Spontaneous Intraventricular Hemorrhage Associated with Prolonged Diosmin Therapy

Background  

The prevalent use of anticoagulation in a growing elderly population has led to an increasing incidence of intracerebral hemorrhage. Furthermore, the understanding of the interactions and adverse effects of oral anticoagulants when used with non-FDA approved drugs is limited. Diosmin is one such non-FDA approved drug which is a semisynthetic, phlebotropic supplement with multiple microcirculatory effects. We report a case of a patient on oral anticoagulation and diosmin, who presented with spontaneous intraventricular hemorrhage, and discuss the possible etiology behind this rare event.     

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage

Background

Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated.

Methods

Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days.

Results

Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4–6) compared to patients without concurrent ischemic lesions.

Conclusions

Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

     

Intraventricular Fibrinolysis for Intracerebral Hemorrhage with Severe Ventricular Involvement

Intraventricular hemorrhage (IVH) has been associated with poor prognosis in patients with spontaneous intracerebral hemorrhage. Several factors contribute to the deleterious effects of IVH, including direct mass effects of the ventricular blood clot on ependymal and subependymal brain structures, mechanical and inflammatory impairment of the Pacchioni granulations by blood and its breakdown products, and disturbance of physiological cerebrospinal fluid (CSF) circulation. Acute obstructive hydrocephalus represents a major life-threatening complication of IVH and is usually treated with an external ventricular drainage (EVD). However, treatment with EVD alone is frequently not sufficiently effective due to obstruction of the catheter by blood. In the past two decades, intraventricular fibrinolysis (IVF) has been increasingly used for maintenance of EVD functionality and acceleration of ventricular clot resolution in such patients. Unfortunately, there is no prospective, randomized controlled trial addressing the effect of IVF on clinical outcome. The available data on IVF consist of small retrospective case series, case reports, and a few prospective case–control studies, which are the subject of the present review article. All these studies, when considered in their entirety, suggest that IVF has a positive impact on mortality and functional outcome, and could be considered as a treatment option for selected patients.     

Autonomic Effects of Intraventricular Extension in Intracerebral Hemorrhage

Background  

Autonomic dysfunction after stroke is common and relates to unfavorable outcome. The pathophysiology of autonomic impairment after intracerebral hemorrhage (ICH) is unknown. This study examined the relationship between intraventricular hemorrhage extension (IVH) and autonomic dysregulation after ICH.     

Warfarin-Induced Intracerebral Hemorrhage Associated with Microbleeds

Background

Microbleeds (MBs), proposed as a biomarker for microangiopathy, have been suggested as a predictor of spontaneous or thrombolysis-related intracerebral hemorrhage (ICH) in acute ischemic stroke. However, the relationship between MBs and warfarin-induced ICH is not clear.

Case Report

We describe two patients who developed warfarin-induced ICH at the site of MBs documented in previous MRI.

Conclusions

The presence of MBs might increase the risk of ICH after warfarin use in ischemic stroke patients. A large cohort study is required to confirm the relationship of MBs with warfarin-induced ICH.     

Prediction of Shunt Dependency After Intracerebral Hemorrhage and Intraventricular Hemorrhage

Background

Spontaneous intracerebral hemorrhage is a disease with high morbidity and mortality. Extension of the hemorrhage into the ventricles is associated with the development of acute hydrocephalus and a poor outcome. Although it can be managed by external ventricular drainage (EVD), a subset of these patients require placement of permanent ventricular shunts. This study aimed to examine the factors on admission that can predict shunt dependency after EVD management.

Methods

Seventy-two patients who underwent EVD were included in this study. Seventeen of these patients underwent placement of a ventriculoperitoneal shunt. Variables analyzed included age, intraventricular hemorrhage (IVH) score, bicaudate index, acute hydrocephalus, initial Glasgow Coma Scale scores, and blood volume in each ventricle.

Results

In univariate analysis, IVH score (p?=?0.020), bicaudate index (p?<?0.001), blood volume in lateral ventricles (p?=?0.025), blood volume in the fourth ventricle (p?=?0.038), and the ratio of blood volume in lateral ventricles to that in third and fourth ventricles (p?=?0.003) were significantly associated with persistent hydrocephalus. The best multiple logistic regression model included blood volume parameters and bicaudate index as predictors with the area under a receiver operating characteristic curve of 0.849. The variance inflation factor (VIF) showed that collinearity was not found among predictors. Patients diagnosed with acute hydrocephalus had less blood volume in the lateral ventricles (OR?=?0.910) and had more blood volume in the third ventricle (OR?=?3.174) and fourth ventricle (OR?=?2.126).

Conclusions

These findings may promote more aggressive monitoring and earlier interventions for persistent hydrocephalus after intraventricular hemorrhage in patients at risk.

