Early versus Later Anticoagulation for Stroke with Atrial Fibrillation.

BACKGROUND: The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. METHODS: We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. RESULTS: Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. CONCLUSIONS: In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor.

OBJECTIVE: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. METHODS: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. RESULTS: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. INTERPRETATION: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726.

The long-term effect of work schedule, shift work disorder, insomnia and restless legs syndrome on headache among nurses: A prospective longitudinal cohort study.

BACKGROUND: The preset study aimed to explore whether work schedules and sleep disorders predict the onset of headache. METHODS: A longitudinal study was conducted with questionnaire data from 2014 (baseline) and 2017 (follow-up) on work schedule, number of night shifts, number of quick returns, insomnia, shift work disorder (SWD), restless legs syndrome (RLS) and validated headache diagnoses among 1560 Norwegian nurses. Associations were explored by multivariate regression analyses. RESULTS: Work related factors at baseline did not predict onset of headache three years later. In the adjusted logistic regressions, insomnia at baseline predicted increased risk of new onset of migraine (odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.08-2.33), chronic headache (OR = 2.02; 95% CI = 1.04-4.66) and medication-overuse headache (OR = 3.79; 95% CI = 1.26-11.42) at follow-up. SWD at baseline predicted new onset of migraine (OR = 1.64; 95% CI = 1.07-2.50) and RLS at baseline predicted new onset of headache ≥1 day per month (OR = 1.55; 95% CI = 1.01-2.36) and migraine (OR = 1.55; 95% CI = 1.03-2.32) at follow-up. No factors predicted tension-type headache. CONCLUSIONS: Overall, work related factors did not predict the onset of headache three years later, whereas insomnia, SWD and RLS at baseline all increased the risk of future headaches.

Headaches and facial pain attributed to SARS-CoV-2 infection and vaccination: a systematic review.

BACKGROUND AND PURPOSE: The aim was to provide insights to the characteristics of headache in the context of COVID-19 on behalf of the Headache Scientific Panel and the Neuro-COVID-19 Task Force of the European Academy of Neurology (EAN) and the European Headache Federation (EHF). METHODS: Following the Delphi method the Task Force identified six relevant questions and then conducted a systematic literature review to provide evidence-based answers and suggest specific diagnostic criteria. RESULTS: No data for facial pain were identified in the literature search. (1) Headache incidence during acute COVID-19 varies considerably, with higher prevalence rates in prospective compared to retrospective studies (28.9%-74.6% vs. 6.5%-34.0%). (2) Acute COVID-19 headache is usually bilateral or holocranial and often moderate to severe with throbbing pain quality lasting 2-14 days after first signs of COVID-19; photo-phonophobia, nausea, anosmia and ageusia are common associated features; persistent headache shares similar clinical characteristics. (3) Acute COVID-19 headache is presumably caused by immune-mediated mechanisms that activate the trigeminovascular system. (4) Headache occurs in 13.3%-76.9% following SARS-CoV-2 vaccination and occurs more often amongst women with a pre-existing primary headache; the risk of developing headache is higher with the adenoviral-vector-type vaccines than with other preparations. (5) Headache related to SARS-CoV-2 vaccination is mostly bilateral, and throbbing, pressing, jolting or stabbing. (6) No studies have been conducted investigating the underlying mechanism of headache attributed to SARS-CoV-2 vaccines. CONCLUSION: The results of this joint EAN/EHF initiative provide a framework for a better understanding of headache in the context of SARS-CoV-2 infection and vaccination.

Changes in work schedule affect headache frequency among Norwegian nurses: a 3-year-follow-up study.

