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1.  Cortical plasticity in episodic and chronic cluster headache 
NeuroImage : Clinical  2014;6:415-423.
Cluster headache (CH) is characterized by recurrent episodes of excruciatingly painful, unilateral headache attacks typically accompanied by trigeminal autonomic symptoms. Due to its rhythm with alternating episodes of pain and no-pain, it is an excellent model to investigate whether structural brain changes detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the cause of the disease, may be a consequence of the underlying disease other than pain, or may simply be caused by the sensation of pain itself. We investigated 91 patients with CH in different stages of their disease using VBM and compared them to 78 age- and gender-matched healthy controls. We detected distinct regional gray matter (GM) changes in different brain regions including the temporal lobe, the hippocampus, the insular cortex and the cerebellum. The extent, location and direction of observed GM alterations depended on the state of disease and appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No hypothalamic changes were detected in CH patients compared to healthy controls. The GM changes observed in this study are highly dynamic and thereby reflect the cortical plasticity of the brain in regard to pain. This observed dynamic may provide an explanation of the diverse results of previous VBM studies in pain. Regarding CH the results suggest that the disease is more likely to be caused by a network dysfunction rather than by a single malfunctioning structure.
Highlights
•We identified gray matter (GM) changes in pain processing areas and beyond in patients suffering cluster headache (CH) compared to healthy controls•GM changes significantly differed for different courses of the disease (chronic, episodic inside bout, episodic outside bout).•GM decrease was predominantly observed in chronic CH, while episodic CH showed a more complex and partly opposite behavior.•This dynamic probably reflects the brain's adaptation capacity to changing stimuli in regard to cortical plasticity and may provide an explanation of the diverse results of previous VBM studies in pain
doi:10.1016/j.nicl.2014.10.003
PMCID: PMC4218933  PMID: 25379455
Voxel-based morphometry; Cluster headache; Chronic pain; Neuronal plasticity
2.  Diagnosis, prevalence estimation and burden measurement in population surveys of headache: presenting the HARDSHIP questionnaire 
The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. The Global Campaign against Headache is undertaking initiatives to improve and standardize methods in use for cross-sectional studies. One requirement is for a survey instrument with proven cross-cultural validity. This report describes the development of such an instrument. Two of the authors developed the initial version, which was used with adaptations in population-based studies in China, Ethiopia, India, Nepal, Pakistan, Russia, Saudi Arabia, Zambia and 10 countries in the European Union. The resultant evolution of this instrument was reviewed by an expert consensus group drawn from all world regions. The final output was the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, designed for application by trained lay interviewers. HARDSHIP is a modular instrument incorporating demographic enquiry, diagnostic questions based on ICHD-3 beta criteria, and enquiries into each of the following as components of headache-attributed burden: symptom burden; health-care utilization; disability and productive time losses; impact on education, career and earnings; perception of control; interictal burden; overall individual burden; effects on relationships and family dynamics; effects on others, including household partner and children; quality of life; wellbeing; obesity as a comorbidity. HARDSHIP already has demonstrated validity and acceptability in multiple languages and cultures. Modules may be included or not, and others (eg, on additional comorbidities) added, according to the purpose of the study and resources (especially time) available.
doi:10.1186/1129-2377-15-3
PMCID: PMC3906903  PMID: 24400999
Epidemiology; Burden of headache; Methodology; Diagnostic instrument; Global Campaign against Headache
3.  The methodology of population surveys of headache prevalence, burden and cost: Principles and recommendations from the Global Campaign against Headache 
The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. Among the initiatives of the Global Campaign against Headache to improve and standardize methods in use for cross-sectional studies, the most important is the production of consensus-based methodological guidelines. This report describes the development of detailed principles and recommendations. For this purpose we brought together an expert consensus group to include experience and competence in headache epidemiology and/or epidemiology in general and drawn from all six WHO world regions. The recommendations presented are for anyone, of whatever background, with interests in designing, performing, understanding or assessing studies that measure or describe the burden of headache in populations. While aimed principally at researchers whose main interests are in the field of headache, they should also be useful, at least in parts, to those who are expert in public health or epidemiology and wish to extend their interest into the field of headache disorders. Most of all, these recommendations seek to encourage collaborations between specialists in headache disorders and epidemiologists. The focus is on migraine, tension-type headache and medication-overuse headache, but they are not intended to be exclusive to these. The burdens arising from secondary headaches are, in the majority of cases, more correctly attributed to the underlying disorders. Nevertheless, the principles outlined here are relevant for epidemiological studies on secondary headaches, provided that adequate definitions can be not only given but also applied in questionnaires or other survey instruments.
