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Background General practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management. Methods We invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey. Results 367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients. Conclusion The knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.

Many clinicians lack experience in managing trigeminal autonomic cephalalgias (TACs) in pregnancy and lactation. In addition to cluster headache, TACs include hemicrania continua, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing/autonomic symptoms (SUNCT/SUNA). Treating these rare, severe headache conditions often requires off-label drugs that have uncertain teratogenic potential. In the last few years, several new treatment options and safety documentation have emerged, but clinical guidelines are lacking. This narrative review aimed to provide an updated clinical guide and good clinical practice recommendations for the management of these debilitating headache disorders in pregnancy and lactation. publishedVersion

Background Multimorbidity and prolonged use of addictive medications are prevalent among older patients, and known to increase the risk of adverse drug events. Yet, the relationship between these two entities has remained understudied. Aims This study explored the association between multimorbidity burden and prolonged use of addictive medications in geriatric patients, adjusted for clinically important covariates. Furthermore, we identified comorbidity patterns in prolonged users. Methods We conducted a cross-sectional study on a consecutive sample of 246 patients, aged 65–90 years, admitted to a large public university hospital in Norway. We defined prolonged use of addictive medications as using benzodiazepines, opioids and/or z-hypnotics beyond the duration recommended by clinical guidelines (≥ 4 weeks). Multimorbidity was assessed with the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), based on diagnoses made by independent physicians. Results Compared to non-prolonged use, prolonged use was significantly more common among patients who had psychiatric (19/27, 70%), liver (19/22, 86%), upper gastrointestinal tract (21/32, 66%), musculoskeletal (52/96, 54%), or nervous system disorders (46/92, 50%). Patients with prolonged use had a higher multimorbidity burden than those without such use (CIRS-G score, mean = 7.7, SD = 2.7 versus mean = 4.6, SD = 2.2, p Conclusions Multimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.

Background There was a significant decrease in stroke admissions during the first phase of the COVID-19 pandemic. There are concerns that stroke patients have not sought medical attention and in the months after the lockdown suffer recurrent severe strokes. The aims of this study were to investigate how stroke admission rates and distributions of severity varied before, during and after the lockdown in a representative Norwegian hospital population. Methods All patients discharged from Akershus University Hospital with a diagnosis of transient ischemic attack (TIA) or acute stroke from January to September 2020 were identified by hospital chart review. Results We observed a transient decrease in weekly stroke admissions during lockdown from an average of 21.4 (SD 4.7) before to 15.0 (SD 4.2) during and 17.2 (SD 3.3) after (p p = 0.011). Conclusion The period of COVID-19 lockdown was associated with a temporary reduction in total admissions of strokes. In particular, there were fewer with TIA and mild stroke. Given the need to prevent the worsening of symptoms and risk of recurrence, it is necessary to emphasise the importance to seek medical care even in states of emergency.

Background A major barrier to adequate headache care is the relative lack of formal education and training of healthcare professionals. Concerted efforts should be made to pinpoint major gaps in knowledge in healthcare professionals to facilitate better educational policies in headache training. The aim of this study was to identify deficiencies and barriers in headache training among residents in neurology in Denmark. Methods We conducted a national cross-sectional survey of residents in neurology in Denmark from April 2019 to September 2019. The survey included questions on participant demographics, knowledge of and barriers in headache disorders, guidelines and diagnostic tools usage, contact with primary and tertiary care, medication overuse, and non-pharmacological interventions. Furthermore, respondents were asked to provide a ranked list from most to least interesting for six sub-specializations/disorders, i.e., cerebrovascular disease, dementia, epilepsy, headache, multiple sclerosis, Parkinson's disease. Results Sixty (40%) out of estimated a population of ~ 150 resident across Denmark accepted the invitation. Of these, 54/60 (90%) completed the survey. Although two-thirds, 35/54 (65%), of the respondents had prior formalized training in headache disorders, we identified gaps in all explored domains including diagnosis, management, and referral patterns. Particularly, there was an inconsistent use of guidelines and diagnostic criteria from the Danish Headache Society (2.74 (± 1.14)), the Danish Neurological Society (3.15 (± 0.86)), and the International Classification of Headache Disorders (2.33 (± 1.08)); 1: never/have not heard of, 4: always. Headache was ranked second to last out of six sub-specializations in interest. Conclusions Overall knowledge on headache disorders amongst neurology residents in Denmark do not meet the expectations set out by national and international recommendations. Stakeholders should make strategic initiatives for structured education in headache for improved clinical outcomes in parallel with costs reduction through resource optimization.

