Share

March 20, 2018; 90 (12) Article

Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage

Bastian Volbers, Antje Giede-Jeppe, Stefan T. Gerner, Jochen A. Sembill, Joji B. Kuramatsu, Stefan Lang, Hannes Lücking, Dimitre Staykov, Hagen B. Huttner
First published February 16, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005167
Full PDF
Citation
Permissions

Make Comment

See Comments

Downloads
307

Share

Abstract

Objective To evaluate the association of perihemorrhagic edema (PHE) evolution and peak edema extent with day 90 functional outcome in patients with intracerebral hemorrhage (ICH) and identify pathophysiologic factors influencing edema evolution.

Methods This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE volumes were studied using a validated semiautomatic volumetric algorithm. Multivariable logistic regression and propensity score matching (PSM) accounting for age, ICH volume, and location were used for assessing measures associated with functional outcome and PHE evolution. Clinical outcome on day 90 was assessed using the modified Rankin Scale (0–3 = favorable, 4–6 = poor).

Results A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2). Besides established factors for functional outcome, i.e., ICH volume and location, age, intraventricular hemorrhage, and NIH Stroke Scale score on admission, multivariable logistic regression revealed peak PHE volume (odds ratio [OR] 0.984 [95% confidence interval (CI) 0.973–0.994]) as an independent predictor of day 90 outcome. Peak PHE volume was independently associated with initial PHE increase up to day 3 (OR 1.060 [95% CI 1.018–1.103]) and neutrophil to lymphocyte ratio on day 6 (OR 1.236 [95% CI 1.034–1.477; PSM cohort, n = 124]). Initial PHE increase (PSM cohort, n = 224) was independently related to hematoma expansion (OR 3.647 [95% CI 1.533–8.679]) and fever burden on days 2–3 (OR 1.456 [95% CI 1.103–1.920]).

Conclusion Our findings suggest that peak PHE volume represents an independent predictor of functional outcome after ICH. Inflammatory processes and hematoma expansion seem to be involved in PHE evolution and may represent important treatment targets.

Glossary

CI=
confidence interval;
ICH=
intracerebral hemorrhage;
ICP=
intracranial pressure;
IQR=
interquartile range;
IVH=
intraventricular hemorrhage;
mRS=
modified Rankin Scale;
NIHSS=
NIH Stroke Scale;
NLR=
neutrophil to lymphocyte ratio;
PHE=
perihemorrhagic edema;
PSM=
propensity score–matched;
OR=
odds ratio;
ROC=
receiver operating characteristic

In intracerebral hemorrhage (ICH), there are many detrimental processes and secondary damage cascades, including inflammation and degradation of heme products, initiated immediately after ICH onset. They are hypothesized to contribute to the development of perihemorrhagic edema (PHE), which is suggested to serve as a radiologic marker for secondary injury following ICH.1,–,4 PHE volume may evolve within a period of 8–12 days after ictus and may exceed the initial lesion volume by more than 150%,3 possibly causing clinical deterioration or even herniation.5 Thus, PHE evolution and notably peak PHE volume may represent important outcome measures and treatment targets not only in the (hyper-)acute phase of ICH while established prognostic outcome measures (e.g., initial hematoma volume or age1) are rather inaccessible to a treatment or show limited treatment options.1,6,–,8 Specifically, several research groups reported on an association of early PHE evolution up to 24–72 hours after ICH onset with functional outcome.9,–,12 However, as PHE volume may peak 8–12 days after onset, analyzing PHE evolution merely up to 72 hours after onset may yield limited results. In the present study, we correlated peak PHE volume with long-term outcome in ICH patients. Furthermore, we assessed factors associated with increased PHE evolution.

Methods

Patients

Our study retrospectively included patients with spontaneous supratentorial ICH who were admitted between January 2006 and January 2014 from our prospectively organized institutional database. We defined ICH as spontaneous if exclusively related to hypertension or amyloid angiopathy. Patients with secondary ICH were excluded. Inclusion criteria were at least 2 consecutive CT scans over a period of at least 72 hours, no withdrawal of care within 24 hours after admission, an available modified Rankin Scale score (mRS) on day 90, and a baseline mRS of <4. Furthermore, we excluded patients with surgical hematoma evacuation.

