Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.

OBJECTIVE: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. METHODS: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. RESULTS: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10-24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10-16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10-16 ) increased risk of CVT compared with individuals with blood group O. INTERPRETATION: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.

Occipital intracerebral hemorrhage-clinical characteristics, outcome, and post-ICH epilepsy.

OBJECTIVES: Posterior location affects the clinical presentation and outcome of ischemic stroke, but little is known about occipital intracerebral hemorrhage (ICH). We studied non-traumatic occipital ICH phenotype, outcome, and post-ICH epilepsy. MATERIALS AND METHODS: Occipital ICH patients were retrospectively identified from the Helsinki ICH Study registry of 1013 consecutive ICH patients treated in our tertiary center in 2005-2010. They were compared to non-occipital ICH patients to evaluate the effect of location on functional outcome at discharge (dichotomized modified Rankin Scale, mRS), 3- and 12-month mortality, and incidence of epilepsy. RESULTS: We found 19 occipital ICH patients (5.3% of lobar and 1.9% of all ICH). Compared to non-occipital lobar ICHs, they were younger (median age 63 vs 71 years, P = .007) and had lower National Institutes of Health Stroke Scale on admission (1 vs 8, P < .001), smaller hematoma volume (6.3 vs 17.7 ML, P = .008), and more frequently structural etiology underlying the ICH (26% vs 7%, P = .01). Mortality at both 3 and 12 months was 6%, whereas 84% reached favorable outcome (mRS 0-2) at discharge. Occipital location was associated with favorable outcome at discharge in lobar ICH (OR 11.02, 95% CI 1.55-78.20). Incidence of post-ICH epilepsy (median follow-up 2.7 years) was 18%, equaling to that of non-occipital lobar ICH. CONCLUSIONS: Occipital ICH patients are younger, have less severe clinical presentation, smaller hematoma volume, more often structural etiology, and better outcome than other ICH patients. They exhibit a similar risk of epilepsy as non-occipital ICHs.

Cerebral white matter lesions and post-thrombolytic remote parenchymal hemorrhage.

OBJECTIVE: Parenchymal hematoma (PH) following intravenous thrombolysis (IVT) in ischemic stroke can occur either within the ischemic area (iPH) or as a remote PH (rPH). The latter could be, at least partly, related to cerebral amyloid angiopathy, which belongs to the continuum of cerebral small vessel disease. We hypothesized that cerebral white matter lesions (WMLs)-an imaging surrogate of small vessel disease-are associated with a higher rate of rPH. METHODS: We analyzed 2,485 consecutive patients treated with IVT at the Helsinki University Hospital. Blennow rating scale of 5 to 6 points on baseline computed tomographic head scans was considered as severe WMLs. An rPH was defined as hemorrhage that-contrary to iPH-appears in brain regions without visible ischemic damage and is clinically not related to the symptomatic acute lesion site. The associations between severe WMLs and pure rPH versus no PH, pure iPH versus no PH, and pure rPH versus pure iPH were studied in multivariate logistic regression models. RESULTS: rPHs were mostly (74%) located in lobar regions. After adjustments, the presence of severe WMLs was associated with pure rPH (odds ratio [OR] = 6.79, 95% confidence interval [CI] = 2.57-17.94) but not with pure iPH (OR = 1.45, 95% CI = 0.83-2.53) when compared to patients with no PH. In direct comparison of pure rPH with pure iPH, severe cerebral WMLs were further associated with higher iPH rates (OR = 3.60, 95% CI = 1.06-12.19). INTERPRETATION: Severe cerebral WMLs were associated with post-thrombolytic rPH but not with iPH within the ischemic area. Ann Neurol 2016;80:593-599.

Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with poor clinical outcome in ischemic and hemorrhagic stroke. Admission hyperglycemia has not been investigated in patients with cerebral venous thrombosis. METHODS: Consecutive adult patients with cerebral venous thrombosis were included at the Academic Medical Center, The Netherlands (2000-2014) and the Helsinki University Central Hospital, Finland (1998-2014). We excluded patients with known diabetes mellitus and patients without known admission blood glucose. We defined admission hyperglycemia as blood glucose ≥7.8 mmol/L (141 mg/dL) and severe hyperglycemia as blood glucose ≥11.1 mmol/L (200 mg/dL). We used logistic regression analysis to determine if admission hyperglycemia was associated with modified Rankin Scale (mRS) score of 3 to 6 or mortality at last follow-up. We adjusted for: age, sex, coma, malignancy, infection, intracerebral hemorrhage, deep cerebral venous thrombosis, and location of recruitment. RESULTS: Of 380 patients with cerebral venous thrombosis, 308 were eligible. Of these, 66 (21.4%) had admission hyperglycemia with 8 (2.6%) having severe admission hyperglycemia. Coma (31.3% versus 5.0%, P<0.001) and intracerebral hemorrhage (53.0% versus 32.6%, P=0.002) at presentation were more common among patients with admission hyperglycemia than normoglycemic patients. Patients with admission hyperglycemia had a higher risk of mRS score of 3 to 6 (adjusted odds ratio, 3.10; 95% confidence interval, 1.35-7.12) and mortality (adjusted odds ratio, 4.13; 95% confidence interval, 1.41-12.09). Severe hyperglycemia was even more strongly associated with mRS score of 3 to 6 (adjusted odds ratio, 11.59; 95% confidence interval, 1.74-77.30) and mortality (adjusted odds ratio, 33.36; 95% confidence interval, 3.87-287.28) compared with normoglycemic patients. CONCLUSIONS: Admission hyperglycemia is a strong predictor of poor clinical outcome in patients with cerebral venous thrombosis.

Cancer in young adults with ischemic stroke.

BACKGROUND AND PURPOSE: Cancer is a risk factor for ischemic stroke. Little is known about cancer among young adults with ischemic stroke. We studied the frequency of cancer and its association with long-term risk of death among young patients with first-ever ischemic stroke. METHODS: 1002 patients aged 15 to 49 years, registered in the Helsinki Young Stroke Registry, and with a median follow-up of 10.0 years (interquartile range 6.5-13.8) after stroke were included. Historical and follow-up data were derived from the Finnish Care Register and Statistics Finland. Survival between groups was compared with the Kaplan-Meier life-table method, and Cox proportional hazard models were used to identify factors associated with mortality. RESULTS: One or more cancer diagnosis was made in 77 (7.7%) patients, of whom 39 (3.9%) had cancer diagnosed prestroke. During the poststroke follow-up, 41 (53.2%) of the cancer patients died. Median time from prestroke cancer to stroke was 4.9 (1.0-9.5) years and from stroke to poststroke cancer was 6.7 (2.7-10.9) years. Poststroke cancer was associated with age>40 years, heavy drinking, and cigarette smoking. The cumulative mortality was significantly higher among the cancer patients (68.6%, 95% confidence interval 52.0%-85.3%) compared with patients without cancer (19.7%, 95% confidence interval 16.3%-23.2%). Active cancer at index stroke, melanoma, and lung/respiratory tract cancer had the strongest independent association with death during the follow-up when adjusted for known poststroke mortality prognosticators. CONCLUSIONS: Cancer, and especially active cancer and no other apparent cause for stroke, is associated with unfavorable survival among young stroke patients.

Cerebral computed tomography-graded white matter lesions are associated with worse outcome after thrombolysis in patients with stroke.

BACKGROUND AND PURPOSE: Compared with other stroke causes, small-vessel disease is associated with better 3-month outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. Another question is the impact of coexisting cerebral white matter lesions (WMLs; a surrogate marker of small-vessel disease) on outcome, which was addressed in the current study. METHODS: We analyzed 2485 consecutive intravenous thrombolysis-treated patients at the Helsinki University Central Hospital, 2001 to 2014. WMLs were scored according to 4 previously published computed tomographic visual rating scales from all baseline head scans. The inter-rater agreement was calculated. The primary outcome measure was shift analysis, and the secondary examined all possible binary cutoffs in the modified Rankin Scale at 3 months. The associations of modified Rankin Scale with nominal, ordinal, and continuous variables were analyzed in univariate and adjusted in multivariate binary and ordinal regression (shift analysis) models. RESULTS: In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables, or dichotomized at different cutoff points) were associated with worse outcome at all binary levels and in shift analyses of the modified Rankin Scale. After adjusting for confounders, the statistically strongest association in shift analyses remained for the Blennow scale dichotomized at >3 points, reflecting at least moderate WMLs (odds ratio, 1.90; 95% confidence interval, 1.48-2.44). CONCLUSIONS: WMLs on admission computed tomographic scan are independently associated with worse outcome in intravenous thrombolysis-treated patients with stroke.

