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52. The association between headache and Val158Met polymorphism in the catechol-O-methyltransferase gene: the HUNT Study.

Author

Hagen K, Pettersen E, Stovner LJ, Skorpen F, and Zwart J

Abstract

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception, and one study has found that migraine was less likely among those with the Val/Val polymorphism. In the 1995-97 Nord-Trøndelag Health (HUNT) Study, the association between the Val158Met polymorphism and headache was evaluated in a random sample of 2451 individuals. No association between Val158Met polymorphism and migraine was found. Among women, a lower prevalence of non-migrainous headache was found among individuals with the Val/Val genotype than among those with other genotypes (26.2% vs. 33.6%, p=0.04). That non-migrainous headache was less likely among women with the Val/Val genotype may be an incidental finding, but should be investigated in further studies. [ABSTRACT FROM AUTHOR]

Published
2006
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57. Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway.

Author

Hagen K, Stovner LJ, Vatten L, Holmen J, Zwart J, Bovim G, Hagen, K, Stovner, L J, Vatten, L, Holmen, J, Zwart, J-A, and Bovim, G

Abstract

Objectives: Prevalence studies of the association between blood pressure and headache have shown conflicting results. The aim was to analyse the relation between blood pressure and risk of headache in a prospective study.Methods: A total of 22 685 adults not likely to have headache, had their baseline blood pressure measured in 1984-6, and responded to a headache questionnaire at follow up 11 years later (1995-7). The relative risk of headache (migraine or non-migrainous headache) was estimated in relation to blood pressure at baseline.Results: Those with a systolic blood pressure of 150 mm Hg or higher had 30% lower risk (risk ratio (RR)=0.7, 95% CI 0.6-0.8) of having non-migrainous headache at follow up compared with those with systolic pressure lower than 140 mm Hg. For diastolic blood pressure, the risk of non-migrainous headache decreased with increasing values, and these findings were similar for both sexes, and were not influenced by use of antihypertensive medication. For migraine, there was no clear association with blood pressure.Conclusion: In the first prospective study of blood pressure and the risk of headache, high systolic and diastolic pressures were associated with reduced risk of non-migrainous headache. One possible explanation may be the phenomenon of hypertension associated hypalgesia, which probably involves the baroreflex system influencing nociception in the brain stem or spinal cord. [ABSTRACT FROM AUTHOR]

Published
2002

58. A Human Model for Evaluating Autonomic and Muscle Response to Stressful Work.

Author

Nilsen, KBM, Sand, T, Westgaard, R, Gaarseth, M, Helde, G, Rø, M, White, L, and Stovner, LJ

Subjects
MYALGIA, AUTONOMIC nervous system, PHYSIOLOGICAL stress
Abstract

Background: Pain in the head and shoulder-neck area is a frequent symptom, and a major cause of sick leave and work disability. The physiology behind the pain is most often unknown, and thus difficult to treat. Causal factors for muscle pain are hypothesised to be primarily muscular, vascular, neuropathic, and psychological. The level of pain has generally not been shown to correlate to the level of muscle activity, but a recent hypothesis suggest that pain can be connected to selective overactivity of low-threshold motor units. Another hypothesis is that an autonomic nervous system dysfunction may contribute to pain generation. Such dysfunction may also involve muscular firing patterns. There is for instance evidence of muscular tension induced by sympathetic stimulation in rabbits. A high level of "perceived tension" is a risk factor for developing pain in shoulder and neck. The current experimental model is designed to reveal possible relationships between pain development in the head, shoulder and neck regions and autonomic response to a stressful task. The model also makes it possible to look for any correlation between the autonomic nervous system and muscle activity. Material: 71 persons have been included so far. This group consists of patients with migraine, cervicogenic headache, tension-type headache, chronic myofascial shoulder and neck pain, and fibromyalgia. Healthy controls have also been included. The investigator in the laboratory is blinded for the inclusion status of the subject both during the test procedure and when analysing the data afterwards. Methods: Before the laboratory-investigation all subjects are given a structured interview. Procedure: The subject sits comfortably in a regular office chair, responding to a reaction-time test presented on a PC monitor by pressing one of two keys. The execution is self-paced, but the subject is instructed to carry out the test as fast and accurately as possible. This cognitive stressor lasts ... [ABSTRACT FROM AUTHOR]

Published
2001

60. Photophobia and phonophobia in tension-type and cervicogenic headache.

Author

Vanagaite Vingen, J and Stovner, LJ

Subjects
*PAIN, *HEADACHE, *PHOBIAS
Abstract

Light and sound-induced discomfort and pain thresholds were measured in 26 patients with cervicogenic headache, in 40 patients with tension-type headache, and in 100 headache-free controls. Neither headache group was significantly different as to photophobia and phonophobia, but both were significantly more sensitive to light and sound than controls (p<0.0001), even when patients were tested in the headache-tree period (p<0.05). Episodic and chronic tension-type headache had similar photo- and phonophobia thresholds (p≥0.7). Tension-type headache patients were more photo- and phonophobic during headache than outside attack (p<0.05), but this was not true for cervicogenic headache (p≥0.56). In cervicogenic headache patients, photophobia (p<0.05) but not phonophohia (p=0.28) was greater on the symptomatic side than on the non-symptomatic side. [ABSTRACT FROM AUTHOR]

Published
1998
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63. Prevalence of haemochromatosis gene mutations in Parkinson's disease.

Author

Aamodt AH, Stovner LJ, Thorstensen K, Lydersen S, White LR, Aasly JO, Aamodt, Anne Hege, Stovner, Lars Jacob, Thorstensen, Ketil, Lydersen, Stian, White, Linda R, and Aasly, Jan O

Abstract

The aim of this study was to investigate a possible association between haemochromatosis (HFE) gene mutations and the prevalence of Parkinson's disease. The HFE gene encodes a protein that modulates iron absorption. Several studies have documented increased iron levels in the basal ganglia in patients with Parkinson's disease. In a study on patients with concurrent hereditary haemochromatosis and Parkinson's disease, abnormal deposition of iron in the basal ganglia was suggested as an inductor of Parkinson's disease. In this study, genotype frequencies of the HFE mutations C282Y, H63D and S65C were estimated in 388 patients with Parkinson's disease and compared with frequencies found in comparable studies. No significant differences were found in frequencies between the patients and comparable populations. This study does not indicate increased susceptibility to Parkinson's disease in HFE gene mutation carriers in Norway. [ABSTRACT FROM AUTHOR]

Published
2007

64. Increased Incorporation of L-(U-14C)serine into Phosphatidylserine in Polymorphonuclear Cells from Cluster Headache Patients

Author

Fragoso, YD, Stovner, LJ, Bjerve, KS, and Sjaastad, O

Abstract

It has recently been demonstrated by our group that polymorphonuclear cells (PMNs) from cluster headache patients incorporate more arachidonic acid (AA) into phosphatidylserine (PS) than PMNs from controls. In the present report, the incorporation of L-(U-14C)serine into PS in PMNs from 14 healthy volunteers and 12 cluster headache patients was studied. PMNs from controls incorporated 1194 ± 578 (mean ± SD) cpm of L-(U-14C)serine into PS, 268 ± 292 cpm into phosphatidylethanolamine, and 57 ± 71 cpm into sphingomyeline. The corresponding figures in cluster headache patients were 2365 ± 841 cpm, 291 ± 207 cpm, and 88 ± 66 cpm, respectively. Incorporation of L-(U-14C)serine into PS was significantly increased (p< 0.0004) in PMNs from cluster headache patients, whereas no significant difference was seen in other lipids. The results confirm that patients with cluster headache have an increased incorporation of precursors into PS in isolated PMNs, and they indicate that this is due to an increased de novosynthesis of PS.

Published
1989
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65. Cluster Headache: Increased Incorporation of (1–14C)Arachidonic Acid into Phosphatidylserine in Polymorphonuclear Cells

Author

Fragoso, YD, Seim, A, Stovner, LJ, Mack, M, Bjerve, KS, and Sjaastad, O

Abstract

Vasoactive metabolites deriving from arachidonic acid (AA) have been considered as putative mediators in the pathogenesis of various types of headache. In the present study we therefore compare the ability to synthesize AA containing precursor phospholipids in polymorphonuclear cells (PMNs) from healthy controls and cluster headache patients. 3.7% ± 1.4 (mean ± SD) of the (1– 14C)AA incorporated into total PMN glycerophospholipids (GPLs) was recovered in the phosphatidylserine (PS) in a group of cluster headache patients (n= 12). This was almost twice the value of 1.9% ± 0.8% found in a corresponding group of 24 healthy controls (p< 0.001). A significant decrease in the incorporation of (1– 14C)AA into phosphatidylcholine (PC) (p< 0.01) and an increase in the incorporation of (1– 14C)AA into phosphatidyletanolamine (PE) (p< 0.05) were also found in cluster headache patients when compared to the control group. The increased incorporation of (1– 14C)AA into PS in PMNs from this group of patients is interesting because PS plays an important role in the activation of protein kinase C, an enzyme involved in transmembrane signalling. The clinical implications of the present findings in cluster headache, if any, cannot yet be defined.