BackgroundCentral nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients’ self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates.MethodsThe study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients’ self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models.ResultsPatients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient − 0.19 (95% CI, − 0.31 to − 0.06).ConclusionsOlder patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.

Objectives There are concerns that public anxiety around COVID‐19 discourages patients from seeking medical help. The aim of this study was to see how lockdown due to the pandemic affected the number of admissions of acute stroke. Methods All patients discharged from Akershus University Hospital with a diagnosis of transient ischemic attack (TIA) or acute stroke were identified by hospital chart review. January 3 to March 12 was defined as before, and March 13 to April 30 as during lockdown. Results There were 21.8 admissions/week before and 15.0 admissions/week during the lockdown (P

Background Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients. Findings We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage. We identified 77 cases of CVT after COVID-19 vaccination. Patients’ age was below 60 years in 74/77 (95.8%) cases and 61/68 (89.7%) were women. Headache was described in 38/77 (49.4%) cases, and in 35/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19/77 (24.7%) cases, intracranial hemorrhage in 33/77 (42.9%) cases and 19/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0–9.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7–20.8, p p = 0.213). Conclusion Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.

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.

The interview-based Severity of Dependence Scale (SDS) predicts the outcome of withdrawal therapy in Medication-Overuse Headache (MOH). We aimed to compare the interview-based SDS with a self-administrated written version. Fifty-three MOH patients, 19 chronic headache patients without medication overuse and 25 population controls were recruited from a previous randomized controlled trial. The SDS was scored in a telephone interview by headache experts, further, the participants filled in the SDS as a part of a self-administered questionnaire. The SDS assesses scores dependence through five questions, each scored from 0 to 3. A score of ≥5 is associated with MOH. Mean SDS scores were 2.8 (SD 3.0) vs. 3.1 (SD 2.9), p = 0.12, for the interview vs. the self-reported questionnaire, with a correlation 0.78. There was a non-significant bias of 0.32 (95% limits of agreement of −3.6; 4.2) between the two methods in the Bland-Altman analysis. A self-reported SDS questionnaire can be used, and may yield valuable information as a screening tool prior to headache consultations or studies. The possibilities of designing web-based self-treatment tools based on SDS self-assessment and brief intervention may be a future approach for a large group of patients.

Background Neurology has increasing subspecialization. Some disorders, such as cerebrovascular diseases, dementia and headache, are highly prevalent in the general population, while others, such as movement disorders and multiple sclerosis, are rarer. Thus, there may be a mismatch between neurologists' interests and the population needs. Aims of the study To investigate the perceived prestige of neurological disorders among residents in neurology. Methods The study was conducted as a questionnaire survey among residents in neurology in Norway. Results All the 17 neurological departments in Norway participated. In total, 143 residents participated (86% response rate). Mean age was 32.5 years. The respondents had on average 28 months of clinical training in neurology. The subspecialty with the highest prestige was cerebrovascular diseases, scored by 62% as the most prestigious, followed by multiple sclerosis (36%) and epilepsy (7%). The subspecialties with the lowest prestige were headache (2.8%) and dementia (1.4%). None of the tested variables (gender, age, months in clinical training or type of hospital) were associated with the perceived prestige of neurological disorders. Conclusion Cerebrovascular disease was perceived as the most prestigious subspecialty. Headache and dementia, which are major contributors to worldwide disability, have low status among residents in neurology.

Objectives The aim of the present study was to investigate how the initial phase of the COVID‐19 pandemic affected the hospital stroke management and research in Norway. Materials and methods All neurological departments with a Stroke Unit in Norway (n = 17) were invited to participate in a questionnaire survey. The study focused on the first lockdown period, and all questions were thus answered in regard to the period between 12 March and 15 April 2020. Results The responder rate was 94% (16/17). Eighty‐one % (13/16) reported that the pandemic affected their department, and 63% (10/16) changed their stroke care pathways. The number of new acute admissions in terms of both strokes and stroke mimics decreased at all 16 departments. Fewer patients received thrombolysis and endovascular treatment, and multidisciplinary stroke rehabilitation services were less available. The mandatory 3 months of follow‐up of stroke patients was postponed at 73% of the hospitals. All departments conducting stroke research reported a stop in ongoing projects. Conclusion In Norway, hospital‐based stroke care and research were impacted during the initial phase of the COVID‐19 pandemic, with likely repercussions for patient care and outcomes. In the future, stroke departments will require contingency plans in order to protect the entire stroke treatment chain.