White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Cerebral white matter lesions (WMLs), a surrogate for small-vessel disease, are common in patients with stroke and may be related to an increased intracranial bleeding risk after intravenous thrombolysis in acute ischemic stroke. We aimed to investigate the risk of symptomatic intracerebral hemorrhage (sICH) in the presence of WMLs in a large cohort of ischemic stroke patients treated with intravenous thrombolysis. METHODS: We included 2485 consecutive patients treated with intravenous thrombolysis at the Helsinki University Central Hospital. WMLs were scored according to 4 previously published computed tomography visual rating scales from all baseline head scans. A sICH was classified according to the European Cooperative Acute Stroke Study II criteria. The associations of sICH with nominal, ordinal, and continuous variables were analyzed in a univariate binary regression model and adjusted in multivariate binary regression models. RESULTS: In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables or dichotomized at different cutoff points) were associated with increased risk of sICH. In binary analyses, WML doubled the bleeding risk: the odds ratios of all 4 visual rating scales ranged from 2.22 (95% confidence interval, 1.49-3.30) to 2.70 (1.87-3.90) in univariable and from 2.00 (1.26-3.16) to 2.62 (1.71-4.02) in multivariable analyses. The multivariable-adjusted odds ratio for the association of high load of WMLs with remote parenchymal hemorrhage was 4.11 (2.38-7.10). CONCLUSIONS: WMLs visible on computed tomography are associated with a more than doubled risk of sICH in patients treated with intravenous thrombolysis for acute ischemic stroke.

Gut microbiota are related to Parkinson's disease and clinical phenotype.

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker.

Long-term mortality after first-ever and recurrent stroke in young adults.

BACKGROUND AND PURPOSE: Mortality after first-ever stroke, and particularly after recurrent stroke, and predictors of long-term mortality among young and middle-aged stroke patients are not well-known. We assessed 17-year risk of mortality with focus on the effect of recurrence on the risk of death of young and middle-aged patients with stroke. METHODS: Mortality and recurrent stroke rate of 970 consecutive 30-day survivors of first-ever ischemic stroke aged 15 to 49 years (1994-2007) were studied. Prospective follow-up data came from the Finnish Care Register for Health Care and Statistics Finland. Mean follow-up was 10.2±4.3 years. We compared survival between clinical subgroups and identified factors associated with mortality. Standardized mortality ratio was calculated for demographic and pathogenetic subgroups using mortality data of the general population matched with age, sex, calendar year, and geographical area. RESULTS: At the end of follow-up, 152 (15.7%) patients had died (cumulative risk, 23.0%; 95% confidence interval, 19.1%-26.9%) and 132 (13.6%) had experienced a recurrent stroke. After adjusting for baseline characteristics, recurrent stroke was statistically the most important risk factor for mortality after first-ever ischemic stroke (hazard ratio, 16.68; 95% confidence interval, 2.33-119.56; P=0.005). Observed mortality was 7-fold higher than the expected mortality (standardized mortality ratio, 6.94; 95% confidence interval, 5.84-8.04) and particularly high among patients who experienced a recurrent stroke (standardized mortality ratio, 14.43; 95% confidence interval, 10.11-18.74). CONCLUSIONS: The high mortality rates and the striking impact of recurrent stroke on the risk of death should lead to development of more robust primary and secondary prevention strategies for young patients with stroke.

