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1.  The Effect of Paroxetine on the Reduction of Migraine Frequency is Independent of Its Anxiolytic Effect 
Background and purpose
Anxiety is the most important precipitating factor of migraine attacks, and more than half of migraineurs have coexisting anxiety disorders. Paroxetine, an antidepressant, is one of the selective serotonin reuptake inhibitors (SSRIs) that has an anxiolytic effect, and is also known to be effective for migraine prophylaxis. The aim of this study was to determine the role of the anxiolytic effect of paroxetine on the prevention of migraine.
Methods
This study investigated migraineurs with a general anxiety disorder who visited the neurological clinic. The following efficacy variables were assessed at baseline and after taking paroxetine (20 for 12 weeks: headache frequency, Hamilton Anxiety Rating Scale (HAM-A), Headache Management Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache responsiveness to paroxetine and improvement in anxiety levels was analyzed.
Results
Twenty-four patients (aged 54.96±12.09 years, mean±SD) were included in this study. Paroxetine reduced headache frequency by 49.1% within 12 weeks (p<0.05 vs baseline). HAM-A and HMSE scores also showed an improvement, whereas there was no significant change in HDI score. The baseline HAM-A scores did not differ between paroxetine responders and nonresponders. In addition, the improvement in HAM-A score was not correlated with the reduction in headache frequency.
Conclusions
Paroxetine decreased the headache frequency and reduced anxiety levels. However, the anxiolytic effect of paroxetine was not correlated with the migraine prevention effect. These observation indicate that the anxiolytic effect of paroxetine does not contribute strongly to its prophylactic effect on migraine frequency in migraineurs with anxiety disorder.
doi:10.3988/jcn.2006.2.4.246
PMCID: PMC2854974  PMID: 20396527
Paroxetine; Migraine; Anxiety disorder; Headache frequency
2.  Association between somatic amplification, anxiety, depression, stress and migraine 
Background
The aim of this study is to investigate the associations between migraine related disability and somatosensory amplification, depression, anxiety, and stress.
Method
Fifty-five migraine patients who applied to the outpatient unit of the Neurology Department of Acibadem University School of Medicine, Maslak Hospital in Istanbul, Turkey, and twenty-eight subjects without migraine were recruited for the study. The participants were asked to complete a sociodemographic form, Migraine Disability Assessment Scale (MIDAS), Depression Anxiety Stress Scale, Somatosensory Amplification Scale (SSAS).
Results
Somatosensory amplification scores were significantly higher in the migraineurs than in the control group (29.85+/−6.63 vs 26.07+/−7.1; p=0.027). Somatosensory amplification scores and depression scores were significantly higher in migraineurs with moderate and severe disability than in patients with minimal and mild disability (31.7+/−6.4 vs 27.71+/−5.49; p=0.01, 11.27+/−8.7 vs 7.38+/−8.11; p=0.04, respectively). A significant positive correlation was found between the frequency of migraine attacks for at least three consecutive months (MIDAS A scores) and the SSAS scores (r=0.363, p=0.007) in migraineurs. The MIDAS total scores were also significantly correlated with the DASS depression subcale scores (r=0.267, p=0.04), and the DASS stress subscale scores (r=0.268, p=0.05).
Conclusion
Psychological factors, and vulnerability to bodily sensations may incease the burden of migraine. We point out that the timely assessing of somatic amplification and the evaluation of mental status would help improve the quality of life of in migraineurs.
doi:10.1186/1129-2377-14-53
PMCID: PMC3695888  PMID: 23799958
Migraine; Somatosensory amplification; Migraine disability; Depression; Anxiety; Stress
3.  Evaluating the economic costs of migraine: interest of a comparative approach 
The Journal of Headache and Pain  2003;4(Suppl 1):s63-s66.
The major aim of the paper is to give an epidemiologist's viewpoint on several points related to the evaluation of the costs of migraine and to answer some questions that are important if one wishes to decrease the burden of this disease in the general population. In spite of favourable criteria for the management of migraine, and for epidemiologic and economic studies, the relationship between migraine and cost is not so easy to study. The main reason is that this relation is not determinist, which is a condition for the validity of cost-of-illness studies. Personality of migraineurs, belief in efficacy of the healthcare system, efficacy of the first treatment and attitude of the physician interfere with the relationship between migraine and cost. In our opinion, this fact justifies, in addition to cost-of-illness studies, a comparative approach between migraineurs and non-headache subjects to better appreciate the incremental cost related to migraine
doi:10.1007/s101940300012
PMCID: PMC3611685
Key words Headache; Migraine; Cost; Case control; Prevalence
4.  Evidence of increased restless legs syndrome occurrence in chronic and highly disabling migraine 
Functional Neurology  2012;27(2):91-94.