Objective The COVID‐19 pandemic has led to rapid changes in the delivery of medical care worldwide. The main objective of this survey was to investigate the initial experiences of neurologists with the use of telemedicine for different neurological conditions during the first phase of the COVID‐19. Methods All hospital‐based neurologists in Norway (n = 400) were invited to a questionnaire survey by e‐mail in April 2020. The study focused on telemedicine and all questions were answered with regard to the first weeks of the pandemic lockdown in Norway. Results One‐hundred and thirty‐five neurologists responded. Overall, 87% reported a shift toward more telemedicine, with significantly more use of telephone than video consultations for both new referrals (54% vs. 30%, P

Publisher Copyright: © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. Objective: Identifying common genetic variants that confer genetic risk for cluster headache. Methods: We conducted a case–control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results: An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11-815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene-based mapping yielded ASZ1 as possible fifth locus. RNA-sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation: This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–216.

Background The ongoing COVID-19 pandemic has caused rapid changes in the healthcare system. Workforce reorganization, reduced standard of care and a lack of personal protection equipment (PPE) for health care workers were among the concerns raised in the first wave of the pandemic. Our aim was to explore the experiences, distress and burden among Norwegian neurologists during the first weeks of the pandemic. Methods Hospital-based neurologists in Norway (n = 400) were invited to a web-based survey in April 2020. The study focused on patient management, organizational changes and personal stress during the first weeks of the pandemic lockdown. Work-home interface stress was assessed by the Cooper Job Stress Questionnaire. Results In total, 135 neurologists participated. Seventy-three% experienced a change in their personal work situation, and 67% examined patients with suspected COVID-19 infection and neurological disease. Changed access to resources, and the perception that medical follow-up was unsatisfactory, were associated with a high degree of burden and stress. Neurologists were also worried about the potential lack of PPE and the fear of spreading SARS CoV-2 to close family members. The mean score of work-home interface stress was 2.8 with no significant differences between gender or specialist status. Reduced standard of care was reported for all neurological conditions, and in particular for non-emergency treatments. Conclusion The vast majority of neurologists in Norway experienced a change in their personal work situation during the first phase of the pandemic. The fear of becoming infected and ill was not a major contributor to burden and stress.

BackgroundThe Covid-19 pandemic is causing changes in delivery of medical care worldwide. It is not known how the management of headache patients was affected by the lockdown during the pandemic. The aim of the present study was to investigate how the initial phase of the Covid-19 pandemic affected the hospital management of headache in Denmark and Norway.MethodsAll neurological departments in Denmark (n = 14) and Norway (n = 18) were invited to a questionnaire survey. The study focused on the lockdown and all questions were answered in regard to the period between March 12th and April 15th, 2020.ResultsThe responder rate was 91% (29/32). Of the neurological departments 86% changed their headache practice during the lockdown. The most common change was a shift to more telephone consultations (86%). Video consultations were offered by 45%.The number of new headache referrals decreased. Only 36% administered botulinum toxin A treatment according to usual schemes. Sixty% reported that fewer patients were admitted for in-hospital emergency diagnostics and treatment. Among departments conducting headache research 57% had to halt ongoing projects. Overall, 54% reported that the standard of care was worse for headache patients during the pandemic.ConclusionHospital-based headache care and research was impacted in Denmark and Norway during the initial phase of the Covid-19-pandemic.

