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Brian Y. Hwang, Samuel S. Bruce, Geoffrey Appelboom, Matthew A. Piazza, Amanda M. Carpenter, Paul R. Gigante, Christopher P. Kellner, Andrew F. Ducruet, Michael A. Kellner, Rajeev Deb-Sen, Kerry A. Vaughan, Philip M. Meyers and E. Sander Connolly Jr.

Object

Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated.

Methods

A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3).

Results

Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD.

Conclusions

The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.

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Brad E. Zacharia, Kerry A. Vaughan, Zachary L. Hickman, Samuel S. Bruce, Amanda M. Carpenter, Nils H. Petersen, Stacie Deiner, Neeraj Badjatia and E. Sander Connolly Jr

Object

Intracerebral hemorrhage (ICH) is frequently complicated by acute hydrocephalus, necessitating emergency CSF diversion with a subset of patients, ultimately requiring long-term treatment via placement of permanent ventricular shunts. It is unclear what factors may predict the need for ventricular shunt placement in this patient population.

Methods

The authors performed a retrospective analysis of a prospective database (ICH Outcomes Project) containing patients with nontraumatic ICH admitted to the neurological ICU at Columbia University Medical Center between January 2009 and September 2011. A multiple logistic regression model was developed to identify independent predictors of shunt-dependent hydrocephalus after ICH. The following variables were included: patient age, admission Glasgow Coma Scale score, temporal horn diameter on admission CT imaging, bicaudate index, admission ICH volume and location, intraventricular hemorrhage volume, Graeb score, LeRoux score, third or fourth ventricle hemorrhage, and intracranial pressure (ICP) and ventriculitis during hospital stay.

Results

Of 210 patients prospectively enrolled in the ICH Outcomes Project, 64 required emergency CSF diversion via placement of an external ventricular drain and were included in the final cohort. Thirteen of these patients underwent permanent ventricular CSF shunting prior to discharge. In univariate analysis, only thalamic hemorrhage and elevated ICP were significantly associated with the requirement for permanent CSF diversion, with p values of 0.008 and 0.033, respectively. Each remained significant in a multiple logistic regression model in which both variables were present.

Conclusions

Of patients with ICH requiring emergency CSF diversion, those with persistently elevated ICP and thalamic location of their hemorrhage are at increased odds of developing persistent hydrocephalus, necessitating permanent ventricular shunt placement. These factors may assist in predicting which patients will require permanent CSF diversion and could ultimately lead to improvements in the management of this disorder and the outcome in patients with ICH.

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Natasha Ironside, Brandon Christophe, Samuel Bruce, Amanda M. Carpenter, Trae Robison, Nina Yoh, Serge Cremers, Donald Landry, Hans-Peter Frey, Ching-Jen Chen, Brian L. Hoh, Louis J. Kim, Jan Claassen and Edward Sander Connolly Jr.

OBJECTIVE

Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH.

METHODS

In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH.

RESULTS

Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm.

CONCLUSIONS

The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.

Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov)