Search

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)–associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest. Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis. Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH. Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

Paracoccidioidomycosis is a dimorphic fungal infection endemic in Latin America. We report a patient with a history of pulmonary paracoccidioidomycosis who presented with relapsed disease in the central nervous system 4 years after initial treatment. We review current treatment strategies for paracoccidioidomycosis and neuroparacoccidioidomycosis.

Introduction: Oral Anticoagulation Therapy (OAT) resumption after ICH is a dilemma due to increased risk of recurrent ICH, particularly after lobar ICH caused by underlying Cerebral Amyloid Angiopathy (CAA). Apolipoprotein E ( APOE ) ε2/ε4 alleles are risk factors for recurrent CAA-related ICH. Hypothesis: APOE genotype predicts lobar ICH recurrence after OAT-ICH. Methods: We enrolled survivors of lobar OAT-ICH in a prospective single-center study to determine whether APOE ε2/ε4: 1) are associated with ICH recurrence following OAT-ICH, using time-to-event analyses; 2) improved prediction of ICH recurrence when added to MRI-based CAA markers (cerebral microbleeds [CMBs], white matter hyperintensities [WMH], expanded peri-vascular spaces [EPVS], and cortical superficial siderosis [CSS]), using Harrell’s C-statistic; 3) could be incorporated in a classification scheme to predict ICH recurrence, as defined by recursive partitioning analysis (RPA). Results: We followed 110 lobar OAT-ICH survivors for a median time of 52.2 months (IQR: 33.5-61.7). We observed 26 recurrent ICH events, corresponding to an annual recurrence rate of 5.7%. APOE ε2/ε4 variants were associated with ICH recurrence following OAT-ICH (ε2: HR 2.14, 95% CI 1.20-3.82; ε4: HR 1.50, 95% CI 1.21-3.47). These associations remained significant after adjusting for anticoagulation status, antiplatelet use, CMBs, WMH, EPVS, and CSS. Inclusion of APOE genotype alongside MRI data resulted in improved predictive ability for ICH recurrence (Harrell’s C: 0.76 vs. 0.68, p=0.034). RPA revealed that APOE ε2/ε4 stratified likelihood of ICH recurrence among otherwise low risk individuals based on MRI data alone (Figure). Conclusions: APOE genotype predicts lCH recurrence following lobar OAT-ICH, and improves predictive performance when added to established neuroimaging markers. APOE-based lobar ICH recurrence prediction warrants further investigation and may affect clinical practice.

Perihaematomal oedema (PHO) is an important pathophysiological marker of secondary injury in intracerebral haemorrhage (ICH). In this Review, we describe a novel method to conceptualize PHO formation within the framework of Starling's principle of movement of fluid across a capillary wall. We consider progression of PHO through three stages, characterized by ionic oedema (stage 1) and progressive vasogenic oedema (stages 2 and 3). In this context, possible modifiers of PHO volume and their value in identifying patients who would benefit from therapies that target secondary injury are discussed; the practicalities of using neuroimaging to measure PHO volume are also considered. We examine whether PHO can be used as a predictor of neurological outcome following ICH, and we provide an overview of emerging therapies. Our discussion emphasizes that PHO has clinical relevance both as a therapeutic target, owing to its augmentation of the mass effect of a haemorrhage, and as a surrogate marker for novel interventions that target secondary injury.

Brain edema after acute neurological injury causes significant morbidity and mortality. In this chapter, we highlight the critical role of the sulfonylurea receptor 1–transient receptor potential M4 (SUR1–TRPM4) channel in the pathogenesis of brain edema across various neurocritical care conditions. We emphasize that SUR1–TRPM4 activation is pivotal at every stage in edema formation. It contributes to every type of edema (cytotoxic, ionic, and vasogenic) and to total microvascular failure, which results in the extravasation of blood and the formation of petechial hemorrhages. We present examples from experimental models that demonstrate that selective blockade of SUR1–TRPM4 with glibenclamide results in improvement in edema, lesion volume, mortality, and neurological function. Clinical studies supporting the role of SUR1–TRPM4 in edema formation in humans are also presented. Although definitive phase III studies are needed, the ability to block SUR1–TRPM4 over a broad time window with a safe medication (glibenclamide) is emerging as a highly promising approach to treat brain edema.