Background and Purpose: There are conflicting figures of the incidence of cerebral venous thrombosis (CVT). The incidence was previously estimated to around 0.5/100 000/y, but more recent studies have suggested 1 to 1.5/100 000/y. The purpose of this study was to explore the incidence and mortality of CVT in a Norwegian population. Methods: A retrospective cross-sectional hospital population-based study conducted at Akershus University Hospital serving roughly 10% of the total Norwegian population. Patients were identified through chart reviews based on the relevant International Classification of Diseases ( Tenth Revision ) codes for new CVT cases in a 7-year period between January 1, 2011, and December 31, 2017. Only inhabitants living in the hospital’s catchment area were included. Results: Sixty-two patients aged 0 to 80 years were identified and included. The median age was 46 years and 53% were females. The overall incidence of CVT was 1.75 (95% CI, 1.36–2.23) per 100 000/y with no significant sex differences. The incidence for children and adolescents (50 years with 2.10 (1.38–3.07)/100 000/y. Headache was the most prevalent symptom, reported in 83%, followed by nausea, motor deficits, and seizures observed in 45%, 32%, and 32% of the patients. Transverse sinuses and the jugular vein were the most frequent sites of thrombosis. In most patients (61%), thrombosis occurred in multiple sinuses/veins. Risk factors were found in 73% of the patients, and most of the patients had a combination of 2 or more risk factors. The 30-day and 1-year mortality rates were 3% and 6%. Conclusions: The incidence of CVT in this population was higher than previously reported. The mortality rate was similar to previous studies.

Supplemental Digital Content is available in the text., Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institute of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institute of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institute of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P

OBJECTIVE The aim of this study was to collect and rate Green Flags, that is, symptoms or pieces of information indicating that a patient is more likely to suffer from a primary than from a secondary headache. BACKGROUND When assessing headaches, a central question to be answered is whether the pain is primary or secondary to another disorder. To maximize the likelihood of a correct diagnosis, relevant signs and symptoms must be sought, identified, and weighed against each other. METHODS The project was designed as a Delphi study. In the first round, an expert panel proposed green flags that were rated anonymously in two subsequent rounds. Proposals with an average rating of 4.0 and higher on a scale from 0 to 5 reached consensus. RESULTS Five Green Flags reached consensus: (i) "The current headache has already been present during childhood"; (ii) "The headache occurs in temporal relationship with the menstrual cycle"; (iii) "The patient has headache-free days"; (iv) "Close family members have the same headache phenotype"; and (v) "Headache occurred or stopped more than one week ago." CONCLUSIONS We propose five Green Flags for primary headache disorders. None being a pathognomonic sign, we recommend searching for both Green Flags and Red Flags. If both are present, a secondary headache should be suspected. Overall, the application of the Green Flag concept in clinical practice is likely to increase diagnostic accuracy and improve diagnostic resource allocation. Prospective studies in clinical populations should be conducted to validate these Green Flags.

Background: Obesity has been linked to an increased prevalence of migraine, and to increased migraine attack frequency, but several questions are left unanswered by previous studies. We examined the relationship between obesity and headache in a large, population-based study where we could take into account body fat distribution, migraine subtypes and tension-type headache. Methods: The third population-based Nord-Trøndelag Health Study (HUNT3) included validated headache questionnaires and objective anthropometric measurements. Using a cross-sectional design, our sample consisted of 18,191 women and 14,985 men, aged 19 to 96 years. Of these 4290 (12.9%) had migraine, 4447 (13.4%) had frequent tension-type headache (TTH), and 24,439 were headache-free controls. A total of 5049 individuals with unclassified headache were excluded from the analyses. Using logistic regression, we modeled the association between obesity and headache prevalence, adjusting for relevant confounders. Results: Both total body obesity (TBO) and abdominal obesity (AO) were associated with a higher prevalence of migraine when compared to headache-free controls (OR 1.45 95% CI 1.32–1.59 and OR 1.29 95% CI 1.18–1.41, respectively), in particular for individuals < 50 years of age (OR 1.74 95% CI 1.54–1.98 and OR 1.89 95% CI 1.69–2.11). Similar results were seen for migraine with and without aura. Similar Overall, a weaker associations were as observed between obesity and TTH. There was a dose-response relationship between obesity categories and increased headache frequency in subjects with migraine. TBO was associated with migraine prevalence and attack frequency independent of AO. Conclusion: Both TBO and AO were associated with migraine prevalence and attack frequency. This association was largely limited to individuals < 50 years of age. TBO, rather than AO, may be a better measure of obesity in relation to migraine. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

ObjectivesTo evaluate the association between caesarean section and migraine in a population-based register-linked cohort study.SettingData from the population-based Nord-Trøndelag Health Studies (HUNT2 and HUNT3) were linked to information from the Norwegian Medical Birth Registry.Participants65 343 participants responded to the headache questions in any of the two HUNT studies. Only those answering the headache questions in HUNT2 or 3 and had information about mode of delivery in the Norwegian Medical Birth Registry (born after 1967) were included. Our final sample consisted of 6592 women and 4602 men, aged 19–41 years.OutcomesORs for migraine given caesarean section. Analyses were performed in multivariate logistic regression models.ResultsAfter adjusting for sex, age and fetal growth restriction, delivery by caesarean section was not associated with migraine later in life (OR 0.86, 95% CI 0.64 to 1.15). Delivery by caesarean section was associated with a reduced OR of non-migrainous headache (OR 0.77, 95% CI 0.60 to 0.99).ConclusionNo association was found between caesarean section and migraine in this population-based register-linked study.