Predictors of early mortality in young adults after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Patient and radiological characteristics of intracerebral hemorrhage (ICH), surgical treatment, and outcome after ICH are interrelated. Our purpose was to define whether these characteristics or surgical treatment correlate with mortality among young adults. METHODS: We retrospectively reviewed clinical and imaging data of all first-ever nontraumatic patients with ICH between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 and linked these data with national causes of death registry. A logistic regression analysis of factors associated with 3-month mortality and a propensity score comparison between patients treated conservatively and operatively was performed. RESULTS: Among the 325 eligible patients (59.4% men), factors associated with 3-month mortality included higher National Institutes of Health Stroke Scale score, infratentorial location, hydrocephalus, herniation, and multiple hemorrhages. Adjusted for these factors, as well as demographics, ICH volume, and the underlying cause, surgical evacuation was associated with lower 3-month mortality (odds ratio, 0.06; 95% confidence interval, 0.02-0.21). In propensity score-matched analysis, 3-month case fatality rates were 3-fold in those treated conservatively (27.5% versus 7.8%; P<0.001). CONCLUSIONS: The predictors of short-term case fatality are alike in young and elderly patients with ICH. However, initial hematoma evacuation was associated with lower 3-month case fatality in our young patients with ICH.

The CAVE score for predicting late seizures after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients. METHODS: Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients' province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. RESULTS: Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0-4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age<65 years, volume>10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76-0.86) and 0.69 (0.59-0.78) in the validation cohort. CONCLUSIONS: One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.

Racial disparities in early mortality in 1,134 young patients with acute stroke.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.

Etiologic subtypes of first and recurrent ischemic stroke in young patients using A-S-C-O and TOAST classification criteria: A retrospective follow-up study.

INTRODUCTION: Scarce data exist on the etiology of recurrent ischemic strokes (ISs) among young adults. We analyzed the etiology of first-ever and recurrent events and the differences between them. PATIENTS AND METHODS: Patients aged 15-49 years with a first-ever IS in 1994-2007 were included in the Helsinki Young Stroke Registry. In this retrospective cohort study, data on recurrent ISs were identified from Care Register for Health Care until the end of 2017 and Causes of Death Register and from patient records until the end of 2020. All first-ever and recurrent ISs were classified using Atherosclerosis-Small vessel disease-Cardioembolism-Other Cause (A-S-C-O) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications. RESULTS: A total of 970 patients were included (median age at index IS 46 years, interquartile range 43-48, 33% women), of which 155 (16.0%) patients had recurrent IS, with 8 (5.2%) fatal cases and 5 (3.2%) unverifiable cases. The median follow-up was 17.4 (IQR 13.9-21.7) years. Median time from the index event to the first recurrent event was 4.5 (interquartile range [IQR] 1.6-10.2) years. Recurrence was more often due to definite cardioembolism (10.7% vs 18.0%, p = 0.013), while the proportion of other definite A-S-C-O subgroups remained the same. With TOAST classification, the proportion of true cryptogenic ISs decreased (16.7% vs 6.7%, p = 0.003), while those with incomplete evaluation increased (9.3% vs 19.3%, p = 0.015). Other TOAST phenotypes remained the same. CONCLUSION: The proportion of definite cardioembolism increased at recurrence using the A-S-C-O classification and the number of cryptogenic ISs decreased using the TOAST classification, while cases with incomplete evaluation increased. Most etiologies remained the same.

Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

Preceding and poststroke infections in young adults with first-ever ischemic stroke: effect on short-term and long-term outcomes.

BACKGROUND AND PURPOSE: Poststroke infections (PSIs) worsen the outcome in acute ischemic stroke, but the effect of preceding infection (PI) is controversial. Data on young patients are scarce. We characterized PI and PSI in young adults with first-ever stroke and studied whether they are associated with 3-month and long-term outcomes, recurrent vascular events, and death. METHODS: From our database of 1008 consecutive patients aged 15 to 49 years, we included in the present study those who had brain imaging done within the first 2 days from stroke onset. Outcomes were unfavorable at 3 months and during long-term follow-up, vascular events, and all-cause death. Logistic regression and Cox proportional models were used to determine associations between infections and clinical outcomes. RESULTS: A total of 681 patients (62.3% men) fulfilled the inclusion criteria. Of these, 70 (10.3%) had PI, most commonly upper respiratory tract infection, and 103 (15.1%) had PSI, most commonly pneumonia. After adjusting for sex, age, and risk factors, both PI (odds ratio, 2.86; 95% confidence interval, 1.48-5.54) and PSI (odds ratio, 2.26; 95% confidence interval, 1.08-4.76) were independently associated with unfavorable 3-month outcome. PSI was also associated with long-term (follow-up, 7.8±4.0 years) higher risk of all-cause death. CONCLUSIONS: In young patients with ischemic stroke, both PI and PSIs are associated with unfavorable short-term outcome. PSIs are also associated with higher long-term mortality.

