Leukoaraiosis is Associated with Short- and Long-term Mortality in Patients with Intracerebral Hemorrhage

doi:10.1016/j.jstrokecerebrovasdis.2013.01.017

Journal of Stroke and Cerebrovascular Diseases

Volume 22, Issue 7, October 2013, Pages 919-925

https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.01.017 Get rights and content

Background

There are few recent European studies of mortality after intracerebral hemorrhage (ICH), particularly long-term follow-up studies. No previous European studies have included information on leukoaraiosis.

Methods

We studied all consecutive patients hospitalized with a first-ever intracerebral hemorrhage between 2005 and 2009 in a well-defined area and assessed the prognostic value of various baseline clinical and radiologic factors. Leukoaraiosis was scored on the baseline computed tomographic (CT) scan as described by van Swieten et al, with an overall score from 0 to 4.

Results

One hundred thirty-four patients were followed up for a median of 4.7 years (interquartile range 2.5-6.6). Overall mortality was 23% at 2 days, 30% at 7 days, 37% at 30 days, 46% at 1 year, and 53% at 2 years. Factors independently associated with increased 30-day mortality were warfarin use, leukoaraiosis score, intraventricular hemorrhage, and Glasgow Coma Scale (GCS) score. Factors independently associated with long-term mortality in the 85 patients who survived the first 30 days were leukoaraiosis score, coronary heart disease, and initial GCS score. Recurrent ICH occurred in 4.5% and was significantly more frequent after lobar ICH than after ICH in other locations (11.1% v 0%; P = .025).

Conclusions

In unselected patients in Southern Norway with first-ever ICH, severe leukoaraiosis is independently associated with both 30-day and long-term mortality in 30-day survivors. Warfarin is independently associated with 30-day mortality and coronary heart disease with long-term mortality in 30-day survivors. Recurrent ICH is more frequent after lobar ICH than after ICH in other locations.

Section snippets

Patients

The study includes all consecutive patients hospitalized with a first-ever ICH between 2005 and 2009 at Sørlandet Hospital Kristiansand in Kristiansand, Norway. The hospital serves a well-defined catchment area with 152,000 inhabitants. There is a low-threshold policy of admitting all patients with suspected stroke to the neurologic department regardless of age and stroke severity. There is no neurosurgical department. All patients with suspected stroke are examined in the emergency room by the

Results

In total, 134 patients with a first-ever ICH were followed up for a median of 4.7 years (interquartile range 2.5-6.6 years), for a total of 630 patient-years. No patients were lost to follow-up. Baseline characteristics are shown in total and for each sex in Table 1. There were some sex differences in baseline characteristics. Men were significantly younger, were more often smokers, and had somewhat larger hematomas than women. White patients accounted for 131 of 134 (97.8%) cases. Five

Discussion

This study shows that leukoaraiosis is associated with both 30-day and long-term mortality in patients with first-ever ICH. It also shows that CHD is associated with increased long-term mortality.

The overall mortality at standardized time points is in general agreement with previous reports.5, 8, 13, 27, 28, 29 With volumes exceeding 30 mL, all hematoma locations other than lobar carried a high 30-day mortality rate (Table 2). Smaller cerebellar hematomas had the lowest mortality rates. This is

Acknowledgment

We thank Siv Pettersen and Karen Johanne Olsen for their assistance with data collection and statistician Hugo Pripp, PhD, for assistance with statistical analysis.

References (47)

C.J. van Asch et al.
Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis
Lancet Neurol
(2010)
B.F. Gage et al.
Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall
Am J Med
(2005)
A.G. Thrift et al.
Epidemiology of intracerebral hemorrhage
Epidemiol Rev
(1995)
L. Mathew et al.
The epidemiology of intracerebral hemorrhage
J.C. Hemphill et al.
The ICH score: A simple, reliable grading scale for intracerebral hemorrhage
Stroke
(2001)
M.L. Flaherty et al.
Long-term mortality after intracerebral hemorrhage
Neurology
(2006)
S. Sacco et al.
Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry
Stroke
(2009)
O.G. Nilsson et al.
Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden
J Neurol Neurosurg Psychiatry
(2000)
E. Zia et al.
Three-year survival and stroke recurrence rates in patients with primary intracerebral hemorrhage
Stroke
(2009)
T. Inagawa et al.
Primary intracerebral hemorrhage in Izumo City, Japan: Incidence rates and outcome in relation to the site of hemorrhage
Neurosurgery
(2003)