doi:10.1186/1129-2377-15-5
PMCID: PMC3907133  PMID: 24467862
Burden of headache; Epidemiology; Guidelines; Methodology; Global Campaign against Headache
4.  The impact of headache in Europe: principal results of the Eurolight project 
Background
European data, at least from Western Europe, are relatively good on migraine prevalence but less sound for tension-type headache (TTH) and medication-overuse headache (MOH). Evidence on impact of headache disorders is very limited. Eurolight was a data-gathering exercise primarily to inform health policy in the European Union (EU). This manuscript reports personal impact.
Methods
The study was cross-sectional with modified cluster sampling. Surveys were conducted by structured questionnaire, including diagnostic questions based on ICHD-II and various measures of impact, and are reported from Austria, France, Germany, Italy, Lithuania, Luxembourg, Netherlands, Spain and United Kingdom. Different methods of sampling were used in each. The full methodology is described elsewhere.
Results
Questionnaires were analysed from 8,271 participants (58% female, mean age 43.4 y). Participation-rates, where calculable, varied from 10.6% to 58.8%. Moderate interest-bias was detected. Unadjusted lifetime prevalence of any headache was 91.3%. Gender-adjusted 1-year prevalences were: any headache 78.6%; migraine 35.3%; TTH 38.2%, headache on ≥15 d/mo 7.2%; probable MOH 3.1%. Personal impact was high, and included ictal symptom burden, interictal burden, cumulative burden and impact on others (partners and children). There was a general gradient of probable MOH > migraine > TTH, and most measures indicated higher impact among females. Lost useful time was substantial: 17.7% of males and 28.0% of females with migraine lost >10% of days; 44.7% of males and 53.7% of females with probable MOH lost >20%.
Conclusions
The common headache disorders have very high personal impact in the EU, with important implications for health policy.
doi:10.1186/1129-2377-15-31
PMCID: PMC4045992  PMID: 24884549
Headache; Migraine; Impact; Prevalence; Europe; Eurolight project; Global Campaign against Headache
5.  Headache yesterday in Europe 
Background
Surveys enquiring about burden of headache over a prior period of time (eg, 3 months) are subject to recall bias. To eliminate this as far as possible, we focused on presence and impact of headache on the preceding day (“headache yesterday”).
Methods
Adults (18-65 years) were surveyed from the general populations of Germany, Italy, Lithuania, Luxembourg and the Netherlands, from a work-force population in Spain and from mostly non-headache patient populations of Austria, France and UK. A study of non-responders in some countries allowed detection of potential participation bias where initial participation rates were low.
Results
Participation rates varied between 11% and 59% (mean 27%). Non-responder studies suggested that, because of participation bias, headache prevalence might be overestimated in initial responders by up to 2% (absolute). Across all countries, 1,422 of 8,271 participants (15-17%, depending on correction for participation bias) had headache yesterday lasting on average for 6 hours. It was bad or very bad in 56% of cases and caused absence from work or school in 6%. Among those who worked despite headache, 20% reported productivity reduced by >50%. Social activities were lost by 24%. Women (21%) were more likely than men (12%) to have headache yesterday, but impact was similar in the two genders.
Conclusions
With recall biases avoided, our findings indicate that headache costs at least 0.7% of working capacity in Europe. This calculation takes into account that most of those who missed work could make up for this later, which, however, means that leisure and social activities are even more influenced by headache.
doi:10.1186/1129-2377-15-33
PMCID: PMC4045996  PMID: 24884765
Headache; Impact; Cost of illness; Prevalence; Eurolight project; Global Campaign against Headache
6.  Influences of smoking and caffeine consumption on trigeminal pain processing 
Background
Many human and animal studies have shown the influence of nicotine and caffeine on pain perception and processing. This study aims to investigate whether smoking or caffeine consumption influences trigeminal pain processing.