Summary
The existence of an association between migraine and restless legs syndrome (RLS) has recently been reported, although the possible implications of this for migraine clinical presentation remain poorly understood. The objectives of this study were to determine RLS frequency in a population of migraineurs compared with healthy subjects and to assess RLS occurrence in episodic versus chronic migraine patients; the relationship between migraine-related disability and RLS comorbidity was also evaluated.
Two hundred and seventy-seven consecutive migraineurs (ICHD-II, 2004) were enrolled and compared with 200 controls; migraine was episodic in 175 and chronic in 102 patients. RLS (IRLSSG criteria, 2003) was present in 22.7% of the total sample of migraineurs and in 7.5% of the controls (p<0.0001). RLS occurred significantly more frequently in chronic compared with episodic migraineurs (34.3% vs 16%, respectively, p=0.0006); a significant association between RLS diagnosis and moderate-severe migraine-related disability was also documented (p=0.0003).
In conclusion, the results of the present study not only confirm the higher occurrence of RLS in migraine patients compared with the general population, but also suggest that RLS (the condition itself, or the disruption of sleep patterns often found in patients affected by RLS) might affect migraine clinical presentation, being associated with chronic and highly disabling migraine. These findings could have important therapeutic and prognostic implications in clinical practice.
PMCID: PMC3812772  PMID: 23158580
chronic migraine; migraine; migraine disability; restless legs syndrome; sleep
5.  Feasibility Assessment of Telephone-Administered Behavioral Treatment for Adolescent Migraine 
Headache  2007;47(9):1293-1302.
Objectives
To examine the feasibility of administering behavioral migraine management training by telephone (TAT) and the acceptability of TAT to adolescents with episodic migraine.
Methods
34 adolescents (M = 14 years) with migraine (M = 3.6 migraines/month; M = 29.2 hours duration) were randomly assigned to a two-month telephone administered behavioral migraine management program (TAT) or to a standard Triptan Treatment (TT). Outcome was assessed at three- and eight-month evaluations. Participants completed a daily migraine diary that yielded information about number, duration and severity of migraines and migraine-related disability, as well as the Migraine Specific Quality of Life Questionnaire - Adolescent. In addition, TAT participants evaluated key aspects of the TAT program using 5-point Likert-like rating scales. Lastly, the ability of adolescents to demonstrate specific headache management skills following TAT was assessed.
Results
All fifteen adolescents who entered TAT successfully demonstrated either full or partial mastery of two or more skills and nearly half demonstrated at least partial mastery of all four skills evaluated. Ninety three percent of the TAT participants reported having a positive relationship with their phone counselor. They also reported a preference for the telephone-based treatment over in-clinic visits and rated the manual and tapes as helpful. Treatment effects (in terms of percent improvement) ranged from consistently large across both evaluations for improvement in number of migraines (54% and 71%), disability equivalent hours (80% and 63%) and quality of life (44% and 48%), to moderate or variable for migraine duration (35% and 23%) and severity (30% and 34%). The TT group also showed clinically meaningful reductions in headache parameters and improvements in quality of life.
Conclusions
Completion rates for TAT were high; adolescents evaluated their experience with TAT positively and were able to exhibit key behavioral headache management skills following treatment. While clinically significant improvements in migraine and migraine-related disability/quality of life were observed with both TAT and treatment as usual (triptan therapy), the small study size and the absence of a control group do not permit conclusions about the effectiveness of either treatment. Nonetheless these results indicate TAT may be a promising treatment format for improving access to behavioral treatments for underserved adolescents and justifies further evaluation of TAT both alone and in combination with drug therapy.
doi:10.1111/j.1526-4610.2007.00804.x
PMCID: PMC2128717  PMID: 17927645
migraine; quality of life; behavior; treatment; adolescent; headache
6.  Migraine and periodic limb movement disorders in sleep in children: a preliminary case–control study 
Background
The relationships between sleep and headaches are complex and manifold. About the variety of phenomena that can disrupt the sleep macrostructure and can impact its restorative function, the periodic limb movements disorder (PLMd) can be considered as the most powerful.
No studies are known about the role of PLMd in the pathophysiology of migraine in children.
Aim of study is to assess the prevalence of PLMd and migraine and their relationship with disability and pain intensity in a pediatric sample, referred for migraine without aura by pediatricians.