Published
1989
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66. Cluster Headache: Incorporation of (1–14C)oleic Acid into Phosphatidylserine in Polymorphonuclear Cells

Author

Fragoso, YD, Stovner, LJ, Bjerve, KS, and Sjaastad, O

Abstract

As recently demonstrated by our group, polymorphonuclear cells (PMNs) from cluster headache patients have an increased ability to incorporate arachidonic acid (AA) and L-serine into phosphatidylserine (PS). To evaluate whether there is an increased incorporation into PS also from fatty acids not involved in eicosanoid metabolism, PMNs from controls (n= 14) and cluster headache patients (n= 12) were incubated with (1– 14C)oleic acid. After 1 h 2.7% ± 1.1 (mean value ± SD) of the glycerophospholipid radioactivity was found in PS in controls, whereas 4.2% ± 1.2 was found in cluster headache patients (p< 0.005). For phosphatidylcholine (PC) the corresponding figures were 74.2 ± 5.4 in controls and 66.7 ± 7.6 in cluster headache patients (p< 0.01). The results suggest that the de novobiosynthesis of PS is increased and the biosynthesis of PC is decreased in cluster headache. The results may have an effect on the role of PS as an obligate protein kinase C activator.

Published
1989
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67. The burden attributable to headache disorders in India: estimates from a community-based study in Karnataka State

Author

Rao, GN, Kulkarni, GB, Gururaj, G, Stovner, LJ, and Steiner, TJ

Subjects
Adult, Male, Rural Population, Headache Disorders, Primary, Urban Population, Migraine Disorders, Clinical Neurology, India, Burden, Young Adult, Cost of Illness, Headache disorders, Headache Disorders, Secondary, Prevalence, Humans, Willingness to pay, Migraine, Aged, Middle Aged, Medication-overuse headache, Health policy, Tension-type headache, South-East Asia, Global campaign against headache, Anesthesiology and Pain Medicine, Female, Research Article
Abstract

Background: Headache disorders are common worldwide, causing pain and disability. India appears to have a very high prevalence of migraine, and of other headache disorders in line with global averages. Our objective was to estimate the burdens attributable to these disorders in order to inform health policy. Methods: In a door-to-door survey, biologically unrelated adults (18–65 years) were randomly sampled from urban and rural areas of Bangalore and interviewed by trained researchers. The validated structured questionnaire enquired into several aspects of burden. Results: Of 2,329 participants (non-participation rate 7.4 %), 1,488 (63.9 %; 621 male, 867 female) reported headache in the preceding year. Symptom burden was high. Migraine (1-year prevalence 25.2 %) occurred on average on 28 days/ year but, in 38.0 % of cases (ie, 9.6 % of adults), on ≥3 days/month (≥10 % of days). All causes of headache on ≥15 days/ month (prevalence 3.0 %) occurred on a mean of 245 days/year. Both these and migraine were rated severe in intensity. Participants with headache lost 4.3 % of productive time; those with migraine lost 5.8 % (equating to 1.5 % fromthe adult population). Lost paid worktime accounted for 40 % of this, probably detracting directly from GDP. We estimated population-level disability attributable to migraine using the disability weight from GBD2010 for the ictal state (0.433). Mean disability per person with migraine was 1.8 %, reducing the functional capacity of the entire adult population by 0.46 %. Fewer than one quarter of participants with headache had engaged with health-care services for headache in the last year. Actual expenditure on headache care was greatest among those with headache on ≥15 days/month (especially probable medication-overuse headache), but otherwise not high. Expressed willingness to pay for effective treatment for headache was higher, signalling dissatisfaction with current treatments. Conclusions: In Karnataka State, southern India, prevalent headache disorders, especially migraine, give rise to commensurately heavy burdens. Limited access to health care fails to alleviate these. Structured headache services, with their basis in primary care, are the most efficient, effective, affordable and equitable solution. They could be implemented within the health-care infrastructure of India and are likely to be cost-saving. This solution requires political will, itself dependent on awareness. Keywords: Headache disorders, Migraine, Tension-type headache, Medication-overuse headache, Burden, Health policy, Willingness to pay, India, South-East Asia, Global campaign against headache © 2015 Rao et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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68. Headache disorders and public ill-health in India: prevalence estimates in Karnataka State

Author

Kulkarni, GB, Rao, GN, Gururaj, G, Stovner, LJ, and Steiner, TJ

Subjects
Adult, Male, Headache Disorders, Primary, Epidemiology, Health Status, QUESTIONNAIRE, Clinical Neurology, India, Surveys and Questionnaires, Headache disorders, Prevalence, Humans, GLOBAL CAMPAIGN, Migraine, Population-based study, Science & Technology, Neurology & Neurosurgery, Global Campaign against Headache, TO-DOOR SURVEY, Neurosciences, Middle Aged, Medication-overuse headache, Health policy, Tension-type headache, Cross-Sectional Studies, Anesthesiology and Pain Medicine, Female, Neurosciences & Neurology, Public Health, BURDEN, Life Sciences & Biomedicine, METHODOLOGY, POPULATION SURVEYS
Abstract

Background: Primary headache disorders are among the commonest disorders, affecting people in all countries. India appears to be no exception, although reliable epidemiological data on headache in this highly populous country are not available. Such information is needed for health-policy purposes. Our aim was to estimate the prevalence of each of the headache disorders of public-health importance, and examine their sociodemographic associations, in urban and rural populations of Karnataka, south India. Methods: In a door-to-door survey, 2,329 biologically unrelated adults (aged 18–65 years) were randomly sampled from urban (n = 1,226) and rural (n = 1,103) areas in and around Bangalore and interviewed by trained researchers using a pilot-tested, validated, structured questionnaire. ICHD-II diagnostic criteria were applied. Results: The observed 1-year prevalence of any headache was 63.9 %, with a female preponderance of 4:3. The age-standardised 1 year prevalence of migraine was 25.2 %; prevalence was higher among females than males (OR: 2.1 [1.7-2.6]) and among those from rural areas than urban (OR = 1.5 [1.3-1.8]). The age-standardized 1 year prevalence of TTH was 35.1 %, higher among younger people. The estimated prevalence of all headache on ≥15 days/ month was 3.0 %; that of pMOH was 1.2 %, five-times greater among females than males and with a rural preponderance. Conclusions: There is a very high 1 year prevalence of migraine in south India (the mean global prevalence is estimated at 14.7 %). Explanations probably lie in cultural, lifestyle and/or environmental factors, although the observed associations with female gender and rural dwelling are usual. Levels of TTH, pMOH and other headache on ≥15 days/month are similar to global averages, while the very strong association of pMOH with female gender requires explanation. Until another study is conducted in the north of the country, these are the best data available for health policy in a population of over 1.2 billion people. Keywords: Headache disorders; Migraine; Tension-type headache; Medication-overuse headache; Epidemiology; Population-based study; Prevalence; Health policy; Global Campaign against Headache © 2015 Kulkarni et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

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70. Angiotensin-converting enzyme gene insertion/deletion polymorphism in migraine patients.

Author

Tronvik E, Stovner LJ, Bovim G, White LR, Gladwin AJ, Owen K, Schrader H, Tronvik, Erling, Stovner, Lars J, Bovim, Gunnar, White, Linda R, Gladwin, Amanda J, Owen, Kathryn, and Schrader, Harald

Abstract

Background: The main objective of this study was to investigate the angiotensin converting enzyme (ACE) genotype as a possible risk factor for migraine (both with and without aura) compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to ACE genotype.Methods: 347 migraine patients aged 18-68 (155 migraine without aura (MoA), 187 migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR) was performed on the genomic DNA samples to obtain the ACE insertion (I)/deletion(D) polymorphisms.Results: No significant differences between migraine patients and controls were found with regard to ACE genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups.Conclusion: In our sample there is no association between ACE genotype or allele frequency and migraine. In addition, ACE genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics. [ABSTRACT FROM AUTHOR]

Published
2008
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72. Photic EEG-driving responses related to ictal phases and trigger sensitivity in migraine: A longitudinal, controlled study.

Author

Bjørk, M., Hagen, K., Stovner, LJ, and Sand, T.

