Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke.

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes.

AIM: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD. METHODS: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). RESULTS: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74-83], 75 [70-80], and 75 [72-81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. CONCLUSIONS: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

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

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

Blood pressure levels in the acute phase after intracerebral hemorrhage are associated with mortality in young adults.

BACKGROUND AND PURPOSE: Blood pressure (BP) levels in acute intracerebral hemorrhage (ICH) and mortality have not been thoroughly studied in the young. METHODS: The relationship between BP and mortality was assessed in consecutive patients with first-ever, non-traumatic acute ICH at ≤50 years of age, enrolled in the Helsinki ICH Young Study. BP parameters included systolic BP (SBP), diastolic BP (DBP), mean arterial pressure and pulse pressure (SBP - DBP) at admission and 24 h, and delta (admission-24 h) BP parameters. Outcome measures were 3-month and long-term mortalities, adjusted for demographics and ICH score parameters for short-term and cardiovascular risk factors for long-term prognostics. Cox regression models were used to assess independent BP parameters associated with mortality. RESULTS: Of our 334 patients (61% male), 92 (27%) had pre-stroke hypertension and 54 (16%) used antihypertensive treatment. The follow-up extended to 17 years with a median of 12 (interquartile range, 9.65-14.7) years. Both 3-month (n = 56; 16%) and long-term (n = 97; 29%) mortalities were associated with significantly higher admission SBP and mean arterial pressure levels, but not with 24-h BP levels, compared with survivors. Patients with SBP ≥ 160 mmHg (n = 156; 46%) had a significantly higher mortality rate (n = 59, 17% vs. n = 38, 11%; P = 0.001) and died earlier (9.6; 95% confidence interval, 2.9-12.9 years vs. 11.3; 95% confidence interval, 8.1-13.9 years; P = 0.001) within the follow-up period. In multivariable analyses, admission SBP ≥160 mmHg was independently associated with both 3-month (hazard ratio, 2.50; 95% confidence interval, 1.19-5.24; P < 0.05) and long-term (hazard ratio, 2.02; 95% confidence interval, 1.18-3.43; P < 0.01) mortalities. CONCLUSIONS: In young patients with ICH, acute-phase SBP levels ≥160 mmHg are independently associated with increased mortality.

Diabetes and intracerebral hemorrhage: baseline characteristics and mortality.

BACKGROUND AND PURPOSE: Acknowledging the conflicting evidence for diabetes as a predictor of short- and long-term mortality following an intracerebral hemorrhage (ICH), we compared baseline characteristics and 30-day and long-term mortality between patients with and without diabetes after an ICH, paying special attention to differences between type 1 (T1D) and type 2 (T2D) diabetes. METHODS: Patients with a first-ever ICH were followed for a median of 2.3 years. Adjusting for demographics, comorbidities and documented ICH characteristics increasing mortality after ICH, logistic regression analysis assessed factors associated with case fatality and 1-year survival among the 30-day survivors. Diabetes was compared with patients without diabetes in separate models as (i) any diabetes and (ii) T1D or T2D. RESULTS: Of our 969 patients, 813 (83.9%) had no diabetes, 41 (4.2%) had T1D and 115 (11.9%) had T2D. Compared with patients without diabetes, those with diabetes were younger, more often men and more frequently had hypertension, coronary heart disease and chronic kidney disease, with similar ICH characteristics. Patients with T1D were younger, more often had chronic kidney disease and brainstem ICH, and less often had atrial fibrillation and lobar ICH, than did patients with T2D. Diabetes had no impact on case fatality. Any diabetes (odds ratio, 2.57; 1.19-5.52), T1D (odds ratio, 7.04; 1.14-43.48) and T2D (odds ratio, 2.32; 1.04-5.17) were independently associated with 1-year mortality. CONCLUSIONS: Patients with ICH with diabetes exhibited a distinct pattern of comorbidities and disease characteristics with specific differences between T1D and T2D. Despite their younger age, T1D seems to carry a substantially higher likelihood of long-term mortality after an ICH than does T2D.

Beta-blocker therapy is not associated with mortality after intracerebral hemorrhage.

