Ryan W Snider

Natural History of Perihematomal Edema After Intracerebral Hemorrhage Measured by Serial Magnetic Resonance Imaging

Background and Purpose— Knowledge on the natural history and clinical impact of perihematomal edema (PHE) associated with intracerebral hemorrhage is limited. We aimed to define the time course, predictors, and clinical significance of PHE measured by serial magnetic resonance imaging. Methods— Patients with primary supratentorial intracerebral hemorrhage ≥5 cm3 underwent serial MRIs at prespecified intervals during the first month. Hematoma (Hv) and PHE (Ev) volumes were measured on fluid-attenuated inversion recovery images. Relative PHE was defined as Ev/Hv. Neurologic assessments were performed at admission and with each MRI. Barthel Index, modified Rankin scale, and extended Glasgow Outcome scale scores were assigned at 3 months. Results— Twenty-seven patients with 88 MRIs were prospectively included. Median Hv and Ev on the first MRI were 39 and 46 cm3, respectively. Median peak absolute Ev was 88 cm3. Larger hematomas produced a larger absolute Ev (r2=0.6) and a smaller relative PHE (r2=0.7). Edema volume growth was fastest in the first 2 days but continued until 12±3 days. In multivariate analysis, a higher admission hematocrit was associated with a greater delay in peak PHE (P=0.06). Higher admission partial thromboplastin time was associated with higher peak rPHE (P=0.02). Edema volume growth was correlated with a decline in neurologic status at 48 hours (81 vs 43 cm3, P=0.03) but not with 3-month functional outcome. Conclusions— PHE volume measured by MRI increases most rapidly in the first 2 days after symptom onset and peaks toward the end of the second week. The timing and magnitude of PHE volume are associated with hematologic factors. Its clinical significance deserves further study.

Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.

BACKGROUND Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication. OBJECTIVE To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature. METHODS Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software. RESULTS Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis. CONCLUSION Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.

Magnetic Resonance Imaging Profile of Blood–Brain Barrier Injury in Patients With Acute Intracerebral Hemorrhage

Background Spontaneous intracerebral hemorrhage (ICH) is associated with blood–brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage. Methods and Results Twenty‐five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (Ktrans) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror–image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher Ktrans values than small hematomas (P<0.005). Ktrans values of lobar hemorrhages were significantly higher than the Ktrans values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher Ktrans values were associated with larger edema volumes. Conclusions BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

Natural history and prognostic value of corticospinal tract Wallerian degeneration in intracerebral hemorrhage.

Background The purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST‐WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging. Methods and Results Consecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST‐WD on diffusion‐weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor‐NIHSS. Twenty‐seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST‐WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST‐WD changes evolved into T2‐hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST‐WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor‐NIHSS (5 versus 1, P=0.001) at 3 months. Conclusions Wallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST‐WD is associated with poor motor and functional recovery after ICH.

Depression one year after hemorrhagic stroke is associated with late worsening of outcomes

BACKGROUND Poststroke depression is the most common psychiatric sequelae of stroke, and its independently associated with increased morbidity and mortality. Few studies have examined depression after intracranial hemorrhage (ICH). OBJECTIVE To investigate the relationship between depression, ICH and outcomes. METHODS A substudy of the prospective Diagnostic Accuracy of MRI in Spontaneous Intracerebral Hemorrhage (DASH) study, we included 89 subjects assessed for depression 1 year after hemorrhage. A Hamilton Depression Rating Scale score >10 defined depression. Univariate, multivariable, and trend analyses evaluated relationships between depression, clinical, radiographic, and inflammatory factors and modified Rankin score (mRS) at 90 days and one year. RESULTS Prevalence of depression at one year was 15%. Depression was not associated with hematoma volumes, presence of IVH or admission NIHSS, nor with demographic factors. Despite this, depressed patients had worse 1-year outcomes (p = 0.004) and were less likely to improve between 3 and 12 months, and more likely to worsen (p = 0.042). CONCLUSION This is the first study to investigate depression one year after ICH. Post-ICH depression was common and associated with late worsening of disability unrelated to initial hemorrhage severity. Further research is needed to understand whether depression is caused by worsened disability, or whether the converse is true.