Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Prediction of a time-sensitive condition among patients with dizziness assessed by the emergency medical services.

BACKGROUND: Dizziness is a relatively common symptom among patients who call for the emergency medical services (EMS). AIM: To identify factors of importance for the early identification of a time-sensitive condition behind the symptom of dizziness among patients assessed by the EMS. METHODS: All patients assessed by the EMS and triaged using Rapid Emergency Triage and Treatment (RETTS) for adults code 11 (=dizziness) in the 660,000 inhabitants in the Municipality of Gothenburg, Sweden, in 2016, were considered for inclusion. The patients were divided into two groups according to the final diagnosis (a time-sensitive condition, yes or no). RESULTS: There were 1536 patients who fulfilled the inclusion criteria, of which 96 (6.2%) had a time-sensitive condition. The majority of these had a stroke/transitory ischaemic attack (TIA). Eight predictors of a time-sensitive condition were identified. Three were associated with a reduced risk: 1) the dizziness was of a rotatory type, 2) the dizziness had a sudden onset and 3) increasing body temperature. Five were associated with an increased risk: 1) sudden onset of headache, 2) a history of head trauma, 3) symptoms of nausea or vomiting, 4) on treatment with anticoagulants and 5) increasing systolic blood pressure. CONCLUSION: Among 1536 patients who were triaged by the EMS for dizziness, 6.2% had a time-sensitive condition. On the arrival of the EMS, eight factors were associated with the risk of having a time-sensitive condition. All these factors were linked to the type of symptoms or to clinical findings on the arrival of the EMS or to the recent clinical history.

Anaemia at admission is associated with poor clinical outcome in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Anaemia is associated with poor clinical outcome after ischaemic and haemorrhagic stroke. The association between anaemia and outcome in patients with cerebral venous thrombosis (CVT) was examined. METHODS: Consecutive adult patients with CVT were included from seven centres. Anaemia at admission was scored according to World Health Organization definitions. Poor clinical outcome was defined as a modified Rankin Scale score 3-6 at last follow-up. A multiple imputation procedure was applied for handling missing data in the multivariable analysis. Using binary logistic regression analysis, adjustments were made for age, sex, cancer and centre of recruitment (model 1). In a secondary analysis, adjustments were additionally made for coma, intracerebral haemorrhage, non-haemorrhagic lesion and deep venous system thrombosis (model 2). In a sensitivity analysis, patients with cancer were excluded. RESULTS: Data for 952 patients with CVT were included, 22% of whom had anaemia at admission. Patients with anaemia more often had a history of cancer (17% vs. 7%, P < 0.001) than patients without anaemia. Poor clinical outcome (21% vs. 11%, P < 0.001) and mortality (11% vs. 6%, P = 0.07) were more common amongst patients with anaemia. After adjustment, anaemia at admission increased the risk of poor outcome [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.7, model 1]. Model 2 revealed comparable results (aOR 1.9, 95% CI 1.2-3.2), as did the sensitivity analysis excluding patients with cancer (aOR 2.3, 95% CI 1.3-3.8, model 1). CONCLUSION: The risk of poor clinical outcome is doubled in CVT patients presenting with anaemia at admission.

Vocational outcome in cerebral venous thrombosis: Long-term follow-up study.

OBJECTIVES: Few studies have investigated long-term functional outcome in patients with cerebral venous thrombosis (CVT). We aimed to evaluate return to work (RTW) after CVT and its association with self-reported life satisfaction, quality of life, health, participation, fatigue, depression, and anxiety. METHODS: From hospital records, we identified all patients diagnosed with CVT in Sahlgrenska University Hospital between 1996 and 2016 and invited all survivors to a clinical follow-up visit >1 year after onset. Primary outcome was RTW within the follow-up period which was defined as ≥50% of gainful work or equivalent activity. Patients that were >62 years when they developed CVT were excluded. Cox regression analyses identified associated factors to RTW and Mann-Whitney U tests compared distributions of self-reported questionnaires on life satisfaction and health. RESULTS: Of 62 eligible and consenting patients (median age: 41.5 years (28.75-51.0); 61.3% female), 44 (71.0%) did RTW within the follow-up period (median 135 months, IQR 64-197). Median time to RTW was 7.0 months (IQR 1.4-12.7). Female sex (HR = 0.50, 95% CI = 0.25-0.99, P = .049) and parenchymal lesion detected during acute hospital stay (HR = 0.45, 95% CI = 0.24-0.82, P = .009) were significantly associated with no RTW. Patients with RTW reported significantly higher life satisfaction, quality of life, health, participation and lesser impact of fatigue, depression, and anxiety. CONCLUSIONS: Return to work after CVT is associated with higher life satisfaction, participation, and health. Parenchymal lesion in acute phase and female sex were associated with no RTW. Despite the young age of the patients, a significant portion did not regain working ability.

Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke.

BACKGROUND AND PURPOSE: Visuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. METHODS: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1-5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. RESULTS: The regression model significantly explained variance in the modified Rankin scale (R2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. CONCLUSIONS: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

Editor's Choice - Very Urgent Carotid Endarterectomy is Associated with an Increased Procedural Risk: The Carotid Alarm Study.

OBJECTIVE/BACKGROUND: The aim of the Carotid Alarm Study was to compare the procedural risk of carotid endarterectomy (CEA) performed within 48 hours with that after 48 hours to 14 days following an ipsilateral cerebrovascular ischaemic event. METHODS: Consecutive patients with symptomatic carotid stenosis undergoing CEA were prospectively recruited. Time to surgery was calculated as time from the most recent ischaemic event preceding surgery. A neurologist examined patients before and, after CEA. The primary endpoint was the composite endpoint of death and/or any stroke within 30 days of the surgical procedure. The study was designed to include 600 patients, with 150 operated on within 48 hours. RESULTS: From October 2010 to December 2015, 418 patients were included, of whom 75 were operated within 48 hours of an ischaemic event. The study was prematurely terminated owing to the slow recruitment rate in the group operated on within 48 hours. Patients undergoing CEA within 48 hours had a higher risk of reaching the primary endpoint than those operated on later (8.0% vs. 2.9%). Multivariate logistic regression analyses showed that CEA performed within 48 h (odds ratio [OR] 3.07; 95% confidence interval [CI] 1.04-9.09), CEA performed out of office hours (OR 3.65; 95% CI 1.14-11.67), and use of shunt (OR 4.02; 95% CI 1.36-11.93) were all independently associated with an increased risk of reaching the primary endpoint. CONCLUSION: CEA performed within 48 hours was associated with a higher risk of complications compared with surgery performed 48 hours-14 days after the most recent ischaemic event.

Exome array analysis of ischaemic stroke: results from a southern Swedish study.

BACKGROUND AND PURPOSE: Genome-wide association (GWA) studies have identified a few risk loci for ischaemic stroke, but these variants explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis for ischaemic stroke. METHODS: Patients with ischaemic stroke (n = 2385) and control subjects (n = 6077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis and gene-based tests were performed of exome variants with minor allele frequency of < 5%. A separate GWA analysis was also performed, based on 700 000 genotyped common markers and subsequent imputation. RESULTS: No exome variant or gene was significantly associated with all ischaemic stroke after Bonferroni correction (all P > 1.8 × 10-6 for single-variant and >4.15 × 10-6 for gene-based analysis). The strongest association in single-variant analysis was found for a missense variant in the DNAH11 gene (rs143362381; P = 5.01 × 10-6 ). In gene-based tests, the strongest association was for the ZBTB20 gene (P = 7.9 × 10-5 ). The GWA analysis showed that the sample was homogenous (median genomic inflation factor = 1.006). No genome-wide significant association with overall ischaemic stroke risk was found. However, previously reported associations for the PITX2 and ZFHX3 gene loci with cardioembolic stroke subtype were replicated (P = 7 × 10-15 and 6 × 10-3 ). CONCLUSIONS: This exome array analysis did not identify any single variants or genes reaching the pre-defined significance level for association with ischaemic stroke. Further studies on exome variants should be performed in even larger, well-defined and subtyped samples.

Public stroke awareness and intent to call 112 in Sweden.

