Mixed ICH Patients at Higher Risk of Disability

Damian McNamara

June 04, 2019

MILAN — Patients presenting with mixed intracranial hemorrhage (ICH) features on MRI — that is, ICH or microbleeds in both lobar and deep areas of the brain — are at higher risk for worse outcomes vs those with strictly lobar or deep ICH presentations, a new study suggests.

A diagnosis of mixed ICH was associated with a 30% higher risk for disability or dependence at 90 days, for example, compared with the other subtypes.

"Mixed ICH is associated with unfavorable clinical outcomes," Marco Pasi, a PhD candidate and Stroke Clinical Fellow at Massachusetts General Hospital in Boston, said here at the 5th European Stroke Organisation Conference (ESOC) 2019.

"It is now widely known that patients with lobar ICH predominantly show cerebral amyloid angiopathy," he said. On the other hand, experts attribute deep ICH primarily to arteriosclerosis.

"However, the differences are never so clear-cut, and in clinical practice, we can see patients with lobar ICH and deep microbleeds," Pasi said.

The current findings build on a 2018 study by Pasi and colleagues that evaluated underlying microangiopathy and recurrence risk for 391 consecutive patients with ICH, including 19% with a mixed ICH presentation.

Risk Factors Explored

Certain demographic and clinical risk factors were associated with a higher likelihood for developing mixed ICH in the study as well.

"We wanted to expand our knowledge on mixed ICH," Pasi said, including any influence of race or ethnicity, vascular risk factors or APOE haplotypes on overall risk. For this analysis, investigators compared 403 people with a deep ICH MRI phenotype, 264 with lobar ICH and 267 others with mixed ICH on MRI.

The study population comes from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort. ERICH is a large, case-control study that aims to identify genetic and epidemiologic risk factors for ICH, as well as outcomes for those who develop the condition, with a special focus on minority populations.

Compared with the other cohorts, those with mixed ICH were slightly younger, more likely to be male, more likely black, and less likely to have a positive APOE status.

Mixed ICH predicted a significantly worse functional outcome (adjusted odds ratio, 1.3; 95% confidence interval, 1.1 - 1.5; P = .03), which was not the case for lobar or deep ICH.

The researchers reported dependency at 3 months for 45% of those with deep ICH, 43% with lobar ICH, and 54% of people with mixed ICH.

Table. Risk Factors Associated with Mixed ICH


Odds Ratio vs Lobar ICH

95% Confidence Interval

Odds Ratio vs Deep ICH

95% Confidence Interval

Black Race


1.1 - 2.2


1.01 - 1.7



1.2 - 2.1


1.04 - 1.6

Renal Impairment


1.4 - 2.4


1.1 - 1.6


The mixed ICH group also had a lower prevalence of APOE ε2 positivity. In a univariable analysis, 12% of the mixed ICH group were positive for APOE ε2, for example, compared to 22% of the lobar ICH cohort and 14% of the deep ICH group.

"An Interesting Study"

"ICH is probably not just one disease. It is very likely there are different subgroups with different characteristics and different risks," session co-chair, Karin Klijn, MD, PhD, professor of neurology at Radboud University in Nijmegen, the Netherlands, told Medscape Medical News when asked to comment.

"We have a clear distinction between those who have hypertension as a clear contributor and those with an amyloid pathology," she said. "Then we have patients we cannot classify as either…and those we call mixed ICH."

"At this moment it does not have clinical implications, but it is definitely an interesting study," Klijn added.

"We heard this morning that there is no difference between lobar and deep [ICH] when it comes to restarting antiplatelets or anticoagulants, so is it probably safe to restart antiplatelets," in mixed ICH as well, she added.

The University of Cincinnati sponsored the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) studyPasi and Klijn have disclosed no relevant financial relationships.

5th European Stroke Organisation Conference (ESOC) 2019. Presented May 22, 2019.

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