Chronic Migraine

Chronic migraine as a disease was initially recognized in patients with a large burden of disability from frequent headaches and a history of prior migraines. Over time, this observation was operationalized into multiple diagnostic criteria with requirements for frequent headache days, typically 15 or more, which, on at least 8 days in a month, have the features of migraine headache. Chronic migraine affects 1–2% of the general population, and about 8% of patients with migraine. Understanding disease mechanisms still remains a challenge. Inflammation and central sensitization play significant role in the evolutive mechanisms of chronic migraine. Treatment of this condition should primarily focus on the prevention. The currently available evidence-based prophylactic treatment options are topiramate, valproic acid, onabotulinumtoxin A and recently developed promising anti-CGRP monoclonal antibodies. Chronic migraine research is a dynamic and rapidly advancing area. New developments in this field have the potential to improve the diagnosis, to provide more personalized treatments and to reduce burden of disability

Headache, depression and anxiety: associations in the Eurolight project.

Headache disorders and psychiatric disorders are both common, while evidence, mostly pertaining to migraine, suggests they are comorbid more often than might be expected by chance. There are good reasons for establishing whether they are: symptoms of comorbid illnesses may summate synergistically; comorbidities hinder management, negatively influencing outcomes; high-level comorbidity indicates that, where one disease occurs, the other should be looked for. The Eurolight project gathered population-based data on these disorders from 6624 participants.Eurolight was a cross-sectional survey sampling from the adult populations (18-65 years) of 10 EU countries. We used data from six. The questionnaire included headache-diagnostic questions based on ICHD-II, the Headache-Attributed Lost Time (HALT) questionnaire, and HADS for depression and anxiety. We estimated odds ratios (ORs) to show associations between migraine, tension-type headache (TTH) or probable medication-overuse headache (pMOH) and depression or anxiety.pMOH was most strongly associated with both psychiatric disorders: for depression, ORs (vs no headache) were 5.5 [2.2-13.5] (p < 0.0001) in males, 5.5 [2.9-10.5] (p < 0.0001) in females; for anxiety, ORs were 10.4 [4.9-21.8] (p < 0.0001) and 7.1 [4.5-11.2] (p < 0.0001). Migraine was also associated with both: for depression, ORs were 2.1 [1.3-3.4] (p = 0.002) and 1.8 [1.1-3.1] (p = 0.030); for anxiety 4.2 [2.8-6.3] (p < 0.0001) and 2.4 [1.7-3.4] (p < 0.0001). TTH showed associations only with anxiety: ORs 2.5 [1.7-3.7] (p < 0.0001) for males, 1.5 [1.1-2.1] (p = 0.021) for females. Participants with migraine carried 19.1 % probability of comorbid anxiety, 6.9 % of depression and 5.1 % of both, higher than the representative general-population sample (14.3, 5.6 and 3.8 %). Probabilities in those with MOH were 38.8, 16.9 and 14.4 %; in TTH, they did not exceed those of the whole sample. Comorbid psychiatric disorder did not add to headache-attributed productive time losses, but weak associations existed (R (2)  = 0.020-0.082) for all headache types between lost productive time and probabilities of depression and, less so, anxiety.In this large study we confirmed that depression and especially anxiety are comorbid more than by chance with migraine, and showed the same is true, but more strongly, with MOH. Arguably, migraine patients and, more certainly, MOH patients should be screened with HADS in pursuit of best outcomes

Headache yesterday in Europe

BACKGROUND: Surveys enquiring about burden of headache over a prior period of time (eg, 3 months) are subject to recall bias. To eliminate this as far as possible, we focused on presence and impact of headache on the preceding day (“headache yesterday”). METHODS: Adults (18-65 years) were surveyed from the general populations of Germany, Italy, Lithuania, Luxembourg and the Netherlands, from a work-force population in Spain and from mostly non-headache patient populations of Austria, France and UK. A study of non-responders in some countries allowed detection of potential participation bias where initial participation rates were low. RESULTS: Participation rates varied between 11% and 59% (mean 27%). Non-responder studies suggested that, because of participation bias, headache prevalence might be overestimated in initial responders by up to 2% (absolute). Across all countries, 1,422 of 8,271 participants (15-17%, depending on correction for participation bias) had headache yesterday lasting on average for 6 hours. It was bad or very bad in 56% of cases and caused absence from work or school in 6%. Among those who worked despite headache, 20% reported productivity reduced by >50%. Social activities were lost by 24%. Women (21%) were more likely than men (12%) to have headache yesterday, but impact was similar in the two genders. CONCLUSIONS: With recall biases avoided, our findings indicate that headache costs at least 0.7% of working capacity in Europe. This calculation takes into account that most of those who missed work could make up for this later, which, however, means that leisure and social activities are even more influenced by headache

Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system

Hyperglycemia and Stroke Mortality: Comparison between fasting and 2-h glucose criteria

OBJECTIVE—We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria

The Eurolight project: the impact of primary headache disorders in Europe. Description of methods

The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients’ organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients’ organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe

Stroke in urban and rural populations in north-east Bulgaria: incidence and case fatality findings from a 'hot pursuit' study

BACKGROUND: Bulgaria's official stroke mortality rates are higher for rural than urban areas. Official mortality data has indicated that these rates are amongst the highest in Europe. There has been a lack of studies measuring stroke incidence in urban and rural populations. METHODS: We established intensive notification networks covering 37791 residents in Varna city and 18656 residents (55% of them village-dwellers), all aged 45 to 84, in 2 rural districts. From May 1, 2000 to April 30, 2001 frequent contact was maintained with notifiers and death registrations were scanned regularly. Suspected incident strokes were assessed by study neurologists within a median of 8 days from onset. RESULTS: 742 events were referred for neurological assessment and 351 of these, which met the WHO criteria for stroke, were in persons aged 45 to 84 and were first ever in a lifetime. Incidence rates, standardised using the world standard weights for ages 45 to 84, were 909 (/100000/year) (95% CI 712–1105) and 597 (482–712) for rural and urban males and 667 (515–818) and 322 (248–395) for rural and urban females. Less than half were admitted to hospital (15% among rural females over 65). Twenty-eight day case fatality was 35% (123/351) overall and 48% (46/96) in village residents. The excess case fatality in the villages could not be explained by age or severity. CONCLUSIONS: Rural incidence rates were over twice those reported for western populations but the rate for urban females was similar to other western rates. The high level and marked heterogeneity in both stroke incidence and case fatality merit further investigation

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health