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

BACKGROUND AND PURPOSE: 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. METHODS: A consecutive cohort of 2485 IVT-treated patients at the Helsinki University Central Hospital was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. An 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 analyses, cardioembolism [odds ratio (OR), 1.14; 95% confidence interval (CI), 0.79-1.64] and large-artery atherosclerosis (OR, 1.30; 95% CI, 0.85-2.00) were not associated with sICH, and small-vessel occlusion was associated with lower odds for sICH (OR, 0.18; 95% CI, 0.06-0.57). When adjusted for previously identified factors associated with sICH, none of the TOAST categories was associated with a higher or lower frequency of sICH. CONCLUSIONS: The development of sICH in IVT-treated patients is not related to the cause of stroke.

Post-thrombolytic blood pressure and symptomatic intracerebral hemorrhage.

BACKGROUND AND PURPOSE: 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). METHODS: The study cohort included 1868 consecutive acute ischaemic stroke patients treated with IVT at the Helsinki University Central Hospital. sICH was defined according to the European Cooperative Acute Stroke Study II (ECASS-II) (primary outcome), National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. We evaluated BP at admission, prior to IVT and at 2, 4, 8, 12, 24 and 48 h after thrombolysis. We used univariate and multivariable models to test the effect of BP at various time-points on development of post-thrombolytic sICH. RESULTS: Prevalence of sICH in the cohort was 5.8% (ECASS-II). Patients with sICH had significantly higher systolic BP at several time-points after IVT compared with those without sICH (P < 0.01 at 2 and 4 h; P < 0.05 at 12 and 48 h). The odds ratios for development of sICH per 10 mmHg increase in BP were 1.14 [95% confidence interval (CI), 1.03-1.25], 1.14 (95% CI, 1.03-1.25), 1.12 (95% CI, 1.01-1.23) and 1.12 (95% CI, 1.01-1.23), respectively. At 8 h, we observed a trend (P = 0.07) for ECASS-II and a significant effect (P < 0.05) for National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. Thus, the only time-point with no difference observed was 24 h. CONCLUSIONS: Patients with post-thrombolytic sICH have significantly higher systolic BP at several time-points compared with patients without sICH.

Incidence, risk factors, etiology, severity and short-term outcome of non-traumatic intracerebral hemorrhage in young adults.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a common and severe form of stroke but is scarcely studied in young adults. Our aim was to study risk factors, clinical presentation and early mortality of ICH in the young and compare these features with older patients. METHODS: All consecutive patients aged between 16 and 49 diagnosed with a first-ever ICH at the Departments of Neurology or Neurosurgery of the Helsinki University Central Hospital between January 2000 and March 2010 (n = 336) were analyzed retrospectively. Comparisons were performed amongst demographic subgroups and with patients over 49 years of age enrolled between January 2005 and March 2010 (n = 921). RESULTS: In the young patients, median age was 42 years (interquartile range 34-47), 59.5% were male, and annual incidence was 4.9 (95% confidence interval 4.5-5.3) per 100 000. The most prevalent risk factors were hypertension (29.8%) and smoking (22.3%). Compared with older patients hypertensive microangiopathy was less common (25.0% vs. 34.3%, P = 0.002) and structural lesions more common (25.0% vs. 4.9%, P < 0.001) assumed etiologies of ICH. The cause remained elusive in 32.1% of all young patients and in 22.5% of those who underwent magnetic resonance imaging and any angiography (n = 89, P = 0.023). Three-month mortality rate was lower in young patients compared with older ones (17.0% vs. 32.7%, P < 0.001). Hematoma volumes were similar across all ages (P = 0.324) and independently predicted mortality in older patients but not in the young. CONCLUSIONS: Intracerebral hemorrhage (ICH) in the young appears less fatal and has a different spectrum of causes and factors associated with short-term mortality than for the elderly.