Subjects
*MIGRAINE, *HEADACHE, *PATHOLOGICAL physiology, *EVOKED potentials (Electrophysiology), *ELECTROENCEPHALOGRAPHY
Abstract

Introduction: Photic driving is believed to be increased in migraineurs and has been interpreted as a sign of cortical hyperexcitability. However, most previous studies have included patients in various phases of the migraine cycle. The results are, therefore, difficult to interpret as neurophysiological abnormalities tend to accumulate close to the attack in migraineurs.Subjects and Methods: We recorded steady state visual evoked EEG-responses (SSVEPs) for 6, 12, 18 and 24 Hz flash stimuli from 33 migraineurs without aura, eight migraineurs with aura and 32 healthy controls. Interictal recordings were compared pair-wise with recordings before, during and after attack, as well as with EEGs from healthy controls. Driving power was also correlated with sensory hypersensitivity and severity of migraine.Results: Between attacks, driving responses to 18 Hz and 24 Hz were attenuated in migraineurs without aura. Driving power of 12 Hz increased before the attack. Attack trigger sensitivity, photophobia, pain intensity and a family history of migraine were related to decreased and/or symmetric photic driving.Conclusions: Earlier results may have overestimated the driving response in migraine due to inclusion of recordings during the preictal interval and/or habituation among controls. Abnormal photic driving may be related to the pathophysiology of clinical sensory hypersensitivity. [ABSTRACT FROM PUBLISHER]

Published
2011
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73. Low socio-economic status is associated with increased risk of frequent headache: a prospective study of 22 718 adults in Norway.

Author

Hagen, K, Vatten, L, Stovner, LJ, Zwart, J-A, Krokstad, S, and Bovim, G

Subjects
*HEADACHE, *SOCIAL status
Abstract

Prevalence studies exploring the relation between socio-economic status (SES) and headache have shown conflicting results. This is the first prospective study analysing the relation between SES and risk of headache. A total of 22 685 adults not likely to suffer from headache were classified by SES at baseline in 1984–1986, and responded to a headache questionnaire in a follow-up 11 years later (1995–1997). SES at baseline was defined by educational level, occupation, and income. The risk of frequent headache and chronic headache (>6, and ≥15 days/month, respectively) at follow-up was estimated in relation to SES. When defining SES by educational level or type of occupation, low status was associated with increased risk of frequent and chronic headache at follow-up. The risk of frequent and chronic headache decreased with increasing individual income, but only among men. We conclude that individuals with low SES had higher risk of frequent and chronic headache than people with high SES. [ABSTRACT FROM AUTHOR]

Published
2002
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74. Sleep quality, arousal and pain thresholds in tension-type headache: A blinded controlled polysomnographic study.

Author

Engstrøm, M, Hagen, K, Bjørk, M, Stovner, LJ, Stjern, M, and Sand, T

Subjects
*SOMNOLOGY, *HEADACHE, *PAIN management, *CHRONIC pain, *INSOMNIA
Abstract

Introduction: We aimed to compare subjective and objective sleep quality in tension-type headache (TTH) patients and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls and TTH patients. Methods: A blinded cross-sectional study where polysomnography (PSG) and PT (to pressure, heat and cold) measurements were done in 20 patients with TTH (eight episodic (ETTH) and twelve chronic (CTTH) TTH) and 29 healthy controls. Sleep diaries and questionnaires were applied. Results: TTH patients had more anxiety (p=0.001), insomnia (p<0.0005), daytime tiredness (p<0.0005) and reduced subjective sleep quality (p<0.0005) compared to healthy controls. Sleep diaries revealed more long awakenings in TTH (p=0.01) but no total sleep-time differences. TTH patients had more slow-wave sleep (p=0.002) and less fast arousals (p=0.004) in their PSGs. CTTH subjects had lower pressure PT (p=0.048) and more daytime sleepiness than the controls (p=0.039). Among TTH lower cold PT (CPT) correlated inversely with light sleep (N1) (r=-0.49, p=0.003) while slow arousals correlated inversely with headache-frequency (r=-0.64, p=0.003). Conclusions: We hypothesize that TTH patients need more sleep than healthy controls and might be relatively sleep deprived. Inadequate sleep may also contribute to increased pain sensitivity and headache frequency in TTH. [ABSTRACT FROM AUTHOR]

Published
2014
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75. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Author

James, Spencer L., Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M., Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Zegeye, Abera, Semaw F., Abil, Olifan Zewdie, Abraha, Haftom Niguse, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen M. E., Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Acharya, Pawan, Ackerman, Ilana N., Adamu, Abdu A., Adebayo, Oladimeji M., Adekanmbi, Victor, Adetokunboh, Olatunji O., Adib, Mina G., Adsuar, Jose C., Afanvi, Kossivi Agbelenko, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Agesa, Kareha M., Aggarwal, Rakesh, Aghayan, Sargis Aghasi, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akinyemiju, Tomi, Akseer, Nadia, Al-Aly, Ziyad, Al-Eyadhy, Ayman, Al-Mekhlafi, Hesham M., Al-Raddadi, Rajaa M., Alahdab, Fares, Alam, Khurshid, Alam, Tahiya, Alashi, Alaa, Alavian, Seyed Moayed, Alene, Kefyalew Addis, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Alouani, Mohamed M. L., Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T., Aminde, Leopold N., Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T., Anwari, Palwasha, Arabloo, Jalal, Arauz, Antonio, Aremu, Olatunde, Ariani, Filippo, Armoon, Bahroom, Ärnlöv, Johan, Arora, Amit, Artaman, Al, Aryal, Krishna K., Asayesh, Hamid, Asghar, Rana Jawad, Ataro, Zerihun, Atre, Sachin R., Ausloos, Marcel, Avila-Burgos, Leticia, Avokpaho, Euripide F. G. A., Awasthi, Ashish, Ayala Quintanilla, Beatriz Paulina, Ayer, Rakesh, Azzopardi, Peter S., Babazadeh, Arefeh, Badali, Hamid, Badawi, Alaa, Bali, Ayele Geleto, Ballesteros, Katherine E., Ballew, Shoshana H., Banach, Maciej, Banoub, Joseph Adel Mattar, Banstola, Amrit, Barac, Aleksandra, Barboza, Miguel A., Barker-Collo, Suzanne Lyn, Bärnighausen, Till Winfried, Barrero, Lope H., Baune, Bernhard T., Bazargan-Hejazi, Shahrzad, Bedi, Neeraj, Beghi, Ettore, Behzadifar, Masoud, Behzadifar, Meysam, Béjot, Yannick, Belachew, Abate Bekele, Belay, Yihalem Abebe, Bell, Michelle L., Bello, Aminu K., Bensenor, Isabela M., Bernabe, Eduardo, Bernstein, Robert S., Beuran, Mircea, Beyranvand, Tina, Bhala, Neeraj, Bhattarai, Suraj, Bhaumik, Soumyadeep, Bhutta, Zulfiqar A., Biadgo, Belete, Bijani, Ali, Bikbov, Boris, Bilano, Ver, Bililign, Nigus, Bin Sayeed, Muhammad Shahdaat, Bisanzio, Donal, Blacker, Brigette F., Blyth, Fiona M., Bou-Orm, Ibrahim R., Boufous, Soufiane, Bourne, Rupert, Brady, Oliver J., Brainin, Michael, Brant, Luisa C., Brazinova, Alexandra, Breitborde, Nicholas J. K., Brenner, Hermann, Briant, Paul Svitil, Briggs, Andrew M., Briko, Andrey Nikolaevich, Britton, Gabrielle, Brugha, Traolach, Buchbinder, Rachelle, Busse, Reinhard, Butt, Zahid A., Cahuana-Hurtado, Lucero, Cano, Jorge, Cárdenas, Rosario, Carrero, Juan J., Carter, Austin, Carvalho, Félix, Castañeda-Orjuela, Carlos A., Castillo Rivas, Jacqueline, Castro, Franz, Catalá-López, Ferrán, Cercy, Kelly M., Cerin, Ester, Chaiah, Yazan, Chang, Alex R., Chang, Hsing-Yi, Chang, Jung-Chen, Charlson, Fiona J., Chattopadhyay, Aparajita, Chattu, Vijay Kumar, Chaturvedi, Pankaj, Chiang, Peggy Pei-Chia, Chin, Ken Lee, Chitheer, Abdulaal, Choi, Jee-Young J., Chowdhury, Rajiv, Christensen, Hanne, Christopher, Devasahayam J., Cicuttini, Flavia M., Ciobanu, Liliana G., Cirillo, Massimo, Claro, Rafael M., Collado-Mateo, Daniel, Cooper, Cyrus, Coresh, Josef, Cortesi, Paolo Angelo, Cortinovis, Monica, Costa, Megan, Cousin, Ewerton, Criqui, Michael H., Cromwell, Elizabeth A., Cross, Marita, Crump, John A., Dadi, Abel Fekadu, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I., Daryani, Ahmad, Das Gupta, Rajat, Das Neves, José, Dasa, Tamirat Tesfaye, Davey, Gail, Davis, Adrian C., Davitoiu, Dragos Virgil, De Courten, Barbora, De La Hoz, Fernando Pio, De Leo, Diego, De Neve, Jan-Walter, Degefa, Meaza Girma, Degenhardt, Louisa, Deiparine, Selina, Dellavalle, Robert P., Demoz, Gebre Teklemariam, Deribe, Kebede, Dervenis, Nikolaos, Des Jarlais, Don C., Dessie, Getenet Ayalew, Dey, Subhojit, Dharmaratne, Samath Dhamminda, Dinberu, Mesfin Tadese, Dirac, M. Ashworth, Djalalinia, Shirin, Doan, Linh, Dokova, Klara, Doku, David Teye, Dorsey, E. Ray, Doyle, Kerrie E., Driscoll, Tim Robert, Dubey, Manisha, Dubljanin, Eleonora, Duken, Eyasu Ejeta, Duncan, Bruce B., Duraes, Andre R., Ebrahimi, Hedyeh, Ebrahimpour, Soheil, Echko, Michelle Marie, Edvardsson, David, Effiong, Andem, Ehrlich, Joshua R., El Bcheraoui, Charbel, El Sayed Zaki, Maysaa, El-Khatib, Ziad, Elkout, Hajer, Elyazar, Iqbal R. 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Sharafi, Kiomar, Sharif, Mehdi, Sharif-Alhoseini, Mahdi, Sharma, Meenakshi, Sharma, Rajesh, She, Jun, Sheikh, Aziz, Shi, Peilin, Shibuya, Kenji, Shigematsu, Mika, Shiri, Rahman, Shirkoohi, Reza, Shishani, Kawkab, Shiue, Ivy, Shokraneh, Farhad, Shoman, Haitham, Shrime, Mark G, Si, Si, Siabani, Soraya, Siddiqi, Tariq J, Sigfusdottir, Inga Dora, Sigurvinsdottir, Rannveig, Silva, João Pedro, Silveira, Dayane Gabriele Alve, Singam, Narayana Sarma Venkata, Singh, Jasvinder A, Singh, Narinder Pal, Singh, Virendra, Sinha, Dhirendra Narain, Skiadaresi, Eirini, Slepak, Erica Leigh N, Sliwa, Karen, Smith, David L, Smith, Mari, Soares Filho, Adauto Martin, Sobaih, Badr Hasan, Sobhani, Soheila, Sobngwi, Eugène, Soneji, Samir S, Soofi, Moslem, Soosaraei, Masoud, Sorensen, Reed J D, Soriano, Joan B, Soyiri, Ireneous N, Sposato, Luciano A, Sreeramareddy, Chandrashekhar T, Srinivasan, Vinay, Stanaway, Jeffrey D, Stein, Dan J, Steiner, Caitlyn, Steiner, Timothy J, Stokes, Mark A, Stovner, Lars Jacob, 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Eduardo A, Unutzer, Jurgen, Updike, Rachel L, Usman, Muhammad Shariq, Uthman, Olalekan A, Vaduganathan, Muthiah, Vaezi, Afsane, Valdez, Pascual R, Varughese, Santosh, Vasankari, Tommi Juhani, Venketasubramanian, Narayanaswamy, Villafaina, Santo, Violante, Francesco S, Vladimirov, Sergey Konstantinovitch, Vlassov, Vasily, Vollset, Stein Emil, Vosoughi, Kia, Vujcic, Isidora S, Wagnew, Fasil Shiferaw, Waheed, Yasir, Waller, Stephen G, Wang, Yafeng, Wang, Yuan-Pang, Weiderpass, Elisabete, Weintraub, Robert G, Weiss, Daniel J, Weldegebreal, Fitsum, Weldegwergs, Kidu Gidey, Werdecker, Andrea, West, T Eoin, Whiteford, Harvey A, Widecka, Justyna, Wijeratne, Tissa, Wilner, Lauren B, Wilson, Shadrach, Winkler, Andrea Sylvia, Wiyeh, Alison B, Wiysonge, Charles Shey, Wolfe, Charles D A, Woolf, Anthony D, Wu, Shouling, Wu, Yun-Chun, Wyper, Grant M A, Xavier, Deni, Xu, Gelin, Yadgir, Simon, Yadollahpour, Ali, Yahyazadeh Jabbari, Seyed Hossein, Yamada, Tomohide, Yan, Lijing L, Yano, Yuichiro, Yaseri, Mehdi, Yasin, Yasin Jemal, Yeshaneh, Alex, Yimer, Ebrahim M, Yip, Paul, Yisma, Engida, Yonemoto, Naohiro, Yoon, Seok-Jun, Yotebieng, Marcel, Younis, Mustafa Z, Yousefifard, Mahmoud, Yu, Chuanhua, Zadnik, Vesna, Zaidi, Zoubida, Zaman, Sojib Bin, Zamani, Mohammad, Zare, Zohreh, Zeleke, Ayalew Jejaw, Zenebe, Zerihun Menlkalew, Zhang, Kai, Zhao, Zheng, Zhou, Maigeng, Zodpey, Sanjay, Zucker, Inbar, Vos, Theo, and Murray, Christopher J L

