implicated in pain modulation, emotion, cognition and resilience (anterior insula, anterior cingulate gyrus, and uncinate fasciculus). Results: Fifty-two individuals were enrolled: 19 episodic migraine patients, 18 chronic migraine patients, and 15 controls. The analysis of the fractional anisotropy in the ROIs showed that those patients with the poorest prognosis (i.e., those with chronic migraine despite therapy at six months -long-term chronic migraneurs) had a significantly lower fractional anisotropy in the right ROIs. Participants with higher cognitive reserve also had greater fractional anisotropy in the right anterior insula and both cingulate gyri. Multivariate analysis showed a significant association between cognitive reserve, migraine frequency, and fractional anisotropy in the right-sided regions of interest. Conclusions: Long-term chronic migraine patients show abnormalities in anterior white matter tracts, particularly of the right hemisphere, involved in pain modulation emotion, cognition and resilience. Robustness in these areas is associated with a higher cognitive reserve, which in turn might result in a lower tendency to migraine chronification. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the effectiveness of an educational and physical program in reducing behavioral or somatic symptoms along with headache, neck and shoulder pain in a working community. A controlled, non-randomized trial was carried out in a working community and 384 employees were enrolled and divided into a study group (Group 1) and a control group (Group 2). The Group 1 received a physical and educational intervention, consisting of relaxation and posture exercises and the use of visual feedback. After 6 months, the intervention was administered to the Group 2. Both groups were then followed for an additional 6 months until the end of the trial. The presence of accompanying symptoms was investigated with a semi-structured interview using a checklist of 20 items, along with headache, neck, and shoulder pain parameters and the prevalence of generalized anxiety disorder and depression, in three clinical examinations at baseline, after 6 months and after 12 months. For each symptom, as well as the presence of any type of symptom, the differences between groups in the prevalence at the clinical examinations following the baseline were evaluated by applying logistic models. After 6 months, the probability of the presence of any type of symptom was significantly lower in the Group 1 (OR 0.69, 95% CI 0.56-0.85) with respect to the Group 2. After 12 months, the pooled estimation did not show any significant difference of symptom prevalence between groups (OR 0.80, 95% CI 0.64-1.00). In conclusion, this is the first longitudinal study relative to accompanying symptoms. Its results suggest the effectiveness of this cognitive program in reducing the burden of physical and psychiatric complaints in a large, working population. [ABSTRACT FROM AUTHOR]

lthough anxiety disorders and headaches are comorbid conditions, there have been no studies evaluating the prevalence of primary headaches in patients with generalized anxiety disorder (GAD). The aim of this study was to analyze the lifetime prevalence of primary headaches in individuals with and without GAD. A total of 60 individuals were evaluated: 30 GAD patients and 30 controls without mental disorders. Psychiatric assessments and primary headache diagnoses were made using structured interviews. Among the GAD patients, the most common diagnosis was migraine, which was significantly more prevalent among the GAD patients than among the controls, as were episodic migraine, chronic daily headache and aura. Tension-type headache was equally common in both groups. Primary headaches in general were significantly more common and more severe in GAD patients than in controls. In anxiety disorder patients, particularly those with GAD, accurate diagnosis of primary headache can improve patient management and clinical outcomes. [ABSTRACT FROM AUTHOR]

Data from several studies indicate an association of headache with anxiety disorders. In this study, we assessed and differentiated anxiety disorders in 100 headache patients by using the PSWQ (Penn State Worry Questionnaire) screening tool for generalised anxiety disorder (GAD) and the ACQ (Agoraphobic Cognitions Questionnaire) and BSQ (Body Sensation Questionnaire) for panic disorder (PD). Control groups were constructed: (1) on the basis of epidemiological studies on PD and GAD in the general population and (2) by including neurological patients. 37.0% of headache patients had a GAD. 27% of headache patients met the score for PD in the BSQ, 4.0% in the ACQ. Significant results were obtained in comparison to the general population ( p < 0.001) and with regard to GAD in comparison with a sample of neurological patients ( p < 0.005). The BSQ significantly correlated with the number of medication days ( p < 0.005). The results confirm the increased prevalence of GAD in headache patients. PD seems to increase the risk of medication overuse. [ABSTRACT FROM AUTHOR]

The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients ( p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels. [ABSTRACT FROM AUTHOR]