ObjectivesCentral nervous system depressants (CNSDs) such as opioids, benzodiazepine and Z-hypnotics are commonly used. However, CNSDs may influence cognitive function, especially in older hospitalised patients with comorbidities. The aim was to examine the association between CNSD use and cognitive function in older patients. We assessed global and domain specific cognitive function, among hospitalised older patients, including covariates for comorbidity, anxiety and depression.DesignCross-sectional hospital-based study.SettingsData was collected consecutively from inpatients at somatic wards of a general university hospital.ParticipantsOlder patients between 65 and 90 years with/without CNSD use for ≥4 weeks.Outcome measuresThe main outcome was cognitive function assessed by Cognistat. Secondary outcomes were routine clinical tests in the wards (mini-mental state examination (MMSE), trail making test (TMT) A and B, and clock drawing tests). Analyses were bivariate and multiple linear regression, adjusted for age, gender, and education. Covariates were comorbidity, depression and anxiety scores.ResultsThe main result indicated that CNSD users (n=100) had (β=–3.4, 95% CI 6.27 to –0.58, p=0.017) lower Cognistat score than non-users (n=146), adjusted for age, gender, education, anxiety and depression, but not significant when including covariate for comorbidity (β= –2.50 - 5.45; –0.46, p=0.097). Comorbidity was associated with cognitive function (β=−0.77, 95% CI −1.22 to −0.14, p=0.014). Cognistat subdimensions associated with CNSD use were language (p=0.017) and calculation (p=0.003). In clock drawing test, users had lower scores than non-users (β=−0.80, 95% CI 1.24 to −0.36, p=0.004), but no significant difference was found with MMSE and TMT A or B. Z-hypnotics were associated with reduced cognitive function.ConclusionAmong older hospitalised patients, global cognition and specific cognitive functions were associated with long-term use of CNSD medication as well as with somatic comorbidity.Trial registration numberNCT0316208122 May 2017.

Background: The frequent use of medication to treat migraine attacks can lead to an increase in migraine frequency and is called medication-overuse headache (MOH). Methods: Based on the available literature in this guideline, the first step in patient management is education and counselling. Results: Patients with MOH should be managed by a multidisciplinary team of neurologists or pain specialists and behavioral psychologists. Patients in whom education is not effective should be withdrawn from overused drugs and should receive preventive treatment with drugs of proven efficacy. Patients with MOH in whom preventive treatment is not effective should undergo drug withdrawal. Drug intake can be abruptly terminated or restricted in patients overusing simple analgesics, ergots or triptan medication. In patients with long-lasting abuse of opioids, barbiturates or tranquilizers, slow tapering of these drugs is recommended. Withdrawal can be performed on an outpatient basis or in a daycare or inpatient setting.

Background Variation in mitochondrial DNA (mtDNA) has been indicated in migraine pathogenesis, but genetic studies to date have focused on candidate variants, with sparse findings. We aimed to perform the first mitochondrial genome-wide association study of migraine, examining both single variants and mitochondrial haplogroups. Methods In total, 71,860 participants from the population-based Nord-Trøndelag Health Study were genotyped. We excluded samples not passing quality control for nuclear genotypes, in addition to samples with low call rate and closely maternally related. We analysed 775 mitochondrial DNA variants in 4021 migraine cases and 14,288 headache-free controls, using logistic regression. In addition, we analysed 3831 cases and 13,584 controls who could be reliably assigned to a mitochondrial haplogroup. Lastly, we attempted to replicate previously reported mitochondrial DNA candidate variants. Results Neither of the mitochondrial variants or haplogroups were associated with migraine. In addition, none of the previously reported mtDNA candidate variants replicated in our data. Conclusions Our findings do not support a major role of mitochondrial genetic variation in migraine pathophysiology, but a larger sample is needed to detect rare variants and future studies should also examine heteroplasmic variation, epigenetic changes and copy-number variation.