Standard protocol approvals, registrations, and patient consents

The study was approved by our institutional ethics committee.

Clinical data

We obtained age,1 mRS before symptom onset, NIH Stroke Scale score (NIHSS) on admission,1 and other outcome predicting measures in ICH such as fever burden (defined as number of days with peak temperature ≥38°C) up to day 1213 and serum inflammatory measures14 including lymphocytes, neutrophils, and neutrophil to lymphocyte ratio (NLR; neutrophil count divided by lymphocyte count) on admission and days 4 and 6 as a marker for systemic inflammation also relevant for cardiovascular outcomes15 and elevated intracranial pressure (ICP) burden (number of episodes with ICP >20 mm Hg lasting more than 5 minutes or with patients presenting with symptoms related to elevated ICP [deterioration of consciousness, anisocoria]) up to day 12 from medical records. We used standardized mailed questionnaires for the assessment of functional status before symptom onset and comorbidities if those data were not obtained during hospital stay. Time between symptom onset and admission was assessed as an important predictor of hematoma expansion.16 The day of admission was defined as day 1.

Neuroimaging and volumetric assessment of PHE and ICH

A fourth-generation CT scanner (Somatom 64 or Somatom AS+, Siemens Healthcare, Erlangen) was used for CT scans. Each scan consisted of either a multislice spiral CT dataset, 10–12 slices of 4.8 mm thickness for the skull base and 10–12 slices of 7.2 mm thickness for the cerebrum (Somatom 64), or 22–25 slices of 4.8 mm thickness for the entire brain (Somatom AS+) using the orbitomeatal plane. We used a validated semiautomatic volumetric algorithm as previously described17 for assessment of ICH and PHE volume. For better comparison, we merged different time points of CT scans to time clusters (days 1, 2–3, 4–6, 7–9, 10–12). Initial PHE growth from baseline to 72 hours9,–,12,18 (defined as absolute difference between PHE volume [mL] on day 2–3 and admission), intraventricular hemorrhage (IVH), and hematoma volume on admission19 as well as peak PHE volume and secondary hematoma enlargement (hematoma expansion) volume were recorded. Peak PHE volume was defined as the maximum volume measured in any of the available CT scans. In the context of accuracy of measurements,20,21 a hematoma volume increase ≥ 5 mL between 2 CT scans was defined as hematoma expansion.7

Outcome

We assessed functional outcome on day 90 using the mRS either by mailed standardized questionnaires or phone interviews (performed by trained and certified physicians) with patients or their next of kin if the questionnaire was not returned within 4 weeks.22 In cases of insufficient data retrieval, we contacted primary care physicians. As primary outcome variable, mRS was dichotomized as favorable outcome (mRS 0–3) or poor outcome (mRS 4–6). As secondary outcome measures, we analyzed the correlation of clinical characteristics and inflammatory measures with peak PHE volume and early PHE growth from baseline up to day 3 (72 hours). Patients were dichotomized according to median peak PHE volumes and median early PHE increase volumes.

Statistics

We performed statistical analyses using the IBM SPSS Statistics 21 software package (IBM Corporation, Armonk, NY) and R 2.12.0 (r-project.org). The significance level was set at α = 0.05 and statistical tests were 2-sided. Missing data regarding basic characteristics, neuroimaging, or outcome led to exclusion of patients. We used the Kolmogorov-Smirnov test to evaluate the distribution of data. Data were presented as mean ± SD (statistical test: Student t test), or as median and interquartile range (IQR, statistical test: Mann-Whitney U test), as appropriate. We used Pearson χ2 or Fisher exact test to compare frequency distributions of categorized variables between dichotomized patient groups: (1) mRS 0–3 and 4–6, (2) patients with peak PHE volume smaller and larger than the median peak PHE volume, and (3) patients with an early PHE increase smaller and larger than the median increase of the included cohort (median split). For both groups 2 and 3, we performed a separate additional propensity score matching using the entire cohort (n = 292) based on logistic regression as estimation algorithm (nearest neighbor matching, ratio 1:1, caliper = 0.1) accounting for age, hematoma volume, and hematoma location (basal ganglia vs lobar) and calculated abovementioned univariate testing as well as additional logistic regression. To identify measures independently associated with outcome and peak PHE volume, we calculated stepwise backward inclusion multivariate logistic regression models including clinically meaningful measures showing a statistical trend (p < 0.1) in univariate testing of the entire cohort. As hematoma location (lobar vs basal ganglia) was demonstrated previously to represent an important outcome associated factor23 with a suggested interaction with hematoma volume,24 we also included the interaction term of both factors in our multivariate logistic regression model. Because not all patients had regular CT scans up to day 10–12 based on inclusion criteria, we performed an additional sensitivity analysis including only patients with at least 4 CT scans up to day 9. To explore associations of PHE evolution with outcome, we additionally performed receiver operating characteristic (ROC) curve analyses.