Higher baseline international normalized ratio value correlates with higher mortality in intracerebral hemorrhage during warfarin use.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulation (OAC). Our aim was to investigate the impact of the international normalized ratio (INR) level on mortality in OAC-associated ICH compared with non-OAC-associated ICH. METHODS: A retrospective chart review of consecutive ICH patients treated at the Helsinki University Central Hospital from January 2005 to March 2010 (n = 1013) was performed. An ICH was considered to be OAC-associated if the patient was on warfarin at ICH onset. The association of INR with 3-month mortality was adjusted in a multivariable logistic regression model for factors influencing the crude odds ratios (ORs) in bivariable logistic regression by more than 5%. RESULTS: One in eight ICHs was OAC-associated (n = 132). Of these, 50% had therapeutic INR (2.0-3.0), 7% had INR <2.0 and 43% had high INR (>3.0) on admission. Patients on OAC were older (median 76 vs. 66 years; P < 0.001) with more severe symptoms (median National Institutes of Health Stroke Scale 14 vs. 10; P < 0.001) and larger hematomas (median 11.4 vs. 9.7 ml; P < 0.001) on admission than patients not on OAC. After adjustment for confounders, 3-month mortality in the whole cohort was associated with higher baseline INR (OR 1.06; CI 1.03-1.09 per 0.1 increment). Mortality was higher with both therapeutic (51% at 3 months; OR 3.59; CI 1.50-8.60) and high (61%; OR 5.26; CI 1.94-14.27) INR values compared with non-OAC-associated ICH (29%). CONCLUSIONS: Patients with OAC-associated ICH had more severe strokes and higher mortality compared with patients with ICH not related to OAC. Higher baseline INR was associated with increased 3-month mortality.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors.

BACKGROUND AND PURPOSE: After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days). METHODS: All consecutive patients aged 15-49 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (<137 mm), use of psychiatric medication, stroke severity (NIH Stroke Scale) and anatomical (Bamford criteria) and etiological (Trial of Org in Acute Stroke Treatment) stroke subtype. RESULTS: ASSs emerged in 35 (3.5%) patients. LPSs (n = 102) occurred at a cumulative rate of 6.1% at 1 year, 9.5% at 5 years and 11.5% at 10 years. In multivariate analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.91-46.14), moderate stroke severity (3.95, 1.86-8.41), cortical involvement (3.69, 1.66-8.18) and hyponatremia (3.26, 1.41-7.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94, 7.62-33.33), partial anterior circulation infarct (3.48, 1.52-7.93), history of ASS (3.94, 2.07-7.48), antidepressant use at the time of LPS (3.88, 2.46-6.11), hemorrhagic infarct (1.94, 1.19-3.15), male gender (1.79, 1.10-2.92) and hyperglycemia (1.62, 1.05-2.51). CONCLUSIONS: In young ischaemic stroke patients, the magnitude of seizure risk and the major risk factors were similar to older ischaemic stroke patients but risk factors for ASSs and LPSs differed.

Functional outcome in young adult ischemic stroke: impact of lipoproteins.

AIM: To determine the functional outcome in a cohort of young adults with ischemic stroke patients, focusing on components of lipid profile. METHODS: In our registry including consecutive patients with first-ever ischemic stroke aged 15-49 from 1994 to 2007, we analyzed predictors of 3-month functional outcome (modified Rankin Scale, mRS). Infarct size fell into small, medium, large posterior, or large anterior. Stroke severity was assessed with NIH Stroke Scale (NIHSS). Serum lipids were measured within 72 h after admission. Binary, multinomial ordinal, and Poisson regressions allowed revealing factors associated with size of infarct, stroke severity, and unfavorable outcome or death (mRS, 2-6) or mRS as an ordinal measure. RESULTS: In the 968 patients included (mean age, 41.3 ± 7.6; 62.6% men; 49.5% with mRS 0-1), factors associated with unfavorable outcome after multivariable analysis were increasing age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.05), higher NIHSS score (1.23 per point, 1.17-1.29), large anterior (4.37, 2.26-8.42) or posterior (1.73, 1.05-2.85) infarcts, bilateral lesions (2.28, 1.30-3.98), internal carotid artery dissection (ICAD) (3.65, 1.41-9.47), and inversely high-density lipoprotein (HDL) levels (0.58 per unit increase, 0.38-0.86). Increasing HDL associated with smaller infarct size (0.71, 0.51-0.98). Both higher total and HDL cholesterol associated with lower NIHSS score (0.96, 0.93-0.98 for total cholesterol and 0.82, 0.75-0.88 for HDL) and lower 3-month mRS (0.87, 0.78-0.97 for total cholesterol and 0.65, 0.47-0.90 for HDL). CONCLUSION: In addition to known prognosticators, ICAD and lower HDL levels were independently associated with adverse clinical outcomes in our young adult stroke cohort.

Multiple brain infarcts in young adults: clues for etiologic diagnosis and prognostic impact.