Subjects
YLDs, global burden of disease, General & Internal Medicine, Medicine (all), prevalence, incidence, Human medicine, global burden of disease, YLDs, incidence, prevalence, GBD, years lived with disability
Abstract

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 39% (95% uncertainty interval [UI] 3.1-4. 6) from 1990 to 2017; however, the all-age YLD rate increased by 7.2% (6.0-8.4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7.9% (6 6-9. 2) for males and 6.5% (5.4-7.7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-hatin and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.

Published
2018

76. Patterns of migraine medication use in Norway: A nationwide registry-based observational study.

Author

Stubberud A, Borkenhagen S, Oteiza F, Dueland AN, Bugge C, Sæther EM, Tronvik E, Stovner LJ, and Bjørk MH

Subjects
Humans, Norway epidemiology, Female, Male, Adult, Middle Aged, Aged, Young Adult, Adolescent, Prevalence, Analgesics therapeutic use, Migraine Disorders drug therapy, Migraine Disorders epidemiology, Registries, Tryptamines therapeutic use
Abstract

Objective: The objective of this study was to describe and discuss patterns of migraine medication use in the entire Norwegian population., Methods: In this nationwide, observational study, all individuals with a migraine-related prescription between 2010 and 2020 were identified using the Norwegian Prescription Database. The outcomes of interest were the incidence and 1-year prevalence of migraine medication users, as well as individuals with triptan overuse. Patterns of medication use were statistically compared between women and men adjusted for age, year of treatment start, comorbidities and county of residence calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI)., Results: We identified 327,904 migraine medication users. The incidence ranged from 0.39% to 0.46%, and the 1-year prevalence increased from 1.99% to 2.99%. Preventive use increased >50% during the study period. Preventives were significantly more often prescribed to women than to men (39.72% vs. 33.75%; aOR 1.41, 95% CI 1.38 to 1.44). Triptan overuse was significantly more common among women, but women with overuse were more often using preventives, as compared to men (56.64% vs 52.69%; aOR = 1.43, 95% CI 1.37 to 1.49)., Conclusion: The prevalence of medically treated migraine is low. Overuse of triptans is frequent, especially among women. Clinicians should be encouraged to try out different triptans, recognize triptan overuse, and prescribe preventives when indicated., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AS has received speaker honoraria from Teva.SB is affiliated with Oslo Economics and has completed consultancy assignments for several pharmaceutical companies in recent years. FO is affiliated with Oslo Economics and has completed consultancy assignments for several pharmaceutical companies in recent years. AND has received speaker honoraria and/or consultancy honoraria from AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Roche, Teva. CB is affiliated with Oslo Economics and has completed consultancy assignments for several pharmaceutical companies in recent years. EMS is affiliated with Oslo Economics and has completed consultancy assignments for several pharmaceutical companies in recent years. ET reports personal fees from lectures/advisory boards: Novartis, Eli Lilly, Abbvie, TEVA, Roche, Lundbeck, Pfizer, Biogen. Consultant for and owner of stocks and IP in Man & Science. Stocks and IP in Nordic Brain Tech. Stocks in Keimon Medical. Non-personal research funding from several sources, including EU, Norwegian Research Council, Dam foundation, KlinBeForsk. Commissioned research (non-personal): Lundbeck, Pfizer. LJS reports no disclosures relevant to the manuscript. MHB has received speaker honoraria and/or consultancy honoraria from Teva, Eisai, AbbVie, Pfizer, Novartis, Lundbeck, Angelini Pharma, Jazz pharmaceuticals, and Lilly during the last five years some of which are marked authorization holders of acute and/or preventive migraine drugs. She is affiliated with university of Bergen that has received fees from the marked authorization holders of valproate for a post authorization study of valproate.

Published
2024
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78. Onabotulinum toxin A block of the sphenopalatine ganglion in patients with persistent idiopathic facial pain: a randomized, triple-blind, placebo-controlled, exploratory, cross-over study.