Methods
Sixty healthy subjects were investigated using simultaneous recordings of the nociceptive blink reflex (nBR) and pain related evoked potentials (PREP) following nociceptive electrical stimulation on both sides of the forehead (V1). Thirty subjects were investigated before and after smoking a cigarette, as well as before and after taking a tablet of 400 mg caffeine.
Results
After smoking PREP showed decreased N2 and P2 latencies indicating central facilitation at supraspinal (thalamic or cortical) level. PREP amplitudes were not changed. NBR showed a decreased area under the curve (AUC) indicating central inhibition at brainstem level. After caffeine intake no significant changes were observed comparing nBR and PREP results before consumption.
Conclusions
Smoking influences trigeminal pain processing on supraspinal and brainstem level. In the investigated setting, caffeine consumption does not significantly alter trigeminal pain processing. This observation might help in the further understanding of the pathophysiology of pain disorders that are associated with excessive smoking habits such as cluster headache. Previous smoking has to be taken into account when performing electrophysiological studies to avoid bias of study results.
doi:10.1186/1129-2377-15-39
PMCID: PMC4068369  PMID: 24928141
Central pain processing; Inhibition; Facilitation; Nicotine; Caffeine
7.  Refractory chronic migraine: a Consensus Statement on clinical definition from the European Headache Federation 
The debate on the clinical definition of refractory Chronic Migraine (rCM) is still far to be concluded. The importance to create a clinical framing of these rCM patients resides in the complete disability they show, in the high risk of serious adverse events from acute and preventative drugs and in the uncontrolled application of therapeutic techniques not yet validated.
The European Headache Federation Expert Group on rCM presents hereby the updated definition criteria for this harmful subset of headache disorders. This attempt wants to be the first impulse towards the correct identification of these patients, the correct application of innovative therapeutic techniques and lastly aim to be acknowledged as clinical entity in the next definitive version of the International Classification of Headache Disorders 3 (ICHD-3 beta).
doi:10.1186/1129-2377-15-47
PMCID: PMC4237793  PMID: 25169882
Chronic migraine; Refractory chronic migraine; Disease progression; rCM classification
8.  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
9.  Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia 
Background
Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing.
Methods
Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS.
Results
Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported.
Conclusion
Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.
doi:10.1186/1129-2377-15-78
PMCID: PMC4256974  PMID: 25424567
Trigeminal neuralgia; Pain processing; Transcranial direct current stimulation; Clinical electrophysiology
10.  Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study 
BMC Neurology  2013;13:47.
Background
Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).
Methods
In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.
Results
All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.
Conclusion
Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.
doi:10.1186/1471-2377-13-47
PMCID: PMC3672069  PMID: 23705943
Fabry disease; Pain-related evoked potentials; Small fiber neuropathy; A-delta fibers
12.  Epidemiological profiles of patients with chronic migraine and chronic tension-type headache 
Background
We evaluated risk factors associated with chronic headache (CH) such as age, gender, smoking, frequent drinking of alcoholic beverages (drinking), obesity, education and frequent intake of acute pain drugs to test their usefulness in clinical differentiation between chronic migraine (CM) and chronic tension-type headache (CTTH).
Methods
We used baseline data from the population-based German Headache Consortium Study including 9,944 participants aged 18–65 years, screened 2003–2005, using validated questionnaires. CM and CTTH were defined according to IHS criteria. Multinominal logistic regression analyses were used to investigate the association of CM or CTTH with risk factors by estimating odds ratios (OR) and 95% confidence intervals (95%CI).
Results
The prevalence of CH was 2.6% (N = 255, mean age 46 ± 14.1 years, 65.1% women), CM 1.1% (N = 108, 45 ± 12.9 years, 73.1%), CTTH 0.5% (N = 50, 49 ± 13.9 years, 48.0%). Participants with CM compared to CTTH were more likely to be female (OR: 2.34, 95%CI: 1.00-5.49) and less likely to drink alcohol (0.31, 0.09-1.04). By trend they seemed more likely to smoke (1.81, 0.76-4.34), to be obese (1.85, 0.54-6.27), to report frequent intake of acute pain drugs (1.68, 0.73-3.88) and less likely to be low educated (0.72, 0.27-1.97).
