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Objective: Hematoma enlargement (HE) is associated with clinical outcomes after supratentorial intracerebral hemorrhage (ICH). This study evaluates whether HE characteristics and association with functional outcome differ in deep versus lobar ICH., Methods: Pooled analysis of individual patient data between January 2006 and December 2015 from a German-wide cohort study (RETRACE, I + II) investigating ICH related to oral anticoagulants (OAC) at 22 participating centers, and from one single-center registry (UKER-ICH) investigating non-OAC-ICH patients. Altogether, 1954 supratentorial ICH patients were eligible for outcome analyses, which were separately conducted or controlled for OAC, that is, vitamin-K-antagonists (VKA, n = 1186) and non-vitamin-K-antagonist-oral-anticoagulants (NOAC, n = 107). Confounding was addressed using propensity score matching, cox regression modeling and multivariate modeling. Main outcomes were occurrence, extent, and timing of HE (>33%/>6 mL) and its association with 3-month functional outcome., Results: Occurrence of HE was not different after deep versus lobar ICH in patients with non-OAC-ICH (39/356 [11.0%] vs. 36/305 [11.8%], P = 0.73), VKA-ICH (249/681 [36.6%] vs. 183/505 [36.2%], P = 0.91), and NOAC-ICH (21/69 [30.4%] vs. 12/38 [31.6%], P = 0.90). HE extent did not differ after non-OAC-ICH (deep:+59% [40-122] vs. lobar:+74% [37-124], P = 0.65), but both patients with VKA-ICH and NOAC-ICH showed greater HE extent after deep ICH [VKA-ICH, deep: +94% [54-199] vs. lobar: +56% [35-116], P < 0.001; NOAC-ICH, deep: +74% [56-123] vs. lobar: +40% [21-49], P = 0.001). Deep compared to lobar ICH patients had higher HE hazard during first 13.5 h after onset (Hazard ratio [HR]: 1.85 [1.03-3.31], P = 0.04), followed by lower hazard (13.5-26.5 h, HR: 0.46 [0.23-0.89], P = 0.02), and equal hazard thereafter (HR: 0.96 [0.56-1.65], P = 0.89). Odds ratio for unfavorable outcome was higher after HE in deep (4.31 [2.71-6.86], P < 0.001) versus lobar ICH (2.82 [1.71-4.66], P < 0.001), and only significant after small-medium (1st volume-quarter, deep: 3.09 [1.52-6.29], P < 0.01; lobar: 3.86 [1.35-11.04], P = 0.01) as opposed to large-sized ICH (4th volume-quarter, deep: 1.09 [0.13-9.20], P = 0.94; lobar: 2.24 [0.72-7.04], P = 0.17)., Interpretation: HE occurrence does not differ among deep and lobar ICH. However, compared to lobar ICH, HE after deep ICH is of greater extent in OAC-ICH, occurs earlier and may be of greater clinical relevance. Overall, clinical significance is more apparent after small-medium compared to large-sized bleedings., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Whether time of hospital admission-during or outside regular working hours-affects functional outcome in intracerebral hemorrhage (ICH) is unestablished as previous analyses have focused on mortality only. We here investigate whether on- versus off-hour hospital admission in ICH is associated with levels of invasiveness and clinical outcomes., Methods: Based on the UKER registry (NCT03183167) we grouped ICH-patients according to on- versus off-hour hospital admission. Primary outcome measures was functional outcome after 3 months using the modified Rankin scale (mRS) dichotomized into favorable (mRS = 0-3) and unfavorable (mRS = 4-6). Multivariate regression analyses were used to adjust for baseline imbalances, and subgroup analyses were performed to explore associations of on- versus off-hour admission with invasiveness of therapeutic interventions., Results: A total of 438/1269 (34.5%) of ICH-patients were admitted during regular working hours. Mortality rates were not significantly different among patients with on- versus off-hour admission. On-hour patients showed a significantly larger proportion of patients with favorable outcome (on-hour: mRS = 0-3 after 3 months: 176/416 (42.3%) versus off-hour: 265/784 (33.8%); P = .004). Analysis of invasive therapeutic interventions revealed that likelihood of favorable outcome was significantly increased among on-hour admitted patients who did not require neurosurgical interventions (no external ventricular drain n = 349, OR: 1.67[1.13-2.48], P < .05; no hematoma evacuation surgery n = 423, OR: 1.51[1.07-2.14], P < .05)., Conclusion: This study verified an "off-hour effect" in ICH that relates to functional outcome, rather than mortality, and which may be linked to different levels of invasive therapeutic interventions in patients admitted during off-hour., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine the influence of intracerebral hemorrhage (ICH) location and volume and hematoma surface on perihemorrhagic edema evolution., Methods: Patients with ICH of the prospective Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage (UKER-ICH) cohort study (NCT03183167) between 2010 and 2013 were analyzed. Hematoma and edema volume during hospital stay were volumetrically assessed, and time course of edema evolution and peak edema correlated to hematoma volume, location, and surface to verify the strength of the parameters on edema evolution., Results: Overall, 300 patients with supratentorial ICH were analyzed. Peak edema showed a high correlation with hematoma surface ( R 2 = 0.864, p < 0.001) rather than with hematoma volumes, regardless of hematoma location. Smaller hematomas with a higher ratio of hematoma surface to volume showed exponentially higher relative edema ( R 2 = 0.755, p < 0.001). Multivariable logistic regression analysis revealed a cutoff ICH volume of 30 mL, beyond which an increase of total mass lesion volume (combined volume of hematoma and edema) was not associated with worse functional outcome. Specifically, peak edema was associated with worse functional outcome in ICH <30 mL (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.68-4.12, p < 0.001), contrary to ICH ≥30 mL (OR 1.20, 95% CI 0.88-1.63, p = 0.247). There were no significant differences between patients with lobar and those with deep ICH after adjustment for hematoma volumes., Conclusions: Peak perihemorrhagic edema, although influencing mortality, is not associated with worse functional outcomes in ICH volumes >30 mL. Although hematoma volume correlates with peak edema extent, hematoma surface is the major parameter for edema evolution. The effect of edema on functional outcome is therefore more pronounced in smaller and irregularly shaped hematomas, and these patients may particularly benefit from edema-modifying therapies., (© 2019 American Academy of Neurology.)