Results

Cohort

A total of 875 patients were screened. We excluded 154 patients who received early withdrawal of care, 53 patients because of surgery (hematoma evacuation) prior to control scan, and 140 patients who had only 1 CT scan. A further 38 patients were excluded due to insufficient datasets, 143 due to infratentorial hemorrhage, and 55 due to a mRS prior to the current ICH of >3. This led to 292 patients (161 male [55%]) who met inclusion criteria. A total of 121 (41%) patients presented with lobar hemorrhage and 171 (59%) with basal ganglia hemorrhage. A total of 159 patients (54%) showed an additional IVH. Median age was 70 years (IQR 62–78), median ICH volume on admission 17.7 mL (IQR 7.9–40.2), and median peak ICH volume 22.5 mL (IQR 8.9–46.4). Median PHE volume on admission was 16.3 mL (IQR 9.1–29.2) and increased to a median peak PHE volume of 37.5 mL (IQR 19.0–60.6) over a median period of 7 days (IQR 3–12). Median NIHSS on admission was 13 (IQR 6–21), median mRS on day 90 was 4 (IQR 3 to 5). Time between symptom onset and admission did not differ between patients with and without hematoma expansion up to day 3 (4.2 hours [IQR 2.1–9.0] and 5.0 hours [IQR 2.5–11.9], respectively, p = 0.234).

Factors influencing outcome in ICH patients

A total of 107 patients (37%) had a favorable outcome on day 90. Detailed characteristics of both outcome groups are shown in table 1 and table e-1 (links.lww.com/WNL/A259). Besides established prognostic factors such as ICH volume, location, age, and IVH, frequency of elevated ICP, fever burden, neutrophil to lymphocytes count on day 6, and peak PHE extent differed between both outcome groups in univariate analysis. Lymphocytes, neutrophils, and NLR on admission and day 4 did not differ between the outcome groups (data not shown). Multivariable logistic regression (table 2) revealed only peak PHE (odds ratio[OR]/Exp[B] 0.984 for each mL of PHE) as independent prognostic factor in ICH patients besides the abovementioned and established measures.25 Peak PHE volume also remained the only independent outcome predictor in our sensitivity analysis including only patients with at least 4 CT scans up to day 9 (n = 218) with a comparable OR (OR 0.985 [95% confidence interval (CI) 0.973–0.997], p = 0.012) besides and adjusted for the abovementioned factors.

View this table:
Table 1

Clinical characteristics in favorable and poor outcome groups

View this table:
Table 2

Multivariable logistic regression model modeling the prediction of favorable outcome (modified Rankin Scale 0–3) in the intracerebral hemorrhage cohort (n = 292)

Figure 1 illustrates PHE evolution in patients with favorable and poor outcome: patients with poor outcome showed an immense PHE increase during the first 72 hours after ICH onset compared to patients with a favorable outcome, and PHE increase continued to be less pronounced up to day 10–12.

Figure 1
Figure 1 Evolution of absolute hematoma and perihemorrhagic edema (PHE) volume up to day 10–12 in patients with favorable and poor outcome

Only patients with ≥5 CT scans up to day 10–12 (n = 170) were included. Blue lines represent favorable outcomes, red lines poor outcomes, dotted lines hematoma volumes, and continuous lines perihemorrhagic edema (PHE) volumes. Patients with poor outcome showed not only a higher PHE volume increase during the first 72 hours after onset compared to patients with favorable outcome, but also to a lesser extent up to day 10–12.

