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Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial
Kuohn LR, Witsch J, Steiner T, Sheth KN, Kamel H, Navi BB, Merkler AE, Murthy SB, Mayer SA
Stroke. 2022;:101161strokeaha121037974
Abstract
BACKGROUND In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. METHODS We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). RESULTS Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). CONCLUSIONS In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.
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Intraventricular Hemorrhage Expansion in the CLEAR III Trial: A Post Hoc Exploratory Analysis
Roh DJ, Asonye IS, Carvalho Poyraz F, Magid-Bernstein JR, Joiner EF, Avadhani R, Awad I, Hanley DF, Ziai WC, Murthy SB
Stroke. 2022;:Strokeaha121037438
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Abstract
BACKGROUND The objective of this study was to evaluate factors associated with intraventricular hemorrhage (IVH) expansion and its association with long-term outcomes. METHODS We performed a post hoc analysis of the international, multi-center CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) which enrolled IVH patients between September 1, 2009, and January 31, 2015. The exposure was IVH expansion, defined as >1 mL increase in volume between baseline and stability computed tomography scans, before treatment randomization. We assessed factors associated with IVH expansion and secondarily assessed the relationship of IVH expansion with clinical outcomes: composite of death or major disability (modified Rankin Scale score, >3), and mortality alone at 6 months. The relationship of IVH expansion on ventriculoperitoneal shunt placement was additionally explored. Multivariable logistic regression was used for all analyses. RESULTS Of 500 IVH patients analyzed, the mean age was 59 (±11) years old, 44% were female and 135 (27%) had IVH expansion. In multivariable regression models, factors associated with IVH expansion were baseline parenchymal intracerebral hemorrhage (ICH) volume (adjusted odds ratio [OR], 1.04 per 1 mL increase [95% CI, 1.01-1.08]), presence of parenchymal hematoma expansion: >33% (adjusted OR, 6.63 [95% CI, 3.92-11.24]), time to stability head CT (adjusted OR, 0.71 per 1 hour increase [95% CI, 0.54-0.94]), and thalamic hematoma location (adjusted OR, 1.68 [95% CI, 1.01-2.79]) while additionally adjusting for age, sex, and race. In secondary analyses, IVH expansion was associated with higher odds of poor 6-month outcomes (adjusted OR, 1.84 [95% CI, 1.12-3.02]) but not mortality (OR, 1.40 [95% CI, 0.78-2.50]) after adjusting for baseline ICH volume, thalamic ICH location, age, anticoagulant use, Glasgow Coma Scale score, any withdrawal of care order, and treatment randomization arm. However, there were no relationships of IVH expansion on subsequent ventriculoperitoneal shunt placement (adjusted OR, 1.02 [95% CI, 0.58-1.80]) after adjusting for similar covariates. CONCLUSIONS In a clinical trial cohort of patients with large IVH, acute hematoma characteristics, specifically larger parenchymal volume, hematoma expansion, and thalamic ICH location were associated with IVH expansion. Given that IVH expansion resulted in poor functional outcomes, exploration of treatment approaches to optimize hemostasis and prevent IVH expansion, particularly in patients with thalamic ICH, require further study. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT00784134.
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Permanent CSF shunting after intraventricular hemorrhage in the CLEAR III trial
Murthy SB, Awad I, Harnof S, Aldrich F, Harrigan M, Jallo J, Caron JL, Huang J, Camarata P, Lara LR, et al
Neurology. 2017;89((4):):355-362
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Abstract
OBJECTIVE To study factors associated with permanent CSF diversion and the relationship between shunting and functional outcomes in spontaneous intraventricular hemorrhage (IVH). METHODS Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III), a randomized, multicenter, double-blind, placebo-controlled trial, was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular alteplase improved outcome, in comparison to EVD plus saline. Outcome measures were predictors of shunting and blinded assessment of mortality and modified Rankin Scale at 180 days. RESULTS Among the 500 patients with IVH, CSF shunting was performed in 90 (18%) patients at a median of 18 (interquartile range [IQR] 13-30) days. Patient demographics and IVH characteristics were similar among patients with and without shunts. In the multivariate analysis, black race (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.18-3.34), duration of EVD (OR 1.10; CI 1.05-1.15), placement of more than one EVD (OR 1.93; CI 1.13-3.31), daily drainage CSF per 10 mL (OR 1.07; CI 1.04-1.10), and intracranial pressure >30 mm Hg (OR 1.70; CI 1.09-2.88) were associated with higher odds of permanent CSF shunting. Patients who had CSF shunts had similar odds of 180-day mortality, while survivors with shunts had increased odds of poor functional outcome, compared to survivors without shunts. CONCLUSIONS Among patients with spontaneous IVH requiring emergency CSF diversion, those with early elevated intracranial pressure, high CSF output, and placement of more than one EVD are at increased odds of permanent ventricular shunting. Administration of intraventricular alteplase, early radiographic findings, and CSF measures were not useful predictors of permanent CSF diversion.