BACKGROUND AND AIMS: Recognition of stroke symptoms and activation of emergency services are essential in minimizing delay for acute stroke treatments. In this study, we assessed public stroke awareness in Sweden. METHODS: One thousand and five hundred residents aged 18-79 years participated in a telephone survey. Open-ended questions were used to assess knowledge of stroke symptoms, risk factors, and action if witnessing or experiencing a potential stroke. RESULTS: Seventy-two percentage could report at least one stroke symptom and 86% at least one risk factor. Only 13% could report three or more stroke symptoms. Female sex (OR, 1.79; 95% CI, 1.30-2.45) and high education (OR, 2.30; 95% CI, 1.38-3.80) were associated with knowledge of stroke symptoms. Sixty-five percentage indicated they would call the emergency number 112 if witnessing or experiencing a potential stroke. Female sex (OR, 1.48; 95% CI, 1.18-1.85) and high education (OR, 1.40; 95% CI, 1.01-1.93) were positively associated, while increasing age (OR, 0.99; 95% CI, 0.98-0.99) was negatively associated with intent to call 112. CONCLUSION: We confirm a rather low public awareness of stroke in Sweden, poorer among males and those with low education. With increasing age, a lower proportion indicated intent to call 112 for stroke symptoms.

Pediatric intranasal lobular capillary hemangioma: a case report and review of the literature.

Lobular capillary hemangioma is a benign lesion commonly affecting the head and neck region. However, in children, it is commonly seen in the buccal mucosa, gingiva, and the tongue, but its presence in the nasal cavity is less frequent. The most common symptoms of nasal hemangiomas are epistaxis and nasal obstruction. However, we present a case of a thirteen-year-old male having intranasal lobular capillary hemangioma with a 2-day history of left-sided epistaxis. The diagnosis is confirmed by histological examination, and the treatment is done by endonasal endoscopic excision of the hemangioma with cauterization of the feeding vessel has performed to remove the lesion completely. Moreover, the diagnosis of lobular capillary hemangioma must always be kept in mind when discussing the differential diagnosis of a bleeding mass within the nasal cavity, even though it is a rare condition and surgical excision is still the preferred first-line treatment.

Association between multimorbidity and cognitive decline in the elderly population of the Eastern Province, Saudi Arabia.

BACKGROUND: Cognitive decline affects the quality of life, and dementia affects independence in daily life activities. Multimorbidity in older adults is associated with a higher risk of cognitive impairment. This research aims to study the relationship between cognitive decline and multimorbidity in the elderly population in the Eastern Province, Saudi Arabia. MATERIALS AND METHODS: This cross-sectional research was conducted from July to October 2022 among adults over 60 years. All patients with two or more comorbidities were contacted for a face-to-face interview and cognitive testing to estimate cognitive function by trained family physicians using St. Louis University Mental State Examination. ANOVA and Chi-square test were used to test for statistical significance. Binary logistic regression was used to show the odds of having cognitive impairment and multimorbidity. All tests were performed at 5% level of significance. RESULTS: The study involved 343 individuals; majority (74.1%) aged 60-75 years and were males (67.9%). Hypertension, diabetes, and chronic pain were reported by 56%, 48%, and 44% participants, respectively. Thirty percent participants had 3 or more comorbidities. About 36% had mild neurocognitive disorder and 31.2% had dementia. The results showed that age, gender (female), diabetes, stroke, chronic pain, and multimorbidity were significantly associated with cognitive impairment. In our study, hypertension, coronary artery diseases, depression, and anxiety were not significantly associated with risk of cognitive decline. CONCLUSION: Our study found that multimorbidity is significantly associated with cognitive decline. Controlling comorbidities and preventing risk factors in midlife could help in delaying the progression of the disease.

Risk of Obstructive Sleep Apnea and its Relation to Cognitive Functions Among Saudi Older Adults.

Background: The association between obstructive sleep apnea (OSA) and cognitive decline among older adults is a still a topic of debate. Objective: The aim of this study was to determine the association between risk of OSA and cognitive function among Saudi older adults. Methods: This was a cross-sectional community-based study conducted between July and October 2022. Participants were recruited from gathering areas where older adults are likely attending such as district centers, waiting areas of shopping malls, and mosques. Questionnaires were completed using face-to-face interviews. The questionnaire included questions of sociodemographics, sleep pattern and health status. A validated Arabic version of Athens insomnia scale, STOP-BANG questionnaire, and St. Louis University mental status (SLUMS) questionnaire were used. A multi-Linear regression model was used to determine the association between cognitive functions and OSA. Results: A total of 343 participants were recruited in this study, of which 86% were male. The mean age was 65±9 years. 65% of participants with high risk of sleep apnea were diagnosed with either dementia or mild cognitive impairment (MCI). Most of the participants who were illiterate (83%) had dementia, while only 4% of participants with higher education had dementia. Conclusion: Dementia and mild cognitive impairment is prevalent among Saudi older adults with high risk of OSA. Clinicians and patients should be aware of the risk of developing dementia in patients with OSA, especially if remain untreated.

Genetic variation in the receptor for advanced glycation end-products (RAGE) gene and ischaemic stroke.

BACKGROUND AND PURPOSE: The multi-ligand receptor for advanced glycation end-products (RAGE, alias AGER) is suggested to contribute to the pathogenesis of vascular disease, but its potential role in stroke is unclear. The aim of this study was to investigate whether genetic variation in RAGE gene is associated with ischaemic stroke (IS). METHODS: The Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 Caucasian patients with first ever (n = 732) and recurrent (n = 112) IS, and 668 Caucasian controls. Three tagSNPs were selected to capture genetic variation in the RAGE gene. IS subtypes were determined using TOAST criteria. RESULTS: One SNP, rs1035798, showed significant association with the subtype of small-vessel disease (SVD) after correction for multiple testing (OR 1.56, 95% CI 1.16-2.09), adjusted P-value < 0.05). This association was independent of hypertension, diabetes and smoking. None of the SNPs was associated with overall IS. CONCLUSION: In this sample of patients with IS, genetic variation in RAGE is associated with the IS subtype SVD, but not overall IS.

Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?

BACKGROUND AND PURPOSE: The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. METHODS: We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately. RESULTS: SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. CONCLUSIONS: Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.

The prediction of functional dependency by lateralized and non-lateralized neglect in a large prospective stroke sample.

BACKGROUND AND PURPOSE: Lateralized and non-lateralized impairments in visual attention have been identified as important components in patients with visuospatial neglect. This study investigated the course of these two phenomena across time in relation to neurological symptoms and functional outcome in a large consecutive and prospective stroke sample. METHODS: A total of 375 consecutive stroke patients were divided into three groups (lateralized, non-lateralized or no visual inattention) acutely and 3 months post-stroke using the star cancellation test. Neurological impairments, localization of brain damage, asymmetry in clinical symptoms and functional outcome were assessed. Possible group differences were analysed, and stepwise logistic regressions were performed to examine the relative importance of predictors of functional dependency. RESULTS: Participants with acute lateralized inattention differed (P ≤ 0.05) from the other two groups by more often exhibiting severe neurological symptoms, functional dependency and persisting visual inattention. The regression analyses selected acute lateralized inattention as an important and independent predictor of functional dependency following right hemisphere damage, but not following left hemisphere damage. CONCLUSIONS: The results emphasize the prognostic value of lateralized inattention and the importance of separating lateralized and non-lateralized symptoms of visual inattention at the commencement of rehabilitation.

Stroke subtype predicts outcome in young and middle-aged stroke sufferers.

OBJECTIVES: There are few studies on long-term outcome after ischemic stroke (IS) for young and middle-aged stroke sufferers in relation to etiologic subtypes. Here, we report 2-year outcome in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). MATERIALS AND METHODS: SAHLSIS comprises 600 patients with IS before the age of 70 years. Etiologic subtype of IS was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST). Recurrent vascular events and death were registered using several overlapping methods. Functional outcome was assessed according to the modified Rankin Scale (mRS). RESULTS: After 2 years, 55 (9.2%) patients had suffered a recurrent stroke, 15 (2.5%) had a transient ischemic attack (TIA), 4 (0.7%) had a coronary event, and 24 (4.0%) had died. The number of recurrent stroke, TIA, and death differed significantly between etiologic stroke subtypes. The highest rates were observed in large-vessel disease (LVD), whereas small-vessel disease and cryptogenic stroke showed the lowest recurrence and mortality rates. LVD was a significant predictor of the composite outcome (recurrent stroke, TIA, coronary event and/or death) independently of cardiovascular risk factors and stroke severity. Stroke subtype also predicted functional outcome 2 years after index stroke, but this association was not retained after adjustment for stroke severity. CONCLUSIONS: In young and middle-aged stroke patients, stroke subtype predicts recurrent vascular events and/or death 2 years after index stroke independently of cardiovascular risk factors and stroke severity. Thus, it is important to take the etiologic subtype of IS in account when assessing the risk of recurrence both in the clinical setting and in future studies.

Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration.

BACKGROUND: Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS: Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS: Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (±bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p = 0.044) and proximal ACA occlusions (43% vs. 24%, p = 0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p = 0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION: Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

Genetic variation on chromosome 9p21 shows association with the ischaemic stroke subtype large-vessel disease in a Swedish sample aged ≤ 70.

BACKGROUND: The aim of this study was to investigate whether we could replicate a recent finding of an association between genetic variants on chromosome 9p21 and the ischaemic stroke (IS) subtype large-vessel disease (LVD). METHODS: The Sahlgrenska Academy Study on Ischemic Stroke comprises 844 patients with IS, who suffered IS before reaching the age of 70, and 668 healthy controls. IS subtype was defined according to the TOAST criteria, and 111 patients were categorized as LVD. Seven single-nucleotide polymorphisms (SNPs) on 9p21 were analyzed. Functional outcome was assessed 3 months after IS using the modified Rankin scale. RESULTS: The SNP rs7857345 showed a significant association with the subtype LVD independent of traditional vascular risk factors. In addition, an association between rs7857345 and functional outcome after LVD was observed. CONCLUSION: In this relatively young sample of patients with IS, genetic variation on 9p21 is associated with LVD.

Genetic variation in complement component C3 shows association with ischaemic stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate whether genetic variation at the third complement component (C3) locus is associated with ischaemic stroke (IS). METHODS: The Sahlgrenska Academy Study on Ischaemic Stroke comprises 844 patients with IS, and 668 healthy controls. Sixteen SNPs were analyzed. RESULTS: Two SNPs, rs2277984 and rs3745565, showed a significant association with overall IS. The SNP rs2277984 also showed association with the IS subtype cryptogenic stroke. These associations were independent of hypertension, diabetes, and smoking. The independent association between rs3745565 and overall IS withstands correction for multiple testing. CONCLUSION: In this sample of patients with IS, genetic variation in C3 is associated with IS.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Cancer and risk of cerebral venous thrombosis: a case-control study.

Essentials The risk of cerebral venous thrombosis (CVT) in patients with cancer is not known. We performed a case-control study including 594 patients with CVT and 6278 controls. History of cancer increased the risk of CVT approximately 5-fold. The association was strongest with hematological cancer in the first year after diagnosis. SUMMARY: Background Cancer is an established risk factor for leg vein thrombosis and pulmonary embolism. Controlled studies assessing the risk of cerebral venous thrombosis (CVT) in patients with cancer have not been performed. Objective To assess whether cancer is a risk factor for CVT. Patients/Methods This was a case-control study. We assessed consecutive adult patients with CVT from three academic hospitals from 1987 to 2015, and control subjects from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We adjusted for age, sex and oral contraceptive use, and stratified for type of cancer and time since diagnosis of cancer. Results We included 594 cases and 6278 controls. In total, 53 cases (8.9%) and 160 controls (2.5%) had a history of cancer. Cases were younger (median 42 vs. 48 years), more often female (68% vs. 54%) and more often used oral contraceptives (55% vs. 23%) than controls. The risk of CVT was increased in patients with cancer compared with those without cancer (adjusted odds ratio [aOR], 4.86; 95% confidence interval [CI], 3.46-6.81). Patients with a hematological type of cancer had a higher risk of CVT (aOR, 25.14; 95% CI, 11.64-54.30) than those with a solid type of cancer (aOR, 3.07; 95% CI, 2.03-4.65). The association was strongest in the first year after diagnosis of cancer (hematological aOR, 85.57; 95% CI, 19.70-371.69; solid aOR, 10.50; 95% CI, 5.40-20.42). Conclusions Our study indicates that cancer is a strong risk factor for CVT, particularly within the first year of diagnosis and in patients with a hematological type of cancer.