Turgut Tatlisumak

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 39xa0months (interquartile range 14–95). VTE (one of which was CVT) occurred in 9 (6xa0%) patients, and severe hemorrhagic events in 10 (6xa0%). Functional outcome was good, with 84xa0% scoring 0–1 on the mRS; 42xa0% reported residual symptoms. Altogether, 91 (57xa0%) patients were employed. After adjusting for age and sex, a National Institutes of Health Stroke Scale scorexa0>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.

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

BACKGROUNDnThe 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.nnnMETHODSnThe 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.nnnRESULTSnOf 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]).nnnCONCLUSIONnRoutine 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.

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.

Cerebral white matter lesions and post-thrombolytic remote parenchymal hemorrhage

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.

Medical Acute Complications of Intracerebral Hemorrhage in Young Adults

Background. Frequency and impact of medical complications on short-term mortality in young patients with intracerebral hemorrhage (ICH) have gone unstudied. Methods. We reviewed data of all first-ever nontraumatic ICH patients between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 to identify medical complications suffered. Logistic regression adjusted for known ICH prognosticators was used to identify medical complications associated with mortality. Results. Among the 325 eligible patients (59% males, median age 42 [interquartile range 34–47] years), infections were discovered in 90 (28%), venous thrombotic events in 13 (4%), cardiac complications in 4 (1%), renal failure in 59 (18%), hypoglycemia in 15 (5%), hyperglycemia in 165 (51%), hyponatremia in 146 (45%), hypernatremia in 91 (28%), hypopotassemia in 104 (32%), and hyperpotassemia in 27 (8%). Adjusted for known ICH prognosticators and diabetes, the only independent complication associated with 3-month mortality was hyperglycemia (plasma glucose >8.0u2009mmol/L) (odds ratio: 5.90, 95% confidence interval: 2.25–15.48, P < 0.001). Three or more separate complications suffered also associated with increased mortality (7.76, 1.42–42.49, P = 0.018). Conclusions. Hyperglycemia is a frequent complication of ICH in young adults and is independently associated with increased mortality. However, multiple separate complications increase mortality even further.

Post-thrombolytic blood pressure and symptomatic intracerebral hemorrhage.

Most guidelines for intravenous thrombolysis (IVT) in acute ischaemic stroke patients advise keeping systolic blood pressure (BP) below 180/105 mmHg prior to the bolus injection. Less is known about optimal management of BP thereafter. We assessed temporal changes in post‐thrombolytic systolic BP values and their impact on development of symptomatic intracerebral hemorrhage (sICH).

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.

Symptomatic post-thrombolytic intracerebral hemorrhage is not related to the cause of stroke.

The development of intracerebral hemorrhage following intravenous thrombolysis (IVT) can be influenced by various confounders related to the underlying vessel and tissue conditions. There are some data on association of cause of the stroke and the hemorrhage transformation. We tested the hypothesis that the cause of stroke is associated with the development of symptomatic intracerebral hemorrhage (sICH) following IVT.

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

Abstract 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 durationu2009>120u2009ms 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 >120u2009ms are predictors for future cardiovascular or cardiac events in these patients. No ECG parameters were independently associated with recurrent stroke.