Conclusions
We concluded that the careful assessment of different risk factors might aid in the clinical differentiation between CM and CTTH.
doi:10.1186/1129-2377-14-40
PMCID: PMC3655106  PMID: 23651174
Chronic migraine; Chronic tension-type headache; Epidemiology; Risk factors
13.  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
14.  No evidence of jugular venous valve insufficiency in patients with migraine – a controlled study 
Background
Migraine with aura is associated with patent foramen ovale and right-left-shunt. Jugular venous valve insufficiency is a further vascular anomaly. It is a frequent finding in transient global amnesia which is associated with migraine. Therefore, we investigated the prevalence of jugular venous valve insufficiency in migraine.
Methods
Subjects included in this study were participants of the population based German Headache Study on the prevalence of primary headaches. In 36 patients with migraine with aura, 50 patients with migraine without aura and 43 controls without headaches duration of backward venous flow, peak velocity flow and diameters of the jugular venous valves were assessed by color-coded duplex and Doppler sonography and compared between groups. In all migraine patients, examination was performed between and not during migraine attacks. Therefore, 9 additional patients with chronic daily headache were investigated during headache.
Results
We did not find statistically significant differences in duration of flow, peak velocity flow and diameter of the jugular venous valves in patients with migraine with aura (mean values 0.53 ± 0.43 sec; 35.47 ± 33.87 cm/sec; 8.84 ± 3.17 mm), migraine without aura (0.61 ± 0.63 sec; 33.39 ± 25.80 cm/sec; 8.15 ± 3.02 mm) or controls (0.64 ± 0.51 sec; 35.28 ± 31.76 cm/sec; 8.79 ± 2.97 mm) (group effects p-values >0.41). For all parameters results were the same for the left and the right side of jugular venae (side effects p-values >0.09). Also patients with chronic daily migraine with headache during the examination showed no differences to controls (0.52 ± 0.49 sec; 27.95 ± 21,75 cm/sec; 8.07 ± 2.71 mm) (all p-values > 0.23).
Conclusions
The prevalence of internal jugular venous valve insufficiency is not increased in persons with migraine.
doi:10.1186/1129-2377-14-52
PMCID: PMC3691823  PMID: 23782952
Migraine; Transient global amnesia; Jugular venous valve insufficiency; Ultrasound
15.  Improving quality in population surveys of headache prevalence, burden and cost: key methodological considerations 
Population-based studies of headache disorders are important. They inform needs assessment and underpin service policy for a set of disorders that are a public-health priority. On the one hand, our knowledge of the global burden of headache is incomplete, with major geographical gaps; on the other, methodological differences and variable quality are notable among published studies of headache prevalence, burden and cost.
The purpose here was to start the process of developing standardized and better methodology in these studies. An expert consensus group was assembled to identify the key methodological issues, and areas where studies might fail. Members had competence and practical experience in headache epidemiology or epidemiology in general, and were drawn from all WHO world regions. We reviewed the relevant literature, and supplemented the knowledge gathered from this exercise with experience gained from recent Global Campaign population-based studies, not all yet published. We extracted methodological themes and identified issues within them that were of key importance.
We found wide variations in methodology. The themes within which methodological shortcomings had adverse impact on quality were the following: study design; selection and/or definition of population of interest; sampling and bias avoidance; sample size estimation; access to selected subjects (managing and reporting non-participation); case definition (including diagnosis and timeframe); case ascertainment (including diagnostic validation of questionnaires); burden estimation; reporting (methods and results). These are discussed.
doi:10.1186/1129-2377-14-87
PMCID: PMC4231353  PMID: 24160915
Epidemiology; Burden of headache; Methodology; Global Campaign against Headache
16.  Quality in the provision of headache care. 1: systematic review of the literature and commentary 
The Journal of Headache and Pain  2012;13(6):437-447.