Methods
After a preliminary sleep habits screening with the Sleep Disturbances Scale for Children, 34 migraine subjects affected by migraine without aura (20 M, 14 F) (mean age 9.08; SD ± 2.28) and 51 volunteers healthy children (28 M, 23 F) (mean age 9.37; SD ± 1.81) accepted to underwent overnight PSG recordings in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, in order to define the macrostructural sleep characteristics and the prevalence of PLMd. Subsequently, the migraineurs sample was studied in order to define the relationship between disability, pain intensity, therapeutical responsiveness and the presence of PLMd.
Results
In the migraineurs children group, the individuals with PLM pathological index (PLMI ≥ 5) represent the 26.47% of sample and present higher frequency (p < 0.001), intensity (p < 0.001), duration (p = 0.006) and life impairment as scored in the PedMIDAS (p < 0.001) of headache and lower efficacy of prophylactic (p = 0.001) and acute (p = 0.006) pharmacological treatment than MoA children without PLM pathological index.
Conclusions
This preliminary study indicates the potential value of the determination of the PLMd signs, and the importance of the PSG evaluation in children affected by migraine, particularly when the clinical and pharmacological management tend to fail in the attacks control.
doi:10.1186/1129-2377-14-57
PMCID: PMC3704667  PMID: 23815623
Polysomnography; Periodic limb movements; PLMd; PLMs; Children; Migraine without aura; MoA
7.  Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study 
Background
Our aim was to compare subjective and objective sleep quality and arousal in migraine and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls, interictal, preictal and postictal migraine.
Methods
Polysomnography and PT (to pressure, heat and cold) measurements were done in 34 healthy controls and 50 migraineurs. Subjective sleep quality was assessed by sleep diaries, Epworth sleepiness scale, Karolinska sleep questionnaire and Pittsburgh sleep quality index. Migraineurs who had their sleep registration more than 48 h from an attack were classified as interictal while those who were less than 48 h from an attack were classified as either preictal or postictal.
Results
Migraineurs reported more insomnia and other sleep-related symptoms than controls, but the objective sleep differences were smaller and we found no differences in daytime sleepiness. Interictal migraineurs had more awakenings (p=0.048), a strong tendency for more slow-wave sleep (p=0.050), lower thermal pain thresholds (TPT) (heat pain thresholds p=0.043 and cold pain thresholds p=0.031) than controls. Migraineurs in the preictal phase had shorter latency to sleep onset than controls (p=0.003). Slow-wave sleep correlated negatively with pressure PT and slow bursts correlated negatively with TPT.
Conclusion
Lower PT in interictal migraineurs seems related to increased sleep pressure. We hypothesize that migraineurs on the average suffer from a relative sleep deprivation and need more sleep than healthy controls. Lack of adequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.
doi:10.1186/1129-2377-14-12
PMCID: PMC3620398  PMID: 23565669
Migraine phase; Sleep; Arousal; Pain thresholds
8.  Clinical features, anger management and anxiety: a possible correlation in migraine children 
Background
Psychological factors can increase severity and intensity of headaches. While great attention has been placed on the presence of anxiety and/or depression as a correlate to a high frequency of migraine attacks, very few studies have analyzed the management of frustration in children with headache. Aim of this study was to analyze the possible correlation between pediatric migraine severity (frequency and intensity of attacks) and the psychological profile, with particular attention to the anger management style.
Methods
We studied 62 migraineurs (mean age 11.2 ± 2.1 years; 29 M and 33 F). Patients were divided into four groups according to the attack frequency (low, intermediate, high frequency, and chronic migraine). Pain intensity was rated on a 3-levels graduate scale (mild, moderate and severe pain). Psychological profile was assessed by Picture Frustration Study test for anger management and SAFA-A scale for anxiety.
Results
We found a relationship between IA/OD index (tendency to inhibit anger expression) and both attack frequency (r = 0.328, p = 0.041) and intensity (r = 0.413, p = 0.010). When we analyzed the relationship between anxiety and the headache features, a negative and significant correlation emerged between separation anxiety (SAFA-A Se) and the frequency of attacks (r = −0.409, p = 0.006). In our patients, the tendency to express and emphasize the presence of the frustrating obstacle (EA/OD index) showed a positive correlation with anxiety level (“Total anxiety” scale: r = 0.345; p = 0.033).