N. Hosomi et al.

Predictors of intracerebral hemorrhage severity and its outcome in Japanese stroke patients

Cerebrovasc Dis

(2009)

J.P. Broderick et al.

Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality

Stroke

(1993)

R. Fogelholm et al.

Long term survival after primary intracerebral haemorrhage: A retrospective population based study

J Neurol Neurosurg Psychiatry

(2005)

O.G. Nilsson et al.

Prediction of death in patients with primary intracerebral hemorrhage: A prospective study of a defined population

J Neurosurg

(2002)

M.L. Flaherty et al.

The increasing incidence of anticoagulant-associated intracerebral hemorrhage

Neurology

(2007)

J. Huhtakangas et al.

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: A longitudinal population-based study

Stroke

(2011)

A. Tveiten et al.

Intracerebral hemorrhage in Southern Norway—A hospital-based incidence study

Eur Neurol

(2012)

E.E. Smith

Leukoaraiosis and stroke

Stroke

(2010)

E.M. Arsava et al.

Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke

Neurology

(2009)

N.K. Oksala et al.

Age related white matter changes predict stroke death in long term follow-up

J Neurol Neurosurg Psychiatry

(2009)

Y.S. Won et al.

Leukoaraiosis predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage

Eur Neurol

(2010)

S.H. Lee et al.

White matter lesions and poor outcome after intracerebral hemorrhage: A nationwide cohort study

Neurology

(2010)

R.D. Bailey et al.

Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage

Neurology

(2001)

Cited by (31)

