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.

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.

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.

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.

Return to work after ischemic stroke in young adults: A registry-based follow-up study.

OBJECTIVE: We aimed to investigate the proportion of young patients not returning to work (NRTW) at 1 year after ischemic stroke (IS) and during follow-up, and clinical factors associated with NRTW. METHODS: Patients from the Helsinki Young Stroke Registry with an IS occurring in the years 1994-2007, who were at paid employment within 1 year before IS, and with NIH Stroke Scale score ≤15 points at hospital discharge, were included. Data on periods of payment came from the Finnish Centre for Pensions, and death data from Statistics Finland. Multivariate logistic regression analyses assessed factors associated with NRTW 1 year after IS, and lasagna plots visualized the proportion of patients returning to work over time. RESULTS: We included a total of 769 patients, of whom 289 (37.6%) were not working at 1 year, 323 (42.0%) at 2 years, and 361 (46.9%) at 5 years from IS. When adjusted for age, sex, socioeconomic status, and NIH Stroke Scale score at admission, factors associated with NRTW at 1 year after IS were large anterior strokes, strokes caused by large artery atherosclerosis, high-risk sources of cardioembolism, and rare causes other than dissection compared with undetermined cause, moderate to severe aphasia vs no aphasia, mild and moderate to severe limb paresis vs no paresis, and moderate to severe visual field deficit vs no deficit. CONCLUSIONS: NRTW is a frequent adverse outcome after IS in young adults with mild to moderate IS. Clinical variables available during acute hospitalization may allow prediction of NRTW.

Twelve-lead electrocardiogram and mortality in young adults after ischaemic stroke.

INTRODUCTION: Ischaemic stroke at young age carries an increased risk for mortality in comparison to the general population, but factors associated with mortality have been poorly studied. We studied the role of electrocardiogram in mortality risk stratification in young stroke patients. PATIENTS AND METHODS: The Helsinki Young Stroke Registry encompasses 1008 patients aged <50 years with ischaemic stroke. We included 690 patients for this electrocardiogram substudy. Our endpoints were all-cause and cardiovascular mortality. Cox regression models - adjusted for clinical and demographic characteristics - were used to identify the electrocardiogram parameters associated with these endpoints. RESULTS: At a mean follow-up of 8.8 years, cumulative all-cause and cardiovascular mortality were 16.1 and 9.1%, respectively. Factors associated with both endpoints included diabetes (type 1 for all-cause, type 2 for cardiovascular mortality), heavy drinking, malignancy, as well as stroke severity and aetiology. Of the electrocardiogram parameters, higher heart rate (hazard ratio 1.35 per 10/min, 95% confidence interval 1.21-1.49), a shorter P-wave (hazard ratio 0.78 per 10 ms decrement, 0.64-0.92) and longer QTc interval (1.09 per 10 ms, 1.03-1.16) were associated with increased all-cause mortality. Only a higher heart rate (1.42 per 10/min, 1.24-1.60) was associated with death from cardiovascular causes. CONCLUSIONS: A higher heart rate during the subacute phase after stroke is associated with an elevated risk of all-cause and cardiovascular mortality in young adults. A longer QTc interval is associated only with higher all-cause mortality. P-wave characteristics and their possible association with mortality need further studies.

Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol.

INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated. METHODS AND ANALYSIS: To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease. ETHICS AND DISSEMINATION: BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders.

Are 12-lead ECG findings associated with the risk of cardiovascular events after ischemic stroke in young adults?

INTRODUCTION: Ischemic stroke (IS) in a young patient is a disaster and recurrent cardiovascular events could add further impairment. Identifying patients with high risk of such events is therefore important. The prognostic relevance of ECG for this population is unknown. MATERIALS AND METHODS: A total of 690 IS patients aged 15-49 years were included. A 12-lead ECG was obtained 1-14 d after the onset of stroke. We adjusted for demographic factors, comorbidities, and stroke characteristics, Cox regression models were used to identify independent ECG parameters associated with long-term risks of (1) any cardiovascular event, (2) cardiac events, and (3) recurrent stroke. RESULTS: Median follow-up time was 8.8 years. About 26.4% of patients experienced a cardiovascular event, 14.5% had cardiac events, and 14.6% recurrent strokes. ECG parameters associated with recurrent cardiovascular events were bundle branch blocks, P-terminal force, left ventricular hypertrophy, and a broader QRS complex. Furthermore, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms were associated with increased risks of cardiac events. No ECG parameters were independently associated with recurrent stroke. CONCLUSION: A 12-lead ECG can be used for risk prediction of cardiovascular events but not for recurrent stroke in young IS patients. KEY MESSAGES ECG is an easy, inexpensive, and useful tool for identifying young ischemic stroke patients with a high risk for recurrent cardiovascular events and it has a statistically significant association with these events even after adjusting for confounding factors. Bundle branch blocks, P-terminal force, broader QRS complex, LVH according to Cornell voltage duration criteria, more leftward P-wave axis, prolonged QTc, and P-wave duration >120 ms are predictors for future cardiovascular or cardiac events in these patients. No ECG parameters were independently associated with recurrent stroke.