Widely accepted quality indicators for headache care would provide a basis not only for assessment of care but also, and more importantly, for its improvement. The objective of the study was to identify and summarize existing information on such indicators: specifically, did indicators exist, how had they been developed, what aspects of headache care did they relate to and how and with what utility were they being used? A systematic review of the medical literature was performed. A total of 32 articles met criteria for inclusion. We identified 55 existing headache quality indicators of which 37 evaluated processes of headache care. Most were relevant only to specific populations of patients and to care delivered in high-resource settings. Indicators had been used to describe overall quality of headache care at a national level, but not systematically applied to the evaluation and improvement of headache services in other settings. Some studies had evaluated the use of existing disability and quality of life instruments, but their findings had not been incorporated into quality indicators. Existing headache care quality indicators are incomplete and inadequate for purpose. They emphasize processes of care rather than structure or outcomes, and are not widely applicable to different levels and locations of headache care. Furthermore, they do not fully incorporate accepted evidence regarding optimal methods of care. There is a clear need for consensus-based indicators that fully reflect patients’ and public-health priorities. Ideally, these will be valid across cultures and health-care settings.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-012-0466-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s10194-012-0466-1
PMCID: PMC3464474  PMID: 22736100
Headache; Quality of care; Quality indicators; Systematic review; Global Campaign against Headache
17.  Quality in the provision of headache care. 2: defining quality and its indicators 
The Journal of Headache and Pain  2012;13(6):449-457.
The objective of this study was to define “quality” of headache care, and develop indicators that are applicable in different settings and cultures and to all types of headache. No definition of quality of headache care has been formulated. Two sets of quality indicators, proposed in the US and UK, are limited to their localities and/or specific to migraine and their development received no input from people with headache. We first undertook a literature review. Then we conducted a series of focus-group consultations with key stakeholders (doctors, nurses and patients) in headache care. From the findings we proposed a large number of putative quality indicators, and refined these and reduced their number in consultations with larger international groups of stakeholder representatives. We formulated a definition of quality from the quality indicators. Five main themes were identified: (1) headache services; (2) health professionals; (3) patients; (4) financial resources; (5) political agenda and legislation. An initial list of 160 putative quality indicators in 14 domains was reduced to 30 indicators in 9 domains. These gave rise to the following multidimensional definition of quality of headache care: “Good-quality headache care achieves accurate diagnosis and individualized management, has appropriate referral pathways, educates patients about their headaches and their management, is convenient and comfortable, satisfies patients, is efficient and equitable, assesses outcomes and is safe.” Quality in headache care is multidimensional and resides in nine essential domains that are of equal importance. The indicators are currently being tested for feasibility of use in clinical settings.
doi:10.1007/s10194-012-0465-2
PMCID: PMC3464468  PMID: 22733141
Quality of care; Definition; Indicators; Headache disorders; Global Campaign against Headache
18.  Defining the Differences Between Episodic Migraine and Chronic Migraine 
Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles.
doi:10.1007/s11916-011-0233-z
PMCID: PMC3258393  PMID: 22083262
Chronic migraine; Episodic migraine; Epidemiological profiles; Sociodemographics; Risk factors; Treatment; Chronic daily headache; Chronification; Diagnosis
19.  Will (or can) people pay for headache care in a poor country? 
We asked whether attempts to introduce headache services in poor countries would be futile on grounds of cost and unsustainability. Using data from a population-based survey in the Republic of Georgia, an exemplary poor country with limited health care, and against the background of headache-attributed burden, we report on willingness to pay (WTP) for effective headache treatment. Consecutive households were visited in areas of Tbilisi (urban) and Kakheti (rural), together representative of Georgian habitation. Biologically unrelated adults were interviewed by medical residents using a structured ICHD-II-based diagnostic questionnaire, the MIDAS questionnaire and SF-36. The bidding-game method was employed to assess WTP. Of 1,145 respondents, 50.0% had episodic headache (migraine and/or tension-type headache) and 7.6% had headache on ≥15 days/month, which was not further diagnosed. MIDAS scores were higher in people with headache on ≥15 days/month (mean 11.2) than in those with episodic headache (mean 7.0; P = 0.004). People with headache had worse scores in all SF-36 sub-scales than those without, but no differences were found between headache types. Almost all (93%) respondents with headache reported WTP averaging USD 8 per month for effective headache treatment. WTP did not correlate with headache type or frequency, or with MIDAS or SF-36 scores. Headache is common and headache-attributed burden is high in Georgia, with a profound impact on HRQoL. Even those less affected indicated WTP for effective treatment, if it were available, that would on average cover costs, which locally are low. Headache services in a poor country are potentially sustainable.
