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author:("Siva, amsel")
1.  The global burden of headache in children and adolescents – developing a questionnaire and methodology for a global study 
Background
Burden of headache has been assessed in adults in countries worldwide, and is high, but data for children and adolescents are sparse. The objectives of this study were o develop a questionnaire and methodology for the global estimation of burden of headache in children and adolescents, to test these in use and to present preliminary data.
Methods
We designed structured questionnaires for mediated-group self-administration in schools by children aged 6-11 years and adolescents aged 12-17 years. In two pilot studies, we offered the questionnaires to pupils in Vienna and Istanbul. We performed face-to-face interviews in a randomly selected subsample of 199 pupils to validate the headache diagnostic questions.
Results
Data were collected from 1,202 pupils (mean 13.9 ± 2.4 years; 621 female, 581 male). The participation rate was 81.1% in Istanbul, 67.2% in Vienna. The questionnaire proved acceptable: ≤5% of participants disagreed partially or totally with its length, comprehensibility or simplicity. The sensitivity, specificity, positive and negative predictive values ranged between 0.71 and 0.76 for migraine and between 0.61 and 0.85 for tension-type headache (TTH). Cronbach’s alpha was 0.83. The 1-year prevalence of headache was 89.3%, of migraine 39.3% and of TTH 37.9%. The prevalence of headache on ≥15 days/month was 4.5%. One fifth (20.7%) of pupils with headache lost ≥1 day of school during the preceding 4 weeks and nearly half (48.8%) reported ≥1 day when they could not do activities they had wanted to. The vast majority of pupils with headache experienced difficulties in coping with headache and in concentrating during headache. Quality of life was poorer in pupils with headache than in those without.
Conclusion
These pilot studies demonstrate the usefulness of the questionnaires and feasibility of the methodology for assessing the global burden of headache in children and adolescents, and predict substantial impact of headache in these age groups.
doi:10.1186/1129-2377-15-86
PMCID: PMC4273720  PMID: 25496532
Migraine; Tension-type headache; Burden of headache; Quality of life; Global campaign against headache
2.  Onset of Progressive Phase is an Age Dependent Clinical Milestone in Multiple Sclerosis 
Background
It is unclear if all patients with RRMS ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration dependent. Some forms of progressive MS (e.g. PPMS) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age-of-progression-onset between SPMS and PPMS but may introduce unclear biases.
Objective
To confirm that onset of progressive disease course is more relevant to patient's age than the presence or duration of a pre-progression relapsing disease course in MS.
Methods
We studied a population-based MS cohort (n=210, relapsing-remitting MS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary- (PPMS; n=322), single attack- (SAPMS; n=112) and secondary-progressive (SPMS; n=421). We studied demographics (chi2 or t-test), age-of-progression-onset (t-test) and time-to-EDSS6 (Kaplan-Meier analyses).
Results
Sex-ratio (p=0.58), age-of-progression-onset (p=0.37) and time-to-EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age-of-progression-onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression.
Conclusions
Patients with RRMS do not inevitably develop progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.
doi:10.1177/1352458512451510
PMCID: PMC4029334  PMID: 22736750
Multiple sclerosis; outcome measurement; progressive; relapsing remitting; EDSS; disability
3.  Radiologically Isolated Syndrome: 5-Year Risk for an Initial Clinical Event 
PLoS ONE  2014;9(3):e90509.
Objective
To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria.
Methods
Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model.
Results
Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11–74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01–21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96–0.99); p = 0.03], sex (male) [HR: 1.93 (1.24–2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06–4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event.
Interpretation
These data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.
doi:10.1371/journal.pone.0090509
PMCID: PMC3943959  PMID: 24598783
4.  The impact of depression and ghrelin on body weight in migraineurs 
Background
Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs.
Methods
Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale.
Results
The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative.