BACKGROUND AND PURPOSE: There are little data on the etiology of multiple brain infarcts (MBI) and their impact on clinical outcome in young patients. METHODS: We studied 548 MRI-imaged patients (15-49 years) with a first-ever ischaemic stroke. Ischaemic lesions were categorized into three groups: single lesions, MBI in one or >1 circulation territories. Outcomes were unfavorable 3-month modified Rankin Scale (mRS) score of ≥ 2 and, during long-term follow-up (mean 8.20 ± 4.01 years), recurrent ischaemic stroke or death from any cause. RESULTS: Multiple brain infarcts occurred in 185 patients (33.8%; mean age 39.2 ± 8.2), of which 144 patients (26.3%) had lesions located in a single territory and 41 patients (7.5%) in multiple territories. Patients with MBI in a single territory were more likely than patients with single lesions to have a high-risk source of cardioembolism (CE) (9.0% vs. 3.0%; P = 0.001), large-artery atherosclerosis (8.3% vs. 4.9%; P = 0.012), vertebral (22% vs. 10%; P < 0.001) or carotid artery dissections (8.3% vs. 6.3%; P = 0.036), and MBI in multiple territories a high-risk source of CE (34% vs. 3.0%, P < 0.001). Adjusted for age, gender, baseline stroke severity, size of the largest lesion, and stroke subtype, MBI remained independently associated with an unfavorable 3-month outcome (odds ratio 2.84, 95% confidence interval 1.22-6.61). In multivariate Cox proportional hazards analysis, MBI had independent influence on the risk for death (hazard ratio 3.75, 1.58-8.86), but not on recurrent ischaemic stroke. CONCLUSIONS: Compared with the elderly, young stroke patients have a distinct stroke etiology underlying MBI, being an independent indicator of poor short-term outcome and long-term risk of death.

Diabetes mellitus and ischemic stroke in the young: clinical features and long-term prognosis.

OBJECTIVE: To compare risk factors, stroke characteristics, and long-term prognosis between nondiabetic young ischemic stroke patients and similar patients having either type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D) to provide information for patient management, counseling, and future research in these patient groups. METHODS: Our database comprised 1,008 consecutive patients aged 15 to 49 with first-ever ischemic stroke from 1994 to 2007. Primary outcome measures were 1) nonfatal or fatal recurrent ischemic stroke and 2) composite vascular endpoint (myocardial infarction, any stroke, revascularization, or vascular death). RESULTS: Compared with nondiabetic stroke patients (n = 904), patients with T1D (44) or T2D (60) were more likely to have hypertension and stroke attributable to small-vessel disease (SVD). In addition, when compared with nondiabetic patients, those with T1D more frequently had coronary heart disease and peripheral arterial disease (PAD) and those with T2D more often had obesity, PAD, history of TIA, and stroke attributable to large-artery atherosclerosis, and T2D patients were also more likely to be older and male than were the nondiabetic patients. Mean follow-up in survivors was 9.0 (±3.8) years. Cumulative recurrent ischemic stroke rate at 10 years was 40.9% for T1D (14 events), 29.7% for T2D (15), and 12.0% for nondiabetic patients (94). Corresponding rates for the composite vascular endpoint were 65.1% for T1D (25), 46.9% for T2D (28), and 19.3% for nondiabetic patients (153). CONCLUSIONS: Our findings suggest that ischemic stroke patients with T1D or T2D exhibit a distinct risk-factor and etiologic profile and a worse vascular prognosis than do nondiabetic patients.

Silent brain infarcts, leukoaraiosis, and long-term prognosis in young ischemic stroke patients.