Conclusions
Our results suggest that children suffering from severe migraine tend to inhibit their angry feelings. On the contrary, children with low migraine attack frequency express their anger and suffer from separation anxiety.
doi:10.1186/1129-2377-14-39
PMCID: PMC3653764  PMID: 23651123
Migraine; Anger; Anxiety; Children
9.  Migraine Care Among Different Ethnicities: Do Disparities Exist? 
Headache  2006;46(5):754-765.
Objective
Evaluate whether, in a primary care setting, Caucasians (C) and African Americans (AA) with moderately to severely disabling migraines differed in regards to: utilizing the health-care system for migraine care, migraine diagnosis and treatment, level of mistrust in the health-care system, perceived communication with their physician, and perceived migraine triggers.
Background
Research has documented ethnic disparities in pain management. However, almost no research has been published concerning potential disparities in utilization, diagnosis, and/or treatment of migraine. It is also important to consider whether ethnic differences exist for trust and communication between patients and physicians, as these are essential when diagnosing and treating migraine.
Methods
Adult patients with headache (n = 313) were recruited from primary care waiting rooms. Of these, 131 (AA = 77; C = 54) had migraine, moderate to severe headache-related disability, and provided socioeconomic status (SES) data. Participants completed measures of migraine disability (MIDAS), migraine health-care utilization, diagnosis and treatment history, mistrust of the medical community, patient–physician communication (PPC), and migraine triggers. Analysis of covariance (controlling for SES and recruitment site), chi-square, and Pearson product moment correlations were conducted.
Results
African Americans were less likely to utilize the health-care setting for migraine treatment (AA = 46% vs. C = 72%, P < .001), to have been given a headache diagnosis (AA = 47% vs. C = 70%, P < .001), and to have been prescribed acute migraine medication (AA = 14% vs. C = 37%, P < .001). Migraine diagnosis was low for both groups, and <15% of all participants had been prescribed a migraine-specific medication or a migraine preventive medication despite suffering moderate to severe levels of migraine disability. African Americans had less trust in the medical community (P < .001, η2 = 0.26) and less positive PPC (P < .001, η2 = 0.11). Also, the lower the trust and communication, the less likely they were to have ever seen (or currently be seeing) a doctor for migraine care or to have been prescribed medication.
Conclusions
Migraine utilization, diagnosis, and treatment were low for both groups. However, this was especially true for African Americans, who also reported lower levels of trust and communication with doctors relative to Caucasians. The findings highlight the need for improved physician and patient education about migraine diagnosis and treatment, the importance of cultural variation in pain presentation, and the importance of communication when diagnosing and treating migraine.
doi:10.1111/j.1526-4610.2006.00453.x
PMCID: PMC2443411  PMID: 16643578
migraine; ethnicity; health-care disparities; utilization; migraine diagnosis and treatment; patient–physician communication
10.  Shared genetic factors in migraine and depression 
Neurology  2010;74(4):288-294.
Objective:
To investigate the co-occurrence of migraine and depression and assess whether shared genetic factors may underlie both diseases.
Methods:
Subjects were 2,652 participants of the Erasmus Rucphen Family genetic isolate study. Migraine was diagnosed using a validated 3-stage screening method that included a telephone interview. Symptoms of depression were assessed using the Center for Epidemiologic Studies Depression scale and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). The contribution of shared genetic factors in migraine and depression was investigated by comparing heritability estimates for migraine with and without adjustment for symptoms of depression, and by comparing the heritability scores of depression between migraineurs and controls.
Results:
We identified 360 migraine cases: 209 had migraine without aura (MO) and 151 had migraine with aura (MA). Odds ratios for depression in patients with migraine were 1.29 (95% confidence interval [CI] 0.98–1.70) for MO and 1.70 (95% CI 1.28–2.24) for MA. Heritability estimates were significant for all migraine (0.56), MO (0.77), and MA (0.96), and decreased after adjustment for symptoms of depression or use of antidepressant medication, in particular for MA. Comparison of the heritability scores for depression between patients with migraine and controls showed a genetic correlation between HADS-D score and MA.
Conclusions:
There is a bidirectional association between depression and migraine, in particular migraine with aura, which can be explained, at least partly, by shared genetic factors.
GLOSSARY
= Center for Epidemiologic Studies Depression Scale;
= confidence interval;
= Erasmus Rucphen Family;
= Hospital Anxiety and Depression Scale;
= International Headache Society;
= migraine with aura;
= migraine without aura;
= odds ratio.
doi:10.1212/WNL.0b013e3181cbcd19
PMCID: PMC3122301  PMID: 20071666
11.  Refractory migraine in a headache clinic population 
BMC Neurology  2011;11:94.