Receiver operating characteristic analysis

ROC analysis (figure e-1, links.lww.com/WNL/A258) confirmed a good predictive value of peak PHE regarding favorable outcome, especially compared to the predictive value of initial ICH volume and the well-established ICH score.25 A cutoff value of 26.8 mL peak PHE volume was identified with a sensitivity of 0.54 and a specificity of 0.78 (Youden Index 0.326) to distinguish best between patients with a favorable and a poor outcome.

Measures influencing peak PHE volume

Given that peak PHE extent was identified as an independent predictor of long-term outcome, we studied factors influencing peak PHE volume. As demonstrated in table 3, in univariate analyses various measures including younger age, location of hematoma, IVH, hematoma volume, initial PHE increase up to day 3, fever burden, and reduced lymphocyte count on day 4–6 as well as increased NLR on day 6 were associated with an increased peak PHE volume >37.495 mL (median of the entire cohort). In multivariable testing, initial PHE increase up to day 3 and reduced lymphocytes on day 4 remained independent predictors of an increased peak PHE besides a younger age and a higher ICH volume (table 4).

View this table:
Table 3

Characteristics of patients with larger and smaller peak perihemorrhagic edema (PHE) volume dichotomized according to median peak PHE volume of the entire cohort (37.495 mL)

View this table:
Table 4

Multivariable logistic regression model modeling the prediction of a perihemorrhagic edema (PHE) volume >37.495 mL (median PHE volume of the entire intracerebral hemorrhage cohort [n = 292])

In a propensity score–matched (PSM) subgroup analysis (n = 124) accounting for ICH volume, age, and hematoma location, early PHE increase up to day 3 (OR 1.060 [95% CI 1.018–1.103]) and increased NLR on day 6 (OR 1.236 [95% CI 1.034–1.477]) were associated with an increased peak PHE (see also table e-2, links.lww.com/WNL/A259).

Measures associated with early PHE increase up to day 3

A higher early PHE increase (PSM cohort, n = 224) was significantly associated with a higher fever burden up to day 3 (OR 1.456 [95% CI 1.103–1.920]) and a hematoma expansion >5 mL up to day 3 (OR 3.647 [95% CI 1.533–8.679]) while there was no association with age, hematoma volume on admission, or hematoma location, indicating a well-matched cohort. For more detailed information, see table e-3 (links.lww.com/WNL/A259) (only PSM data shown).

Discussion

This study suggests that peak PHE volume is an independent predictor of day 90 outcome in ICH patients and is associated with age, hematoma volume, initial PHE increase up to day 3, and inflammatory measures. Each milliliter of additional peak PHE volume increased the absolute risk for a poor outcome by 1.5%. In turn, initial PHE increase was related to hematoma expansion and fever burden. These results may help to direct further research in order to shed light into the pathophysiologic mechanisms that act beyond perihemorrhagic edema evolution and to open up avenues for potential treatment targets in patients with ICH.

After ICH ictus, many inflammatory processes are initiated.1,2 Animal studies have revealed a rise of proinflammatory mediators within hours after cerebral injury suggesting a hyperinflammatory state in the initial stages of acute brain injury26 associated with the development of brain edema.27 Rare human data also suggested an association of edema evolution with inflammatory measures (e.g., NLR,28 certain interleukins,29 or matrix metalloproteinase-9 concentrations30). Furthermore, the influence of immunomodulating therapies on PHE evolution also supports this association.31,32 Those inflammatory processes start within hours after ICH onset and continue up to several days.1 This underlines their importance regarding PHE evolution both in the acute phase and in the postacute period when PHE volume continues to increase.3 This link between PHE evolution and inflammatory measures as well as the role of PHE as an imaging marker of inflammatory processes in ICH patients is further strengthened and confirmed in light of the findings of our study. It also supports an independent prognostic effect of peak PHE volume on outcome.

