Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

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.

NCOR2 is a novel candidate gene for migraine-epilepsy phenotype.

HYPOTHESIS: To identify genetic factors predisposing to migraine-epilepsy phenotype utilizing a multi-generational family with known linkage to chr12q24.2-q24.3. METHODS: We used single nucleotide polymorphism (SNP) genotyping and next-generation sequencing technologies to perform linkage, haplotype, and variant analyses in an extended Finnish migraine-epilepsy family (n = 120). In addition, we used a large genome-wide association study (GWAS) dataset of migraine and two biobank studies, UK Biobank and FinnGen, to test whether variants within the susceptibility region associate with migraine or epilepsy related phenotypes in a population setting. RESULTS: The family showed the highest evidence of linkage (LOD 3.42) between rs7966411 and epilepsy. The haplotype shared among 12 out of 13 epilepsy patients in the family covers almost the entire NCOR2 and co-localizes with one of the risk loci of the recent GWAS on migraine. The haplotype harbors nine low-frequency variants with potential regulatory functions. Three of them, in addition to two common variants, show nominal associations with neurological disorders in either UK Biobank or FinnGen. CONCLUSION: We provide several independent lines of evidence supporting association between migraine-epilepsy phenotype and NCOR2. Our study suggests that NCOR2 may have a role in both migraine and epilepsy and thus would provide evidence for shared pathophysiology underlying these two diseases.

Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families.

BACKGROUND: Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine. METHODS: We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project. RESULTS: Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02-0.12; p = 0.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08-0.18; p < 0.001), migraine headache (mean 0.17; 95% CI 0.14-0.21; p < 0.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26-0.33; p < 0.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31-0.43; p < 0.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk. CONCLUSIONS: The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.

Self-Reported Efficacy of Treatments in Cluster Headache: a Systematic Review of Survey Studies.

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.

The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families.

Objective To study the position of hemiplegic migraine in the clinical spectrum of migraine with aura and to reveal the importance of CACNA1A, ATP1A2 and SCN1A in the development of hemiplegic migraine in Finnish migraine families. Methods The International Classification of Headache Disorders 3rd edition criteria were used to determine clinical characteristics and occurrence of hemiplegic migraine, based on detailed questionnaires, in a Finnish migraine family collection consisting of 9087 subjects. Involvement of CACNA1A, ATP1A2 and SCN1A was studied using whole exome sequencing data from 293 patients with hemiplegic migraine. Results Overall, hemiplegic migraine patients reported clinically more severe headache and aura episodes than non-hemiplegic migraine with aura patients. We identified two mutations, c.1816G>A (p.Ala606Thr) and c.1148G>A (p.Arg383His), in ATP1A2 and one mutation, c.1994C>T (p.Thr665Met) in CACNA1A. Conclusions The results highlight hemiplegic migraine as a clinically and genetically heterogeneous disease. Hemiplegic migraine patients do not form a clearly separate group with distinct symptoms, but rather have an extreme phenotype in the migraine with aura continuum. We have shown that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of the disease in Finnish hemiplegic migraine patients, suggesting that there are additional genetic factors contributing to the phenotype.

Premonitory symptoms in migraine: A cross-sectional study in 2714 persons.

AIM: To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors. METHODS: In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%. RESULTS: Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% (p < 0.001) and 0.5 symptoms (p < 0.001) among 491 persons with non-migraine headaches. Yawning was the most commonly reported symptom (34%) among migraineurs. Females reported PS more frequently than males (81 versus 64%, p < 0.001) and experienced a higher number of different symptoms (mean 3.3 versus 1.8, p < 0.001). All measures of migraine severity were associated with a higher burden of PS. Light and sound sensitivity showed the highest co-occurrence (kappa = 0.51, 95% CI 0.47-0.55). In a generalized linear model, age, gender, higher frequency, duration and intensity of headache, reduced working capacity, most aura symptoms, and associated symptoms of the headache phase were significantly associated with an increased in the number of PS. CONCLUSION: PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.

Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set.

BACKGROUND: Before the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set. METHODS: We selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500 kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls. RESULTS: None of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately. CONCLUSION: The available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine.

The relationship between headache and religious attendance (the Nord-Trøndelag health study-HUNT).

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.

Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.

BACKGROUND AND PURPOSE: Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. METHODS: In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. RESULTS: One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5-2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0-5.0) compared with 7.9% (95% confidence interval, 7.2-8.7) in ischemic strokes. CONCLUSIONS: In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Stroke mimics and intravenous thrombolysis.

STUDY OBJECTIVE: The necessity for rapid administration of intravenous thrombolysis in patients with acute ischemic stroke may lead to treatment of patients with conditions mimicking stroke. We analyze stroke patients treated with intravenous thrombolysis in our center to characterize cases classified as stroke mimics. METHODS: We identified and reviewed all cases with a diagnosis other than ischemic stroke in our large-scale single-center stroke thrombolysis registry. We compared these stroke mimics with patients with neuroimaging-negative and neuroimaging-positive ischemic stroke results. RESULTS: Among 985 consecutive intravenous thrombolysis-treated patients, we found 14 stroke mimics (1.4%; 95% confidence interval 0.8% to 2.4%), 694 (70.5%) patients with neuroimaging-positive ischemic stroke results, and 275 (27.9%) patients with neuroimaging-negative ischemic stroke results. Stroke mimics were younger than patients with neuroimaging-negative or -positive ischemic stroke results. Compared with patients with neuroimaging-positive ischemic stroke results, stroke mimics had less severe symptoms at baseline and better 3-month outcome. No differences appeared in medical history or clinical features between stroke mimics and patients with neuroimaging-negative ischemic stroke results. None of the stroke mimics developed symptomatic intracerebral hemorrhage compared with 63 (9.1%) among patients with neuroimaging-positive ischemic stroke results and 6 (2.2%) among patients with neuroimaging-negative ischemic stroke results. CONCLUSION: Stroke mimics were infrequent among intravenous thrombolysis-treated stroke patients in this cohort, and their treatment did not lead to harmful complications.