Conclusions
Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.
doi:10.1186/1129-2377-15-23
PMCID: PMC4016645  PMID: 24762133
Body weight; Ghrelin; Migraine; Psychiatric comorbidity; Depression; Anxiety
5.  Refractory chronic cluster headache: a consensus statement on clinical definition from the European Headache Federation 
Chronic cluster headache (CCH) often resists to prophylactic pharmaceutical treatments resulting in patients’ life damage. In this rare but pragmatic situation escalation to invasive management is needed but framing criteria are lacking. We aimed to reach a consensus for refractory CCH definition for clinical and research use. The preparation of the final consensus followed three stages. Internal between authors, a larger between all European Headache Federation members and finally an international one among all investigators that have published clinical studies on cluster headache the last five years. Eighty-five investigators reached by email. Proposed criteria were in the format of the International Classification of Headache Disorders III-beta (description, criteria, notes, comments and references). Following this evaluation eight drafts were prepared before the final. Twenty-four (28.2%) international investigators commented during two rounds. Refractory CCH is described in the present consensus as a situation that fulfills the criteria of ICHD-3 beta for CCH with at least three severe attacks per week despite at least three consecutive trials of adequate preventive treatments. The condition is rare, but difficult to manage and invasive treatments may be needed. The consensus addresses five specific clinical and paraclinical diagnostic criteria followed by three notes and specific comments. Although refractory CCH may be not a separate identity these specific diagnostic criteria should help clinicians and investigators to improve patient’s quality of life.
doi:10.1186/1129-2377-15-79
PMCID: PMC4256964  PMID: 25430992
Chronic cluster headache; Refractory chronic cluster headache; Invasive treatments
6.  Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations 
Journal of Neurology  2013;261(9):1662-1676.
Neuro-Behçet’s disease (NBD) is one of the more serious manifestations of Behçet’s disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments.
doi:10.1007/s00415-013-7209-3
PMCID: PMC4155170  PMID: 24366648
Neuro-Behçet’s disease; Behçet’s disease; Delphi method; Consensus; Diagnosis; Management
7.  Framing education on headache disorders into the Global Burden of Disease Study 2010. The European Headache Federation stands ready 
Framing education on headache disorders into the Global Burden of Disease Study 2010. The European Headache Federation stands ready.
doi:10.1186/1129-2377-14-41
PMCID: PMC3671171  PMID: 23663423
9.  Impact of sex hormonal changes on tension-type headache and migraine: a cross-sectional population-based survey in 2,600 women 
The Journal of Headache and Pain  2012;13(7):557-565.
Sex hormones have some implications on headaches. The objective of the study was to investigate the effects of hormonal changes comparatively on tension-type headache (TTH) and migraine, in a population-based sample. A nationwide face-to-face prevalence study was conducted using a structured electronic questionnaire. 54.3 % of the migraineurs reported that the probability of experiencing headache during menstruation was high, whereas 3.9 % had headache only during menstruation. Forward logistic regression analysis revealed that menstruation was a significant trigger for migraine in comparison to TTH. On the other hand, nearly double the number of TTH sufferers reported “pure menstrual headache” compared to migraineurs (p = 0.02). Menstrual headaches caused significantly higher MIDAS grades. One-third of the definite migraineurs reported improvement during pregnancy and oral contraceptives significantly worsened migraine. Menopause had a slight improving effect on migraine compared to TTH. Sex hormonal changes have major impacts particularly on migraine; however, the effects of hormonal fluctuations on TTH should not be underestimated.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-012-0475-0) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-012-0475-0
PMCID: PMC3444543  PMID: 22935969
Sex hormones; Headache; Migraine; Tension-type headache; Menstruation; Menopause
10.  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
11.  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
12.  The validation of ID migraine™ screener in neurology outpatient clinics in Turkey 
The Journal of Headache and Pain  2007;8(4):217-223.
The aim of this study was to investigate the validity of the ID Migraine™ test in neurology outpatient clinics (NOCs), regardless of their presenting complaints. Patients admitted to 41 NOCs were screened. Eligible subjects (n=3682) were evaluated by a neurologist for headache diagnosis according to the International Headache Society criteria and asked the 3-item screening questions of the ID Migraine™ test. Of 3682 patients, 917 (24.9%) were diagnosed as migraine, whereas 1171 (31.8%) were ID Migraine™ test positive. The sensitivity of the ID Migraine™ test for neurologist’s diagnosis of migraine was 91.8%, specificity was 63.4%, positive predictive value was 71.9% and negative predictive value was 88.4%. The ID Migraine™ test is easy to use and a practical test that could alert the neurologist to diagnose patients having other complaints. This test would help to increase the diagnosis and treatment rate of undiagnosed migraine patients in NOCs.
doi:10.1007/s10194-007-0397-4
PMCID: PMC3451667  PMID: 17901923
Diagnosis; ID Migraine™; Migraine; Prevalence

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