doi:10.1007/s10194-011-0398-1
PMCID: PMC3253156  PMID: 22045235
Headache-related health care; Burden of disease; Quality of life; Health economics; Willingness to pay; Republic of Georgia
20.  Will (or can) people pay for headache care in a poor country? 
We asked whether attempts to introduce headache services in poor countries would be futile on grounds of cost and unsustainability. Using data from a population-based survey in the Republic of Georgia, an exemplary poor country with limited health care, and against the background of headache-attributed burden, we report on willingness to pay (WTP) for effective headache treatment. Consecutive households were visited in areas of Tbilisi (urban) and Kakheti (rural), together representative of Georgian habitation. Biologically unrelated adults were interviewed by medical residents using a structured ICHD-II-based diagnostic questionnaire, the MIDAS questionnaire and SF-36. The bidding-game method was employed to assess WTP. Of 1,145 respondents, 50.0% had episodic headache (migraine and/or tension-type headache) and 7.6% had headache on ≥15 days/month, which was not further diagnosed. MIDAS scores were higher in people with headache on ≥15 days/month (mean 11.2) than in those with episodic headache (mean 7.0; P = 0.004). People with headache had worse scores in all SF-36 sub-scales than those without, but no differences were found between headache types. Almost all (93%) respondents with headache reported WTP averaging USD 8 per month for effective headache treatment. WTP did not correlate with headache type or frequency, or with MIDAS or SF-36 scores. Headache is common and headache-attributed burden is high in Georgia, with a profound impact on HRQoL. Even those less affected indicated WTP for effective treatment, if it were available, that would on average cover costs, which locally are low. Headache services in a poor country are potentially sustainable.
doi:10.1007/s10194-011-0398-1
PMCID: PMC3253156  PMID: 22045235
Headache-related health care; Burden of disease; Quality of life; Health economics; Willingness to pay; Republic of Georgia
21.  Evaluating integrated headache care: a one-year follow-up observational study in patients treated at the Essen headache centre 
BMC Neurology  2011;11:124.
Background
Outpatient integrated headache care was established in 2005 at the Essen Headache Centre in Germany. This paper reports outcome data for this approach.
Methods
Patients were seen by a neurologist for headache diagnosis and recommendation for drug treatment. Depending on clinical needs, patients were seen by a psychologist and/or physical therapist. A 5-day headache-specific multidisciplinary treatment programme (MTP) was provided for patients with frequent or chronic migraine, tension type headache (TTH) and medication overuse headache (MOH). Subsequent outpatient treatment was provided by neurologists in private practice.
Results
Follow-up data on headache frequency and burden of disease were prospectively obtained in 841 patients (mean age 41.5 years) after 3, 6 and 12 months. At baseline mean headache frequency was 18.1 (SD = 1.6) days per month, compared to measurement at 1 year follow-up a mean reduction of 5.8 (SD = 11.9) headache days per month was observed in 486 patients (57.8%) after one year (TTH patients mean: -8.5 days per month; migraine mean: -3.2 days per month, patients with migraine and TTH mean: -5.9 days per month). A reduction in headache days ≥ 50% was observed in 306 patients (36.4%) independent of diagnosis, while headache frequency remains unchanged in 20.9% and increase in 21.3% of the patient.
Conclusion
Multidisciplinary outpatient headache centres offer an effective way to establish a three-tier treatment offer for difficult headache patients depending on clinical needs.
doi:10.1186/1471-2377-11-124
PMCID: PMC3203041  PMID: 21985562
24.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence
25.  Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study 
The Journal of Headache and Pain  2011;12(4):475-483.
This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.
doi:10.1007/s10194-011-0348-y
PMCID: PMC3139052  PMID: 21544647
Migraine; Headache; Multidisciplinary treatment program; Adherence

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