Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

ObjectiveBlood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.MethodsWe selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.ResultsWe included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1–19). Median ICH volume was 17.0 mL (IQR 1.4–88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = −0.003, 95% CI −0.003–0.03, p = 0.83), nor for any of the individual radiological cSVD markers.ConclusionWe found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE

Secondary Hematoma Evacuation and Outcome After Initial Conservative Approach for Patients with Cerebellar Hematoma Larger than 3 cm

Background: In patients with spontaneous cerebellar intracerebral hemorrhage (ICH) guidelines advocate evacuation when the hematoma diameter is > 3 cm. We studied outcome in patients with cerebellar ICH > 3 cm who did not undergo immediate hematoma evacuation. Methods: We included consecutive patients with cerebellar ICH > 3 cm at two academic hospitals between 2008 and 2017. Patients who died 3 cm of whom 22 (23%) died 24 h, of whom 1 (14%) had received an EVD 3 cm is often considered an indication for immediate hematoma evacuation, there may be a subgroup of patients in whom surgery can be safely deferred. Further data are needed to assess the optimal timing and indications of surgical treatment in these patients

Histopathology of Cerebral Microinfarcts and Microbleeds in Spontaneous Intracerebral Hemorrhage

In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study

International audienceBACKGROUND:Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH.METHODS:In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation.RESULTS:We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23–100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15–80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2–2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6–3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4–1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1–0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7–50 months), with a cumulative hazard of 47% at 10 years.CONCLUSIONS:The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

Long-Term Outcomes in Patients with Spontaneous Cerebellar Hemorrhage: An International Cohort Study

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

Cortical microinfarcts on 7 T MRI in patients with spontaneous intracerebral hemorrhage

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Multivariable hazard ratio’s for risk factors for intracerebral hemorrhage in general, lobar and non-lobar hemorrhage.

<p>The number of patients included in the analyses varied from 8,453 to 11,643 in the combined cohort and from 7,232 to 8,953 in the SMART cohort. Abbreviations: SMART, Second Manifestations of ARTerial disease study; ESPRIT, European/Australasian Stroke Prevention in Reversible Ischaemia Trial; ICH, intracerebral hemorrhage; aHR, adjusted Hazard Ratio; SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate; I, index event; A, age; P, antiplatelet medication; C, anticoagulant medication; G, sex; S, systolic blood pressure.</p><p>Multivariable hazard ratio’s for risk factors for intracerebral hemorrhage in general, lobar and non-lobar hemorrhage.</p

Risk Factors for Lobar and Non-Lobar Intracerebral Hemorrhage in Patients with Vascular Disease

<div><p>Introduction</p><p>Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location.</p><p>Methods</p><p>In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses.</p><p>Results</p><p>During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19–42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26–51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17–3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20–10.2) and male sex (HR 3.79; 95% CI 1.13–12.8) increased the risk of non-lobar but not lobar ICH.</p><p>Conclusion</p><p>This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH.</p></div

Baseline characteristics of patients.

<p>For the combined cohort, data were missing in 0.2% of patients or less, except for hyperlipidemia (1.4%). For the SMART cohort data were missing for impaired renal function (0.8%), hyperhomocysteinemia (7.1%), alcohol use (0.7%) and statins in 27.2% of patients. Abbreviations: SMART, Second Manifestations of ARTerial disease study; ESPRIT, European/Australasian Stroke Prevention in Reversible Ischaemia Trial; SD, standard deviation; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein.</p><p>Baseline characteristics of patients.</p