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Third Ventricle Obstruction by Thalamic Intracerebral Hemorrhage Predicts Poor Functional Outcome Among Patients Treated with Alteplase in the CLEAR III Trial

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Abstract

Introduction

The Clot Lysis: Evaluating Accelerated Resolution of IVH trial examined whether irrigating the ventricular system with alteplase improved functional outcomes in patients with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH). Thalamic ICH location was common and was associated with poor outcome. One possible explanation is thalamic ICH-associated mass effect obstructing the third ventricle. We hypothesized that patients with thalamic ICH obstructing the third ventricle would have worse functional outcomes compared to patients without obstructing lesions.

Methods

ICH obstruction of third ventricle was defined as third ventricle compression on 1 or more axial computed tomography slices visually impeding cerebral spinal fluid flow. If the third ventricle was casted with IVH, it was scored as such. Multivariable logistic regression analyses were used to determine whether obstruction of the third ventricle predicts poor functional outcomes defined as modified Rankin score (mRS) 4–6, higher mRS, and mortality at 180 days. Models were adjusted for thalamic ICH location, ICH volume, IVH volume, age, hydrocephalus, baseline Glasgow coma scale, and percentage of low cerebral perfusion pressures during treatment.

Results

Among saline-treated patients, obstruction of the third ventricle by IVH was a significant predictor of higher mRS at 180 days (OR 1.87, CI 1.01–3.47) and mortality at 180 days (OR 2.73, CI 1.27–5.87) while obstruction by ICH was not. In contrast, among alteplase-treated patients, obstruction by ICH was a significant predictor of mRS 4–6 (OR 3.20, CI 1.30–7.88) and higher mRS at 180 days (OR 2.33, CI 1.24–4.35), while obstruction by IVH was not.

Conclusions

Poor outcomes were associated with mass-related obstruction of the third ventricle from thalamic ICH in alteplase-treated patients and from IVH in saline-treated patients. Once the ventricular system is cleared with alteplase, obstruction of cerebral spinal fluid flow from thalamic ICH might become important in functional recovery.

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Acknowledgments

We wish to thank the CLEAR III patients and their families and the CLEAR III investigators and coordinators who provided and cared for them. The CLEAR III study was funded by the National Institute of Neurological Disorders and Stroke.

Funding

Dr. Daniel F. Hanley was awarded significant research support of Grants R01NS046309, 5U01 NS062851-05, and 5U01 NS080824-02.

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Authors and Affiliations

  1. Division of Brain Injury Outcomes, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Natalie L. Ullman & Daniel F. Hanley

  2. Division of Neurosciences Critical Care, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Pouya Tahsili-Fahadan & Wendy C. Ziai

  3. Neuroscience Intensive Care Unit, Department of Medicine, Virginia Commonwealth University, INOVA campus, Falls Church, VA, USA

    Pouya Tahsili-Fahadan

  4. Biotstatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Carol B. Thompson

Authors
  1. Natalie L. Ullman
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  2. Pouya Tahsili-Fahadan
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  3. Carol B. Thompson
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  4. Wendy C. Ziai
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  5. Daniel F. Hanley
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Contributions

NLU contributed to study conception and design, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. PTF contributed to study conception and design, acquisition of data, and critical revision to the manuscript. CBT contributed to analysis and interpretation of data, and critical revisions to the manuscript. WCZ contributed to acquisition of data, analysis and interpretation of data, and critical revision to the manuscript. DFH contributed to study conception and design and critical revision to the manuscript.

Corresponding author

Correspondence to Natalie L. Ullman.

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Conflict of interest

Ms. Thompson, Dr. Hanley, Dr. Ullman, and Dr. Ziai report grants from the National Institutes of Health (NINDS) during the conduct of the study. Dr. Tahsili-Fahadan has nothing to disclose.

Clinical trial registration

ClinicalTrials.gov NCT00784134.

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Ullman, N.L., Tahsili-Fahadan, P., Thompson, C.B. et al. Third Ventricle Obstruction by Thalamic Intracerebral Hemorrhage Predicts Poor Functional Outcome Among Patients Treated with Alteplase in the CLEAR III Trial. Neurocrit Care 30, 380–386 (2019). https://doi.org/10.1007/s12028-018-0610-0

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  • DOI: https://doi.org/10.1007/s12028-018-0610-0

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