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Background: The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear. Methods: The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. Results: In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results. Conclusion: Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them. [ABSTRACT FROM AUTHOR]

Background: Migraine is a disabling neurological disorder with the pathophysiology yet to be understood. The microstructural alteration in brain white matter (WM) has been suggested to be related to migraine in recent studies, but these evidence are observational essentially and cannot infer a causal relationship. The present study aims to reveal the causal relationship between migraine and microstructural WM using genetic data and Mendelian randomization (MR). Methods: We collected the Genome-wide association study (GWAS) summary statistics of migraine (48,975 cases / 550,381 controls) and 360 WM imaging-derived phenotypes (IDPs) (31,356 samples) that were used to measure microstructural WM. Based on instrumental variables (IVs) selected from the GWAS summary statistics, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between migraine and microstructural WM. In forward MR analysis, we inferred the causal effect of microstructural WM on migraine by reporting the odds ratio (OR) that quantified the risk change of migraine for per 1 standard deviation (SD) increase of IDPs. In reverse MR analysis, we inferred the causal effect of migraine on microstructural WM by reporting the β value that represented SDs of changes in IDPs were caused by migraine. Results: Three WM IDPs showed significant causal associations (p < 3.29 × 10− 4, Bonferroni correction) with migraine and were proved to be reliable via sensitivity analysis. The mode of anisotropy (MO) of left inferior fronto-occipital fasciculus (OR = 1.76, p = 6.46 × 10− 5) and orientation dispersion index (OD) of right posterior thalamic radiation (OR = 0.78, p = 1.86 × 10− 4) exerted significant causal effects on migraine. Migraine exerted a significant causal effect on the OD of left superior cerebellar peduncle (β = − 0.09, p = 2.78 × 10− 4). Conclusions: Our findings provided genetic evidence for the causal relationships between migraine and microstructural WM, bringing new insights into brain structure for the development and experience of migraine. [ABSTRACT FROM AUTHOR]

Purpose of Review: The use and efficacy of various substances in the treatment of CH have been studied in several retrospective surveys. The aim of the study is to systematically review published survey studies to evaluate the reported efficacies of both established and unconventional substances in abortive and prophylactic treatment of both episodic and chronic CH, specifically assessing the consistency of the results. Recent Findings: No systematic review have been conducted of these studies previously. A systematic literature search with a set of search terms was conducted on PubMed. Retrospective surveys that quantified the self-reported efficacy of two or more CH treatments, published in English during 2000–2020, were included. Several key characteristics and results of the studies were extracted. A total of 994 articles were identified of which 9 were found to be eligible based on the selection criteria. In total, 5419 respondents were included. Oxygen and subcutaneous triptan injections were most reported as effective abortive treatments, while psilocybin and lysergic acid diethylamide were most commonly reported as effective prophylactic treatments. The reported efficacy of most substances was consistent across different studies, and there were marked differences in the reported efficacies of different substances. The reported order of efficacy is generally in agreement with clinical studies. The findings suggest that retrospective surveys can be used to obtain supporting information on the effects of various substances used in the treatment of CH and to form hypotheses about novel treatment methods. The consistently reported efficacy of psilocybin and LSD in prophylactic treatment indicates need for clinical studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). Methods: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age‐ and sex‐matched (±5 years) stroke‐free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist‐to‐hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. Results: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63–3.76) and MA (OR = 3.50, 95% CI = 2.19–5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61–5.47; OR = 4.32 for MA, 95% CI = 2.16–8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32–4.61; OR = 3.61 for MA, 95% CI = 1.75–7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right‐to‐left shunt in patients with PFO. Interpretation: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242–253 [ABSTRACT FROM AUTHOR]