Background Excessive daytime sleepiness (EDS, defined as Epworth sleepiness scale score > 10) is a common symptom, with a prevalence of 10–20% in the general population. It is associated with headache and other chronic pain disorders. However, little is known about the prevalence of EDS among people with secondary chronic headaches. Findings A total of 30,000 persons aged 30–44 from the general population was screened for headache by a questionnaire. The 633 eligible participants with self-reported chronic headache were interviewed and examined by a headache specialist who applied the International Classification of Headache Disorders with supplementary definitions for chronic rhinosinusitis and cervicogenic headache. A total of 93 participants had secondary chronic headache and completed the ESS. A total of 47 participants had chronic post-traumatic headache (CPTH) and/or cervicogenic headache (CEH), 39 participants had headache attributed to chronic rhinosinusitis (HACRS), while 7 had other secondary headaches. 23.3% of those with CPTH, CEH or HACRS reported EDS. In multivariable logistic regression analysis the odds ratios of EDS were not significantly different in people with CPTH/CEH or HACRS. Conclusion Almost one out of four subjects with secondary chronic headache reported EDS with no differences between the various secondary chronic headaches.

Introduction A relationship between headache and excessive daytime sleepiness (EDS) has been suggested. This study investigated this association in relation to people with chronic migraine or chronic tension-type headaches. Methods A total of 30,000 persons aged 30–44 from the general population were screened for chronic headache. Those eligible were interviewed by a headache specialist. EDS was defined as Epworth sleepiness scale score >10. Logistic regression models were used. Results Among the 323 eligible participants, 21.1% had EDS. In multivariable logistic regression analysis, the odds ratios (OR) of EDS were not significantly different in people with CM and CTTH. However, high headache frequency was associated with EDS (OR 2.03 (95% CI 1.11–3.73, p = 0.022)) for those with ≥ 80 compared to Conclusions Increased EDS was associated with higher headache frequency, but not with specific headache diagnoses.

Background and purpose Withdrawal therapy improves the headache situation for many patients with medication-overuse headache (MOH), but relapses are common. The objective was to assess the long-term effectiveness of a general practitioner conducted brief intervention (BI) for MOH. Methods Sixty MOH patients initially participating in a blinded cluster-randomized controlled trial evaluating BI versus business as usual (BAU) were followed up for 16 months. Follow-up was open after 6 months. Headache and medication days per month were evaluated in three groups: BI early (BI throughout the study, n = 24), BI late (initial BAU, then cross-over to BI, n = 22) and BAU throughout the study (n = 14). Results Fifty-five of 60 initially included patients completed the follow-up. The mean change over 16 months’ observation in the BI early group was a reduction of 8.4 (5.4–11.4) headache and 13.5 (9.6–17.3) medication days per month. The relapse rate into medication overuse was 8.3%. Patients in the BI late group also improved significantly after a BI. BAU showed no significant improvement. Conclusions Treatment for MOH in primary care through a BI is a simple intervention with lasting effects and low relapse rate. This approach may be a logical first step in MOH treatment, and referral should generally be reserved for primary care non-responders.

Background In older patients, timely recognition and treatment of medication misuse and dependence are crucial to secure medication safety and to avoid increasing health expenditure. Nonetheless, the detection of this condition remains challenging due to the paucity of screening instruments validated for older people. This study assesses diagnostic accuracy, reliability, validity and the factor structure of the Severity of Dependence Scale (SDS) in detecting medication misuse and dependence among hospitalized older patients, focusing on prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics. Methods 246 adults aged 65–90 were recruited consecutively from somatic departments of the Akershus University Hospital, Norway. Among these, 100 patients were identified as prolonged users of CNSDs. Diagnostic accuracy and validity of the SDS were assessed using DSM-IV criteria for substance abuse and dependence as the reference standard. We also performed an exploratory factor analysis and assessment of internal consistency using Cronbach’s alpha. Results The area under the ROC curve was 0.86 (95%CI = 0.79–0.93; p