Objective: To investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: We analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018-2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature <36°C or >38°C, respiratory rate >20 per minute, heart rate >90 per minute, or white blood cell count <4,000/μL or >12,000/μL in the absence of infection. The primary outcome consisted of the modified Rankin Scale (mRS) at 3 and 12 months investigated by adjusted ordinal shift analyses. Bias and confounding were addressed by propensity score matching and multivariable regression models., Results: Of 780 patients with ICH, 21.8% (n = 170) developed SIRS during hospitalization. Patients with SIRS showed more severe ICH compared with those without; i.e., larger ICH volumes (18.3 cm 3 , interquartile range [IQR 4.6-47.2 cm 3 ] vs 7.4 cm 3 , IQR [2.4-18.6 cm 3 ]; p < 0.01), increased intraventricular hemorrhage (57.6%, n = 98/170 vs 24.8%, n = 79/319; p < 0.01), and poorer neurologic admission status (NIH Stroke Scale score 16, IQR [7-30] vs 6, IQR [3-12]; p < 0.01). ICH severity-adjusted analyses revealed an independent association of SIRS with poorer functional outcome after 3 (OR 1.80, 95% CI [1.08-3.00]; p = 0.025) and 12 months (OR 1.76, 95% CI [1.04-2.96]; p = 0.034). Increased ICH volumes on follow-up imaging (OR 1.38, 95% CI [1.01-1.89]; p = 0.05) and previous liver dysfunction (OR 3.01, 95% CI [1.03-10.19]; p = 0.04) were associated with SIRS., Conclusions: In patients with ICH, we identified SIRS to be predictive of poorer long-term functional outcome over the entire range of mRS estimates. Clinically relevant associations with SIRS were documented for previous liver dysfunction and hematoma enlargement.

Background and Objective: Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished., Methods: We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH -assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0-3) and unfavorable outcome (mRS = 4-6). Secondary outcomes included mortality at 3  months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome., Results: Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0-3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); p = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; p = 0.083). Multivariable analysis revealed that a Graeb score >2 was independently associated with unfavorable outcome (mRS 4-6: OR 3.16 [1.54-6.48]; p = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40-4.74]; p = 0.002) in IVH patients., Conclusions: Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients., (© 2019 S. Karger AG, Basel.)