Neurosurgeons increasingly use decompressive craniectomy (DC) in neurocritical care. In this review, the authors summarize the topic of DC for the neurointensivist. Following a brief overview of the procedure, the major indications for the procedure are described. This includes a review of the literature regarding well-established indications, such as infarction and traumatic brain injury, as well as lesser known indications, including intracerebral hemorrhage, ruptured cerebrovascular malformations, sinus thrombosis, and infection. Complications unique to DC, specifically syndrome of the trephined, hygroma, and hydrocephalus, also are reviewed with a discussion of their management, both in the immediate and the postoperative period.

Objectives Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage. Design Retrospective cohort study. Setting Tertiary medical center. Patients One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013. Interventions None. Measurements and main results Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate at 24 hours and 90-day modified Rankin Scale score. Perihematomal edema expansion rate between admission and 24-hours postintracerebral hemorrhage was a significant predictor of 90-day mortality (odds ratio, 2.97; 95% CI, 1.48-5.99; p = 0.002). This association persisted after adjusting for all components of the intracerebral hemorrhage score (odds ratio, 2.21; 95% CI, 1.05-4.64; p = 0.04). Similarly, higher 24-hour perihematomal edema expansion rate was associated with poorer modified Rankin Scale score in an ordinal shift analysis (odds ratio, 2.40; 95% CI, 1.37-4.21; p = 0.002). The association persisted after adjustment for all intracerebral hemorrhage score components (odds ratio, 2.07; 95% CI, 1.12-3.83; p = 0.02). Conclusions Faster perihematomal edema expansion rate 24-hours postintracerebral hemorrhage is associated with worse outcome. Perihematomal edema may represent an attractive translational target for secondary injury after intracerebral hemorrhage.

Background Perihaematomal edema (PHE) expansion rate may be a predictor of outcome after intracerebral haemorrhage (ICH). We determined whether PHE expansion rate in the first 72 hours after ICH predicts outcome, and how it compares against other PHE measures. Methods We included patients from the Virtual International Stroke Trials Archive. We calculated PHE expansion rate using the equation: (PHE at 72 hours PHE at baseline)/(time to 72-hour CT scan time to baseline CT scan). Outcomes of interest were mortality and poor 90-day outcome (modified Rankin Scale score of ≥3). Logistic regression was used to assess relationships with outcome. Results A total of 596 patients with ICH were included. At baseline, median haematoma volume was 15.0 mL (IQR 7.9–29.2) with median PHE volume of 8.7 mL (IQR 4.5–15.5). Median PHE expansion rate was 0.31 mL/hour (IQR 0.12–0.55). The odds of mortality were greater with increasing PHE expansion rate (OR 2.63, CI 1.10 to 6.25), while the odds of poor outcome also increased with greater PHE growth (OR 1.67, CI 1.28 to 2.39). Female sex had an inverse relationship with PHE growth, but baseline haematoma volume had a direct correlation. Among other PHE measures, only interval increase in PHE correlated with poor outcome. There was no significant difference between the 2 measures of PHE volume expansion. Conclusions Rate of PHE growth over 72 hours was an independent predictor of mortality and poor functional outcomes following ICH. Baseline haematoma volume and gender appear to influence PHE growth.