Background In Norway, as in most other countries, the training program for clinical neurology has no mandatory headache program. Knowledge in headache management must therefore be acquired during everyday clinical training. The objectives of this study were to investigate neurology residents’ knowledge of headache. Methods A questionnaire survey was undertaken among neurology residents in Norway. Results All 17 neurological departments in Norway participated, and 143 residents responded (86%). Sixty percent were women, mean age was 32.5 years, and the respondents had an average of 28 months clinical training in neurology. Fifty-six percent knew the approximate prevalence of migraine and chronic headache. Thirty-seven percent asked their patients about disability, quality of life, and social functioning at every consultation. Further, 72% would prescribe prophylaxis for chronic tension-type headache and 97% for very frequent migraine. One third wrongly stated that use of the most common headache prophylactics could lead to medication-overuse headache. Headache diaries were used regularly by 63% for diagnostic purposes, and 73% requested an MRI for all long-lasting headaches referred to neurological outpatient clinics. Conclusion Although a major public health problem, headache knowledge is moderate at best, and its management clearly varies. There is an unmet need for a better and more structured headache training program in Norway.

Korrekt diagnostikk av ulike hodepinetyper kan være utfordrende, men det er den viktigste forutsetningen for optimal behandling. Det anbefales kontrollert bruk av anfallsmedisin og forebyggende tiltak. Hodepinesykdommer er ifølge sykdomsbyrdeprosjektet Global Burden of Disease blant de vanligste årsakene til funksjonsnedsettelse (1). Lidelsene påvirker i stor grad samfunnet, personene som rammes og de pårørende. Enkle diagnostiske verktøy og terapeutiske tiltak kan utgjøre en stor forskjell. Formålet med denne artikkelen er å gi konkrete råd for diagnostikk, behandling og oppfølging av hodepinepasienter. Vi vil også omtale noen nye behandlingsmuligheter. Artikkelen er basert på litteratursøk i PubMed, egne kliniske erfaringer og NevroNEL (2). Open Access CC-BY-ND

ObjectivesTimely recognition of medication misuse and dependence is crucial to avoid both adverse drug events and increasing health expenditure. Yet the detection of these disorders in older people remains challenging due to the paucity of evidence on characteristics of patients at risk. This study investigates sociodemographic, pharmacological and clinical characteristics and factors associated with prolonged medication use, misuse and dependence in hospitalised older patients, focusing on three commonly prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics.DesignA prospective, cross-sectional study complying with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.SettingSomatic departments of the Akershus University Hospital, Norway.Participants246 patients aged 65–90 were included.Outcome measuresProlonged use was defined as using CNSDs for ≥4 weeks. Misuse and dependence were assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for substance abuse and dependence. We used descriptive statistics to report patients’ characteristics and logistic regression to demonstrate factors associated with prolonged use, and misuse or dependence.ResultsForty per cent of participants reported using CNSDs for ≥4 weeks. The odds of prolonged use were higher for patients aged 75–84 (OR=2.32, 95% CI 1.16 to 4.65) and ≥85 (OR=3.33, 95% CI 1.25 to 8.87) vs ConclusionCNSD overuse is prevalent among hospitalised older patients, despite clear guidelines and recommendations. Our findings underline a need for stronger focus on responsible prescribing, timely detection and prevention of this issue, with special attention towards older patients, those with enhanced pain, polypharmacy and/or concurrent use of several CNSDs.Trial registration numberNCT03162081.

Sleep disturbances cause great impairment in quality of life. In this cross-sectional study, we analysed questionnaire-collected data from 12,655 persons (30-87 years) who participated in the sixth survey of the Tromsø Study carried out in 2007-2008. First, using this community-based sample representative of the general population of northern Norway, we performed a simple screening to identify individuals with self-reported sleeplessness among those survey participants who provided information about their sleep patterns. Self-reported sleeplessness was defined as responding “More than once a week” to the research question “How often have you suffered from sleeplessness during the last 12 months?” Second, we analysed the associations between selfreported sleeplessness and the following variables: age, gender, living with a spouse or not, level of education, employment status, income, smoking, alcohol consumption, body mass index, level of self-reported health, and psychological distress. Self-reported sleeplessness had a prevalence of 12.6% in this study population. For both men and women, the variables having the strongest association with sleeplessness were low levels of self-reported health (men, OR=8.70; women, OR=5.73) and the presence of psychological distress (men, OR=4.15; women, OR=2.76). In men, high levels of household income and education were both inversely related to the frequency of self-reported sleeplessness, while being unemployed was much more strongly associated with sleeplessness than being employed. We conclude that sleeplessness was frequent in this large population sample, affecting up to one in eight individuals. Subjects with self-reported sleeplessness had a distinctly different socio-economic profile and self-perceived health than those without complaints of sleeplessness.