Previous reports found a strong correlation between PHE volume and outcome in ICH patients when analyzing PHE evolution up to 72 hours after onset. Wu and colleagues12 reported that the early edema extension distance increase up to 72 hours after onset independently influenced mortality after ICH. An analysis by Venkatasubramanian and colleagues33 including 27 patients found a correlation of PHE volume growth up to 48 hours with clinical status at 48 hours while there was no association of total PHE volume growth with 3-month functional outcome. A pooled analysis of the INTERACT data showed that early PHE increase up to 24 hours after onset is an independent predictor of death and dependency on day 90 after ICH.9 Similar results could also be shown by Urday et al.11 and Murthy et al.,34 leading to consistent results observed in about 3,000 patients. Our data revealed an unadjusted association of early PHE increase with outcome. Furthermore, as we included PHE data of a wide temporal range, our data suggest that it is primarily the peak PHE volume that matters regarding outcome measures. On the other hand, our analysis also demonstrated an independent correlation of early PHE increase with peak PHE volume. Thus, early PHE increase may serve as a predictor of peak PHE volume. The latter was independently associated with poor outcome in our cohort.

Several therapeutic options targeting the abovementioned mechanisms may evolve. At first sight, removing the blood clot might be the most pragmatic approach. However, so far a general superiority of surgical intervention in ICH patients as compared to conservative treatment could not be shown.35 A minimally invasive approach is currently tested in the MISTIE trial, so far yielding promising results concerning PHE reduction in the phase II trial,36 however, with an increased rate of asymptomatic bleeding in patients treated with minimally invasive surgery plus alteplase for clot removal.7 Hematoma expansion could be limited by administration of a hemostatic therapy with rFVIIa, however, with no improvement in survival or functional outcome. PHE evolution was not analyzed in this trial.8 Another approach targeting multiple pathophysiologic pathways associated with PHE evolution is therapeutic hypothermia.26 Therapeutic hypothermia effectively reduced PHE volume,32 especially when initiated early after ICH onset.37 These findings underline the importance of early inflammatory processes regarding PHE evolution, as suggested in our study. However, the question how long to treat and which target temperature to obtain to improve outcome needs to be elucidated in future research. A third possible treatment target is inflammation. Only a few studies with small patient numbers analyzed the effect of corticosteroids in ICH patients and found no effect on mortality and infections.38 Thus, European Stroke Organisation guidelines do not recommend the use of corticosteroids at this time.39 Other anti-inflammatory substances, e.g., fingolimod, are under clinical investigation.31 However, it remains to be elucidated whether the inflammatory response related to PHE evolution represents rather a reaction to the occurrence of blood within brain parenchyma, a reaction to additional infectious diseases in severely ill patients, or both, and whether an immunosuppressive strategy, an anti-infectious strategy, or both will resolve the inflammatory dilemma in ICH patients.

There are several strengths of the present study: we could include a sound cohort of an adequate size with available long-term data regarding PHE evolution and outcome assessment. Furthermore, a validated measurement was used for quantification of PHE and ICH volume,17 yielding reliable and robust results.

There are also several limitations. Despite the proper size of the included cohort, only patients from a single center were included. Due to the retrospective design, there were no standardized time points of imaging. To obtain comparable results, we merged imaging data within prespecified time clusters. This procedure might lead to an underestimation of peak PHE volume and also to a distorted representation of early PHE volume increase up to day 3 and the time axis of PHE evolution. However, this bias exists for all outcome groups. Due to the exclusive inclusion of supratentorial ICH patients, no statement about the association of PHE with functional outcome in infratentorial ICH patients is yet possible. A further selection bias also cannot be excluded as we did not include patients with early withdrawal of care and patients with only 1 CT scan (n = 294) and excluded 38 patients due to missing data. Because length of hospital stay and number of CT scans varied between individuals, in some patients the real peak PHE volume might not have been assessed. We used the method of median split to assess measures influencing peak PHE volume leading to a possible loss of power in this analysis. Validation of our methodology was performed up to day 5 after admission. We cannot exclude that due to ongoing hematoma degradation a certain inaccuracy may affect our PHE assessment between day 6 and 12, even if our method corrects for hematoma degradation. Time between symptom onset and admission did not differ between patients with and without hematoma expansion. However, as this measure differed between individual patients, it might pose possible bias in this complex relation among hematoma evolution, PHE evolution, outcome, and time.