[Treatment of prolonged migraine attack (status migrenosus)]. / Pitkittyneen migreenikohtauksen (status migrenosus) hoito.

If a migraine attack takes more than 72 hours it is called status migrenosus (SM). The most important contributing factor in SM is prolonged excessive use of anti-migraine drugs. Before starting any treatments for SM, severe causes underlying the prolonged pain should be excluded. The cornerstones of pharmacological therapy for SM are parenterally administered anti-inflammatory drugs and triptans as well as valproate and dopamine antagonists. With regard to long-term prognosis, the recognition and treatment of medication overuse headache is essential.

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

Intravenous thrombolysis of basilar artery occlusion: predictors of recanalization and outcome.

BACKGROUND AND PURPOSE: Basilar artery occlusion has a high mortality rate (85% to 95%) if untreated. We describe a large single-center cohort treated mostly with intravenous alteplase and heparin. METHODS: The cohort included 116 patients with angiography-verified basilar artery occlusion. We studied baseline characteristics, frequencies of recanalization and symptomatic intracranial hemorrhage, and 3-month outcome (modified Rankin Scale [mRS]). RESULTS: Thirty patients (25.9%) had mRS 0 to 2, 42 patients (36.2%) had moderate outcome (mRS, 0-3), 26 patients (22.4%) required daily help (mRS, 4-5), and 48 patients (41.4%) died. Eighteen patients (15.7%) developed symptomatic intracranial hemorrhage. In patients with post-treatment angiogram available (n=91), 59 patients (64.8%) had a complete or partial recanalization. Radiological location of basilar artery occlusion was known in 55 of 91 instances, and recanalization was associated directly with clot location at the top-of-basilar (odds ratio, 4.8 [1.1-22]; P=0.048). Independent outcome (mRS 0-2) was associated with lower age and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Age, nil or minimal recanalization, and symptomatic intracranial hemorrhage were independently associated with fatal outcome. Sixteen of 71 patients (22.5%) who presented with coma eventually reached moderate outcome, and additional 8 patients (11.3%) progressed to mRS 4. CONCLUSIONS: Whereas recanalization after intravenous thrombolysis strongly predicts survival and moderate outcome, therapeutic techniques should concentrate on clot location. Although most adverse baseline variables, age, symptom severity, but also coma are beyond control, it should not preclude thrombolysis, which may permit independent survival.

Outcome by stroke etiology in patients receiving thrombolytic treatment: descriptive subtype analysis.

BACKGROUND AND PURPOSE: treating ischemic stroke with thrombolytic therapy is effective and safe, but limited data exist on its efficacy and safety in different etiologic subtypes. METHODS: patients with acute ischemic stroke treated with intravenous thrombolysis between 1995 and 2008 at our hospital were classified according to the Trial of ORG 10172 in Acute Stroke Treatment criteria based on diagnostic evaluation. Clinical outcome of the stroke subtypes by 3-month modified Rankin Scale was compared by multivariate logistic regression. A good outcome was defined as modified Rankin Scale ≤ 2. Symptomatic intracranial hemorrhage was defined according to both National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study criteria. RESULTS: of the 957 eligible patients, 41% (389) had cardioembolisms, 23% (217) large-artery atherosclerosis, and 11% (101) small-vessel disease (SVD). A good outcome was more common in SVD than in the other subtypes. Patients with SVD were more often male (64% versus 54%), had a lower baseline National Institutes of Health Stroke Scale score, lower mortality rate, and experienced no symptomatic intracranial hemorrhage. Patients with SVD had a prior stroke more often (20% versus 11%), whereas hypertension, diabetes, hypercholesterolemia, and transient ischemic attacks were equally distributed in all subtypes. Patients with SVD had a better outcome even after adjusting for baseline National Institutes of Health Stroke Scale and glucose level, age, and hyperdense artery sign (OR, 1.81; 1.01 to 3.23). In the adjusted multivariate model, other etiologic groups showed no significant correlation to good outcome. CONCLUSIONS: patients with SVD were spared from bleeding complications and had the best outcome even after adjustment for confounding factors.

Consistently replicating locus linked to migraine on 10q22-q23.

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.

Recurrent ischemic events in young adults after first-ever ischemic stroke.

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.

Post-thrombolytic hyperglycemia and 3-month outcome in acute ischemic stroke.

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.

Off-label thrombolysis is not associated with poor outcome in patients with stroke.

BACKGROUND AND PURPOSE: Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. METHODS: All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. RESULTS: One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. CONCLUSIONS: Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.

Valsalva maneuver as migraine inducer: a case report of a woman with patent foramen ovale and an ischemic stroke.

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.