OBJECTIVE: To investigate prognostic relevance of silent brain infarcts (SBIs) and leukoaraiosis (LA) in young patients with ischemic stroke. METHODS: This observational cohort study included consecutive MRI-scanned patients aged 15 to 49 with first-ever ischemic stroke treated at Helsinki University Central Hospital (1994-2007) with long-term follow-up data available. Outcome measures were 1) nonfatal or fatal ischemic stroke, 2) composite vascular endpoint, and 3) death from any cause. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and Bamford criteria allowed for stroke subtyping. Number of SBIs was categorized into none, single, or multiple. LA fell into groups of none, mild, or moderate to severe (validated visual rating scale). RESULTS: The 655 patients (mean age 40.0 ± 8.0 years) included were followed for a mean 8.7 ± 3.8 years (survivors). Of the 86 (13.1%) patients with SBIs, 46 had single and 40 had multiple SBIs. In the 50 (7.6%) patients with LA, these changes were mild in 21 and moderate to severe in 29. In Cox regression analysis, multiple SBIs independently raised the risk for recurrent ischemic stroke (odds ratio 2.48; 95% confidence interval 1.24-4.94) adjusted for age, gender, risk factors, stroke etiology, and LA. After further adjustment for initial stroke severity, TOAST and Bamford subgroups, and presence of SBIs, moderate to severe LA increased the risk for death (3.43; 1.58-7.42). Neither SBIs nor LA associated with the composite vascular endpoint. CONCLUSIONS: MRI-defined SBIs and LA are prognostically valuable in young adults after their first-ever ischemic stroke.

Migraine with aura is a risk factor for cervical artery dissection: a case-control study.

BACKGROUND: Cervical artery dissection (CAD) is the most common single etiology for stroke in young adults. Migraine, especially with aura (MA), is a known risk factor for ischemic stroke. The association between CAD and migraine was suggested based on a few small studies, but there are no large-scale case-control data, and the mechanisms are not yet clear. METHODS: We compared the lifetime prevalence of migraine and migraine characteristics in 313 CAD patients with 313 healthy age- and sex-matched controls. We also analyzed clinical and radiological characteristics of CAD with respect to migraine subtypes to investigate whether clear phenotypical associations can be found that might help in the search for a possible shared genetic background for migraine and CAD. RESULTS: Migraine was clearly more common in CAD patients than in controls (36 vs. 23%; OR 2.15; 95% CI 1.48-3.14), and the association was also highly significant for MA (23 vs. 12%; OR 2.41; 95% CI 1.53-3.80). Percentages of reported migraine history and MA of CAD patients vs. controls compared separately for both sexes were as follows: for women, migraine 54 vs. 35% (OR 2.30; 95% CI 1.28-4.13), MA 35 vs. 18% (OR 2.79; 95% CI 1.40-5.59); for men, migraine 27 vs. 16% (OR 2.02; 95% CI 1.23-3.31), MA 16 vs. 10% (OR 2.21; 95% CI 1.19-4.11). Over 60% of the CAD patients with still active migraine at the time of dissection reported later alleviation of migraine activity. CONCLUSION: Our observations suggest that patients with CAD are a significant link between ischemic stroke and migraine. This connection may represent a common pathophysiological or genetic background, or both. Migraine activity appears to be alleviated by CAD.

Adult cervicocerebral artery dissection: a single-center study of 301 Finnish patients.

BACKGROUND AND PURPOSE: There are only few small studies assessing potential risk factors, comorbidity, and prognostic factors in adult spontaneous cervicocerebral artery dissection (CAD). METHODS: We conducted a retrospective, hospital-based analysis on the prognostic factors and association of CAD with vascular risk factors in 301 consecutive Finnish patients, diagnosed from 1994 to 2007. RESULTS: Two thirds of the patients were men (68%). Women were younger than men. Migraine (36% of all patients), especially with visual aura (63% of all migraineurs), and smoking were more common in patients with CAD compared with the general Finnish population. At 3 months, 247 (83%) patients reached a favorable outcome. Occlusion of the dissected artery, internal carotid artery dissection (ICAD), and recent infection in infarction patients were associated with a poorer outcome. ICAD patients had less often brain infarction, but the strokes they had were more severe. Seven (2.3%) patients died during the follow-up (mean 4.0 years, 1186 patient years). Six (2%) patients had verified CAD recurrence. CONCLUSIONS: This study provides evidence for the association of CAD with male sex, and possible association with smoking and migraine. Occlusion of the dissected artery, ICAD, and infection appear to be associated with poorer outcome.

Is D-dimer helpful in evaluating stroke patients? A systematic review.