Author

Jamtøy KA, Thorstensen WM, Stovner LJ, Rosén A, Maarbjerg S, Bratbak D, Simpson MR, and Tronvik E

Subjects
Humans, Cross-Over Studies, Facial Pain drug therapy, Botulinum Toxins, Type A therapeutic use, Ganglia, Parasympathetic
Abstract

Objective: To investigate the efficacy and safety of injecting onabotulinum toxin A (BTA) towards the sphenopalatine ganglion (SPG) using the MultiGuide® in patients with persistent idiopathic facial pain (PIFP)., Methods: This cross-over, exploratory study compared the injection of 25 units BTA versus placebo in patients who met modified ICDH-3 criteria for PIFP. Daily pain diaries were registered for a 4-week baseline, a 12-week follow-up after each injection, and an 8-week conceptual washout period in between. The primary efficacy endpoint was the change from baseline to weeks 5-8 in average pain intensity using a numeric rating scale. Adverse events were recorded., Results: Of 30 patients who were randomized to treatment, 29 were evaluable. In weeks 5-8, there was no statistically significant difference in average pain intensity between BTA versus placebo (0.00; 95% CI = -0.57 to 0.57) ( P =  0.996). Following both BTA and placebo injections, five participants reported at least a 30% reduction in average pain during weeks 5-8 ( P  = 1.000). No serious adverse events were reported. Post-hoc analyses indicated a possible carry-over effect., Conclusions: Injection of BTA toward the SPG with the MultiGuide® did not appear to provide a reduction in pain reduction at 5-8 weeks, although this finding may be influenced by a carry-over effect. The injection appears to otherwise be safe and well-tolerated in patients with PIFP. Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT03462290) and EUDRACT (number: 2017-002518-30).

Published
2023
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79. The HARDSHIP databases: a forthcoming free good from the Global Campaign against Headache.

Author

Steiner TJ, Husøy A, Thomas H, and Stovner LJ

Subjects
Adolescent, Adult, Child, Humans, Databases, Factual, Information Sources, Schools, Headache epidemiology, Headache therapy, Health Policy
Abstract

In order to pursue its purpose of reducing the global burden of headache, the Global Campaign against Headache has gathered data on headache-attributed burden from countries worldwide. These data, from the individual participants in adult population-based studies and child and adolescent schools-based studies, are being collated in two databases, which will be powerful resources for research and teaching and rich information sources for health policy.Here we briefly describe the structure and content of these databases, and announce the intention to make them available in due course as a free good., (© 2023. The Author(s).)

Published
2023
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80. Insufficient sleep may alter cortical excitability near the migraine attack: A blinded TMS crossover study.

Author

Mykland MS, Uglem M, Stovner LJ, Brenner E, Snoen MS, Gravdahl GB, Sand T, and Omland PM

Subjects
Humans, Cross-Over Studies, Sleep Deprivation, Evoked Potentials, Motor physiology, Transcranial Magnetic Stimulation methods, Migraine Disorders, Cortical Excitability
Abstract

Background: Migraine is a brain disorder with a multifaceted and unexplained association to sleep. Brain excitability likely changes periodically throughout the migraine cycle. In this study we examine the effect of insufficient sleep on neuronal excitability during the course of the migraine cycle., Methods: We examined 54 migraine patients after two nights of eight-hour habitual sleep and two nights of four-hour restricted sleep in a randomised, blinded crossover study. We performed transcranial magnetic stimulation and measured cortical silent period, short- and long-interval intracortical inhibition, intracortical facilitation and short-latency afferent inhibition. We analysed how responses changed before and after attacks with linear mixed models., Results: Short- interval intracortical inhibition was more reduced after sleep restriction compared to habitual sleep the shorter the time that had elapsed since the attack ( p  = 0.041), and specifically in the postictal phase ( p  = 0.013). Long-interval intracortical inhibition was more increased after sleep restriction with time closer before the attack ( p  = 0.006), and specifically in the preictal phase ( p  = 0.034). Short-latency afferent inhibition was more decreased after sleep restriction with time closer to the start of the attack ( p  = 0.026)., Conclusion: Insufficient sleep in the period leading up to a migraine attack may cause dysfunction in cortical GABAergic inhibition. The results also suggest that migraine patients may have increased need for sufficient sleep during a migraine attack to maintain normal neurological function after the attack.

Published
2023
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81. Global epidemiology of migraine and its implications for public health and health policy.

Author

Steiner TJ and Stovner LJ

Subjects
Humans, Reproducibility of Results, Prevalence, Global Health, Health Policy, Public Health, Migraine Disorders epidemiology
Abstract

Migraine is one of more than 200 headache disorders but stands out among these as a major cause of population ill health. In migraine epidemiology, the key variable is prevalence, but, from the perspective of public health, prevalence is uninformative without burden estimates. Here, we discuss how migraine epidemiology, from a quite recent start, has evolved into the respectable though imperfect science of today, but with the legacy that much of the large corpus of older literature is of questionable reliability. Newer studies have benefited from a universally accepted definition of migraine, while methodological developments have broadened the scope of migraine caseness, and published guidelines address important methodological issues. In the light of these developments, we question the apparent increase in migraine prevalence over time, offering explanations as to why this may be illusory. We suggest that the current best estimates are that global migraine prevalence is 14-15%, and that migraine accounts for 4.9% of global population ill health quantified in years lived with disability (YLDs). These evaluations are probably under-quantified rather than over-quantified, and YLDs are not a comprehensive measure of migraine-attributed burden. Despite these uncertainties, such high estimates of population ill health have clear implications for health policy., (© 2023. Springer Nature Limited.)

Published
2023
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82. Continuous positive airway pressure in cluster headache: A randomized, placebo-controlled, triple-blind, crossover study.

Author

Gravdahl GB, Aakerøy L, Stovner LJ, Engstrøm M, Müller KI, Bjørk MH, and Tronvik E

Subjects
Humans, Male, Middle Aged, Continuous Positive Airway Pressure, Cross-Over Studies, Double-Blind Method, Treatment Outcome, Cluster Headache therapy
Abstract

Background: Oxygen inhalation aborts cluster headache attacks, and case reports show the effect of continuous positive airway pressure. The aim of this study was to investigate the prophylactic effect of continuous positive airway pressure in chronic cluster headache., Methods: This was a randomized placebo-controlled triple-blind crossover study using active and sham continuous positive airway pressure treatment for chronic cluster headache. Patients entered a one month's baseline period before randomly being assigned to two months' active continuous positive airway pressure treatment followed by a four weeks' washout period and two months' sham continuous positive airway pressure or vice versa. Primary outcome measure was number of cluster headache attacks/week., Results: Of the 30 included participants (12 males, median age 49.5 years, min-max 20-66 years), 25 completed both treatment/sham cycles (two discontinued, three lost to follow-up). The median number of cluster headache attacks per week was reduced from 8.25 (0.75-89.75) attacks to 6.25 (0-56.00) attacks for active continuous positive airway pressure and to 7.50 (0.50-43.75) attacks for sham continuous positive airway pressure, but there was no difference in active versus sham (p = 0.904). One patient had a serious adverse event during active treatment, none occurred during sham treatment., Conclusions: Continuous positive airway pressure treatment did not reduce the number of cluster headache attacks compared to sham treatment in chronic cluster headache patients., Trial Registration Clinicaltrials.gov: NCT03397563 .

Published
2023
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83. FollowTheSutures: Piloting a new way to administer onabotulinumtoxinA for chronic migraine.

Author

Stovner LJ, Hagen K, Tronvik E, Bruvik Gravdahl G, Burstein R, and Dodick DW

Subjects
Double-Blind Method, Female, Headache chemically induced, Humans, Pilot Projects, Treatment Outcome, Botulinum Toxins, Type A, Migraine Disorders chemically induced, Migraine Disorders drug therapy
Abstract

Background: Anatomical and experimental data indicate that onabotulinimtoxin A could be more efficient and cost-effective for treating chronic migraine with injections targeting the cranial sutures, where collaterals from the meninges penetrate the skull., Methods: A new injection paradigm (FollowTheSutures) was tested for safety, tolerability and feasibility in a Phase II, open-label, non-controlled, single-center pilot study. Ninety units of onabotulinimtoxin A (Botox®), were injected in 18 sites over the area of the cranial sutures. Adverse events and potential beneficial effects were recorded in a headache diary at least 4 weeks before, and for 12 weeks after the injections. A higher dilution than normal of onabotulinimtoxin A was used to get better diffusion., Results: Nineteen (of 20 included) women with chronic migraine received the injections and were evaluable. There was only one treatment-related adverse event (reduced power of chewing for some weeks). Otherwise, the procedure was overall well tolerated. Patients improved on most efficacy parameters after the injections. There was little or no effect on glabellar or forehead lines., Conclusions: The protocol was safe and well tolerated. Lower risk of unblinding due to the absence of cosmetic effects should make the injection procedure well suited for a large, randomized, placebo-controlled study. If efficacy is confirmed, it will be markedly less costly than the standard procedure.Trial registration: EUDRACT (2017-002516-13), ClinicalTrials.gov (NCT03543254).

Published
2022
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84. Pain thresholds and suprathreshold pain after sleep restriction in migraine - A blinded crossover study.

Author

Neverdahl JP, Uglem M, Matre D, Hansen JO, Engstrøm M, Tronvik E, Stovner LJ, Sand T, and Omland PM

Subjects
Cross-Over Studies, Humans, Pain, Sleep, Migraine Disorders complications, Pain Threshold
Abstract

Objective: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls., Methods: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep., Results: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group., Conclusion: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Published
2022
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85. The Global Campaign turns 18: a brief review of its activities and achievements.