Author contributions

Bastian Volbers: acquisition, analysis and interpretation of data, drafting the work, final approval, agreement to be accountable for all aspects of the work. Antje Giede-Jeppe: analysis of data, final approval, agreement to be accountable for all aspects of the work. Stefan Gerner: critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Jochen Sembill: critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Joji B. Kuramatsu: interpretation of data, critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Stefan Lang: interpretation of data, critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Hannes Lücking: analysis of data, critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Dimitre Staykov: critically revising the work for important intellectual content, final approval, agreement to be accountable for all aspects of the work. Hagen B. Huttner: analysis and interpretation of data, conceptualization the work, final approval, agreement to be accountable for all aspects of the work.

Study funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received July 11, 2017.
  • Accepted in final form December 18, 2017.

References

  1. 1.↵
    1. Qureshi AI,
    2. Mendelow AD,
    3. Hanley DF
    . Intracerebral haemorrhage. Lancet 2009;373:1632–1644.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Xi G,
    2. Keep RF,
    3. Hoff JT
    . Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006;5:53–63.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Staykov D,
    2. Wagner I,
    3. Volbers B, et al
    . Natural course of perihemorrhagic edema after intracerebral hemorrhage. Stroke 2011;42:2625–2629.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Ziai WC
    . Hematology and inflammatory signaling of intracerebral hemorrhage. Stroke 2013;44:S74–S78.
    OpenUrlFREE Full Text
  5. 5.↵
    1. Mayer SA,
    2. Sacco RL,
    3. Shi T,
    4. Mohr JP
    . Neurologic deterioration in noncomatose patients with supratentorial intracerebral hemorrhage. Neurology 1994;44:1379–1384.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Hanley DF,
    2. Lane K,
    3. McBee N, et al
    . Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial. Lancet 2017;389:603–611.
    OpenUrl
  7. 7.↵
    1. Hanley DF,
    2. Thompson RE,
    3. Muschelli J, et al
    . Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial. Lancet Neurol 2016;15:1228–1237.
    OpenUrlPubMed
  8. 8.↵
    1. Mayer SA,
    2. Brun NC,
    3. Begtrup K, et al
    . Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008;358:2127–2137.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Yang J,
    2. Arima H,
    3. Wu G, et al
    . Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke 2015;46:1009–1013.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Murthy SB,
    2. Urday S,
    3. Beslow LA, et al
    . Rate of perihaematomal oedema expansion is associated with poor clinical outcomes in intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 2016;87:1169–1173.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Urday S,
    2. Beslow LA,
    3. Dai F, et al
    . Rate of perihematomal edema expansion predicts outcome after intracerebral hemorrhage. Crit Care Med 2016;44:790–797.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Wu TY,
    2. Sharma G,
    3. Strbian D, et al
    . Natural history of perihematomal edema and impact on outcome after intracerebral hemorrhage. Stroke 2017;48:873–879.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Schwarz S,
    2. Hafner K,
    3. Aschoff A,
    4. Schwab S
    . Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 2000;54:354–361.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Giede-Jeppe A,
    2. Bobinger T,
    3. Gerner ST, et al
    . Lymphocytopenia is an independent predictor of unfavorable functional outcome in spontaneous intracerebral hemorrhage. Stroke 2016;47:1239–1246.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Lattanzi S,
    2. Cagnetti C,
    3. Provinciali L,
    4. Silvestrini M
    . Neutrophil-to-Lymphocyte ratio predicts the outcome of acute intracerebral hemorrhage. Stroke 2016;47:1654–1657.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Brouwers HB,
    2. Chang Y,
    3. Falcone GJ, et al
    . Predicting hematoma expansion after primary intracerebral hemorrhage. JAMA Neurol 2014;71:158–164.
    OpenUrl
  17. 17.↵
    1. Volbers B,
    2. Staykov D,
    3. Wagner I, et al
    . Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography. Eur J Neurol 2011;18:1323–1328.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Grunwald Z,
    2. Beslow LA,
    3. Urday S, et al
    . Perihematomal edema expansion rates and patient outcomes in deep and lobar intracerebral hemorrhage. Neurocrit Care 2017;26:205–212.