D-dimer (DD) is a fibrin degradation product present in negligible amounts in healthy individuals, but in thrombotic/fibrinolytic conditions substantially increases in plasma. Over the last two decades numerous studies have explored whether DD measurements would help stroke clinicians. An easy, reliable, and inexpensive test for stroke diagnosis, determination of stroke subtype, severity, prognosis, and recurrence risk is being sought. We searched the database, of studies indexed in English on MEDLINE, using the keywords 'cerebral venous thrombosis, D-dimer, deep vein thrombosis, intracerebral hemorrhage, ischemic stroke, outcome, prognosis, and subarachnoid hemorrhage' for relevant studies. Here, we systematically review current evidence on plasma DD levels in patients with ischemic and hemorrhagic strokes, transient ischemic attacks, and cerebral venous thrombosis. Numerous studies showed that patients with various strokes and stroke-related diseases had acutely increased plasma DD levels. Plasma DD levels, however, are neither sensitive nor specific enough to be utilized in stroke diagnostics and cannot replace either clinical or radiological evaluation. Regarding prediction of patient outcome, good clinical evaluation is clearly superior to DD testing.

Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke.

High plasma levels of homocysteine (Hcy) may predispose to ischemic stroke (IS), but results of previous studies have been conflicting. We decided to determine in IS patients whether their Hcy levels are elevated, whether levels vary at different time points following stroke, whether levels are associated with stroke severity, outcome, recurrence, etiology, infarct volume, or risk factors, and whether levels are correlated with hemostatic factors or C-reactive protein values. We measured plasma Hcy levels in 102 consecutive IS patients on admission and at 1 week, 1 month, and 3 months after stroke and once in 102 control subjects. Hemostatic factors were measured in 55 patients. Compared with controls, plasma Hcy levels in patients were significantly lower on admission but not at later time points, with levels increasing by week and remaining at this level for 3 months. Hcy levels showed a positive correlation with age and a negative correlation with Mini-Mental State Examination (MMSE) scores. Plasma Hcy levels inversely correlated with plasminogen activator inhibitor type-1. Decreased Hcy levels on admission may reflect the strength of the acute-phase response rather than a pathogenetic event. The negative correlation between Hcy levels and MMSE scores is more probably age-related than stroke-related.

Serial changes in fibrinolysis and coagulation activation markers in acute and convalescent phase of ischemic stroke.

BACKGROUND: The changes in the activity of a number of plasma markers of coagulation and fibrinolysis have previously been studied in patients with ischemic stroke, with conflicting results. We aimed to find out the changes in the activities of a wide array of markers of the coagulation and the fibrinolytic system of mildly or moderately affected first-ever ischemic stroke patients. METHODS: In a prospective, longitudinal, case-control study, we studied plasma plasminogen activator inhibitor type-1 (PAI-1) activity, tissue-type plasminogen activator antigen (t-PA:Ag), d-dimer, prothrombin fragment 1+2 (F 1+2), and thrombin-antithrombin III complex (TAT) levels in 55 consecutive patients on admission, 1 week, 1 month, and 3 months after an ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: PAI-1 activity was increased in the acute phase and at 3 months, D-dimer levels were significantly higher at 1 week and 1 month after stroke, whereas t-PA:Ag, TAT and F 1+2 levels remained stable during the whole study period. CONCLUSIONS: The changes of the fibrinolytic and coagulation system activity in the patients with mild or moderate ischemic stroke appeared minor compared with the results of previous studies, which included more severely ill patients.

Natural anticoagulants (antithrombin III, protein C, and protein S) in patients with mild to moderate ischemic stroke.

BACKGROUND AND PURPOSE: The role of the natural anticoagulants, antithrombin III (AT III), protein C (PC), and protein S (PS), in patients with mild to moderate ischemic stroke remains uncertain. We aimed to find out whether their levels in peripheral blood correlated with the severity of neurological deficit or can predict clinical outcome and recurrence. METHODS: We studied AT III, PC, and free PS levels in 55 consecutive patients likely to survive the study period on admission, 1 week, 1 month and 3 months after a first-ever ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent a full neurological examination and blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: AT III level was found to be significantly lower at all time points after stroke; PC level was significantly increased on admission and normal at subsequent measurements, and PS level was normal on admission but significantly decreased later. The levels of the natural anticoagulants did not correlate with the etiology of stroke, any stroke risk factor, or neurological scores, except that the AT III level on admission showed significant correlation with stroke severity and disability at 3 months. Natural anticoagulant levels did not predict recurrence of ischemic stroke. CONCLUSIONS: The measurements of the level of AT III, PC, or PS did not deliver useful information for management of patients with mild or moderate ischemic stroke, expect that AT III level on admission might predict outcome.