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate whether genetic variants in the hypocretin receptor 1 ( HCRTR1) gene could modify the occurrence and the clinical features of migraine. Using a case-control strategy we genotyped 384 migraine patients and 259 controls for three SNPs in the HCRTR1 gene. Genotypic and allelic frequencies of the rs2271933 non-synonymous polymorphism resulted different ( χ = 9.872, p = 0.007; χ = 8.108, p = 0.004) between migraineurs and controls. The carriage of the A allele was associated with an increased migraine risk (OR 1.42, 95% CI 1.11-1.81). When we divided the migraine patients into different subgroups, the difference reached the level of statistical significance only in migraine without aura. The different genotypes had no significant effect on the examined clinical characteristics of the disease. In conclusion, our data supports the hypothesis that the HCRTR1 gene could represent a genetic susceptibility factor for migraine without aura and suggests that the hypocretin system may have a role in the pathophysiology of migraine. [ABSTRACT FROM AUTHOR]

ymmetric dimethylarginine (ADMA) has been found as correlated with endothelial dysfunction and oxidative stress. There are few studies regarding ADMA and nitric oxide (NO) levels in patients with migraine and alterations of ADMA and NO levels during migraine attack are not well-known. Therefore, in present study, we aimed to measure NO and ADMA levels in patients with migraine and compare them with the control group to investigate the correlation between migraine, oxidative stress and endothelial dysfunction. The migraine group consisted of 59 patients, including 22 suffering from migraine with aura and 37 suffering from migraine without aura. The control group consisted of 31 healthy volunteers without headache. The patients in migraine group were divided into subgroups based on whether attack period was present or not and whether it was migraine with or without aura. Plasma ADMA levels were measured using an enzyme-linked immunosorbent assay method. Migraine patients had higher concentrations of NO (35.6 ± 7.7, 31.0 ± 6.2 μmol/L, respectively, p = 0.005) and ADMA (0.409 ± 0.028, 0.381 ± 0.044 μmol/L, respectively, p = 0.001) levels when compared with the healthy controls. During migraine attack, NO and ADMA levels were found to be significantly higher in migraine group as compared to control group (respectively, p = 0.015, p = 0.014). Similarly, NO and ADMA levels in the patients with migraine in the interictal period were found to be significantly higher as compared to control group ( p = 0.011, p = 0.003). In conclusion, higher ADMA and NO levels of patients with migraine supported that oxidative stress and endothelial dysfunction may have a role in migraine pathogenesis. [ABSTRACT FROM AUTHOR]

The objective of this study was to test the validity, in the Chinese population, of the Lifting The Burden diagnostic questionnaire for the purpose of a population-based survey of the burden of headache in China. From all regions of China, a population-based sample of 417 respondents had completed the structured questionnaire in a door-to-door survey conducted by neurologists from local hospitals calling unannounced. They were contacted for re-interview by telephone by headache specialists who were unaware of the questionnaire diagnoses. A screening question ascertained whether headache had occurred in the last year. If they had, the specialists applied their expertise and ICHD-II diagnostic criteria to make independent diagnoses which, as the gold standard, were later compared with the questionnaire diagnoses. There were 18 refusals; 399 interviews were conducted in 202 women and 197 men aged 18-65 years (mean age 44.4 ± 12.6 years). In comparison to the specialists' diagnoses, the sensitivity, specificity, positive predictive value, negative predictive value and Cohen's kappa (95% CI) of the questionnaire for the diagnosis of migraine were 0.83, 0.99, 0.83, 0.99 and 0.82 (0.71-0.93), respectively; for the diagnosis of tension-type headache (TTH), they were 0.51, 0.99, 0.86, 0.92 and 0.59 (0.46-0.72), respectively. In conclusion, the questionnaire was accurate and reliable in diagnosing migraine (agreement level excellent), less so, but adequate, for TTH (sensitivity relatively low, false negative rate relatively high and agreement level fair to good). The non-specific features of TTH do not lend themselves well to diagnosis by questionnaire. [ABSTRACT FROM AUTHOR]