Association of prestroke statin use and lipid levels with outcome of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: It is unclear whether blood lipid profiles and statin use before intracerebral hemorrhage (ICH) are associated with its outcome. METHODS: The Helsinki ICH Study, a single-center observational registry of consecutive ICH patients, was used to study the associations between premorbid statin use, baseline lipid levels, and clinical outcome. RESULTS: The registry includes 964 ICH patients. Statin users (n=187; 19%) were significantly older, had more frequent comorbidities and medication, lower lipid levels, and higher admission Glasgow Coma Scale compared with nonusers. Modified Rankin Scale at discharge or mortality did not differ between statin users and nonusers. Compared with survivors, significantly lower total cholesterol and low-density lipoprotein cholesterol levels were observed in patients who died in hospital (median, 4.1 mmol/L [interquartile range, 3.6-4.4] versus 4.5 [3.8-5.1]; P<0.01; 1.9 mmol/L [1.4-2.5] versus 2.4 [1.8-3.0]; P<0.001, respectively), at 3 or 12 months. After adjusting for known ICH prognostic factors based on univariate analysis that is, age, National Institutes of Health Stroke Scale, Glasgow Coma Scale, ICH volume, and intraventricular location, lower low-density lipoprotein levels were independently associated with in-hospital mortality (odds ratio, 0.54 [95% confidence interval, 0.31-0.93]; P=0.028). CONCLUSIONS: Premorbid statin use did not affect the outcome of ICH, but lower low-density lipoprotein levels were associated with higher in-hospital mortality.

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.

Age of onset of cerebral venous thrombosis: the BEAST study.

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, ~12 years younger, in those with multiple (⩾1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors.

How does number of risk factors affect prognosis in young patients with ischemic stroke?

BACKGROUND AND PURPOSE: We aimed to explore clinical features of young patients with ischemic stroke with no traditional vascular risk factors and to assess the impact of risk factor counts on outcomes. METHODS: We included 990 patients aged 15 to 49 years with first-ever ischemic stroke followed for a mean of 9.0 ± 3.8 years (survivors). Risk factors were categorized as well-documented and less well-documented. Outcome measures were unfavorable functional outcome (3-month modified Rankin Scale 2-6); recurrent ischemic stroke; myocardial infarction or other arterial noncerebrovascular event; and death from any cause. RESULTS: Compared with those with at least 1 well-documented risk factor, the 127 (12.8%) patients without risk factors were younger (median age, 37 versus 44 years; P<0.001), likely to be females (54.3% versus 34.9%; P<0.001), and they had more frequently a low-risk source of cardioembolism (21.3% versus 8.1%; P<0.001), internal carotid artery dissection (12.6% versus 6.4%; P=0.011), or vertebral artery dissection (17.3% versus 7.2%; P<0.001). The groups had similar 3-month functional outcomes. Patients without well-documented risk factors had less frequently recurrent ischemic strokes (4.7% versus 13.6%; log rank P=0.014), noncerebrovascular arterial events (0% versus 6.1%; P=0.008), and lower long-term mortality (3.4% versus 14.3%; P=0.003) than did those with at least 1 risk factor. Adjusted for demographics and stroke etiology, the number of well-documented risk factors was associated with higher risk for noncerebrovascular events. Increasing count of less well-documented risk factors was, in turn, independently associated with higher long-term mortality. CONCLUSIONS: In young adults with first-ever ischemic stroke, risk factor counts added independent prognostic information regarding noncerebrovascular events and mortality.