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.

Cardiovascular events after ischemic stroke in young adults: A prospective follow-up study.

OBJECTIVES: To study the long-term risk of recurrent cardiac, arterial, and venous events in young stroke patients, and whether these risks differed between etiologic subgroups. METHODS: The study population comprised 970 patients aged 15-49 years from the Helsinki Young Stroke Registry (HYSR) who had an ischemic stroke in 1994-2007. We obtained follow-up data until 2012 from the Finnish Care Register and Statistics Finland. Cumulative 15-year risks were analyzed with life tables, whereas relative risks and corresponding confidence intervals (CI) were based on hazard ratios (HR) from Cox regression analyses. RESULTS: There were 283 (29.2%) patients with a cardiovascular event during the median follow-up of 10.1 years (range 0.1-18.0). Cumulative 15-year risk for venous events was 3.9%. Cumulative 15-year incidence rate for composite vascular events was 34.0 (95% CI 30.1-38.2) per 1,000 person-years. When adjusted for age and sex, patients with an index stroke caused by high-risk sources of cardioembolism had the highest HR for any subsequent cardiovascular events (3.7; 95% CI 2.6-5.4), whereas the large-artery atherosclerosis group had the highest HR (2.7; 95% CI 1.6-4.6) for recurrent stroke compared with patients with stroke of undetermined etiology. CONCLUSIONS: The risk for future cardiovascular events after ischemic stroke in young adults remains high for years after the index stroke, in particular when the index stroke is caused by high-risk sources of cardioembolism or large-artery atherosclerosis.

Long-term outcome after cerebral venous thrombosis: analysis of functional and vocational outcome, residual symptoms, and adverse events in 161 patients.

Cerebral venous thrombosis (CVT) affects mainly working-aged individuals. Functional recovery after CVT is generally considered good with about 3/4 of patients achieving short-term independence. However, vascular events, long-term functional outcome, and employment after CVT remain poorly investigated. We identified consecutive adult CVT patients treated at the Helsinki University Hospital (1987-2013) and invited them to a follow-up visit. Each clinical examination was combined with interview. We also recorded recurrent venous thromboembolism (VTE) and hemorrhagic events during follow-up and antithrombotic medication use. A modified Rankin Scale (mRS) served to assess functional outcome. Logistic regression served to identify independent factors associated with unemployment and functional recovery. Of the 195 patients identified, 21 died, 9 declined to participate, and 4 were excluded from the study. Thus, 161 patients (106 women) underwent an examination after a median of 39 months (interquartile range 14-95). VTE (one of which was CVT) occurred in 9 (6%) patients, and severe hemorrhagic events in 10 (6%). Functional outcome was good, with 84% scoring 0-1 on the mRS; 42% reported residual symptoms. Altogether, 91 (57%) patients were employed. After adjusting for age and sex, a National Institutes of Health Stroke Scale score>2 at admission and low education level, associated with both unfavorable functional outcome and unemployment. Long-term functional outcome after CVT may appear good if measured with mRS, but patients often have residual symptoms and are frequently unable to return to their previous work.

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.

Helsinki experience on nonvitamin K oral anticoagulants for treating cervical artery dissection.

BACKGROUND: Cervical artery dissection (CeAD) patients with or without stroke are frequently treated with either antiplatelet agents or vitamin K antagonists (VKAs), but few data are reported on the use of nonvitamin K oral anticoagulants (NOACs). METHODS: Between November 2011 and January 2014, we recorded data from patients with a stroke due to vertebral (VAD) or internal carotid artery dissection (ICAD). Patients using oral anticoagulants were included in the study and were divided into two treatment groups: patients using NOACs and those using VKAs. Excellent outcome was defined on modified Rankin Scale (mRS) ≤1 at 6 months. RESULTS: Of 68 stroke patients (67% male; median age 45 [39-53]), six (8.8%; two with VAD and four with ICAD) were treated with NOACs: three with direct thrombin inhibitor dabigatran and three with direct factor Xa inhibitor rivaroxaban. National Institutes of Health Stroke Scale score at baseline was 4 (3-7) in the NOAC versus 2 (1-7) in the VKA groups. Complete recanalization at 6 months was seen in most patients in the NOAC (n = 5; 83%) and VKA (n = 34; 55%) groups. All the patients using NOACs had mRS ≤1 at 6 months and none had an intracerebral hemorrhage (ICH). In the VKA group most patients (n = 48; 77%) had mRS ≤1, one patient (1.7%) had an ICH and one died. CONCLUSIONS: In this small, consecutive single-center patient sample treating ischemic stroke patients with CeAD with NOACs did not bring up safety concerns and resulted in similar, good outcomes compared to patients using VKAs.

Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes.

OBJECTIVE: To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months. METHODS: Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke-II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0-1 or equal to prestroke mRS) and good (mRS score 0-2 or equal to prestroke mRS) outcomes at 3 months. RESULTS: We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [adjOR] for an increase of 1,000 neutrophils = 1.21 and adjOR 1.11, respectively), death (adjOR 1.16 and adjOR 1.08), and excellent (adjOR 0.87 and adjOR 0.85) and good (adjOR 0.86 and adjOR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR ≥4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adjOR: 1.97-6.98) compared to patients with NLR <4.80. CONCLUSIONS: Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.

Undetermined stroke with an embolic pattern--a common phenotype with high early recurrence risk.

INTRODUCTION: Undetermined strokes with an embolic pattern (USEP) represent a common phenotype. We assessed their frequency and compared USEP with cardioembolic stroke with a known source and non-cardioembolic stroke etiology. METHODS: Study patients were 540 consecutive ischemic stroke patients admitted to Helsinki University Hospital with primary end-point of recurrent stroke in a 21-month follow-up. Cox regression adjusting for CHA2DS2-VASc and anticoagulation estimated the risk of USEP on recurrent stroke. RESULTS: A total of 229 (42.4%) patients had a non-cardioembolic stroke etiology, 184 (34.1%) had a cardioembolic stroke with a known source, and 127 (23.5%) were classified as USEP. USEP patients had less diabetes and prior TIA, with more severe symptoms than the non-cardioembolic stroke cases. They were younger, had fewer comorbidities, and less severe symptoms than the cardioembolic stroke patients. Cumulative risk of recurrent stroke was 10.0% (95% CI 4.1%-15.9%) for USEP, 5.0% (1.1%-8.9%) for cardioembolic strokes, and 5.0% (3.0%-7.0%) for non- cardioembolic strokes (P = 0.089). USEP associated with a higher risk of recurrent stroke compared to non-cardioembolic strokes (hazard ratio 2.36, 95% CI 1.02-5.47; P = 0.046) and cardioembolic stroke with a known source (1.83, 1.07-3.14; P = 0.028). CONCLUSIONS: Despite their younger age and more favorable risk factor profile compared with other phenotypes, USEP exhibited a high risk of stroke recurrence.

Resting 12-lead electrocardiogram reveals high-risk sources of cardioembolism in young adult ischemic stroke.

BACKGROUND: The diagnostic work-up to reveal etiology in a young ischemic stroke (IS) patient includes evaluation for high-risk source of cardioembolism (HRCE), since this subtype associates with high early recurrence rate and mortality. We investigated the association of ECG findings with a final etiologic subgroup of HRCE in a cohort of young patients with first-ever IS. METHODS: The Helsinki Young Stroke Registry includes IS patients aged 15 to 49 years admitted between 1994 and 2007. Blinded to other clinical data, we analyzed a 12-lead resting ECG obtained 1-14 days after the onset of stroke symptoms in 690 patients. We then compared the ECG findings between a final diagnosis of HRCE (n=78) and other/undetermined causes (n=612). We used multivariate logistic regression to study the association between ECG parameters and HRCE. RESULTS: Of our cohort (63% male), 35% showed ECG abnormality, the most common being T-wave inversion (16%), left ventricular hypertrophy (14%), prolonged P-wave (13%), and prolonged QTc (12%). 3% had atrial fibrillation (AF), and 4% P-terminal force (PTF). Of the continuous parameters, longer QRS-duration, QTc, and wider QRS-T-angle independently associated with HRCE. After AF, PTF had the strongest independent association with HRCE (odds ratio=44.32, 95% confidence interval=[10.51-186.83]), followed by a QRS-T angle >110° (8.29 [3.55-19.32]), T-wave inversion (5.06, 2.54-10.05), and prolonged QTc (3.02 [1.39-6.56]). CONCLUSION: Routine ECG provides useful information for directing the work-up of a young IS patient. In addition to AF, PTF in particular showed a strong association with etiology of HRCE.

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.

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.