Objective is to investigate the relationship between migraine and obstructive sleep apnea in the general population. A cross-sectional population-based study. A random age and gender stratified sample of 40,000 persons aged 20-80 years residing in Akershus, Hedmark or Oppland County, Norway, were drawn by the National Population Register. A postal questionnaire containing the Berlin Questionnaire was used to classify respondents to be of either high or low risk of obstructive sleep apnea. 376 persons with high risk and 157 persons with low risk of sleep apnea aged 30-65 years were included for further investigations. They underwent an extensive clinical interview, a physical and a neurological examination by physicians, and in-hospital polysomnography. Those with apnea hypopnoea index (AHI) ≥5 were classified with obstructive sleep apnea. Migraine without aura (MO) and migraine with aura (MA) was diagnosed according to the International Classification of Headache Disorders. MO and MA occurred in 12.5 and 6.8% of the participants with obstructive sleep apnea. The logistic regression analyses showed no relationship between the two types of migraine and obstructive sleep apnea, with adjusted odds ratios for MO 1.15 (0.65-2.06) and MA 1.15 (0.95-2.39). Further, estimates using cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea, did not reveal any significant relationship between migraine and the AHI. Migraine and obstructive sleep apnea are unrelated in the general population. [ABSTRACT FROM AUTHOR]

Our aim was to describe the referred pain pattern and areas from trigger points (TrPs) in head, neck, and shoulder muscles in children with chronic tension type headache (CTTH). Fifty children (14 boys, 36 girls, mean age: 8 ± 2) with CTTH and 50 age- and sex- matched children participated. Bilateral temporalis, masseter, superior oblique, upper trapezius, sternocleidomastoid, suboccipital, and levator scapula muscles were examined for TrPs by an assessor blinded to the children's condition. TrPs were identified with palpation and considered active when local and referred pains reproduce headache pain attacks. The referred pain areas were drawn on anatomical maps, digitalized, and also measured. The total number of TrPs was significantly greater in children with CTTH as compared to healthy children ( P < 0.001). Active TrPs were only present in children with CTTH ( P < 0.001). Within children with CTTH, a significant positive association between the number of active TrPs and headache duration ( r = 0.315; P = 0.026) was observed: the greater the number of active TrPs, the longer the duration of headache attack. Significant differences in referred pain areas between groups ( P < 0.001) and muscles ( P < 0.001) were found: the referred pain areas were larger in CTTH children ( P < 0.001), and the referred pain area elicited by suboccipital TrPs was larger than the referred pain from the remaining TrPs ( P < 0.001). Significant positive correlations between some headache clinical parameters and the size of the referred pain area were found. Our results showed that the local and referred pains elicited from active TrPs in head, neck and shoulder shared similar pain pattern as spontaneous CTTH in children, supporting a relevant role of active TrPs in CTTH in children. [ABSTRACT FROM AUTHOR]

Hyperventilation is often associated with stress, an established trigger factor for migraine. Between attacks, migraine is associated with a deficit in habituation to visual-evoked potentials (VEP) that worsens just before the attack. Hyperventilation slows electroencephalographic (EEG) activity and decreases the functional response in the occipital cortex during visual stimulation. The neural mechanisms underlying deficient-evoked potential habituation in migraineurs remain unclear. To find out whether hyperventilation alters VEP habituation, we recorded VEPs before and after experimentally induced hyperventilation lasting 3 min in 18 healthy subjects and 18 migraine patients between attacks. We measured VEP P100 amplitudes in six sequential blocks of 100 sweeps and habituation as the change in amplitude over the six blocks. In healthy subjects, hyperventilation decreased VEP amplitude in block 1 and abolished the normal VEP habituation. In migraine patients, hyperventilation further decreased the already low block 1 amplitude and worsened the interictal habituation deficit. Hyperventilation worsens the habituation deficit in migraineurs possibly by increasing dysrhythmia in the brainstem-thalamo-cortical network. [ABSTRACT FROM AUTHOR]