Impact of white matter hypodensities on outcome after intracerebral hemorrhage
2023, Journal of Stroke and Cerebrovascular Diseases
White matter hypodensities (WMH), a surrogate of small vessel disease, associate with cognitive decline and stroke risk. The impact of WMH on functional outcome after intracerebral hemorrhage (ICH) has differed between studies. We aimed to examine factors associated with the severity of WMH in ICH, and whether there is an independent association between the extent of WMH and outcome.
This was a prospective study of consented patients with non-traumatic primary ICH, admitted to the Helsinki University Hospital between May 2014 and December 2018. To evaluate the extent of the WMH, modified van Swieten score of the side contralateral to the ICH was obtained. Patients were grouped into 3 categories of the scores. We performed univariate and multivariable analyses to find out factors associated with the severity of WMH, and whether WMH associate with functional outcome and mortality up to 12 months, adjusted for the known major outcome predictors.
In our cohort of 417 ICH patients, WMH severity associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT. We found an independent association between WMH severity and poor functional outcome at 3 months (OR 1.72, 95% CI 1.27-2.33), and 1 year (OR 2.16, 95% CI 1.57-2.95), and mortality at 1 year (OR 1.91, 95% CI 1.29-2.85).
In our ICH patients, vascular comorbidities and older age associated with the presence of WMH, which, in turn, strongly associated with poor functional outcome.
Total small vessel disease score and functional outcomes following acute intracerebral hemorrhage: Total SVD score and outcomes after ICH
2020, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
Recent studies have suggested that the total small vessel disease (SVD) score, which integrates all individual SVD markers, may better represent the total brain burden than a single marker.1 In patients after intracerebral hemorrhage (ICH), each SVD marker is an independent predictor for poor prognosis2–4; however, few studies have examined the association between functional disabilities and the global SVD burden.4 We hypothesized that the likelihood of worse functional outcomes following ICH might vary with the underlying SVD burden.
Individual cerebral small vessel disease (SVD) markers are independent predictors for poor prognosis following intracerebral hemorrhage (ICH), however, the impact of the cumulative SVD burden on outcomes remains unclear. We aimed to investigate the association between the global SVD burden and functional outcomes following ICH.
We retrospectively evaluated a consecutive cohort of patients with ICH who underwent brain magnetic resonance imaging and magnetic resonance angiography, from a prospective registry. We identified the presence and severity of the SVD markers (cerebral microbleeds, lacunar infarctions, periventricular hyperintensities, and deep white matter hyperintensities) and summed them to obtain the modified total SVD score (0-4). Poor functional outcomes were defined as a modified Rankin Scale score at discharge ≥ 3. A multivariate logistic regression model was used to assess the association between patient outcomes and the SVD score.
A total of 144 patients were included (65.0 ± 12.2 years, 67.4% male). The modified total SVD score was potentially associated with poor functional outcomes (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.97-3.03) after adjustment for age, sex, history of stroke, chronic kidney disease, prior use of antithrombotic agents, the National Institutes of Health Stroke Scale score on admission, the non-lobar location of ICH, and hematoma volume on admission. Moreover, among older patients (≥ 65 years), the SVD score was associated with poor outcomes (OR 3.11, 95% CI 1.01-9.55). Among those with supratentorial ICH, the score remained significant (OR 2.06, 95% CI 1.11-3.83).
The modified total SVD score may have predictive value for poor functional outcomes following ICH.
Progression of White Matter Injury After Intracerebral Hemorrhage: A Magnetic Resonance Imaging Study
2019, World Neurosurgery
Citation Excerpt :
Several studies have previously examined the association between the extent of WMI and outcomes for patients with ICH.4-6 They found that the severity of WMI on the baseline scan was associated with worse functional outcomes or mortality after spontaneous ICH.4-6 We found no difference in the baseline severity of WMI between patients with versus without WMIP, and the severity of WMI on the baseline MRI scan was not associated with unfavorable 90-day outcomes in our study.
White matter injury (WMI) has been observed after experimental intracerebral hemorrhage (ICH). The supporting clinical data have been sparse. We assessed the presence, extent, and progression of WMI in patients with ICH.
We performed a retrospective review of data from 65 consecutive patients with spontaneous supratentorial ICH who had undergone baseline brain magnetic resonance imaging (MRI) within 7 days of ICH onset and repeat MRI afterward. We used the Fazekas scale (FZKS) to grade the severity of WMI. The clinical and imaging characteristics of the patients with and without WMI progression (WMIP) were compared using uni- and multivariate logistic regression analyses.
We observed WMIP in 23 patients (35.4%). WMIP was noted in both hemispheres but more commonly ipsilateral to the ICH (33% vs. 21%). The mean total FZKS score had increased from 3 (interquartile range [IQR], 1–4) at baseline to 4 (IQR, 2–5) on repeat MRI (P < 0.0001). Patients with lobar ICH had a greater median FZKS score than those with deep ICH (median, 3; IQR, 2–4; vs. 1.5, IQR, 1–3.25; P = 0.027). The baseline parenchymal ICH volume (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.018–1.119; P = 0.007) and ventricular volume on baseline MRI (OR, 1.073; 95% CI, 1.019–1.130; P = 0.007) were predictors of WMIP after adjustment. Multivariate analyses showed an independent association between WMIP and unfavorable 3-month outcomes (OR, 5.196; 95% CI, 1.059–25.483; P = 0.042).
WMI will progress over time in patients with ICH, and WMIP has been associated with worse outcomes. This novel finding could represent a potential therapeutic target. Future prospective larger studies are needed to confirm our findings.
Prognostic significance of leukoaraiosis in intracerebral hemorrhage: A meta-analysis
2019, Journal of the Neurological Sciences
Patients with intracerebral hemorrhage (ICH) have high disability and mortality. Leukoaraiosis refers to the diffuse abnormalities of white matter on neuroimaging, which has been suggested to be with poor outcome in patients with ICH. This meta-analysis was performed to summarize the current evidence on the prognostic significance of leukoaraiosis in ICH patients.
Databases were searched for published studies about leukoaraiosis and prognosis in patients with ICH. Data from eligible studies were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) from each study were combined with DerSimonian–Laird method and random effect model for quantitative analysis. Begg's funnel plot was adopted to assess the publication bias.
A total of nine studies with 4948 patients were finally included in this meta-analysis. Six studies reported functional outcome, two studies reported mortality, and another study reported both functional outcome and mortality. The meta-analysis showed that leukoaraiosis was significantly associated with worse functional outcome in patients with ICH (OR = 1.40, 95%CI 1.17–1.68, P < .001). In addition, leukoaraiosis was also significantly associated with higher mortality in patients with ICH (OR = 1.59, 95%CI 1.21–2.08, P = .001).
Leukoaraiosis is significantly associated with both worse functional outcome and higher mortality in patients with ICH. Leukoaraiosis can be a useful imaging marker for predicting outcome in patients with ICH.
Predictors of long-term survival after spontaneous intracerebral hemorrhage in southern Portugal: A retrospective study of a community representative population
2018, Journal of the Neurological Sciences
Citation Excerpt :
Nevertheless, increasing age is consistently shown to aggravate SICH long-term prognosis [2,3], possibly due to the cumulative burden of coexistent comorbidities or underlying chronic generalized vascular disease [3,23]. The main causes of long-term death after SICH vary between studies, but infections with pneumonia ahead, recurrent stroke and cardiovascular complications are commonly reported [15,22]. Better adherence to preventive strategies, control of blood pressure, mobilization, healthy life style are among the interventions that may reduce these complications.
Response to Commentary on “Short-Term Outcome of Spontaneous Intracerebral Hemorrhage in Algarve, Portugal: Retrospective Hospital-Based Study”
2018, Journal of Stroke and Cerebrovascular Diseases