Background: Religious belief can be used as a pain coping strategy. Our purpose was to evaluate the relationship between headache and religious activity using prospective data from a large population-based study. Methods: This longitudinal cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Survey (HUNT 2 and 3) performed in 1995-1997; and 2006-2008. Among the 51,383 participants aged ≥ 20 years who answered headache questions at baseline, 41,766 were eligible approximately 11 years later. Of these, 25,177 (60%) completed the question in HUNT 3 regarding religious activity. Frequent religious attendees (fRA) (used as a marker of stronger religious belief than average) were defined as those who had been to church/prayer house at least once monthly during the last six months. Results: In the multivariate analyses, adjusting for known potential confounders, individuals with headache 1-14 days/month in HUNT 2 were more likely to be fRA 11 years later than headache-free individuals. Migraine at baseline predisposed more strongly to fRA at follow-up (OR = 1.25; 95% CI 1.19-1.40) than did non-migrainous headache (OR = 1.13; 95% 1.04-1.23). The odds of being fRA was 48% increased (OR 1.48; 95% 1.19-1.83) among those with migraine 7-14 days/month at baseline compared to subjects without headache. In contrast, headache status at baseline did not influence the odds of being frequent visitors of concerts, cinema and/or theatre at follow-up 11 years later. Conclusions: In this prospective study, headache, in particular migraine, at baseline slightly increased the odds of being fRA 11 years later. [ABSTRACT FROM AUTHOR]

Background Thrombolysis of ischemic stroke patients presenting with mild symptoms is controversial. Aim We aimed to describe the clinical outcome and frequency of infarcts and symptomatic intracerebral hemorrhages on follow-up imaging of such thrombolysis-treated patients. Methods Our cohort included 1398 consecutive ischemic stroke patients treated with intravenous thrombolysis at the Helsinki University Central Hospital, years 1995-2010. We analyzed the patients according to baseline National Institutes of Health Stroke Scale: ≤2, 3-4, 5-6, and >6. In our institution, visualization of an artery occlusion or perfusion deficit is required for thrombolysis with National Institutes of Health Stroke Scale ≤ 2. We used univariate and multivariable methods to describe the cohort and study associations between the variables. Excellent three-month outcome was defined as modified Rankin Scale 0-1. Results Fifty-eight (4·1%) patients were treated with National Institutes of Health Stroke Scale ≤ 2, another 194 (13·6%) with 3-4 points, and 236 (16·5%) with 5-6 points. With National Institutes of Health Stroke Scale ≤ 2, 45 (78%) of the patients had excellent three-month outcome, achieved in 116 (59%) patients with National Institutes of Health Stroke Scale 3-4, in 130 (55%) with National Institutes of Health Stroke Scale 5-6, and in 241 (26%) with National Institutes of Health Stroke Scale > 6. Frequencies of symptomatic intracerebral hemorrhage ( European Cooperative Acute Stroke Study-2) were 0%, 2·6%, 2·1%, and 8·1%, and visible infarcts on follow-up imaging 48%, 43%, 48%, and 74%, respectively. In patients with baseline National Institutes of Health Stroke Scale ≤ 6, poor outcome was associated with previous stroke, diabetes, elevated admission blood glucose, and development of intracerebral hemorrhage. Conclusions Half of patients presenting with National Institutes of Health Stroke Scale 0-6 developed an infarction despite thrombolysis, and 40% had poor outcome, which was associated with glucose metabolism and hemorrhagic complications. Managing thrombolysis candidates with mild symptoms warrants individual consideration often supported by multimodal imaging. [ABSTRACT FROM AUTHOR]