Fasting for approximately 1 month is an obligatory practice for Muslims during the month of Ramadan. We attempted to evaluate the effect of the Ramadan fasting on the frequency of migraine attacks among observant Muslim migraine sufferers using a cohort cross-over study. Thirty-two observant Muslim migraine sufferers filled a migraine diary during the Ramadan month and the following month (control). Two patients failed to complete the fast because of migraine suffering. During the Ramadan month, the patient expressed 9.4 ± 4.3 migraine days in average (range 3-20) when compared with 3.7 ± 2.1 migraine days in average (range 1-10) during the control month ( p < 0.001). This phenomenon was associated with longer duration of migraine, lower frequency of migraine attacks, and migraine with aura. It seemed to be less pronounced in patients experiencing throbbing headaches and in married patients. Previous prophylactic therapy did not dampen this. Physicians treating Muslim migraine patients should discuss potential Ramadan month exacerbation with their patients and provide counseling regarding the prevention of dehydration and caffeine withdrawal. Pharmacological prophylactic treatment should be considered. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence implicating inflammatory cytokines and brain-derived neurotropic factor (BDNF) in the generation of migraine pain. No previous study evaluated BNDF levels during migraine attacks and there are conflicting results regarding tumor necrosis factor-alpha (TNF-alpha) serum levels. This study compared serum levels of TNF-alpha, soluble TNF receptors 1 and 2 (sTNF-R1 and sTNF-R2), and BDNF during migraine attacks and in headache-free periods. Nine patients with episodic migraine were clinically evaluated during a migraine attack and in a headache-free period. Blood sample of each patient in both occasions was collected and all serum was submitted to TNF-alpha, sTNF-R1, sTNF-R2, and BDNF determination by ELISA. There was no significant difference in the serum levels of TNF-alpha, sTNF-R1 and sTNF-R2 in migraine attack period and headache-free period. BDNF serum levels were significantly higher during migraine attack than in pain-free period. This is the first report showing that BDNF serum levels increase during migraine attack. This reinforces the view that BDNF may be implicated in the physiopathology of migraine. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to analyze the differences in neck mobility between children with chronic tension type headache (CTTH) and healthy children, and to determine the influence of cervical mobility on headache intensity, frequency and duration. Fifty children, 13 boys and 37 girls (mean age 8.5 ± 1.6 years) with CTTH associated to peri-cranial tenderness (IHS 2.3.1) and 50 age- and sex matched children without headache (13 boys, 37 girls, mean age 8.5 ± 1.8 years, P = 0.955) participated. Cervical range of motion (CROM) was objectively assessed with a cervical goniometer by an assessor blinded to the children's condition. Children completed a headache diary for 4 weeks to confirm the diagnosis. Children with CTTH showed decreased CROM as compared to children without headache for flexion ( z = −6.170; P < 0.001), extension ( z = −4.230; P < 0.001), right ( z = −4.505; P < 0.001) and left ( z = −4.768; P < 0.001) lateral-flexions, but not for rotation (right z = −0.802; P = 0.425; left z = −1.254; P = 0.213) and also for total range of motion for flexion-extension ( z = −4.267; P < 0.001) and lateral-flexion ( z = −4.801; P < 0.001), but not for rotation ( z = −1.058; P = 0.293). Within CTTH children, CROM was not correlated with headache intensity, frequency or duration. Additionally, age ( P > 0.125) or gender ( P > 0.250) did not influence CROM in either children with CTTH or without headache. Current results support the hypothesis that the cervical spine should be explored in children with headache. Further research is also needed to clearly define the potential role of the cervical spine in the genesis or maintenance of CTTH. [ABSTRACT FROM AUTHOR]

The objectives of this study were: (1) to assess relative frequency of migraine in multiple sclerosis (MS) patients using the validated self-administered diagnostic questionnaire, and to compare the migraine rates in MS outpatients to age- and gender-matched historical population controls; (2) to compare clinical and radiographic characteristics in MS patients with migraine and headache-free MS patients. We conducted a cross-sectional study to assess the demographic profiles, headache features and clinical characteristics of MS patients attending a MS clinic using a questionnaire based on the American Migraine Prevalence and Prevention (AMPP) study. We compared the relative frequency of migraine in MS clinic patients and AMPP cohort. We also compared clinical and radiographic features in MS patients with migraine to an MS control group without headache. Among 204 MS patients, the relative frequency of migraine was threefold higher than in population controls both for women [55.7 vs. 17.1%; prevalence ratio (PR) = 3.26, p < 0.001] and men (18.4 vs. 5.6%; PR = 3.29, p < 0.001). In a series of logistic regression models that controlled for age, gender, disease duration, β-interferon use, and depression, migraine in MS patients was significantly associated ( p < 0.01) with trigeminal and occipital neuralgia, facial pain, Lhermitte's sign, temporomandibular joint pain, non-headache pain and a past history of depression. Migraine status was not significantly associated with disability on patient-derived disability steps scale or T2 lesion burden on brain MRI. Migraine is three-times more common in MS clinic patients than in general population. MS-migraine group was more symptomatic than the MS-no headache group. [ABSTRACT FROM AUTHOR]