Author

Steiner TJ, Birbeck GL, Jensen RH, Martelletti P, Stovner LJ, Uluduz D, Leonardi M, Olesen J, and Katsarava Z

Subjects
Cost-Benefit Analysis, Humans, World Health Organization, Headache, Headache Disorders
Abstract

The Global Campaign against Headache, as a collaborative activity with the World Health Organization (WHO), was formally launched in Copenhagen in March 2004. In the month it turns 18, we review its activities and achievements, from initial determination of its strategic objectives, through partnerships and project management, knowledge acquisition and awareness generation, to evidence-based proposals for change justified by cost-effectiveness analysis., (© 2022. The Author(s).)

Published
2022
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86. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates.

Author

Stovner LJ, Hagen K, Linde M, and Steiner TJ

Subjects
Headache epidemiology, Humans, Prevalence, Headache Disorders epidemiology, Migraine Disorders epidemiology, Tension-Type Headache epidemiology
Abstract

Background: According to the Global Burden of Disease (GBD) study, headache disorders are among the most prevalent and disabling conditions worldwide. GBD builds on epidemiological studies (published and unpublished) which are notable for wide variations in both their methodologies and their prevalence estimates. Our first aim was to update the documentation of headache epidemiological studies, summarizing global prevalence estimates for all headache, migraine, tension-type headache (TTH) and headache on ≥15 days/month (H15+), comparing these with GBD estimates and exploring time trends and geographical variations. Our second aim was to analyse how methodological factors influenced prevalence estimates., Methods: In a narrative review, all prevalence studies published until 2020, excluding those of clinic populations, were identified through a literature search. Prevalence data were extracted, along with those related to methodology, world region and publication year. Bivariate analyses (correlations or comparisons of means) and multiple linear regression (MLR) analyses were performed., Results: From 357 publications, the vast majority from high-income countries, the estimated global prevalence of active headache disorder was 52.0% (95%CI 48.9-55.4), of migraine 14.0% (12.9-15.2), of TTH 26.0% (22.7-29.5) and of H15+ 4.6% (3.9-5.5). These estimates were comparable with those of migraine and TTH in GBD2019, the most recent iteration, but higher for headache overall. Each day, 15.8% of the world's population had headache. MLR analyses explained less than 30% of the variation. Methodological factors contributing to variation, were publication year, sample size, inclusion of probable diagnoses, sub-population sampling (e.g., of health-care personnel), sampling method (random or not), screening question (neutral, or qualified in severity or presumed cause) and scope of enquiry (headache disorders only or multiple other conditions). With these taken into account, migraine prevalence estimates increased over the years, while estimates for all headache types varied between world regions., Conclusion: The review confirms GBD in finding that headache disorders remain highly prevalent worldwide, and it identifies methodological factors explaining some of the large variation between study findings. These variations render uncertain both the increase in migraine prevalence estimates over time, and the geographical differences. More and better studies are needed in low- and middle-income countries., (© 2022. The Author(s).)

Published
2022
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87. OnabotulinumtoxinA injection towards the SPG for treating symptoms of refractory chronic rhinosinusitis with nasal polyposis: a pilot study.

Author

Jamtøy KA, Tronvik E, Bratbak DF, Crespi J, Stovner LJ, Aschehoug I, and Thorstensen WM

Subjects
Chronic Disease, Female, Humans, Male, Middle Aged, Nasal Obstruction drug therapy, Nasal Obstruction etiology, Neuromuscular Agents administration & dosage, Pilot Projects, Prospective Studies, Rhinitis etiology, Rhinorrhea drug therapy, Rhinorrhea etiology, Sinusitis etiology, Botulinum Toxins, Type A administration & dosage, Injections instrumentation, Nasal Polyps complications, Rhinitis drug therapy, Sinusitis drug therapy
Abstract

Background and Objective: The main objective of this prospective, open, uncontrolled pilot study was to investigate the safety of administering onabotulinumtoxinA (BTA) towards the sphenopalatine ganglion (SPG) in 10 patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) using a novel injection tool, the MultiGuide ® ., Material and Methods: A one-month baseline period was followed by bilateral injections of 25 U BTA in the SPG and a follow-up of 12 weeks. The primary outcome was adverse events (AE), and the main efficacy outcome was a 50% reduction in visual analogue scale (VAS) symptoms for nasal obstruction and rhinorrhea in months 2 and 3 post-treatment compared to baseline., Results: We registered 13 AEs, none of which were serious, however, one patient experienced diplopia which moderately affected his daily activities. The symptoms slowly improved and resolved 4 weeks after injection. Five patients were treatment responders with at least 50% median reduction in the nasal obstruction, and four were treatment responders concerning rhinorrhea., Conclusions: Injection of BTA toward the SPG using the MultiGuide ® in patients with CRSwNP appears to be safe but with a potential for moderately disabling side effects. The study indicates a beneficial effect on nasal obstruction.

Published
2021
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88. Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

Author

Steiner TJ, Jensen R, Katsarava Z, Stovner LJ, Uluduz D, Adarmouch L, Al Jumah M, Al Khathaami AM, Ashina M, Braschinsky M, Broner S, Eliasson JH, Gil-Gouveia R, Gómez-Galván JB, Gudmundsson LS, Herekar AA, Kawatu N, Kissani N, Kulkarni GB, Lebedeva ER, Leonardi M, Linde M, Luvsannorov O, Maiga Y, Milanov I, Mitsikostas DD, Musayev T, Olesen J, Osipova V, Paemeleire K, Peres MFP, Quispe G, Rao GN, Risal A, de la Torre ER, Saylor D, Togha M, Yu SY, Zebenigus M, Zewde YZ, Zidverc-Trajković J, and Tinelli M

Subjects
Delivery of Health Care, Humans, Primary Health Care, Headache therapy, Headache Disorders
Abstract

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses., (© 2021. The Author(s).)

Published
2021
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89. Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.

Author

Feigin VL, Vos T, Alahdab F, Amit AML, Bärnighausen TW, Beghi E, Beheshti M, Chavan PP, Criqui MH, Desai R, Dhamminda Dharmaratne S, Dorsey ER, Wilder Eagan A, Elgendy IY, Filip I, Giampaoli S, Giussani G, Hafezi-Nejad N, Hole MK, Ikeda T, Owens Johnson C, Kalani R, Khatab K, Khubchandani J, Kim D, Koroshetz WJ, Krishnamoorthy V, Krishnamurthi RV, Liu X, Lo WD, Logroscino G, Mensah GA, Miller TR, Mohammed S, Mokdad AH, Moradi-Lakeh M, Morrison SD, Shivamurthy VKN, Naghavi M, Nichols E, Norrving B, Odell CM, Pupillo E, Radfar A, Roth GA, Shafieesabet A, Sheikh A, Sheikhbahaei S, Shin JI, Singh JA, Steiner TJ, Stovner LJ, Wallin MT, Weiss J, Wu C, Zunt JR, Adelson JD, and Murray CJL

Subjects
Humans, United States epidemiology, Cost of Illness, Disability-Adjusted Life Years trends, Global Burden of Disease trends, Global Health trends, Nervous System Diseases diagnosis, Nervous System Diseases epidemiology
Abstract

Importance: Accurate and up-to-date estimates on incidence, prevalence, mortality, and disability-adjusted life-years (burden) of neurological disorders are the backbone of evidence-based health care planning and resource allocation for these disorders. It appears that no such estimates have been reported at the state level for the US., Objective: To present burden estimates of major neurological disorders in the US states by age and sex from 1990 to 2017., Design, Setting, and Participants: This is a systematic analysis of the Global Burden of Disease (GBD) 2017 study. Data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of major neurological disorders were derived from the GBD 2017 study of the 48 contiguous US states, Alaska, and Hawaii. Fourteen major neurological disorders were analyzed: stroke, Alzheimer disease and other dementias, Parkinson disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus., Exposures: Any of the 14 listed neurological diseases., Main Outcome and Measure: Absolute numbers in detail by age and sex and age-standardized rates (with 95% uncertainty intervals) were calculated., Results: The 3 most burdensome neurological disorders in the US in terms of absolute number of DALYs were stroke (3.58 [95% uncertainty interval [UI], 3.25-3.92] million DALYs), Alzheimer disease and other dementias (2.55 [95% UI, 2.43-2.68] million DALYs), and migraine (2.40 [95% UI, 1.53-3.44] million DALYs). The burden of almost all neurological disorders (in terms of absolute number of incident, prevalent, and fatal cases, as well as DALYs) increased from 1990 to 2017, largely because of the aging of the population. Exceptions for this trend included traumatic brain injury incidence (-29.1% [95% UI, -32.4% to -25.8%]); spinal cord injury prevalence (-38.5% [95% UI, -43.1% to -34.0%]); meningitis prevalence (-44.8% [95% UI, -47.3% to -42.3%]), deaths (-64.4% [95% UI, -67.7% to -50.3%]), and DALYs (-66.9% [95% UI, -70.1% to -55.9%]); and encephalitis DALYs (-25.8% [95% UI, -30.7% to -5.8%]). The different metrics of age-standardized rates varied between the US states from a 1.2-fold difference for tension-type headache to 7.5-fold for tetanus; southeastern states and Arkansas had a relatively higher burden for stroke, while northern states had a relatively higher burden of multiple sclerosis and eastern states had higher rates of Parkinson disease, idiopathic epilepsy, migraine and tension-type headache, and meningitis, encephalitis, and tetanus., Conclusions and Relevance: There is a large and increasing burden of noncommunicable neurological disorders in the US, with up to a 5-fold variation in the burden of and trends in particular neurological disorders across the US states. The information reported in this article can be used by health care professionals and policy makers at the national and state levels to advance their health care planning and resource allocation to prevent and reduce the burden of neurological disorders.

