New Risk Factors for Poor Outcomes in ICH Identified

Megan Brooks

March 18, 2022

A new study validates two commonly used prognostic scores for neurologic disability or death after intracerebral hemorrhage (ICH) and identifies several additional factors associated with poor outcomes.

"Strikingly, the development of any infection [such as urinary tract infection or pneumonia] had a similar association with outcomes as hematoma expansion or requiring treatment for increased intracranial pressure," write the investigators, led by Daniel Woo, MD, University of Cincinnati College of Medicine, Ohio.

The findings were published online March 15 in JAMA Network Open.

Beyond Traditional Scores

The ICH prognostic score includes the following factors associated with mortality at 30 days after ICH: age older than 80 years, lower admission Glasgow Coma Scale (GCS) score, ICH volume greater than 30 cm3, intraventricular hemorrhage, and infratentorial ICH.

The FUNC score identifies age, GCS score, ICH location, ICH volume, and pre-ICH cognitive impairment as factors associated with disability at 90 days after ICH.

The current investigators wanted to go beyond the ICH and FUNC scores and identify additional factors associated with outcomes after ICH.

They used data from 2568 White, Black, and Hispanic patients with spontaneous ICH from the ERICH study cohort.

At 90 days, 115 patients (4.5%) had no symptoms, as defined as a modified Rankin Scale (mRS) score of zero; 401 patients (15.6%) had no significant disability (mRS, 1); 414 patients (16.1%) had slight disability (mRS, 2); 383 (14.9%) had moderate disability (mRS, 3); 480 (18.7%) had moderately severe disability (mRS, 4); 210 (8.2%) had severe disability (mRS, 5); and 565 patients (22%) had died.

The researchers screened individual characteristics for their association with 90-day outcome of neurologic disability or mortality, as determined by mRS score of 4 or greater vs 3 or less under a logistic regression model.

All of the individual variables that make up the ICH and FUNC scores were associated with poor outcome, corroborating their individual contributions to risk, the investigators note.

Clinically Useful?

The final multiple logistic regression model had a significantly higher area under the receiver operating characteristics curve (C = .88) compared with either the ICH score alone (C = .76) or the FUNC score alone (C = .76).

Of note, the presence of infection independently predicted a 90-day mRS score of 3 or less (odds ratio [OR], 1.85; 95% CI, 1.42 - 2.41; P < .001).

Other factors associated with poor outcome were larger ICH volume (OR, 2.74; 95% CI, 2.36 - 3.19; P < .001), lobar location (OR, 0.22; 95% CI, 0.16 - 0.30; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02 - 1.05; P < .001) and pre-ICH mRS score (OR, 1.62; 95% CI, 1.41 - 1.87; P < .001).

In addition, several simple measures on the initial CT, including white matter lesion burden, Graeb score, and atrophy, were associated with disability at 90 days.

"Further evaluation is needed to determine which levels of each may contribute to redefining a future score," the researchers write.

"A notable absence" as a risk factor for poor outcomes was anticoagulant use at time of admission or international normalized ratio.

Once controlling for the larger hemorrhage volume and higher rates of hematoma expansion, prior use of anticoagulants dropped out of the final model, the investigators report. 

Race and ethnicity were not independently associated with outcomes.

The additional risk factors identified in this analysis "may be clinically useful to treating physicians to improve on estimation of outcomes beyond the traditional scores," the researchers write.

Like Forecasting the Weather

In an invited commentary on the study, J. Claude Hemphill III, MD, MAS, University of California, San Francisco, and Wendy Ziai, MD, MPH, Johns Hopkins University, Baltimore, Maryland, note there have been at least 60 different published prognostic tools for post-ICH outcomes over the past two decades.

"We probably do not need more prognostic models that use the same standard parameters but just with slightly different cutoff points or organization," they write.

They add that clinicians should also "resist the urge to provide precise outcome prognosis at onset, or probably even early after" an ICH has occurred.

"We need to hold ICH prognostication to the same standards that we do for our weather forecast or travel times on navigation apps: uncertainty is inherent, but a framework for possible outcomes is still useful," Hemphill and Ziai write.

In addition, post-acute rehabilitation care, advanced assessment of cerebral functional integrity, and capacity for recovery should be among included factors in future outcome prognostic models, they note.

"The purpose of providing a prognosis for ICH outcomes should be the same as the purpose of a clinical trial: trying to identify treatments that can help patients. We believe that we are just getting started," the editorialists conclude.

The study was funded by the National Institute of Neurological Diseases and Stroke. Woo and Hemphill have disclosed no relevant financial relationships. Ziai has received personal fees from C. R. Bard.

JAMA Netw Open. Published online March 15, 2022. Full text, Editorial

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