Background Maintaining a steady thrombolysis service for treatment of acute ischemic stroke 24 h/7 days is challenging. Diurnal and seasonal variability of stroke onset affects the clinical outcome of these patients. Hypothesis We state that a 24 h/7 days availability of stroke-trained physicians ameliorates weekend effects and other seasonal, weekday, or non-office-hour-related influences on outcome of ischemic stroke patients treated with intravenous thrombolysis. Methods All consecutive ischemic stroke patients treated with thrombolysis at the Helsinki University Central Hospital were prospectively registered ( n = 1581). Patients with basilar artery occlusion ( n = 154) were excluded. Door-to-needle time, three-month clinical outcome as measured by the modified Rankin Scale dichotomized at 0 to 2 vs. 3 to 6, and symptomatic intracerebral hemorrhage were analyzed with logistic regression models adjusting for baseline variables. The treating physician was defined as experienced after 18 decisions made to give thrombolysis treatment. Results Door-to-needle time or clinical outcome did not differ with regard to time of day or season of presentation. Higher rates of symptomatic intracerebral hemorrhage occurred in spring (odds ratio 2·06, 95% confidence interval 1·03-4·11) and fall (odds ratio 2·08, 95% confidence interval 1·03-4·18). Physician experience reduced the door-to-needle time (odds ratio 0·40, 95% confidence interval 0·32-0·50) but was not associated with patient outcome (modified Rankin scale 3 to 6, odds ratio 1·22, 95% confidence interval 0·95-1·59) or symptomatic intracerebral hemorrhage (odds ratio 0·80, 95% confidence interval 0·51-1·27) rates. Conclusions Thrombolytic therapy can be delivered at a steady service level at all times. With proper training, less-experienced physicians can provide high quality thrombolysis, but experience translates into faster treatment. [ABSTRACT FROM AUTHOR]

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10?5 for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10?4; combined P = 7.06 × 10?11) and at 3p24 (near TGFBR2; replication P = 1.0 × 10?4; combined P = 1.17 × 10?9). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10?8 and P = 0.02; combined P = 3.86 × 10?8, respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. [ABSTRACT FROM AUTHOR]

Background: Treating hyperglycemia in acute ischemic stroke may be beneficial, but knowledge on its prognostic value and optimal target glucose levels is scarce. We investigated the dynamics of glucose levels and the association of hyperglycemia with outcomes on admission and within 48 h after thrombolysis. Methods: We included 851 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in the Helsinki University Central Hospital during 1998-2008. Outcome measures were unfavorable 3- month outcome (3-6 on the modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH) according to NINDS criteria. Hyperglycemia was defined as a blood glucose level of ≥8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia), (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent hyperglycemia (baseline plus 48-hour hyperglycemia). Results: 480 (56.4%) of our patients (median age 70 years; onset-to-needle time 199 min; National Institutes of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) = 2.33, 95% confidence interval (CI) = 1.41-3.86, and OR = 2.17, 95% CI = 1.30-3.38, respectively], death (OR = 6.63, 95% CI = 3.25-13.54, and OR = 3.13, 95% CI = 1.56-6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68-5.43, and OR = 1.89, 95% CI = 1.04-3.43, respectively), whereas baseline hyperglycemia did not. Conclusions: Hyperglycemia (≥8.0 mmol/l) during 48 h after intravenous thrombolysis of ischemic stroke is strongly associated with unfavorable outcome, sICH, and death. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective:: Data on recurrence of vascular events and their prognostic factors in young (<50 years of age) stroke patients are not well defined. Methods:: We assessed the occurrence of arterial thrombotic events in consecutive first-ever ischemic stroke patients aged 15 to 49 years entered into the Helsinki Young Stroke Registry (January 1994-October 2004) within 5-year follow-up. Follow-up was conducted with a structured telephone interview or letter, and review of all patient records; mortality data came from Statistics Finland. Primary outcomes were (1) nonfatal or fatal recurrent ischemic stroke; (2) nonfatal or fatal myocardial infarct, other arterial thrombotic event, or revascularization procedure; and (3) any combination of these, whichever occurred first (composite endpoint). We used Kaplan-Meier analysis to estimate cumulative risks and Cox proportional hazard model-adjusted for age, gender, relevant risk factors, and stroke subtype-for identifying predictors of recurrence. Results:: In the 807 patients followed (mean age, 41.5 ± 7.4 years; 62.9% male), cumulative 5-year recurrence rate was 9.4% (95% confidence interval [CI], 7.3-11.5%) for nonfatal or fatal ischemic stroke, 2.4% (95% CI, 1.3-3.5%) for nonfatal or fatal myocardial infarct or other arterial endpoint, and 11.5% (95% CI, 9.2-13.7%) for the composite endpoint. Independent predictors of the composite endpoint were type 1 diabetes mellitus (hazard ratio [HR], 4.39; 95% CI, 2.28-8.45), large-artery atherosclerosis underlying the index stroke (HR, 2.82; 95% CI, 1.36-5.83), heart failure (HR, 2.96; 95% CI, 1.17-7.50), previous transient ischemic attack (HR, 2.33; 95% CI, 1.40-3.88), and increasing age (HR, 1.05; 95% CI, 1.01-1.10). Interpretation:: Despite their young age, these individuals were at marked risk of recurrent arterial events, predicted by mostly modifiable baseline factors.ANN NEUROL 2010;68:661-671 [ABSTRACT FROM AUTHOR]