Published
2021
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91. High sensitivity C-reactive protein and risk of migraine in a 11-year follow-up with data from the Nord-Trøndelag health surveys 2006-2008 and 2017-2019.

Author

Hagen K, Stovner LJ, and Zwart JA

Subjects
Adult, Aged, Biomarkers blood, C-Reactive Protein analysis, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Health Surveys methods, Humans, Male, Middle Aged, Migraine Disorders epidemiology, Norway epidemiology, Risk Factors, Time Factors, C-Reactive Protein metabolism, Health Surveys trends, Migraine Disorders blood, Migraine Disorders diagnosis
Abstract

Background: Several previous studies have reported a cross-sectional association between elevated high sensitivity C-reactive protein (hs-CRP) and migraine. The aim of this population-based follow-up study was to investigate the influence of hs-CRP at baseline on the risk of developing migraine 11 years later., Methods: Data from the Nord-Trøndelag Health Study performed in 2006-2008 (baseline) and 2017-2019 were used. A total of 19,574 participants without migraine at baseline were divided into three groups based on hs-CRP levels (< 3 mg/L, 3-9.99 mg/L and 10.00-20 mg/L). Poisson regression was used to evaluate the associations between hs-CRP levels and risk ratios (RRs) of migraine, and precision of the estimates was assessed by 95% confidence interval (CIs)., Results: In the multi-adjusted model, increased risk of migraine (RR 1.46, 95% CI 1.05-2.04) was found in the highest hs-CRP levels group compared to the lowest group. In the group with the highest hs-CRP levels, a nearly three times higher risk of chronic migraine (RR 2.81, 95% CI 1.12-7.06) was found, whereas no evident relationship was found between high hs-CRP level and risk of developing episodic migraine., Conclusions: The main finding in this 11-year follow-up was that hs-CRP levels between 10.00-20.00 mg/L at baseline was associated with increased risk of chronic migraine.

Published
2020
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93. Time trends of major headache diagnoses and predictive factors. Data from three Nord-Trøndelag health surveys.

Author

Hagen K, Stovner LJ, and Zwart JA

Subjects
Adult, Aged, Cross-Sectional Studies, Female, Follow-Up Studies, Headache diagnosis, Headache Disorders, Secondary diagnosis, Humans, Longitudinal Studies, Male, Middle Aged, Migraine Disorders diagnosis, Norway epidemiology, Predictive Value of Tests, Prevalence, Tension-Type Headache diagnosis, Tension-Type Headache epidemiology, Young Adult, Data Analysis, Headache epidemiology, Headache Disorders, Secondary epidemiology, Health Surveys trends, Migraine Disorders epidemiology
Abstract

Aims: The primary aim of this study was to investigate time trends of major headache diagnoses using cross-sectional data from two population-based health surveys. In addition, we aimed to perform a longitudinal assessment of baseline characteristics and subsequent risk for having headache at 22-years' follow-up among those participating in three health surveys., Methods: Data from the Nord-Trøndelag Health Study (HUNT) performed in 1995-1997 (HUNT2), 2006-2008 (HUNT3) and 2017-2019 (HUNT4) were used. The 1-year prevalence time trends of major headache diagnoses were estimated among 41,460 participants in HUNT4 and among 39,697 participants in HUNT3, two surveys with identical headache questions. 16,118 persons participated in all three surveys, and among these, a Poisson regression was used to evaluate health-related baseline information in HUNT2 and the risk ratios (RRs) with 95% confidence interval (CIs) of consistently reporting headache during follow-up., Results: Compared with the 1-year prevalence in HUNT3, a higher proportion of participants in HUNT4 had tension-type headache (20.7% vs. 15.9%, p < 0.001), whereas a lower 1-year prevalence was found for migraine (11.1% vs. 12.0%, p < 0.001) and medication overuse headache (MOH) (0.3% vs. 1.0%, p < 0.001). Participants in the age group 20-39 years at baseline nearly three times increased risk (RR = 2.8, 95% CI 2.5-3.1) of reporting headache in HUNT2, HUNT3 and HUNT4 than persons aged 50 years or more. Female sex, occurrence of chronic musculoskeletal complaints and high score of depression or anxiety at baseline doubled the risk of having headache in all three surveys., Conclusions: The 1-year prevalence of migraine and MOH was lower in HUNT4 than in HUNT3. Young age, female sex, and occurrence of musculoskeletal complaints and high score of anxiety and/or depression were all associated with substantially increased risk of reporting headache in all three surveys.

Published
2020
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94. The crossover design for migraine preventives: an analyses of four randomized placebo-controlled trials.

Author

Jenssen AB, Stovner LJ, Tronvik E, Sand T, Helde G, Gravdahl GB, and Hagen K

Subjects
Adult, Cross-Over Studies, Double-Blind Method, Female, Headache drug therapy, Headache prevention & control, Humans, Male, Migraine Disorders prevention & control, Norway, Treatment Outcome, Migraine Disorders drug therapy
Abstract

Aims: To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs)., Methods: In order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment., Results: Only 26 (10%) dropped out during the follow-up period of 30-48 weeks, the majority (n = 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (p = 0.59) and for headache 25.0% vs. 24.8% (p = 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (- 0.9 vs. -1.3, p = 0.46) and migraine (- 1.2 vs. -0.9, p = 0.35, Student's t-test)., Conclusions: Summary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.

Published
2019
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95. The impact of C-reactive protein levels on headache frequency in the HUNT study 2006-2008.

Author

Hagen K, Stovner LJ, Nilsen KB, Kristoffersen ES, and Winsvold BS

Subjects
Adult, Aged, Comorbidity, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Migraine Disorders epidemiology, Norway, Young Adult, C-Reactive Protein, Migraine Disorders blood, Migraine Disorders physiopathology, Sleep Initiation and Maintenance Disorders epidemiology
Abstract

Background: Increased high sensitivity C- reactive protein (hs-CRP) levels have been found in many earlier studies on migraine, and recently also in persons with migraine and insomnia. The aim of this study was to see whether these findings could be reproduced in a large-scale population-based study., Methods: A total of 50,807 (54%) out of 94,194 invited aged ≥20 years or older participated in the third wave of the Nord-Trøndelag Health Study study performed in 2006-2008. Among these, 38,807 (41%) had valid measures of hs-CRP and answered questions on headache and insomnia. Elevated hs-CRP was defined as > 3.0 mg/L. The cross-sectional association with headache was estimated by multivariate analyses using multiple logistic regression. The precision of the odds ratio (OR) was assessed with 95% confidence interval (CI)., Results: In the fully adjusted model, elevated hs-CRP was associated with migraine (OR 1.14, 95% CI 1.04-1.25) and migraine with aura (OR 1.15, 95% CI 1.03-1.29). The association was strongest among individuals with headache ≥15 days/month for any headache (OR 1.26, 95% CI 1.08-1.48), migraine (OR 1.62, 95% CI 1.21-2.17), and migraine with aura (OR 1.84, 95% CI 1.27-2.67). No clear relationship was found between elevated hs-CRP and headache less than 7 days/month or with insomnia., Conclusions: Cross-sectional data from this large-scale population-based study showed that elevated hs-CRP was associated with headache ≥7 days/month, especially evident for migraine with aura.

Published
2019
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96. Diffusion tensor imaging in middle-aged headache sufferers in the general population: a cross-sectional population-based imaging study in the Nord-Trøndelag health study (HUNT-MRI).

Author

Kattem Husøy A, Eikenes L, Håberg AK, Hagen K, and Stovner LJ

Subjects
Adult, Aged, Anisotropy, Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging methods, Female, Humans, Male, Middle Aged, Headache diagnostic imaging, Headache pathology, Migraine Disorders diagnostic imaging, Migraine Disorders pathology, White Matter diagnostic imaging, White Matter pathology
Abstract

Background: Several studies have investigated white matter with diffusion tensor imaging (DTI) in those suffering from headache, but so far only in clinic based samples and with conflicting results., Methods: In the present study, 1006 individuals (50-66 years) from the general population (Nord-Trøndelag Health Study) participated in an imaging study of the head at 1.5 T (HUNT-MRI). Hundred and ninety-six individuals were excluded because of errors in the data acquisition or brain pathology. Two hundred and forty-six of the remaining participants reported suffering from headache (69 from migraine and 76 from tension-type headache) the year prior to the scanning. DTI data were analysed with Tract-Based Spatial Statistics and automated tractography. Type of headache, frequency of attacks and evolution of headache were investigated for an association with white matter fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), radial diffusivity (RD) and tract volume. Correction for various demographical and clinical variables were performed., Results: Headache sufferers had widespread higher white matter MD, AD and RD compared to headache free individuals (n = 277). The effect sizes were mostly small with the largest seen in those with middle-age onset headache, who also had lower white matter FA. There were no associations between white matter microstructure and attack frequency or type of headache., Conclusion: Middle-age onset headache may be related to a widespread process in the white matter leading to altered microstructure.