Background: Troponin I is a widely used and reliable marker of myocardial damage and its levels are routinely measured in acute stroke care. So far, the influence of troponin I elevations during hospital stay on functional outcome in patients with atraumatic intracerebral hemorrhage (ICH) is unknown., Methods: Observational single-center study including conservatively treated ICH patients over a 9-year period. Patients were categorized according to peak troponin I level during hospital stay (≤0.040, 0.041-0.500, > 0.500 ng/mL) and compared regarding baseline and hematoma characteristics. Multivariable analyses were performed to investigate independent associations of troponin levels during hospital stay with functional outcome - assessed using the modified Rankin Scale (mRS; favorable 0-3/unfavorable 4-6) - and mortality after 3 and 12 months. To account for possible confounding propensity score (PS)-matching (1: 1; caliper 0.1) was performed accounting for imbalances in baseline characteristics to investigate the impact of troponin I values on outcome., Results: Troponin elevations (> 0.040 ng/mL) during hospital stay were observed in 308 out of 745 (41.3%) patients and associated with poorer status on admission (Glasgow Coma Scale/National Institute of Health Stroke Scale). Multivariable analysis revealed troponin I levels during hospital stay to be independently associated with unfavorable outcome after 12 months (risk ratio [95% CI]: 1.030 [1.009-1.051] per increment of 1.0 ng/mL; p = 0.005), but not with mortality. After PS-matching, patients with troponin I elevation (≥0.040 ng/mL) versus those without had a significant higher rate of -unfavorable outcome after 3 and 12 months (mRS 4-6 at 3 months: < 0.04 ng/mL: 159/265 [60.0%] versus ≥0.04 ng/mL: 199/266 [74.8%]; p < 0.001; at 12 months: < 0.04 ng/mL: 141/248 [56.9%] versus ≥0.04 ng/mL: 179/251 [71.3%]; p = 0.001)., Conclusions: Troponin I elevations during hospital stay occur frequently in ICH patients and are independently associated with functional outcome after 3 and 12 months but not with mortality., (© 2018 S. Karger AG, Basel.)

Background There is conflicting evidence about the influence of sex on outcome after spontaneous intracerebral hemorrhage (sICH) and the majority of the research focused on mortality and short-term outcome only. We investigated sex differences in long-term functional outcome after sICH. Methods We used data from a prospective hospital registry and included all consecutive patients with ICH admitted to our institution between January 2006 and July 2014. Functional outcome was assessed by modified Rankin Scale evaluated 3 and 12 months after ICH. We explored the influence of sex on long-term functional outcome using multivariable regression models and additionally by means of propensity score matching. Results We analyzed 823 patients, of whom 380 (46%) women. Women were on average three years older (p < 0.001), men had more often deep hematomas (p = 0.01). Unadjusted mortality rates were significantly increased in women at three months (42% vs. 35%; odds ratio (OR): 1.35; 95% confidence interval (CI): 1.02-1.80). After adjusting for baseline prognostic factors there were no differences between men and women in short- and long-term mortality (OR = 1.01; 95% CI = 0.66-1.54 and OR = 1.04; 95%CI = 0.69-1.57, respectively) and short- and long-term unfavorable outcome (OR = 1.02; 95%CI = 0.67-1.55 and OR = 0.96; 95% CI = 0.62-1.48, respectively). Conclusion We found no sex-related differences in long-term functional outcome in patients with sICH. The apparently worse functional outcome in women can be explained by differences in age.

Background and Purpose: Several studies have reported a better functional outcome in lobar intracerebral hemorrhage (ICH) compared with deep location. However, among lobar ICH, a correlation of hemorrhage site-involving the specific lobes-with functional outcome has not been established., Methods: Conservatively treated patients with supratentorial ICH, admitted to our hospital over a 5-year period (2008-2012), were retrospectively analyzed. Lobar patients were classified as isolated or overlapping ICH according to affected lobes. Demographic, clinical, and radiological characteristics were recorded and compared among lobar ICH patients using above subclassification. Functional outcome-dichotomized into favorable (modified Rankin Scale, 0-3) and unfavorable (modified Rankin Scale, 4-6)-was assessed after 3 and 12 months. Multivariate regression analysis was performed to identify predictors for favorable outcome., Results: Of overall 553 patients, 260 had lobar ICH. In isolated lobar ICH, median hematoma-volume decreased from rostral (frontal, 22.4 mL [7.3-55.5 mL]) to caudal (occipital, 7.1 mL [5.2-16.4 mL]; P =0.045), whereas the proportion of patients with favorable outcome increased (frontal: 23/63 [36.5%] versus occipital: 10/12 [83.3%]; P =0.003). Patients with overlapping lobar ICH had larger ICH volumes than isolated lobar ICH (overlapping, 48.9 mL [22.6-78.5 mL] versus 15.3 mL [5.0-44.6 mL]; P <0.001) and poorer clinical status on admission (Glasgow Coma Scale and National Institutes of Health Stroke Scale). Correlations with anatomic aspects provided evidence of a rostrocaudal gradient with increasing gray/white-matter ratio and decreasing hematoma-volume and rate of hematoma enlargement from frontal to occipital ICH location. Multivariate analysis revealed affection of occipital lobe (odds ratio, 3.75 [1.38-10.22]) and affection of frontal lobe (odds ratio, 0.52 [0.28-0.94]) to be independent predictors for favorable outcome and unfavorable outcome, respectively., Conclusions: Among patients with lobar ICH radiological and outcome characteristics differed according to location. Especially affection of the frontal lobe was frequent and associated with unfavorable outcome after 3 months., (© 2017 American Heart Association, Inc.)