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10−9, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10−11 (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10−5, permuted threshold for genome-wide significance 7.7 × 10−5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine. [ABSTRACT FROM AUTHOR]

A slight predominance of cluster pain on the right side has been reported in several studies. The aim of this large retrospective Nordic multicenter study was to estimate the prevalence of right- and left-sided pain in cluster headache (CH) patients with side-locked pain, the prevalence of side shifts in episodic and chronic CH patients, and the occurrence of cranial autonomic symptoms related to pain side. Among 383 cluster patients, 55 (14%) had experienced pain side shift. Of the remaining 328 individuals without side shift, there was no significant difference between the occurrence of right-sided and left-sided pain (54 vs. 46%). The prevalence of side shift was similar for episodic and chronic CH and the occurrence of cranial autonomic symptoms was not influenced by the pain side. In conclusion, previous reports of a side difference in location of cluster pain could not be confirmed in this large Nordic sample. [ABSTRACT FROM AUTHOR]

We thank the authors for their interest in our study1 and presenting interesting new results based on the Italian Project on Stroke at Young Age (IPSYS). As Dr. Mazzoleni and colleagues correctly point out, our study was probably underpowered to detect any weak association between migraine without aura and CIS. Taken together, the results by Mazzoleni et al improve our knowledge on the complex association among migraine, PFO, and CIS in young adults. [Extracted from the article]

Background: Deep brain stimulation of the posterior hypothalamic area is one of the neuromodulation treatments used for chronic cluster headache, but the number of published patients remains low. Aim: The aim of this article was to present the retrospective results of 12 consecutive chronic cluster headache patients treated with deep brain stimulation at Helsinki University Hospital. Materials and Methods: All chronic cluster headache patients treated with deep brain stimulation between 2004 and 2012 were included in the study. Patients were interviewed and their hospital files analyzed. Treatment effect was classified as good, partial, or no effect. Results: Of the 12 patients, four had a good treatment effect, five had partial, and three had no effect of deep brain stimulation. In contrast to previous studies, our patients reported an almost immediate benefit after the onset of stimulation. Conclusions: Deep brain stimulation provides clinically meaningful benefit to a subgroup of chronic cluster headache patients. [ABSTRACT FROM AUTHOR]

An abstract of the article "Migraine without aura: genome-wide association analysis identifies several novel susceptibility" by Boukje de Vries, Tobias Freilinger, Verneri Anttila, Rainer Malik, Mikko Kallela, Gisela M. Terwindt, Patricia Pozo-Rosich, Bendik Winsvold, and colleagues is presented.

The association between patent foramen ovale, ischemic stroke, and migraine with aura is well known. It is, however, complicated and generates a considerable debate about the features and clinical consequences of the phenomenon. We report a case of a woman for whom patent foramen ovale has possibly acted as an inducer of both migraine attacks and ischemic stroke. [ABSTRACT FROM AUTHOR]