Plasma endothelin-1 levels neither increase nor correlate with neurological scores, stroke risk factors, or outcome in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors and may play a role in the pathophysiology of several diseases. Limited and controversial data exist on their role in human ischemic stroke. We planned a prospective, observational, and longitudinal clinical study to test whether ET-1 levels increase in various phases of ischemic stroke and whether the ET-1 levels correlate with neurological scores, stroke etiology, stroke risk factors, or final outcome. METHODS: We measured plasma ET-1 levels with a sandwich-enzyme immunoassay method in 101 consecutive patients with ischemic stroke on admission and 1 week, 1 month, and 3 months after stroke and in 101 sex- and age-matched control subjects. At each sampling, the patients underwent a complete neurological evaluation. All stroke risk factors were recorded, an array of laboratory tests were performed, and the subtype of ischemic stroke was determined. The patients were contacted 3 years later for prognostic determination. RESULTS: ET-1 levels in patients (2.4+/-1.3 pg/mL on admission, 2.2+/-1.4 pg/mL at 1 week, 2.1+/-1.4 pg/mL at 1 month, and 2.1+/-1.2 pg/mL at 3 months) were not different from those of the control subjects (2.2+/-0.9 pg/mL) at any time point. No correlation was found between the ET-1 levels and stroke etiology, stroke risk factors, stroke recurrence risk, age, sex, or neurological scores, except that ET-1 levels correlated with the use of warfarin and with body mass index. CONCLUSIONS: Plasma ET-1 levels were normal in patients with ischemic stroke. Our findings cannot exclude a role of ETs in the pathophysiology of ischemic stroke because plasma levels might not accurately reflect intracerebral concentrations, but they also do not support the occurrence of a major plasma ET-1 level increase at any phase of stroke. Our patient population is the largest ever reported in whom ET-1 levels were measured, but it consisted of mild and moderately ill patients with stroke due to the study design, of which the aim was long-term observation, which excludes severely ill patients.

Plasminogen activator inhibitor-1 in patients with ischemic stroke.

Low fibrinolytic activity may increase the risk of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. We examined the PAI-1 levels in patients with ischemic stroke. Plasma levels of PAI-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 55 consecutive patients (age 60.2 +/- 11.4, 40 males and 15 females) with ischemic stroke. The PAI-1 assessments as well as neurological examinations using validated stroke scales were conducted at admission and 1 week, 1 month, and 3 months after stroke. Sex- and age-matched controls (+/- 4 years) underwent plasma PAI-1 measurement once. Etiology of the stroke was classified using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All pertinent stroke risk factors were recorded. All patients were contacted 3 years after stroke for recurrent vascular thrombotic disease. The plasma PAI-1 levels were 17.2 +/- 7.8 IU at admission, 11.2 +/- 9.2 IU at 1 week, 14.4 +/- 7.9 IU at 1 month, and 17.8 +/- 7.8 IU at 3 months among patients and 11.8 +/- 9.5 IU among controls (p values are < .002, .7, .12, and < .0005, respectively). As a rule, the neurological scores did not show a correlation to the PAI-1 levels. Presence of diabetes, hypertension, obesity, smoking, anticoagulant treatment, and sleep apnea did not affect the PAI-1 levels at any time point. Females had slightly higher PAI-1 levels. Age was a strong determinant for PAI-1 levels being higher in younger patients at every sampling time point (p values .02, .02, .02, and .03 respectively). The etiology of the ischemic stroke did not have an impact on PAI-1 levels. In 16 patients recurrent thrombosis had occurred. The high PAI-1 levels at admittance may reflect either an acute phase response or a chronic state. Normalized levels at 1 week and 1 month may be due to hospital diet, antithrombotic medication, weight loss, active physical therapy, and better care for diabetes. PAI-1 levels at 3 months after stroke did not predict recurrent thrombosis.

Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience.

BACKGROUND: Despite improved treatment results achieved in Hodgkin's disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB-IVB) of HD in younger patients in an unselected population-based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post-CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected. PATIENTS AND METHODS: Between 1985-92, 307 patients between 17-59 yr of age (median 36) were diagnosed with HD in stages IIB-IVB in 5/6 health care regions in Sweden. Median follow-up time was 7.8 yr (1.3-13). Retrospectively, laboratory parameters were collected. RESULTS: In total, 267 (87%) patients had a complete response (CR). The overall and disease-free 10-yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT + RT. In univariate analyses survival was affected by age, stage IVB, bone-marrow involvement, B-symptoms, S-LDH, S-Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant. CONCLUSIONS: The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.