BACKGROUND: Beta-blocker therapy has been suggested to have neuroprotective properties in the setting of acute stroke; however, the evidence is weak and contradictory. We aimed to examine the effects of pre-admission therapy with beta-blockers (BB) on the mortality following spontaneous intracerebral hemorrhage (ICH). METHODS: Retrospective analysis of the Helsinki ICH Study database. RESULTS: A total of 1013 patients with ICH were included in the analysis. Patients taking BB were significantly older, had a higher premorbid mRS score, had more DNR orders, and more comorbidities as atrial fibrillation, hypertension, diabetes mellitus, ischemic heart disease, and heart failure. After adjustment for age, pre-existing comorbidities, and prior use of antithrombotic and antihypertensive medications, no differences in in-hospital mortality (OR 1.1, 95% CI 0.8-1.7), 12-month mortality (OR 1.3, 95% CI 0.9-1.9), and 3-month mortality (OR 1.2, 95% CI 0.8-1.7) emerged. CONCLUSION: Pre-admission use of BB was not associated with mortality after ICH.

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

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

Embolic strokes of undetermined source in young adults: baseline characteristics and long-term outcome.

BACKGROUND AND PURPOSE: Embolic strokes of undetermined source (ESUS) are a recent entity, not yet thoroughly investigated in young stroke patients. The clinical characteristics and long-term risks of vascular events and all-cause mortality between young-onset ESUS and other aetiological subgroups were compared. METHODS: Patients with ESUS were identified amongst the 1008 patients aged 15-49 years with first-ever ischaemic stroke in Helsinki Young Stroke Registry, and primary end-points were defined as recurrent stroke, composite vascular events and all-cause mortality. Cumulative 15-year risks for each end-point were analysed with life tables and adjusted risks were based on Cox proportional hazard analyses. RESULTS: Of the 971 eligible patients, 203 (20.9%) were classified as ESUS. They were younger (median age 40 years, interquartile range 32-46 vs. 45 years, 39-47), more often female (43.3% vs. 35.7%) and had fewer cardiovascular risk factors than other modified TOAST groups. With a median follow-up time of 10.1 years, ESUS patients had the second lowest cumulative risk of recurrent stroke and composite vascular events and lowest mortality compared to other TOAST groups. Large-artery atherosclerosis and small vessel disease carried significantly higher risk for recurrent stroke than did ESUS, whilst no difference appeared between cardioembolism from high-risk sources and ESUS. CONCLUSIONS: In our cohort, ESUS patients were younger and had milder cardiovascular risk factor burden and generally better long-term outcome compared to other causes of young-onset stroke. The comparable risk of recurrent stroke between ESUS and high-risk sources of cardioembolism might suggest similarities in their pathophysiology.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

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.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

Intracerebral hemorrhage at young age: long-term prognosis.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disorder associated with dismal outcomes. The long-term mortality and functional outcome of ICH in young patients was studied - areas so far poorly investigated. METHODS: A follow-up study was performed on a cohort of patients. Clinical and imaging data on ICH patients aged 16-49 were retrospectively obtained and linked with a nationwide cause-of-death register. The modified Rankin Scale (mRS) was evaluated for 30-day survivors at a visit 9.7 (7.0-12.0) years after ICH onset. Independent factors associated with mortality and unfavorable functional outcome (mRS 2-5) were sought by multivariate analysis. RESULTS: Amongst the 268 1-month survivors, 1-year survival was 98.1% [95% confidence interval (CI) 96.2%-100%], 5-year survival 93.2% (89.3%-97.1%) and 10-year survival 88.8% (84.9%-92.7%). After adjustment for age and intraventricular hematoma extension, male sex [odds ratio (OR) 3.36, 95% CI 1.28-8.80] and diabetes (OR 2.64, 1.01-6.89) were associated with increased mortality. Unfavorable functional outcome emerged in 49%. After adjustment for confounders, age (OR 1.09 per 1 year, 95% CI 1.03-1.15), initial stroke severity (1.17 per one National Institutes of Health Stroke Scale score point, 1.08-1.27) and intraventricular hemorrhage (3.26, 1.11-9.55) were associated with unfavorable functional outcome. CONCLUSIONS: Of every 10 survivors of acute phase ICH at a young age, one died within 10 years after onset, male sex and diabetes being associated with increased mortality. Half the survivors did not achieve a favorable functional outcome, which was predicted by increasing age, initial stroke severity and intraventricular hemorrhage.