OBJECTIVES: To explore whether changes in work schedule, number of night shifts and number of quick returns were related to changes in headache frequencies. METHODS: A longitudinal study with questionnaire data from 2014 (baseline) and 2017 (follow-up) on work schedule (day only, shift work without nights and shift work with nights), number of night shifts, number of quick returns (less than 11 hours in-between shifts) and validated headache diagnoses among 1104 Norwegian nurses. Associations were explored by adjusted multivariate regression analyses. RESULTS: The median age at baseline was 37 years (IQR 31-43) and 90.5% were women. In the adjusted logistic regression analysis of changed work schedule between baseline and follow-up, changing from night work was associated with increased odds for reversion from headache >1 days/month to no headache at all last year (OR 2.77 (1.29; 5.95)). Changes towards less night shifts (>10) or quick returns (>10) during the last year were associated with increased odds of reversion of headache to no headache (OR 2.23 (1.20; 4.17) and OR 1.90 (1.04; 3.49)). Only decrease in number of night shifts (>10) during the last year reduced risk of onset of any new headache between baseline and follow-up (OR of 0.39 (0.18; 0.84)). CONCLUSION: Changing from night work and reducing the number of night shifts and quick returns were associated with less headache in this 3-year-follow-up of Norwegian nurses. This adds to the growing body of evidence that night work may have direct negative health consequences.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Prehospital Blood Pressure and Clinical and Radiological Outcomes in Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND: High blood pressure (BP) is associated with poor outcome in acute spontaneous intracerebral hemorrhage. Little is known about the predictive value of prehospital BP in intracerebral hemorrhage. We aimed to investigate the relationship between prehospital BP and clinical and radiological outcomes. METHODS: This is a retrospective, hospital-based study of all adult intracerebral hemorrhage patients admitted within 24 hours of symptom onset to a large primary stroke centre during 2012 to 2019. The first prehospital and on-admission BP were recorded as systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. The absolute differences between prehospital and on-admission BP were calculated (BPchange). Primary outcomes were in-hospital death, early neurological deterioration, and hematoma expansion. Associations between prehospital BP, BPchange, and outcomes were explored by regression with adjustment for relevant confounders. RESULTS: We included 426 patients aged median 76 (interquartile range 67-85) years and 203 (48%) were female. Median prehospital systolic BP was 179 (interquartile range 158-197) and diastolic BP was 100 (interquartile range 86-112) mm Hg. In-hospital death occurred in 121/426 (28%), early neurological deterioration in 107/295 (36%), and hematoma expansion in 50/185 (27%) patients. There were linear associations between 5 mm Hg increment of prehospital systolic BP (odds ratio 1.06, [95% CI, 1.01-1.12]) and mean arterial pressure (odds ratio 1.08, [95% CI, 1.01-1.15]) and in-hospital death, and between 5 mm Hg increment of prehospital diastolic BP (odds ratio 1.10, [95% CI, 1.00-1.21]) and mean arterial pressure (odds ratio 1.09, [95% CI, 1.00-1.18]) and hematoma expansion. There was a nonlinear association between prehospital systolic BP and in-hospital death. No consistent associations between prehospital BPchange and outcomes were found. CONCLUSIONS: In patients with acute intracerebral hemorrhage, elevated prehospital BP parameters were associated with in-hospital death and hematoma expansion. Changes in prehospital BP were not consistently associated with outcome. A possible U-shaped association between prehospital BP and in-hospital death needs further investigation.

Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache.

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.

Telemedicine in headache care: A systematic review.

OBJECTIVE: Telemedicine is defined as video-based consultations with synchronous video and sound. This systematic review investigated the use of telemedicine for headache patients. The primary outcomes of interest were treatment efficacy, feasibility, safety, convenience, compliance, and patient satisfaction. METHODS: A systematic literature search was performed using PubMed and Embase. Thirteen articles met the eligibility criteria and were included in the review. A systematic review protocol was registered on the International Prospective Register of Systematic Reviews, registration number CRD42021265875. RESULTS: There were no significant differences in treatment efficacy, patient satisfaction, compliance or safety using telemedicine when compared to traditional consultations. Telemedicine was found to be convenient due to being less time-consuming and expensive, especially for patients with limited access to health care. Despite the frequent occurrence of technical errors, telemedicine was found to be feasible. CONCLUSION: Telemedicine consultations are similar in quality to traditional in-office headache consultations and can be a more convenient solution for eligible headache patients.

Reasons and predictors of non-thrombolysis in patients with acute ischemic stroke admitted within 4.5 h.

OBJECTIVES: Thrombolytic treatment in acute ischemic stroke (AIS) reduces stroke-related disability. Nearly 40% of all patients with AIS (<4.5 h) receive thrombolysis, but there is a large variation in the use between hospitals. Little is known about reasons and predictors for not giving thrombolytic treatment. Therefore, we aimed to investigate reasons for non-thrombolysis in patients admitted within 4.5 h. METHODS: All patients with AIS (<4.5 h) admitted to Akershus University Hospital, Norway, between January 2015 and December 2017 were examined. Patient characteristics and reasons for not giving thrombolysis were registered. Descriptive statistics and logistic regression analyses were performed. RESULTS: Of 535 patients admitted with AIS (<4.5 h), 250 (47%) did not receive thrombolysis and of these only 26% had an absolute contraindication to treatment. Among the 74% with relative contraindications, the most common reasons given were mild and improving symptoms. Previous stroke (OR 3.32, 95%CI 1.99-5.52), arriving between 3 h and 4.5 h after onset (OR 7.76, 95%CI 3.73-16.11) or having mild symptoms (OR 2.33, 95%CI 1.56-3.49) were all significant predictors of not receiving thrombolytic treatment in the multivariable logistic regression model. CONCLUSION: A large proportion of patients with AIS do not receive thrombolysis. This study highlights up-to-date findings that arriving late in the time window, mild symptoms, and previous stroke are strong predictors of non-treatment. It is uncertain whether there is an underuse of thrombolysis in AIS. Increasing the utility of thrombolysis in the 4.5 h time window must be weighed against possible harms.