Background
Many migraineurs who seek care in headache clinics are refractory to treatment, despite advances in headache therapies. Epidemiology is poorly characterized, because diagnostic criteria for refractory migraine were not available until recently. We aimed to determine the frequency of refractory migraine in patients attended in the Headache Unit in a tertiary care center, according to recently proposed criteria.
Methods
The study population consisted of a consecutive sample of 370 patients (60.8% females) with a mean age of 43 years (range 14-86) evaluated for the first time in our headache unit over a one-year period (between October 2008 and October 2009). We recorded information on clinical features, previous treatments, Migraine Disability Assessment Score (MIDAS), and final diagnosis.
Results
Overall migraine and tension-type headache were found in 46.4% and 20.5% of patients, respectively. Refractory migraine was found in 5.1% of patients. In refractory migraineurs, the mean MIDAS score was 96, and 36.8% were medication-overusers.
Conclusions
Refractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.
doi:10.1186/1471-2377-11-94
PMCID: PMC3163184  PMID: 21806790
12.  Prevalence and risk factors for depression and anxiety among outpatient migraineurs in mainland China 
The Journal of Headache and Pain  2012;13(4):303-310.
This study aimed to investigate the prevalence and risk factors for anxiety and depression symptoms in outpatient migraineurs in mainland China. In addition, we evaluated whether the Hospital Anxiety and Depression Scale (HADS) provided sufficient validity to screen depression and anxiety. A cross-sectional study was conducted consecutively at our headache clinic. Migraine was diagnosed according to International Classification of Headache Disorders, 2nd edition (ICHD-II). Demographic characteristics and clinical features were collected by headache questionnaire. Anxiety and depression symptoms about migraineurs were assessed using HADS. Several questionnaires were simultaneously used to evaluate patients with depressive disorder including the Hamilton Depression Rating Scale-17 (HAMD), Hamilton Anxiety Rating Scale (HAMA) and HADS. Pearson correlation analysis was applied to test the validity of HADS. 176 outpatients with migraine (81.8 % female) were included. Overall, 17.6 and 38.1 % participants had depression and anxiety, respectively. Possible risk factors for depression in migraineurs included headache intensity of first onset of migraine, migraine with presymptom, migraine with family history and migraine disability. The possible risk factors for anxiety included fixed attack time of headache in one day and poor sleeping, and age represented a protective factor for anxiety. The correlation coefficient of HADS-A and HADS-D with HAMA and HAMD was 0.666 and 0.508, respectively (P < 0.01). This study demonstrates that depression and anxiety comorbidity in our mainland Chinese migraineurs are also common, and several risk factors were identified that may provide predictive value. These findings can help clinicians to identify and treat anxiety and depression in order to improve migraine management.
doi:10.1007/s10194-012-0442-9
PMCID: PMC3356469  PMID: 22466285
Anxiety; Cross-sectional study; Depression; Migraine; Risk factor
13.  Associations between Medical Student Empathy and Personality: A Multi-Institutional Study 
PLoS ONE  2014;9(3):e89254.
Background
More empathetic physicians are more likely to achieve higher patient satisfaction, adherence to treatments, and health outcomes. In the context of medical education, it is thus important to understand how personality might condition the empathetic development of medical students. Single institutional evidence shows associations between students' personality and empathy. This multi-institutional study aimed to assess such associations across institutions, looking for personality differences between students with high empathy and low empathy levels.
Methods
Participants were 472 students from three medical schools in Portugal. They completed validated adaptations to Portuguese of self-report measures of the NEO-Five Factor Inventory(NEO-FFI) and the Jefferson Scale of Physician Empathy(JSPE-spv). Students were categorized into two groups: “Bottom” (low empathy, N = 165) and “Top” (high empathy, N = 169) according to their empathy JSPE-spv total score terciles. Correlation analysis, binary logistic regression analysis and ROC curve analysis were conducted.
Results
A regression model with gender, age and university had a predictive power (pseudo R2) for belonging to the top or bottom group of 6.4%. The addition of personality dimensions improved the predictive power to 16.8%. Openness to experience and Agreeableness were important to predict top or bottom empathy scores when gender, age and university were considered.” Based on the considered predictors the model correctly classified 69.3% of all students.
