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Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage

Yogendrakumar, Vignan, MD1; Smith, Eric E., MD, MPH, FRCPC2; Demchuk, Andrew M., MD, FRCPC2; Aviv, Richard I., MBChB, MRCP, FRCR3; Rodriguez-Luna, David, MD4; Molina, Carlos A., MD, PhD4; Silva Blas, Yolanda, MD5; Dzialowski, Imanuel, MD6; Kobayashi, Adam, MD, PhD7,8; Boulanger, Jean-Martin, MD, FRCPC, CSPQ9; Lum, Cheemun, MD, FRCPC, DABR10,†; Gubitz, Gord, MD, FRCPC11; Padma, Vasantha, MD12; Roy, Jayanta, MD13; Kase, Carlos S., MD14; Bhatia, Rohit, MD, DNB12; Ali, Myzoon, PhD15; Lyden, Patrick, MD16; Hill, Michael D., MD, MSc, FRCPC2; Dowlatshahi, Dar, MD, PhD, FRCP(C)1 on behalf of the Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]/Sunnybrook ICH CTA Study Group and the Virtual International Stroke Trials Archive (VISTA)-ICH Collaborators

doi: 10.1097/CCM.0000000000002962
Online Clinical Investigations

Objectives: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes.

Design: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). Validation: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]).

Setting: Neurocritical and ICUs.

Patients: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients.

Interventions: None.

Measurements and Main Results: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4–6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2–6, 3–6, 5–6, 6). We employed Youden’s J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four–hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden’s method showed an optimum cut point at –0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25–7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08–36.66]). All definitions reproduced well in the validation cohort.

Conclusions: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

1Division of Neurology, Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada.

2Calgary Stroke Program, Department of Clinical Neurosciences, Department of Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

3Division of Neuroradiology and Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

4Department of Neurology, Hospital Universitari Vall d’Hebron, Barcelona, Spain.

5Department of Neurology, Dr. Josep Trueta University Hospital, Institut d’Investigació Biomèdica Girona (IDIBGi) Foundation, Girona, Spain.

6Department of Neurology, Elblandklinikum Meissen Academic Teaching Hospital of the Technische University, Dresden, Germany.

72nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.

8Department of Experimental and Clinical Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland.

9Department of Medicine, Charles LeMoyne Hospital, University of Sherbrooke, Montreal, QC, Canada.

10Department of Diagnostic Imaging, Neuroradiology Section, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

11Department of Neurology, Dalhousie University, Halifax, NS, Canada.

12Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.

13Department of Neuromedicine, Apollo Gleneagles Hospitals, Kolkata, India.

14Department of Neurology, Boston Medical Center, Boston, MA.

15Institutes of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

16Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA.

† Deceased.

Data collection took place at varying sites. Primary analysis was conducted at the University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Drs. Yogendrakumar, Smith, and Dowlatshahi were responsible for study concept, design, and statistical analysis. Drs. Yogendrakumar and Dowlatshahi were responsible for drafting the article. All authors participated in acquisition of data (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT] and Virtual International Stroke Trials Archive) and in critical revisions of the article for intellectual content.

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Dr. Demchuk’s institution received funding from Canadian Stroke Consortium and NovoNordisk Canada, and he disclosed off-label product use of recombinant factor VIIa (administered for intracerebral hemorrhage in a limited fashion within the PREDICT study). Dr. Aviv received support for article research from the Canadian Institutes of Health Research. Dr. Lyden’s institution received funding from the National Institute of Health (National Institute of Neurological Disorders and Stroke), and he received funding from expert testimony. Dr. Hill disclosed that the PREDICT study was supported by a grant from the Canadian Stroke Consortium. Dr. Dowlatshahi was funded by a uOttawa Department of Medicine Clinician-Scientist Research Chair award and a Heart & Stroke Foundation of Canada New Investigator Award. Dr. Dowlatshahi received funding from Bayer Canada, BMS/Pfizer, and Boerhinger Ingleheim. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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