Diagnostics and management of headache in general practice.

BACKGROUND: Headache disorders are globally prevalent and insufficient treatment contribute to low quality of life, increased disability, and socioeconomic costs. However, headache can to a large extent be treated appropriately by general practitioners. OBJECTIVE: To explore general practitioners' (GPs') management of patients with headache lasting ≥6 months. METHODS: In this retrospective descriptive cross-sectional study based on medical audit, all GPs practicing in Vejle municipality (population 116,992), Denmark, were invited to review their latest 20 patients with headache. Outcome measures were headache diagnostics, treatment, and referrals. Factors associated with referral to neurological treatment were examined by logistic regression. RESULTS: Of 26 invited practices, 19 participated reporting on 367 patients with lasting headache (71.4% women; mean-age 48.5 years). One hundred and sixty-one patients had migraine (44%; IQR: 28-60%), 140 (38%; IQR: 25-44%) had tension-type headache; 243 (66%; IQR: 50-79%) used simple analgesics, 147 (40%; IQR: 29-59%) triptans, 37 (10%; IQR: 0-14%) opioids, 93 (25%; IQR: 20-35%) were prescribed preventive medication; 176 (48%; IQR: 48-59%) were referred to neurologist, and 92 (25%; IQR: 10-37%) were referred to CT or MRI scan. Associated factors for referral were >1 headache diagnosis (aOR 1.75 [95% CI: 1.05-2.95]; P = 0.03), post-traumatic headache (aOR 2.53 [95% CI: 1.25-5.38]; P = 0.01), unspecific headache (aOR 2.04 [95% CI: 1.08-3.93]; P = 0.03), and using preventive treatment (aOR 2.75 [95% CI: 1.68-4.57]; P < 0.001). CONCLUSION: This study provides insights to how GPs manage patients with long-lasting headache. Focus should be on reducing opioids, increasing preventive treatment, and keeping more patients in primary care.

The Norwegian PraksisNett: a nationwide practice-based research network with a novel IT infrastructure.

PURPOSE: Clinical research in primary care is relatively scarce. Practice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary care. In Norway, almost all 5.4 million inhabitants have access to a general practitioner (GP) through a patient-list system. This gives opportunity for a PBRN with reliable information about the general population. The aim of the current paper is to describe the establishment, organization and function of PraksisNett (the Norwegian Primary Care Research Network). MATERIALS AND METHODS: We describe the development, funding and logistics of PraksisNett as a nationwide PBRN. RESULTS: PraksisNett received funding from the Research Council of Norway for an establishment period of five years (2018-2022). It is comprised of two parts; a human infrastructure (employees, including academic GPs) organized as four regional nodes and a coordinating node and an IT infrastructure comprised by the Snow system in conjunction with the Medrave M4 system. The core of the infrastructure is the 92 general practices that are contractually linked to PraksisNett. These include 492 GPs, serving almost 520,000 patients. Practices were recruited during 2019-2020 and comprise a representative mix of rural and urban settings spread throughout all regions of Norway. CONCLUSION: Norway has established a nationwide PBRN to reduce hurdles for conducting clinical studies in primary care. Improved infrastructure for clinical studies in primary care is expected to increase the attractiveness for studies on the management of disorders and diseases in primary care and facilitate international research collaboration. This will benefit both patients, GPs and society in terms of improved quality of care.Key pointsPractice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary careImproved infrastructure for clinical studies in primary care is expected to increase the attractiveness for studies on the management of disorders and diseases in primary care and facilitate international research collaborationWe describe PraksisNett, a Norwegian PBRN consisting of 92 general practices including 492 GPs, serving almost 520,000 patientsAn advanced and secure IT infrastructure connects the general practices to PraksisNett and makes it possible to identify and recruit patients in a novel way, as well as reuse clinical dataPraksisNett will benefit both patients, GPs and society in terms of improved quality of careThis paper may inform and inspire initiatives to establish PBRNs elsewhere.