Conclusions
The present multi-institutional cross-sectional study in Portugal revealed across-school associations between the Big5 dimensions Agreeableness and Openness to experience and the empathy of medical students and that personality made a significant contribution to identify the more empathic students. Therefore, medical schools may need to pay attention to the personality of medical students to understand how to enhance the empathy of medical students.
doi:10.1371/journal.pone.0089254
PMCID: PMC3956603  PMID: 24637613
14.  Shall Migraine be Considered a Simple Benign Headache Disorder? 
Migraine is a primary headache disorder which has received little attention from health care policies and physicians. This has led to ineffective management and more suffering to the patients and society. Migraine per se is a disabling disease which has its impact on the patient, family and work. It is associated with high incidence of psychiatric co-morbidities, especially depression and anxiety as well as other mental disorders. Depression affects around 80% of chronic migraineurs, an association that adds to the suffering. It has been confirmed as risk factors for developing radiographic and clinically evident ischemic cerebrovascular infarctions. Lately, it was associated with angina, myocardial infarction and intracerebral hemorrhage. Migraine plays a central role in the pathogenesis of these diseases, not just a simple association. These comorbidities and the disabilities migraine makes should change our views of migraine as a simple headache disorder, and directs our efforts to a better recognition and an effective management for the prevention of the disease associated morbidity.
PMCID: PMC3068717  PMID: 21475481
15.  Long-term effects of a sensitisation campaign on migraine: the Casilino study 
The Journal of Headache and Pain  2010;11(2):129-135.
In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs’ waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 ± 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (−13.9%; p < 0.0001) and mean HIT-6 score (−6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (−51.7%; p < 0.0001), pain intensity (−21.8%; p < 0.0001), headache duration (−18.1%; p = 0.0008) and HIT-6 score (−11.7%; p < 0.0001). Our data suggest that the effects of a “single shot” campaign are beneficial not only in a short-term perspective, but even in the long term. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency, severity or duration of headache worsen should be promptly referred to the headache clinic.
doi:10.1007/s10194-009-0183-6
PMCID: PMC3452285  PMID: 20058047
Sensitisation campaign; Migraine; Follow-up; Disability
16.  Impact of a public sensitization campaign on migraine management in France 
The Journal of Headache and Pain  2009;10(4):241-247.
Migraine is a common and frequently disabling condition. Nevertheless, many migraine sufferers do not consult for migraine, are not medically followed up and self-treat the attacks. “Tour de France of migraine” consisted of free-access conferences held in six large towns in France following a wide public information campaign. This sensitization campaign aimed at providing participants with educational information on migraine disease and on current therapies. Headache sufferers were then invited to respond to two consecutive questionnaires delivered at the end of the conferences and 3 months later to assess the influence of the information delivered on their migraine management. Tour de France of migraine recruited mainly severe migraine sufferers, most of whom had already consulted and were medically followed up. However, migraine management was often suboptimal in these subjects since most of them found their acute treatment of attacks ineffective and only few of them received a prophylactic treatment. Three months after the conferences, more than half of respondents had consulted for headaches. There was a significant improvement in migraine-related disability, as reflected by a significant decrease in mean Headache Impact Test 6-item score, which might have been related to the higher proportion of subjects receiving a prophylactic treatment of migraine. The Tour de France of migraine campaign revealed the difficulty in sensitizing migraine sufferers towards the necessity of being medically followed up. Mainly patients with severe migraine attended the conferences and derived clinical benefit from the educational program. Other strategies should be developed to reach a wider population of migraine sufferers.
doi:10.1007/s10194-009-0128-0
PMCID: PMC3451749  PMID: 19484351
Migraine; Medical follow-up; Burden of migraine; Patient education
17.  Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse 
The Journal of Headache and Pain  2011;12(4):459-466.
Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient’s outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic attitudes can be taken.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0340-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0340-6
PMCID: PMC3139058  PMID: 21499917
Chronic migraine; Medication overuse; Episodic migraine; Orbitofrontal cortex; Dorsolateral cortex
18.  Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse 
The Journal of Headache and Pain  2011;12(4):459-466.
Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient’s outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic attitudes can be taken.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-011-0340-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-011-0340-6
PMCID: PMC3139058  PMID: 21499917
Chronic migraine; Medication overuse; Episodic migraine; Orbitofrontal cortex; Dorsolateral cortex
19.  Smoking as a precipitating factor for migraine: a survey in medical students 
The Journal of Headache and Pain  2009;10(2):101-103.