     

Determinants of External Ventricular Drain Placement and Associated Outcomes in Patients with Spontaneous Intraventricular Hemorrhage

Background

External ventricular drain (EVD) usage in patients with intraventricular hemorrhage (IVH) is variable in current practice and in clinical trials, and its impact on outcome remains controversial. The objective of this study was to identify the clinical predictors of EVD utilization, and associated outcome in adults with spontaneous IVH with or without intracerebral hemorrhage (ICH).

Methods

Retrospective review of 183 consecutive IVH patients admitted to a University Hospital between 2003 and 2010. Clinical and radiographic data were analyzed for associations between EVD placement and mortality, poor outcome, and improvement in Glasgow Coma Scale score (GCS) using multivariate logistic regression models.

Results

Average age was 62 ± 15.6 years, and average ICH and IVH volumes were 35.8 ± 40.9 cc and 19.7 ± 25.3 cc, respectively. Independent predictors of EVD placement within first 5 days of admission were GCS ≤ 8 (OR 11.5; P < 0.001), Graeb score >5 (OR 4.6; P = 0.001), and non-lobar ICH ≤ 30 cc (OR 9.7; P < 0.001). Median GCS increased from 5 (IQR 3–7) 48 h post-EVD (P < 0.001). EVD placement was an independent predictor of reduced mortality (OR 0.31; P = 0.04) and modified Rankin score 0–3 (OR 15.7; P = 0.01) at hospital discharge. In patients with hydrocephalus on presentation, EVD was associated with reduced mortality for patients with GCS > 3 after controlling for ICH and IVH severity (OR 0.02; P = 0.01).

Conclusions

Patients with lower GCS, higher IVH severity, and lower ICH volume are more likely to have an EVD placed. EVD placement is associated with reduced mortality and improved short-term outcomes in patients with IVH after adjusting for known severity factors. EVD use should be protocolized in clinical trials of ICH management where IVH is included.     

Management of Spontaneous Intracerebral Hemorrhage

Purpose of Review

We review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH).

Recent Findings

Therapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH. In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab. PCC are recommended for ICH related to FXa inhibitors, whereas specific reversal agents are not yet approved. While awaiting ongoing trials studying minimally invasive approaches or hemicraniectomy, the role of surgery in ICH remains to be defined. Therapies targeting downstream molecular cascades in order to prevent secondary neuronal damage are promising, but the complexity and multi-phased nature of ICH pathophysiology is challenging. Finally, in addition to blood pressure control, antithrombotic prevention after ICH has to consider the risk of recurrent bleeding as well as the risk of ischemic events.

Summary

Treatment of acute ICH remains challenging, and many promising interventions for acute ICH await further evidence from trials.

     

Seizures after Spontaneous Intracerebral Hemorrhage

Objective

In patients with spontaneous intracerebral hemorrhage (ICH), the risk factors for seizure and the effect of prophylactic anticonvulsants are not well known. This study aimed to determine the risk factor for seizures and the role for prophylactic anticonvulsants after spontaneous ICH.

Methods

Between 2005 and 2010, 263 consecutive patients with spontaneous ICH were retrospectively assessed with a mean follow-up of 19.5 months using medical records, updated clinical information and, when necessary, direct patient contact. The seizures were classified as early (within 1 week of ICH) or late (more than 1 week after ICH). The outcomes were measured with the Glasgow Outcome Scale at discharge and the modified Rankin Scale (mRS) at both 2 weeks and discharge.

Results

Twenty-two patients (8.4%; 9 patients with early seizures and 13 patients with late seizures) developed seizures after spontaneous ICH. Out of 263 patients, prophylactic anticonvulsants were administered in 216 patients. The prophylactic anticonvulsants were not associated with a reduced risk of early (p=0.094) or late seizures (p=0.326). Instead, the factors associated with early seizure were cortical involvement (p<0.001) and younger age (60 years or less) (p=0.046). The risk of late seizure was increased by cortical involvement (p<0.001) and communicating hydrocephalus (p=0.004). The prophylactic anticonvulsants were associated with a worse mRS at 2 weeks (p=0.024) and at last follow-up (p=0.034).

Conclusion

Cortical involvement may be a factor for provoked seizures. Although the incidence of early seizures tended to decrease in patients prescribed prophylactic anticonvulsants, no statistical difference was found.     

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage

ObjectivesSystemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear.Materials and methodsWe performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis.ResultsOf 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 – 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02).ConclusionSIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.     

Impact of Intraventricular Hemorrhage upon Intracerebral Hematoma Expansion

Background  

The purpose of this study is to determine whether intraventricular hemorrhage (IVH) exerts a “decompressive” effect that limits intracerebral hemorrhage (ICH) enlargement.     