Background: Data on clinical characteristics and outcome of patients with intracerebral hemorrhage (ICH) and concomitant systemic cancer disease are very limited., Methods: Nine hundred and seventy three consecutive primary ICH patients were analyzed using our prospective institutional registry over a period of 9 years (2006-2014). We compared clinical and radiological parameters as well as outcome - scored using the modified Rankin Scale (mRS) and analyzed in a dichotomized fashion as favorable outcome (mRS = 0-3) and unfavorable outcome (mRS = 4-6) - of ICH patients with and without cancer. Relevant imbalances in baseline clinical and radiological characteristics were adjusted using propensity score (PS) matching., Results: Prevalence of systemic cancer among patients with ICH was 8.5% (83/973). ICH patients with cancer were older (77 [70-82] vs. 72 [63-80] years; p = 0.002), had more often prior renal dysfunction (19/83 [22.9%] vs.107/890 [12.0%]; p = 0.005), and smaller hemorrhage volumes (10.1 [4.8-24.3] vs. 15.3 [5.4-42.9] mL; p = 0.017). After PS-matching there were no significant differences neither in mortality nor in functional outcome both at 3 months (mortality: 33/81 [40.7%] vs. 55/158 [34.8%]; p = 0.368; mRS = 0-3: 28/81 [34.6%] vs. 52/158 [32.9%]; p = 0.797) and 12 months (mortality: 39/78 [50.0%] vs. 70/150 [46.7%]; p = 0.633; mRS = 0-3: 25/78 [32.1%] vs. 53/150 [35.3%]; p = 0.620) among patients with and without concomitant systemic cancer. ICH volume tended to be highest in patients with hematooncologic malignancy and smallest in urothelial cancer., Conclusions: Patients with ICH and concomitant systemic cancer on average are older; however, they show smaller ICH volumes compared to patients without cancer. Yet, mortality and functional outcome is not different in ICH patients with and without cancer. Thus, the clinical history or the de novo diagnosis of concomitant malignancies in ICH patients should not lead to unjustified treatment restrictions., (© 2017 S. Karger AG, Basel.)

Background: Seizures are a common complication after intracerebral hemorrhage (ICH) but there is a substantial lack of information on the long-term incidence in ICH survivors and whether post-ICH seizures affect functional long-term outcome., Methods: Over a five-year period 464 consecutive patients with spontaneous ICH were analyzed. Focussing on 1-year ICH survivors, clinical, and radiological parameters were retrieved from institutional prospective databases. The occurrence of seizures was categorized as early (≤7 days) or late (>7 days). Functional outcome was assessed by mailed questionnaires and telephone interviews, and was categorized into good vs. poor (mRS: 0-2 vs. 3-5) and favorable vs. unfavorable (mRS: 0-3 vs. 4-5). Multivariate regression models were calculated to investigate risk factors associated with post-ICH seizures including an a priori defined subgroup analysis of lobar ICH patients., Results: Among 203 long-term ICH survivors, 19.7 % developed seizures of which 55 % occurred late. Factors associated with seizures were lobar location (OR 8.10; 95 % CI 3.04-21.59; p < 0.001), sepsis (OR 4.59; 95 % CI 1.20-17.53; p = 0.026), and history of alcohol abuse (OR 3.36; 95 % CI 1.25-9.06; p = 0.017). Subgroup analysis of lobar ICH patients revealed history of alcohol abuse as the only independent predictor of post-ICH seizures (OR 5.22; 95 % CI 1.25-21.78; p = 0.024). Functional long-term outcome among survivors was slightly worse in patients with post-ICH seizures (p = 0.059). In multivariate regression modeling for prediction of poor outcome, the parameter "post-ICH seizures" again reached a statistical trend (p = 0.065), and established parameters such as age, GCS, and hemorrhage volume were independently related to poor outcome., Conclusions: Post-ICH seizures among long-term ICH survivors are common and may contribute to unfavorable functional outcome. Especially lobar ICH patients with a history of alcohol abuse are at risk to develop post-ICH seizures. Therefore, this subgroup may represent a target population for a prophylactic anticonvulsive treatment approach, preferably investigated in a prospective randomized trial.