Barriers and gaps in headache education: a national cross-sectional survey of neurology residents in Denmark.

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.

Perceptions on basilar artery occlusion management in China versus other countries: Analysis of the after the BEST of BASICS (ABBA) survey.

INTRODUCTION: Uncertainty remains on the optimal management of basilar artery occlusion (BAO). Two large randomized controlled trials (RCTs) in 2019 and 2021 demonstrated neutral results with respect to the use of endovascular therapy (EVT) for BAO. This study aimed to understand regional variation in physicians' perceptions towards the treatment of BAO as stratified by physician respondents from China versus outside China, prior to the publication of studies demonstrating a benefit of EVT for BAO. METHODS: An international online survey was conducted of stroke neurologists and neurointerventionalists from January to March 2022. Survey questions evaluated physician opinions toward the use of EVT in BAO, as well as the clinical and imaging features underlying treatment decisions. Respondents were dichotomized as either from China or from other countries and differences between groups were analyzed. RESULTS: There were 1245 physician respondents across 73 countries of which 295 (23.7%) were from China. Compared to respondents from the rest of the world, respondents from China were more likely to be interventionalists (71.5% vs 35.0%; p < 0.0001). Overall, more than 95% of respondents believed that EVT was superior to medical therapy under certain circumstances. Chinese respondents were more likely to believe that further RCTs were necessary than respondents from other countries (93.6% vs 76.2%; p < 0.0001). Chinese respondents were more likely to use advanced imaging in later time windows and use a premorbid mRS threshold of ≤2 for BAO selection to EVT. CONCLUSION: Most stroke physicians believe EVT is beneficial in selected patients with BAO. Clinical and imaging modality differences were observed in the selection criteria used for EVT. There was greater inclination to enroll all trial eligible patients in a BAO RCT by respondents from China as compared to other parts of the world.

Management of cluster headache and other trigeminal autonomic cephalalgias in pregnancy and breastfeeding.

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.

Green Flags and headache: A concept study using the Delphi method.

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.

Acute stroke care during the first phase of COVID-19 pandemic in Norway.

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.

Stroke admission rates before, during and after the first phase of the COVID-19 pandemic.

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 < 0.011). The proportion of mild ischemic and haemorrhagic strokes was also lower during lockdown with 66% before, 57% during and 68% after (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.

The patterns and burden of multimorbidity in geriatric patients with prolonged use of addictive medications.

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 < 0.001). Multivariable logistic regression indicated a significant association between multimorbidity burden and prolonged addictive medication use (OR = 1.72, 95% CI 1.42-2.08). Predictive margins postestimation showed a systematic increase in the predicted CIRS-G scores when the number of addictive drug used increases. CONCLUSIONS: Multimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.

Is there a causal relationship between stress and migraine? Current evidence and implications for management.

BACKGROUND: The purpose of this narrative review is to examine the literature investigating a causal relationship between stress and migraine and evaluate its implications for managing migraine. METHODS: PubMed, PsycINFO and CINAHL were searched from 1988 to August 2021, identifying 2223 records evaluating the relationship between stress and migraine. Records were systematically screened. All potentially relevant records were thematically categorized into six mechanistic groups. Within each group the most recent reports providing new insights were cited. RESULTS: First, studies have demonstrated an association of uncertain causality between high stress loads from stressful life events, daily hassles or other sources, and the incidence of new-onset migraine. Second, major stressful life events seem to precede the transformation from episodic to chronic migraine. Third, there is some evidence for changes in levels of stress as a risk factor for migraine attacks. Research also suggests there may be a reversed causality or that stress-trigger patterns are too individually heterogeneous for any generalized causality. Fourth, migraine symptom burden seems to increase in a setting of stress, partially driven by psychiatric comorbidity. Fifth, stress may induce sensitization and altered cortical excitability, partially explaining attack triggering, development of chronic migraine, and increased symptom burden including interictal symptom burden such as allodynia, photophobia or anxiety. Finally, behavioral interventions and forecasting models including stress variables seem to be useful in managing migraine. CONCLUSION: The exact causal relationships in which stress causes incidence, chronification, migraine attacks, or increased burden of migraine remains unclear. Several individuals benefit from stress-oriented therapies, and such therapies should be offered as an adjuvant to conventional treatment and to those with a preference. Further understanding the relationship between stress, migraine and effective therapeutic options is likely to be improved by characterizing individual patterns of stress and migraine, and may in turn improve therapeutics.