View all citing articles on Scopus

: Dr. Tveiten is supported by the Norwegian Health Association.

View full text

Review ArticleLeukoaraiosis is Associated with Short- and Long-term Mortality in Patients with Intracerebral Hemorrhage

Background

Methods

Results

Conclusions

Section snippets

Patients

Results

Discussion

Acknowledgment

Lancet Neurol

Am J Med

Epidemiology of intracerebral hemorrhage

Epidemiol Rev

The epidemiology of intracerebral hemorrhage

The ICH score: A simple, reliable grading scale for intracerebral hemorrhage

Stroke

Long-term mortality after intracerebral hemorrhage

Neurology

Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry

Stroke

Incidence of intracerebral and subarachnoid haemorrhage in southern Sweden

J Neurol Neurosurg Psychiatry

Three-year survival and stroke recurrence rates in patients with primary intracerebral hemorrhage

Stroke

Primary intracerebral hemorrhage in Izumo City, Japan: Incidence rates and outcome in relation to the site of hemorrhage

Neurosurgery

Predictors of intracerebral hemorrhage severity and its outcome in Japanese stroke patients

Cerebrovasc Dis

Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality

Stroke

Long term survival after primary intracerebral haemorrhage: A retrospective population based study

J Neurol Neurosurg Psychiatry

Prediction of death in patients with primary intracerebral hemorrhage: A prospective study of a defined population

J Neurosurg

The increasing incidence of anticoagulant-associated intracerebral hemorrhage

Neurology

Effect of increased warfarin use on warfarin-related cerebral hemorrhage: A longitudinal population-based study

Stroke

Intracerebral hemorrhage in Southern Norway—A hospital-based incidence study

Eur Neurol

Leukoaraiosis and stroke

Stroke

Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke

Neurology

Age related white matter changes predict stroke death in long term follow-up

J Neurol Neurosurg Psychiatry

Leukoaraiosis predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage

Eur Neurol

White matter lesions and poor outcome after intracerebral hemorrhage: A nationwide cohort study

Neurology

Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage

Neurology

Review Article
Leukoaraiosis is Associated with Short- and Long-term Mortality in Patients with Intracerebral Hemorrhage