Post-Stroke Depression in Patients with Large Spontaneous Intracerebral Hemorrhage

ObjectivesTo determine factors associated with post-stroke depression (PSD) and relationship between PSD and functional outcomes in spontaneous intracerebral hemorrhage (ICH) using prospective data from a large clinical trial.Materials and MethodsMISTIE III, a randomized, multicenter, placebo-controlled trial, was conducted to determine if minimally invasive surgery with thrombolysis improves outcome compared to standard medical care. Our primary outcome was post-stroke depression at 180 days. Secondary outcomes were change in blinded assessment of modified Rankin Scale (mRS) from 30 to 180 days, and from 180 to 365 days. Logistic regression models were used to assess the relationship between PSD and outcomes.ResultsAmong 379 survivors at day 180, 308 completed Center for Epidemiologic Studies Depression Scale, of which 111 (36%) were depressed. In the multivariable analysis, female sex (Adjusted Odds Ratio [AOR], 95% Confidence Interval [CI]: 1.93 [1.07-3.48]), Hispanic ethnicity (3.05 [1.19-7.85]), intraventricular hemorrhage (1.88 [1.02-3.45]), right-sided lesions (3.00 [1.43-6.29]), impaired mini mental state examination at day 30 (2.50 [1.13-5.54]), and not being at home at day 30 (3.17 [1.05-9.57]) were significantly associated with higher odds of PSD. Patients with PSD were significantly more likely to have unchanged or worsening mRS from day 30 to 180 (42.3% vs. 25.9%; p=0.004), but not from day 180 to 365.ConclusionsWe report high burden of PSD in patients with large volume ICH. Impaired cognition and not living at home may be more important than physical limitations in predicting PSD. Increased screening of high-risk post-stroke patients for depression, especially females and Hispanics may be warranted.     

Neuroendocrine Changes in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

Background

Neuroendocrine changes have been reported after ischemic stroke, subarachnoid hemorrhage, and brain trauma. As there are no corresponding data in patients with intracerebral hemorrhage (ICH) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH.

Methods

Twenty patients with ICH were prospectively enrolled in the study. Patients were a priori parted into two groups: Ten non-ventilated patients treated on the stroke-unit (hemorrhage volumes <20 ml, “small ICH”), and 10 ventilated patients treated on the neurocritical care unit (hematoma volumes >20 ml with possible additional ventricular involvement (“large ICH”). Neuroendocrine parameters were compared between both groups referring to reference values. The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH: thyrotropin, free thiiodothyronine and thyroxine, human growth hormone, insulin-like growth factor 1, luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, adrenocorticotropic hormone, and cortisol.

Results

Small ICH patients were in a median 71 (54–88) years old and had a mean ICH volume of 9.5 ± 6.5 ml, whereas large ICH patients were 65 (47–80) years old and showed a mean volume of 56 ± 30.2 ml. None of the patients revealed pathological alterations for thyrotropin, free thiiodothyronine, thyroxine, human growth hormone, insulin-like growth factor 1, and testosterone. There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients. Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period. Large ICH patients showed a marked increase of prolactin that developed during the course.

Conclusions

Overall, neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage. The clinical significance of increased LH and FSH levels in small ICH is unclear, whereas elevation of prolactin in large ICH was anticipated. Future randomized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome.     

缺血性脑白质病变的研究进展

缺血性脑白质病变是最常见的白质脑病类型之一。文章就其危险因素、发病机制、遗传学、临床表现、影像学、治疗等方面的进展做一综述。     

Older Age Is Not Associated with Worse Outcomes Following Decompressive Hemicraniectomy for Spontaneous Intracerebral Hemorrhage

Background: Decompressive hemicraniectomy (DHC) is commonly offered after large spontaneous intracerebral hemorrhage (ICH) as a life-saving measure. Based on limited available evidence, surgery is sometimes avoided in the elderly. The association between age and outcomes following DHC in spontaneous ICH remains largely understudied. Objective: The goal of this study is to investigate the influence of older age on outcomes of patients who undergo DHC for spontaneous ICH. Methods: In this retrospective cohort study, inpatient data were obtained from the United States Nationwide Inpatient Sample from 2000 to 2011. Using International Classification of Diseases, ninth revision designations, patients with a primary diagnosis of nontraumatic ICH who underwent DHC were identified. The primary outcome of interest was the association of age to inpatient mortality and poor outcome. Subjects were grouped by age: 18-50, 51-60, 61-70, and more than 70 years. Sample characteristics were compared across age groups using χ² testing, and univariate and multivariate Poisson Regression was performed using a generalized equation to estimate rate ratios for primary and secondary outcomes. Results: One thousand one hundred and forty four patient cases were isolated. Death occurred in an estimated 28.9% and poor outcome in 86.4%. In multivariate Poisson regression models, there was no difference in hospital mortality or poor outcome by age group. Although younger patients were more likely to be diagnosed with herniation, total complication rate was similar between age groups. Conclusions: Our study results do not provide evidence that age independently predicts in-hospital mortality or poor outcomes. The true influence of age on outcomes is unclear, and further study is needed to determine which factors may be best in selecting candidates for DHC following spontaneous ICH.