Impact of white matter hypodensities on outcome after intracerebral hemorrhage.

OBJECTIVES: White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome. MATERIALS AND METHODS: This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors. RESULTS: In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85). CONCLUSIONS: In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome.

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

[Figure: see text].

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.

Triggering factors in non-traumatic intracerebral hemorrhage.

BACKGROUND: In ischemic stroke and subarachnoid hemorrhage, there are known preceding triggering events that predispose to the stroke by, for example, abruptly raising blood pressure. We explored, whether triggering events can be identified in non-traumatic intracerebral hemorrhage (ICH). METHODS: We used structured questionnaires to interview consented patients with ICH treated in a tertiary teaching hospital, between 2014 and 2016. We asked of possible trigger factors, including Valsalva-inducing activity, heavy physical exertion, sexual activity, abrupt change in position, a heavy meal, a sudden change in temperature, exposure to traffic jam, and the combination of the first three (any physical trigger) during the hazard period of 0-2 h prior to ICH. The ratio of the reported trigger during the hazard period was compared to the same 2-h period the previous day (control period) to calculate the relative risks for each factor (case-crossover design). RESULTS: Of our 216 consented ICH patients, 97 (35.0%) could be interviewed for trigger questions. Reasons for not able to provide consistent and reliable responses included lowered level of consciousness, delirium, impaired memory, and aphasia. None of the studied possible triggers alone were more frequent during the hazard period compared to the control period. However, when all physical triggers were combined, we found an association with the triggering event and onset of ICH (risk ratio 1.32, 95% confidence interval 1.01-1.73). CONCLUSIONS: Obtaining reliable information on the preceding events before ICH onset was challenging. However, we found that physical triggers as a group were associated with the onset of ICH.

Risk Factors of Intracerebral Hemorrhage: A Case-Control Study.

BACKGROUND: Hypertension is a well-known risk factor for intracerebral hemorrhage (ICH). On many of the other potential risk factors, such as smoking, diabetes, and alcohol intake, results are conflicting. We assessed risk factors of ICH, taking also into account prior depression and fatigue. METHODS: This is a population-based case-control study of 250 primary ICH patients, conducted in Helsinki University Hospital, Finland. The controls (n = 750) were participants of the FINRISK study, a large Finnish population survey on risk factors of chronic noncommunicable diseases, matched with cases by sex and age. Ages were matched in 5-year age bands. However, as the oldest FINRISK participants were 74-year-olds, controls for the age group 75-84 were selected from the age group of 70-74 years. Patients aged greater than or equal to 85 years were excluded. Patients and controls were compared in univariate analyses. The age categories less than 70, and greater than or equal to 70 years were also analyzed separately. Binary logistic regression analysis was performed for variables with P less than .1 in univariate analysis. RESULTS: Analyzing all cases and controls, the cases had more hypertension, history of heart attack, lipid-lowering medication, and reported more frequently fatigue prior to ICH. In persons aged less than 70 years, hypertension and fatigue were more common among cases. In persons aged greater than or equal to 70 years, factors associated with risk of ICH were fatigue prior to ICH, use of lipid-lowering medication, and overweight. CONCLUSIONS: Hypertension was associated with risk of ICH among all patients and in the group of patients under 70 years. Fatigue prior to ICH was more common among all ICH cases.

Overlap in the Genetic Architecture of Stroke Risk, Early Neurological Changes, and Cardiovascular Risk Factors.

Background and Purpose- The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits. In this study, we compare the genetic architecture of stroke risk, stroke severity, and early neurological changes with that of 2 stroke risk factors: type 2 diabetes mellitus (T2DM) and hypertension. Methods- We assessed the degree of overlap in the genetic architecture of stroke risk, T2DM, hypertension, and 2 acute stroke phenotypes based on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 for no stroke symptoms to 21 to 42 for a severe stroke: baseline (within 6 hours after onset) and change in NIHSS (ΔNIHSS=NIHSS at baseline-NIHSS at 24 hours). This was done by (1) single-nucleotide polymorphism by single-nucleotide polymorphism comparison, (2) weighted polygenic risk scores with sentinel variants, and (3) whole-genome polygenic risk scores using multiple P thresholds. Results- We found evidence of genetic architecture overlap between stroke risk and T2DM ( P=2.53×10-169), hypertension ( P=3.93×10-04), and baseline NIHSS ( P=0.03). However, there was no evidence of overlap between ΔNIHSS and stroke risk, T2DM, or hypertension. Conclusions- The genetic architecture of stroke risk is correlated with that of T2DM, hypertension, and initial stroke severity (NIHSS within 6 hours of stroke onset). However, the genetic architecture of early neurological change after stroke (ΔNIHSS) is not correlated with that of ischemic stroke risk, T2DM, or hypertension. Thus, stroke risk and early neurological change after stroke have distinct genetic architectures.

Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Quality of life and depression 3 months after intracerebral hemorrhage.

OBJECTIVES: Quality of life (QoL) after intracerebral hemorrhage (ICH) is poorly known. This study investigated factors affecting QoL and depression after spontaneous ICH. MATERIALS AND METHODS: This prospective study included patients admitted to Helsinki University Hospital between May 2014 and December 2016. Health-related QoL (HRQoL) at 3 months after ICH was measured using the European Quality of Life Scale (EQ-5D-5L), and the 15D scale. Logistic regression analyses were used to test factors affecting HRQoL. EQ-5D-5L anxiety/depression dimension was used to analyze factors associated with anxiety/depression. RESULTS: Of 277 patients, 220 were alive, and sent QoL questionnaire. The questionnaire was returned by 124 patients. Nonreturners had more severe strokes with admission National Institutes of Health Stroke Scale (NIHSS) 7.8 (IQR 3.0-14.8) versus 5.0 (IQR 2.3-11.0); p = 0.018, and worse outcome assessed as modified Rankin Scale 3-5 at 3 months 59.4% versus 44.4% (p = 0.030). Predictors for lower HRQoL by both scales were higher NIHSS with OR 1.28 (95% CI 1.13-1.46) for EQ-5D-5L, and OR 1.28 (1.15-1.44) for 15D, older age (OR 1.10 [1.03-1.16], and OR 1.09 [1.03-1.15]), and chronic heart failure (OR 18.12 [1.73-189.27], and OR 12.84 [1.31-126.32]), respectively. Feeling sad/depressed for more than 2 weeks during the year prior to ICH was predictor for lower EQ-5D-5L (OR 10.64 [2.39-47.28]), and history of ICH for lower 15D utility indexes (OR 11.85 [1.01-138.90]). Prior feelings of sadness/depression were associated with depression/anxiety at 3 months after ICH with OR 3.62 (1.14-11.45). CONCLUSIONS: In this cohort of ICH patients with milder deficits, HRQoL was affected by stroke severity, comorbidities and age. Feelings of depression before ICH had stronger influence on reporting depression/anxiety after ICH than stroke severity-related and outcome parameters. Thus, simple questions on patient's premorbid feelings of sadness/depression could be used to identify patients at risk of depression after ICH for focusing follow-up and treatment.

Effect of baseline hypocalcaemia on volume of intracerebral haemorrhage in patients presenting within 72 hours from symptom onset.

INTRODUCTION: Calcium has a pivotal role in haemostasis. We investigated the association of baseline calcium levels with admission intracerebral haemorrhage (ICH) volume. METHODS: This is a retrospective analysis of consecutive ICH patients in an academic hospital between January 2005 and March 2010. Computed tomography (CT) of the brain and serum/plasma ionized calcium had to be taken within 72 h of symptom onset and within 12 h of each other in order to fulfil the study criteria. ICH cases related to trauma or tumour as well as sole intraventricular haemorrhages were excluded. Baseline haematoma volumes were calculated using semiautomated planimetry. The hypocalcaemic (Ca-ion <1.16 mmol/L) and normocalcaemic (1.16-1.30 mmol/L) patient groups were compared in univariate analyses. Association between admission hypocalcaemia and haematoma volume was studied using multivariable regression models. RESULTS: Out of 1013 consecutive patients, 447 fulfilled the study criteria. Hypocalcaemic patients (n = 178; 39.8%) had larger baseline hematoma volumes (median 30.2 mL, IQR 11.4-58.7 mL), compared to normocalcaemic patients (n = 255; 57.0%; median 16.8 mL, IQR 7.4-44.2 mL). The median ICH volume among hypercalcaemic patients (n = 14; 3.1% of included patients) was 6.5 mL (IQR 3.1-34.6 mL). On linear regression, admission hypocalcaemia was independently associated with larger hematoma volumes (ß = 11.77; 95% CI 4.66-18.87, P = 0.01). Patients with larger haematoma volumes had higher mortality. CONCLUSION: Hypocalcaemia is associated with larger admission haematoma volumes among ICH patients. Higher mortality among hypocalcaemic patients is very likely mediated through larger ICH volumes.

Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

OBJECTIVE: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). METHODS: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. RESULTS: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [p = 0.11]). CONCLUSIONS: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.