Our aim was to analyse the relationship between migraine and smoking in medical students. Medical students who had already received teaching on migraine were asked to answer an ad hoc questionnaire. A total of 361 students filled in the questionnaire: 245 (68%) were women. International Headache Society criteria were fulfilled by 58 (prevalence of migraine 16%) students. A total of 74 (20%) were current smokers: 21 males (18% of men were smokers) and 53 females (22% smokers). Within those 58 students with migraine, 17 (29%) smoke: only 2 were males (14% of males with migraine smoked) while the remaining 15 were females (34% of women with migraine smoked). Within those 17 students who were smokers and migraineurs, 12 (71%) thought that smoking worsens migraine and 10 (59%) that smoking precipitates attacks. The minimum number of cigarettes which subjectively precipitates attacks was 5. Migraine prevalence in the 20s in Spain is 16%. Our data obtained in medical students suggest that smoking can be a precipitating factor for migraine attacks, as the prevalence of active smoking is one-third higher in migraineurs and as there seems to be a relationship between the number of cigarettes and the development of migraine attacks.
doi:10.1007/s10194-009-0098-2
PMCID: PMC3451643  PMID: 19184325
Migraine; Smoking
20.  Cephalalgiaphobia as a feature of high-frequency migraine: a pilot study 
Background
Cephalalgiaphobia is the fear of having a headache attack during a pain-free period that may induce patients to use analgesic in the absence of pain to prevent headache and to improve their performances. This study aims at assessing if cephalalgiaphobia is related to migraine frequency or medication overuse, and if it is per se a predictor of increase in migraine frequency.
Methods
This is a pilot prospective cohort study on 126 consecutive migraineurs referred to a tertiary Headache Centre. A headache specialist collected data regarding migraine features, frequency and medications at baseline (T0) and 2 years later (T1). Cephalalgiaphobia was investigated at T0 and T1 through a score determined by a 4 items questionnaire.
Results
Moderate-high migraine frequency was associated with higher risk of cephalalgiaphobia (p < 0.001). Chronic migraineurs with medication overuse had higher score of cephalalgiaphobia than those without medication overuse (p < 0.001). Patients with increased migraine frequency between T0 and T1 had higher cephalalgiaphobia score (p < 0.001).
Conclusions
Cephalalgiaphobia may represent a high-frequency migraine feature and may play a role in chronicization. Therefore, it should be better investigated by clinicians and treated or prevented in order to reduce the risk of disability and the increase in migraine frequency.
doi:10.1186/1129-2377-14-49
PMCID: PMC3686604  PMID: 23759110
Migraine; Cephalalgiaphobia; Anxiety disorders; Chronic migraine
21.  Empathy Training for Resident Physicians: A Randomized Controlled Trial of a Neuroscience-Informed Curriculum 
Journal of General Internal Medicine  2012;27(10):1280-1286.
Background
Physician empathy is an essential attribute of the patient–physician relationship and is associated with better outcomes, greater patient safety and fewer malpractice claims.
Objective
We tested whether an innovative empathy training protocol grounded in neuroscience could improve physician empathy as rated by patients.
Design
Randomized controlled trial.
Intervention
We randomly assigned residents and fellows from surgery, medicine, anesthesiology, psychiatry, ophthalmology, and orthopedics (N = 99, 52% female, mean age 30.6 ± 3.6) to receive standard post-graduate medical education or education augmented with three 60-minute empathy training modules.
Main Measure
Patient ratings of physician empathy were assessed within one-month pre-training and between 1–2 months post-training with the use of the Consultation and Relational Empathy (CARE) measure. Each physician was rated by multiple patients (pre-mean = 4.6 ± 3.1; post-mean 4.9 ± 2.5), who were blinded to physician randomization. The primary outcome was change score on the patient-rated CARE.
Key Results
The empathy training group showed greater changes in patient-rated CARE scores than the control (difference 2.2; P = 0.04). Trained physicians also showed greater changes in knowledge of the neurobiology of empathy (difference 1.8; P < 0.001) and in ability to decode facial expressions of emotion (difference 1.9; P < 0.001).
Conclusions
A brief intervention grounded in the neurobiology of empathy significantly improved physician empathy as rated by patients, suggesting that the quality of care in medicine could be improved by integrating the neuroscience of empathy into medical education.
doi:10.1007/s11606-012-2063-z
PMCID: PMC3445669  PMID: 22549298
empathy; randomized controlled trial; communication skills; graduate medical education; patient–physician relationship
22.  Comparison of validity and reliability of the Migraine disability assessment (MIDAS) versus headache impact test (HIT) in an Iranian population 
Iranian Journal of Neurology  2011;10(3-4):39-42.
Background
Migraine is one of the most common headaches that affect 11% or more adult population. Recently, researchers have designed two questionnaires, namely Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS), with the aim of improving migraine care. These two tests provide a standard measurement about migraine's effects on people's life style that divide patients into 4 groups (grades) based on headaches intensity. The aim of this study was to compare the validity and reliability of these two tests.