Introduction: Perihematomal edema (PHE) expansion rate may be an independent predictor of poor functional outcome following spontaneous intracerebral hemorrhage (ICH). We examined whether this association varies by ICH location. Hypothesis: The effect size of PHE expansion rate on mortality and poor functional outcome will be greater for deep ICH compared to lobar ICH. Methods: Subjects (n=139) were retrospectively identified from a prospective ICH cohort enrolled from 2000-2013. Inclusion criteria: ≥18 years of age, spontaneous supratentorial ICH, and known time of onset. Exclusion criteria: infratentorial or primary intraventricular hemorrhage, subsequent surgery, trauma, or warfarin-related ICH. ICH, PHE, and intraventricular hemorrhage (IVH) volumes were measured from CT scans. PHE expansion rates were calculated from serial PHE volume measurements. Logistic regression assessed the association between PHE expansion rate and mortality or poor functional outcome (modified Rankin Scale >2) at 90 days. Odds ratios are per 0.04 mL/h. Results: PHE expansion rate from baseline to 24 hours (PHE24) predicts mortality for deep (p=0.03, OR 1.13[1.02-1.26]) and lobar ICH (p=0.02, OR 1.03[1.00-1.06]) in unadjusted regression, and in models adjusted for age (Deep: p=0.02; Lobar: p=0.03), blood pressure (Deep: p=0.02; Lobar: p=0.04), IVH volume (Deep: p=0.02; Lobar: p=0.05), Glasgow Coma Scale (Deep: p=0.03; Lobar: p=0.02), or time to baseline CT (Deep: p=0.05; Lobar: p=0.05). PHE24 also predicts mortality for lobar ICH adjusting for ICH volume (p=0.05, OR 1.03[1-1.06]). A significant interaction exists between ICH location and PHE expansion rate from baseline to 72 hours (PHE72) in models predicting mRS>2 (p=0.04). PHE72 predicts mRS>2 for deep but not lobar ICH (p-values not shown) in models that are unadjusted (p=0.02, OR 4.04[1.25-13.04]) or adjusted for ICH volume (p=0.02, OR 4.3[1.25-14.98]), age (p=0.03, OR 5.4[1.21-24.11]), blood pressure (p=0.05, OR 3.28[1.02-10.57]), IVH volume (p=0.02, OR 4.59[1.28-16.41]), GCS (p=0.02, OR 4.19[1.2-14.55]), or time to first CT (p=0.03, OR 4.02[1.19-13.56]). Conclusion: PHE72 predicts poor functional outcomes exclusively after deep ICH, whereas PHE24 predicts mortality for deep and lobar ICH.

Background and Purpose: There have been conflicting reports regarding the association between peri-hematomal edema (PHE) in spontaneous intracerebral hemorrhage (ICH) and outcome. We hypothesized that PHE expansion rate from baseline to 24 hours predicts mortality and poor functional outcome after ICH. Methods: ICH, PHE and intraventricular hemorrhage volumes were measured for 139 subjects who presented with primary ICH and received head computed tomography scans at baseline and 24-hours post-ICH. Subjects were retrospectively identified from a prospective cohort study of ICH. Inclusion criteria were age over 18 years with primary spontaneous supratentorial ICH. Exclusion criteria were infratentorial hemorrhage, primary intraventricular hemorrhage, or any suspected cause of secondary ICH. Logistic regression was performed to evaluate the relationship between PHE expansion rate and 90-day mortality and functional outcome. Poor functional outcome was defined as a modified Rankin Scale (mRS) score > 2. Results: There was a strong association between PHE expansion rate and mortality (OR 1.42, p = 0.0025) and a trend in the correlation between PHE expansion rate and poor outcome (OR 1.50, p = 0.07). In a multivariable model accounting for hematoma volume and time from symptom onset to 24 hour scan, PHE expansion rate was a significant predictor of mortality (OR 1.07, p = 0.032). In a multivariable model accounting for hematoma volume, age, Glasgow Coma Scale score, presence of intraventricular hemorrhage and time from symptom onset to 24 hour scan, PHE expansion rate predicted poor functional outcome (OR 2.58, p = 0.05). Conclusions: PHE expansion rate predicts outcome in ICH and may represent a novel therapeutic target.