Depression, anxiety, and cognitive functioning after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) is an important complication of stroke. We studied long-term PSD after intracerebral hemorrhage (ICH) at young age, as well as anxiety, and cognitive functioning of the survivors. METHODS: We gathered clinical and imaging data of 336 young ICH patients between age 16 and 49 treated in the Helsinki University Central Hospital. After a median follow-up of 9.7 (7.0-12.0) years, we interviewed 130 survivors with structural questionnaires including Beck Depression Inventory II (BDI-II), Hospital Anxiety and Depression Scale (HADS), Pain Anxiety Symptoms Scale (PASS), Brief Pain Inventory (BPI), and Montreal Cognitive Assessment (MoCA). Univariate and multivariate analysis was performed to identify factors associated with PSD (BDI-II score >13). Degree of disability was measured by modified Rankin Scale score (mRS). RESULTS: PSD was present among 30 (23.1%) and anxiety among 52 (40.0%) patients (HADS score >6). Higher degree of disability was associated with symptoms of depression (higher BDI-II scores, P = 0.001), emotional distress (higher HADS scores, P = 0.004), and pain (higher PASS scores, P = 0.008, and higher BPI scores, P = 0.003). The only baseline factor identified to associate with PSD was hydrocephalus (P = 0.014). Median PASS score was 9 (IQR 0-25), median BPI score was 5 (0-23), and median MoCA score was 26 (22-28) hinting to normal or mild cognitive dysfunction. Antidepressants were used by 9.2%. CONCLUSIONS: One of four survivors of ICH at young age suffers long-term PSD. Higher degree of disability predicted occurrence of PSD. Treatment of depression appears as an unmet need in young ICH survivors.

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.

In-hospital cardiac complications after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Data on cardiac complications and their precipitants after intracerebral hemorrhage are scarce. We examined the frequency and risk factors for serious in-hospital cardiac events in a large cohort of consecutive intracerebral hemorrhage patients. METHODS: A retrospective chart review of 1013 consecutive patients with nontraumatic intracerebral hemorrhage treated at the Helsinki University Central Hospital (2005-2010). We excluded patients with intraparenchymal hematoma related to sub-arachnoid hemorrhage or intracerebral hemorrhage because of fibrinolytic therapies for acute ischemic stroke or myocardial infarction. Serious in-hospital cardiac event was defined as any of in-hospital poststroke acute myocardial infarction, ventricular fibrillation or tachycardia, moderate to serious acute heart failure, or cardiac death. RESULTS: Among the 948 patients included, ≥1 serious in-hospital cardiac event occurred in 39 (4·1%) patients after a median delay of two-days from stroke onset (acute myocardial infarction in three patients, ventricular fibrillation or tachycardia in three patients, acute heart failure in 36 patients, and cardiac death in three patients). Hospital stay was longer in patients with serious in-hospital cardiac event than in those without (median 12, interquartile range 7-19 vs. 8, 3-14; P = 0·001), with no difference in in-hospital mortality (23·1% vs. 24·3%; P = 0·86). In multivariable logistic regression analysis adjusted for age, gender, and diabetes, atrial fibrillation during hospitalization (odds ratio 6·68 for new-onset atrial fibrillation, 95% confidence interval 2·11-21·18; 4·46 for old atrial fibrillation, 2·08-9·56), and history of myocardial infarction (3·20, 1·18-8·66) were independently associated with serious in-hospital cardiac events. CONCLUSIONS: After intracerebral hemorrhage, 4% of patients suffer an acute serious cardiac complication. Those with history of myocardial infarction or in-hospital atrial fibrillation are at greater risk for such events.

Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation. METHODS: A chart review was carried out by a multi-professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010. RESULTS: In all, 955 patients had follow-up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non-existent and do-not-resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm(3) (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012. CONCLUSIONS: A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end-of-life care.

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.