Methods
This study was designed as a multicenter, descriptive study to compare validity and reliability of Persian version of MIDAS and HIT questionnaires in 240 males and females with a migraine diagnosis according to criteria for headache and facial pain of the International Headache Society (IHS). The patients were enrolled in the study from 3 neurology clinics in Isfahan, Iran, between July 2004 and January 2005 and were evaluated at baseline (visit 1) and 4 weeks later (visit 2).
Results
According to our study, there was a high correlation between two tests (r = 0.94). This decreased their MIDAS grade in comparison to their grade HIT questionnaire.
Conclusion
These findings demonstrated that Persian version of HIT have the same validity and reliability as MIDAS. Replying to HIT questionnaire was easier than MIDAS for Iranian patients. Physicians can reliably use the Persian translation of both MIDAS and HIT questionnaires to define the severity of illness and its treatment strategy as a self-administered report by migraine patients. However, we recommend HIT for its simplicity in headache clinics.
PMCID: PMC3829228  PMID: 24250844
Migraine; Headache Impact Test; Migraine Disability Assessment; Validity; Reliability
23.  Disability and migraine: MIDAS 
The Journal of Headache and Pain  2001;2(Suppl 1):s25-s27.
Migraine is an heterogeneous disorder. Most patients are disabled both in work and in non–work activities. Different instruments to assess migraine–related disability have been developed. Among these, the migraine disability assessment (MIDAS) questionnaire is the most studied. Population–based studies have shown that MIDAS is a simple but reliable and scientifically sound instrument. This instrument improves patient–physician communication. It can help healthcare professionals to understand migraine severity in individual patients, and rapidly assess treatment needs (screening instrument). Furthermore, reduction in headache–related disability is a major goal of migraine treatment. Change in MIDAS score after treatment intervention may be a useful end point, both in everyday practice and in clinical trials. Ongoing studies will confirm the potential of MIDAS as a valid outcome measure.
doi:10.1007/s101940170005
PMCID: PMC3451820
Migraine; Disability; Migraine disability assessment (MIDAS) questionnaire; Communication; Outcome measure
24.  A review of current European treatment guidelines for migraine 
Migraine is one of the ten most disabling disorders worldwide, and despite recent developments in the management of migraine, it remains underdiagnosed and undertreated. Guidelines for the management of migraine aim to improve the quality of patient care and to assist professionals in decision making in relation to the overall healthcare process. Most European countries have published national clinical practice guidelines for migraine treatment. These guidelines need to be kept up-to-date with the most recent best clinical evidence and therapeutic strategies to ensure their optimal use to improve health outcomes. The aim of this review is to compare the English language guidelines available across Europe, analyzing differences and similarities, in order to provide a general overview to assist in assessing whether a European consensus on migraine treatment can be achieved.
doi:10.1007/s10194-009-0179-2
PMCID: PMC3452183  PMID: 20020170
National guidelines; Migraine management; Stratified care; Stepped care
25.  Effectiveness of empathy in general practice: a systematic review 
Background
Empathy as a characteristic of patient–physician communication in both general practice and clinical care is considered to be the backbone of the patient–physician relationship. Although the value of empathy is seldom debated, its effectiveness is little discussed in general practice. This literature review explores the effectiveness of empathy in general practice. Effects that are discussed are: patient satisfaction and adherence, feelings of anxiety and stress, patient enablement, diagnostics related to information exchange, and clinical outcomes.
Aim
To review the existing literature concerning all studies published in the last 15 years on the effectiveness of physician empathy in general practice.
Design and setting
Systematic literature search.
Method
Searches of PubMed, EMBASE, and PsychINFO databases were undertaken, with citation searches of key studies and papers. Original studies published in English between July 1995 and July 2011, containing empirical data about patient experience of GPs’ empathy, were included. Qualitative assessment was applied using Giacomini and Cook’s criteria.
Results
After screening the literature using specified selection criteria, 964 original studies were selected; of these, seven were included in this review after applying quality assessment. There is a good correlation between physician empathy and patient satisfaction and a direct positive relationship with strengthening patient enablement. Empathy lowers patients’ anxiety and distress and delivers significantly better clinical outcomes.
Conclusion
Although only a small number of studies could be used in this search, the general outcome seems to be that empathy in the patient–physician communication in general practice is of unquestionable importance.
doi:10.3399/bjgp13X660814
PMCID: PMC3529296  PMID: 23336477
empathy; general practice; general practitioner

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