Published
2019
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97. Cerebral cortical dimensions in headache sufferers aged 50 to 66 years: a population-based imaging study in the Nord-Trøndelag Health Study (HUNT-MRI).

Author

Husøy AK, Håberg AK, Rimol LM, Hagen K, Vangberg TR, and Stovner LJ

Subjects
Aged, Brain Mapping, Cohort Studies, Female, Humans, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Male, Middle Aged, Migraine Disorders diagnostic imaging, Surveys and Questionnaires, Tension-Type Headache diagnostic imaging, Cerebral Cortex diagnostic imaging, Headache diagnostic imaging
Abstract

Based on previous clinic-based magnetic resonance imaging studies showing regional differences in the cerebral cortex between those with and without headache, we hypothesized that headache sufferers have a decrease in volume, thickness, or surface area in the anterior cingulate cortex, prefrontal cortex, and insula. In addition, exploratory analyses on volume, thickness, and surface area across the cerebral cortical mantle were performed. A total of 1006 participants (aged 50-66 years) from the general population were selected to an imaging study of the head at 1.5 T (HUNT-MRI). Two hundred eighty-three individuals suffered from headache, 80 with migraine, and 87 with tension-type headache, whereas 309 individuals did not suffer from headache and were used as controls. T1-weighted 3D scans of the brain were analysed with voxel-based morphometry and FreeSurfer. The association between cortical volume, thickness, and surface area and questionnaire-based headache diagnoses was evaluated, taking into consideration evolution of headache and frequency of attacks. There were no significant differences in cortical volume, thickness, or surface area between headache sufferers and nonsufferers in the anterior cingulate cortex, prefrontal cortex, or insula. Similarly, the exploratory analyses across the cortical mantle demonstrated no significant differences in volume, thickness, or surface area between any of the headache groups and the nonsufferers. Maps of effect sizes showed small differences in the cortical measures between headache sufferers and nonsufferers. Hence, there are probably no or only very small differences in volume, thickness, or surface area of the cerebral cortex between those with and without headache in the general population.

Published
2019
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98. The burden of headache disorders in the Eastern Mediterranean Region, 1990-2016: findings from the Global Burden of Disease study 2016.

Author

Vosoughi K, Stovner LJ, Steiner TJ, Moradi-Lakeh M, Fereshtehnejad SM, Farzadfar F, Heydarpour P, Malekzadeh R, Naghavi M, Sahraian MA, Sepanlou SG, Tehrani-Banihashemi A, Majdzadeh R, Feigin VL, Vos T, Mokdad AH, and Murray CJL

Subjects
Adult, Bayes Theorem, Female, Headache Disorders diagnosis, Humans, Male, Mediterranean Region epidemiology, Middle Aged, Prevalence, Quality-Adjusted Life Years, Disabled Persons psychology, Global Burden of Disease trends, Global Health trends, Headache Disorders epidemiology, Headache Disorders psychology
Abstract

Objectives: Using the findings of the Global Burden of Disease Study (GBD), we report the burden of primary headache disorders in the Eastern Mediterranean Region (EMR) from 1990 to 2016., Methods: We modelled headache disorders using DisMod-MR 2.1 Bayesian meta-regression tool to ensure consistency between prevalence, incidence, and remission. Years lived with disability (YLDs) were calculated by multiplying prevalence and disability weight (DW) of migraine and tension-type headache (TTH). We assumed primary headache disorders as non-fatal, so their YLD is equal to disability-adjusted life years (DALYs)., Results: Migraine and TTH were the second and twentieth leading causes of YLDs in EMR. Between 1990 and 2016, the absolute YLD numbers of migraine and TTH increased from 2.3 million (95% uncertainty interval (UI): 1.5-3.2) to 4.7 million (95%UI: 3-6.5) and from 383 thousand (95%UI: 240-562) to 816 thousand (95%UI: 516-1221), respectively. During the same period, age-standardised YLD rates of migraine and TTH in EMR increased by 0.7% and 2.5%, respectively, in comparison to a small decrease in the global rates (0.2% decrease in migraine and TTH). The bulk of burden due to headache occurred in the 30-49 year age group, with a peak at ages 35-44 years. The age-standardised YLD rates of both headache disorders were higher in women with female to male ratio of 1.69 for migraine and 1.38 for TTH. All countries of the EMR except for Somalia and Djibouti had higher age-standardised YLD rates for migraine and TTH in compare to the global rates. Libya and Saudi Arabia had the highest increase in age-standardised YLD rates of migraine and TTH, respectively., Conclusion: The findings of this study show that primary headache disorders are a major and a growing cause of disability in EMR. Since 1990, burden of primary headache disorders has constantly been higher in EMR compared to rest of the world, which indicates that health systems in EMR must focus further on developing and implementing preventive and management strategies to control headache.

Published
2019
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99. Volume and shape of subcortical grey matter structures related to headache: A cross-sectional population-based imaging study in the Nord-Trøndelag Health Study.

Author

Husøy AK, Pintzka C, Eikenes L, Håberg AK, Hagen K, Linde M, and Stovner LJ

Subjects
Aged, Brain diagnostic imaging, Cross-Sectional Studies, Female, Gray Matter diagnostic imaging, Headache diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Brain pathology, Gray Matter pathology, Headache pathology
Abstract

Background: The relationship between subcortical nuclei and headache is unclear. Most previous studies were conducted in small clinical migraine samples. In the present population-based MRI study, we hypothesized that headache sufferers exhibit reduced volume and deformation of the nucleus accumbens compared to non-sufferers. In addition, volume and deformation of the amygdala, caudate, hippocampus, pallidum, putamen and thalamus were examined., Methods: In all, 1006 participants (50-66 years) from the third Nord-Trøndelag Health Survey, were randomly selected to undergo a brain MRI at 1.5 T. Volume and shape of the subcortical nuclei from T1 weighted 3D scans were obtained in FreeSurfer and FSL. The association with questionnaire-based headache categories (migraine and tension-type headache included) was evaluated using analysis of covariance. Individuals not suffering from headache were used as controls. Age, sex, intracranial volume and Hospital Anxiety and Depression Scale were used as covariates., Results: No effect of headache status on accumbens volume and shape was present. Exploratory analyses showed significant but small differences in volume of caudate and putamen and in putamen shape between those with non-migrainous headache and the controls. A post hoc analysis showed that caudate volume was strongly associated with white matter hyperintensities., Conclusion: We did not confirm our hypothesis that headache sufferers have smaller volume and different shape of the accumbens compared to non-sufferers. No or only small differences in volume and shape of subcortical nuclei between headache sufferers and non-sufferers appear to exist in the general population.

Published
2019
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100. Remission of chronic headache: An 11-year follow-up study. Data from the Nord-Trøndelag Health Surveys 1995-1997 and 2006-2008.

Author

Hagen K, Kristoffersen ES, Winsvold BS, Stovner LJ, and Zwart JA

Subjects
Adult, Aged, Cohort Studies, Female, Health Surveys, Humans, Longitudinal Studies, Male, Middle Aged, Norway, Remission, Spontaneous, Headache Disorders
Abstract

Objectives: To estimate remission rates of chronic headache and predictors of remission., Methods: In this longitudinal population-based cohort study, we used validated headache questionnaire data from the second (1995-1997, baseline; n = 51,856 aged ≥ 20 years, response rate: 55%) and third wave (2006-2008, follow-up, response rate: 42%) of the Nord-Trøndelag Health Study. Chronic headache was defined as ≥15 headache days/month during the last year. Chronic headache remission was defined as headache less than 15 days/month at follow-up. Potential predictors of remission were evaluated using logistic regression., Results: At baseline, 1266 (2.4%) participants reported chronic headache. Of these, 605 (48%) answered headache questions at follow-up. Remission was observed in 452 (74.7%), the proportion being almost identical in men and women (74.4% vs. 74.9, p = 0.92). In analyses adjusting for age, gender and education level, remission at follow-up was more than two times more likely among individuals without medication overuse headache (OR = 2.4, 95% CI 1.7-3.6) and without chronic musculoskeletal complaints (OR = 2.9, 95% CI 1.5-5.0) at baseline., Conclusions: In this longitudinal population-based cohort study, three-quarters of chronic headache participants remitted from chronic headache. Remission was associated with no medication overuse headache and no chronic musculoskeletal complaints at baseline.

Published
2018
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