    OpenUrl
  19. 19.↵
    1. Broderick JP,
    2. Brott TG,
    3. Duldner JE,
    4. Tomsick T,
    5. Huster G
    . Volume of intracerebral hemorrhage: a powerful and easy-to-use predictor of 30-day mortality. Stroke 1993;24:987–993.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Ziai W,
    2. Carhuapoma JR,
    3. Nyquist P,
    4. Hanley DF
    . Surgical strategies for spontaneous intracerebral hemorrhage. Semin Neurol 2016;36:531–541.
    OpenUrl
  21. 21.↵
    1. Webb AJ,
    2. Ullman NL,
    3. Morgan TC, et al
    . Accuracy of the ABC/2 score for intracerebral hemorrhage: systematic review and analysis of MISTIE, CLEAR-IVH, and CLEAR-III. Stroke 2015;46:2470–2476.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Kuramatsu JB,
    2. Bobinger T,
    3. Volbers B, et al
    . Hyponatremia is an independent predictor of in-hospital mortality in spontaneous intracerebral hemorrhage. Stroke 2014;45:1285–1291.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Delcourt C,
    2. Sato S,
    3. Zhang S, et al
    . Intracerebral hemorrhage location and outcome among INTERACT2 participants. Neurology 2017;88:1408–1414.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Sembill JA,
    2. Gerner ST,
    3. Volbers B, et al
    . Severity assessment in maximally treated ICH patients: the max-ICH score. Neurology 2017;89:423–431.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Hemphill JC III.,
    2. Bonovich DC,
    3. Besmertis L,
    4. Manley GT,
    5. Johnston SC
    . The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32:891–897.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Polderman KH
    . Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009;37:S186–S202.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Chen S,
    2. Yang Q,
    3. Chen G,
    4. Zhang JH
    . An update on inflammation in the acute phase of intracerebral hemorrhage. Transl Stroke Res 2015;6:4–8.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Gusdon AM,
    2. Gialdini G,
    3. Kone G, et al
    . Neutrophil-lymphocyte ratio and perihematomal edema growth in intracerebral hemorrhage. Stroke 2017;48:2589–2592.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Wang XM,
    2. Zhang YG,
    3. Li AL, et al
    . Expressions of serum inflammatory cytokines and their relationship with cerebral edema in patients with acute basal ganglia hemorrhage. Eur Rev Med Pharmacol Sci 2016;20:2868–2871.
    OpenUrl
  30. 30.↵
    1. Abilleira S,
    2. Montaner J,
    3. Molina CA,
    4. Monasterio J,
    5. Castillo J,
    6. Alvarez-Sabin J
    . Matrix metalloproteinase-9 concentration after spontaneous intracerebral hemorrhage. J Neurosurg 2003;99:65–70.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Fu Y,
    2. Hao J,
    3. Zhang N, et al
    . Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol 2014;71:1092–1101.
    OpenUrl
  32. 32.↵
    1. Staykov D,
    2. Wagner I,
    3. Volbers B,
    4. Doerfler A,
    5. Schwab S,
    6. Kollmar R
    . Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care 2013;18:178–183.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Venkatasubramanian C,
    2. Mlynash M,
    3. Finley-Caulfield A, et al
    . Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke 2011;42:73–80.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Murthy SB,
    2. Moradiya Y,
    3. Dawson J, et al
    . Perihematomal edema and functional outcomes in intracerebral hemorrhage: influence of hematoma volume and location. Stroke 2015;46:3088–3092.
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Mendelow AD,
    2. Gregson BA,
    3. Rowan EN, et al
    . Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013;382:397–408.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Mould WA,
    2. Carhuapoma JR,
    3. Muschelli J, et al
    . Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke 2013;44:627–634.
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Volbers B,
    2. Herrmann S,
    3. Willfarth W, et al
    . Impact of hypothermia initiation and duration on perihemorrhagic edema evolution after intracerebral hemorrhage. Stroke 2016;47:2249–2255.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Feigin VL,
    2. Anderson N,
    3. Rinkel GJ,
    4. Algra A,
    5. van Gijn J,
    6. Bennett DA
    . Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane Database Syst Rev 2005:CD004583.
  39. 39.↵
    1. Steiner T,
    2. Al-Shahi Salman R,
    3. Ntaios G
    . The European Stroke Organisation (ESO) guidelines. Int J Stroke 2014;9:838–839.
    OpenUrlCrossRefPubMed

Letters: Rapid online correspondence

Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
Advertisement

Related Articles

  • No related articles found.

Topics Discussed

Alert Me

Recommended articles