Full Functional Recovery Possible in Severe Intracerebral Hemorrhage

A significant reduction in hematoma and IVH volumes was associated with long-term functional recovery among patients.

Among patients who survive severe intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) with an initial poor functional outcome, more than 40% demonstrate recovery to a good outcome by 1 year, according to study findings published in JAMA Neurology

The current post hoc analysis pooled all individual patient data from 2 clinical trials:

the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 trial (CLEAR-III; ClinicalTrials.gov Identifier: NCT00784134) and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial (MISTIE-III; ClinicalTrials.gov Identifier: NCT01827046) from multiple centers across the United States, Canada, Europe, and Asia. Patients enrolled between August 1, 2020, and September 30, 2018, with a follow-up duration of 1 year.

Researchers sought to describe the 1-year recovery trajectories among survivors of ICH and IVH who experienced initial severe disability, as well as to evaluate the relationship between hospital events and long-term recovery. Participants from
CLEAR-III were randomly assigned to intraventricular alteplase or placebo. MISTIE-III participants were randomly assigned to stereotactic thrombolysis of hematoma or standard medical care.

The primary study outcome measure was 1-year modified Rankin Scale (mRS) score. In both CLEAR-III and MISTIE-III, blinded mRS evaluations were carried out at days 30, 180, and 365. Secondary study outcomes were 1-year mortality, withdrawal of life-sustaining treatment, home discharge, and European Quality-of-Life Visual Analog Scale score, which was self-reported by survivors at days 30, 180, and 365.

Avoiding early pessimistic prognostication and delaying prognostication until after treatment may improve ability to predict future recovery.

Patients were divided into 2 groups according to 1-year mRS outcome: good (mRS score 0 to 3) or poor (mRS score 4 to 6). Among 999 patients, 115 died and 147 experienced a good outcome (mRS 0 to 3) at day 30, whereas 22 lacked any mRS data. The final pooled cohort thus comprised 715 patients with a poor outcome (mRS 4 to 5) at day 30 — 218 of whom had an mRS score of 4 and 497 of whom had an mRS sore of 5. The mean participant age was 60.3±11.7 years.

Overall, 58.3% of the participants were men, 24.3% of them were Black, 68.7% were White, and 6.9% of them were of other races.

Overall, 43% of the participants in both CLEAR-III and in MISTIE-III recovered to experience a good outcome at 1 year. Median improvement in mRS was 1 (range, 0 to 2). A 2-point improvement or more in mRS score was reported in 214 patients, and a 1-point improvement occurred in 248 participants.

In adjusted models for the combined study cohort, all of the following was associated with lack of recovery:

  • Diabetes (adjusted odds ratio [aOR], 0.50; 95% CI, 0.26-0.96)
  • National Institutes of Health Stroke Scale (aOR, 0.93; 95% CI, 0.90-0.96)
  • Severe leukoaraiosis (aOR, 0.30; 95% CI, 0.16-0.54)
  • Pineal gland shift (aOR, 0.87; 95% CI, 0.76-0.99)
  • Acute ischemic stroke (aOR, 0.44; 95% CI, 0.21-0.94)
  • Gastrostomy (aOR, 0.30; 95% CI, 0.17-0.50)
  • Persistent hydrocephalus by day 30 (aOR, 0.37; 95% CI, 0.14-0.98)

By day 30, the following were associated with recovery to good outcome:

Resolution of ICH (aOR, 1.82; 95% CI, 1.08-3.04)

IVH (aOR, 2.19; 95% CI, 1.02-4.68)

In CLEAR-III, these additional factors linked to a poor outcome:

  • Cerebral perfusion pressure of <60 mm Hg (aOR, 0.30; 95% CI, 0.13-0.71)
  • Sepsis (aOR, 0.05; 95% CI, 0.00- 0.80)
  • Prolonged mechanical ventilation (aOR, 0.96; 95% CI, 0.92-1.00 per day)

In MISTIE-III, the need for intracranial pressure monitoring (aOR, 0.35; 95% CI, 0.12-0.98) was an additional factor associated with a poor outcome.

Several limitations of the current analysis warrant mention. To begin, generalizability of the findings may be limited because of the strict inclusion criteria of the 2 clinical trials. Further, combining the CLEAR-III and MISITE-III cohorts may have some drawbacks, because of significant differences in patient characteristics and trial interventions.

The researchers concluded “Hospital events were strongly associated with long-term functional recovery and may be potential targets for intervention” They added that “Avoiding early pessimistic prognostication and delaying prognostication until after treatment may improve ability to predict future recovery.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Shah VA, Thompson RE, Yenokyan G, et al. One-year outcome trajectories and factors associated with functional recovery among survivors of intracerebral and intraventricular hemorrhage with initial severe disabilityJAMA Neurol. Published online July 25, 2022. doi:10.1001/jamaneurol.2022.1991