Background Primary headaches are associated with psychological distress, neuroticism and disability. However, little is known about headache-related disability and psychological distress among people with secondary chronic headaches. Methods 30,000 persons aged 30–44 from the general population was screened for headache by a questionnaire. The responder rate was 71%. The International Classification of Headache Disorders with supplementary definitions for chronic rhinosinusitis and cervicogenic headache were used. The Hopkins Symptom Checklist-25 assessed high psychological distress, the Migraine Disability Assessment questionnaire assessed disability, and Eysenck Personality Questionnaire assessed neuroticism. Results Ninety-five of the 113 eligible participants (84%) completed the self-reported questionnaire. A total of 38 people had chronic post-traumatic headache, 21 had cervicogenic headache, and 39 had headache attributed to chronic rhinosinusitis, while 9 had co-occurrence of chronic post-traumatic and cervicogenic headache. Six persons had miscellaneous secondary chronic headaches. Overall, 49% of those with secondary chronic headache reported high psychological distress, which is significantly higher than in the general population. A high level of neuroticism was significantly more common in those with secondary chronic headache than in the general population. Severe headache-related disability was reported by 69%. 92 persons were followed up after 3 years. A low headache frequency was the only significant predictor of improvement of ≥ 25% in headache days. Having post-traumatic or cervicogenic headache and not headache attributed to chronic rhinosinusitis predicted an increased risk > 25% worsening of headache days or having a severe disability at 3 years follow-up. Conclusion Psychological distress and neuroticism were more common among people with secondary chronic headache than in the general population. Only a high headache frequency was significantly associated with increased headache disability at baseline and a poor prognosis in the long term.

Background Chronic headache (headache ≥15 days/month) is a leading cause of disability. Illness perception, beliefs and cognitive models are likely central for patient understanding of their chronic pain condition and are associated with treatment outcome. However, these factors are insufficiently described in chronic headache. Objective To describe illness perception, and to explore the effect of background variables and headache characteristics on illness perceptions in primary and secondary chronic headaches in the general population. Methods 30,000 persons aged 30 44 from the general population were screened for chronic headache by a mailed questionnaire. Those with self-reported chronic headache were interviewed by headache specialists. The questionnaire response rate was 71%, and the interview participation rate was 74%. The International Classification of Headache Disorders III was applied. Illness perception was assessed by the Revised Illness Perception Questionnaire (IPQ-R). The statistical approach was exploratory. Results 405 of the 516 eligible participants (78%) completed the IPQ-R. Confirmatory factor analysis showed good internal validity in chronic headache. People believed their chronic headache to be long-lasting, with negative life consequences including emotional distress. Severe headache-related disability was associated with more perception of chronicity, more perceived consequences, emotional load and illness identity and less illness coherence. People with secondary chronic headache scored significantly higher on chronicity and life consequences, and had less personal control than those with primary chronic headache. Conclusion Chronic primary and secondary headache is associated with a high symptom burden and chronicity with large perceived negative consequences for daily living, suggesting multidisciplinary management may be necessary.

BackgroundData on the socioeconomic burden of chronic headache (≥15 days/last month or >180 days/year) is lacking. This study investigated the impact of chronic headache on sickness absence, unemployment and disutility in the general population in Norway.Methods30 000 persons aged 30–44 from the general population were screened for chronic headache by a screening questionnaire. The responder rate was 71%. The International Classification of Headache Disorders was used. We analysed the association of chronic headache with lost workdays, days with ≥50% reduced productivity, sick leave, unemployment and disutility, as assessed with the Short-Form Six-Dimension (SF-6D) in separate regression analyses.ResultsEighty-three per cent (427/516, 79% women) of the eligible participants completed the data on workdays and utility. They reported a mean of 9.7 (SD 24.8) workdays lost over the last 3 months, because of headache. The mean disutility score (1-SF-6D score) was 0.41. Thirty-three per cent were on long-term (>1 year) sick leave. The OR for being on sick leave was 1.9 (95% CI 1.1 to 3.2, p=0.017) for those with secondary compared with primary chronic headache. Similarly, the OR for increased number of workdays lost to headache was 3.5 (95% CI 1.8 to 6.5, pConclusionsThe burden of chronic headache in the general population is substantial with high rates of lost workdays and disutility.