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Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established., Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH., Design, Setting, and Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015)., Exposure: Surgical hematoma evacuation vs conservative treatment., Main Outcomes and Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH., Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02)., Conclusions and Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH., Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC., Results: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC., Conclusions: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention., Competing Interests: Competing interests: JBK reports grants from Covidien (Medtronic), personal fees from Bayer, Pfizer and Sanofi. ME reports grants and other from Bayer, other from Boehringer Ingelheim, BMS/Pfizer and Daiichi Sankyo during the conduct of the study; grants from DFG, BMBF, EU, Corona Foundation and Fondation Leducq, other from Amgen, GSK, Novartis, Sanofi and Covidien. KGH reports grants and personal fees from Bayer, personal fees from Daiichi Sankyo, BMS, Pfizer, Boehringer Ingelheim, Sanofi-Aventis and Edwards Lifesciences, non-financial support from Getemed, personal fees from EIP Pharma and Medtronic. JS reports personal fees from Bayer, Pfizer/BMS, Daiichi and Boehringer Ingelheim. PAR reports personal fees from Boehringer Ingelheim, Bayer, Daiichi Sankyo and Pfizer. JCP reports personal fees from Boehringer Ingelheim and Pfizer. TR reports personal fees from BMS Pfizer, Bayer Healthcare, Daiichi Sankyo and Boehringer Ingelheim. JV reports grants from Medtronic and Boston Scientific and fees from Medtronic, St Jude, Boston Scientific, UCB, Merz, Allergan, Teva, Novartis and AbbVie. WM reports personal fees from Boehringer Ingelheim and Bayer Pharma. PK reports personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer/Bristol-Myers Squibb. FE reports grants and personal fees from Boehringer Ingelheim, personal fees from Bayer Pharma, Pfizer Pharma, Bristol-Myers Squibb and Daiichi Sankyo. MN reports personal fees from Speaker’s fee Pfizer/BMS and Boehringer Ingelheim. PDS reports personal fees from Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi and Medtronic. JG reports personal fees from Pfizer. UJK reports other from Daiichi Sankyo and Bayer. GRF reports personal fees from Bayer and Boehringer. CD reports speaking fees from Bayer, UCB, Daiichi Sankyo and Pfizer. JM reports personal fees from Boehringer Ingelheim and Bayer Healthcare. HN reports personal fees from Boehringer Ingelheim and Daiichi. JR reports personal fees from Bayer, Boehringer, Pfizer and Bristol Myers Squibb. MS reports grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and the European Union (EU) and fees from Bristol-Myers Squibb, GlaxoSmithKline, Merz Pharmaceuticals, Novartis Pharma, Orion Pharma, Pharmacia, Roche, Sanofi, Teva Pharma and UCB Pharma. GR reports personal fees from Boehringer Ingelheim, Pfizer and Bayer, grants from Daiichi. HB reports personal fees from Honoraria for lectures from Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo. HS reports grants from Bayer Healthcare. FP reports personal fees from Pfizer/BMS, Bayer, Boehringer Ingelheim and Daiichi Sankyo. JCW reports personal fees from Boehringer Ingelheim Pharma GmbH & Co. KGH reports personal fees from Daiichi Sankyo Pharma. AG reports personal fees from Daiichi Sankyo, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb/Pfizer. GFH reports participation in the Respect-ESUS trial. SS reports personal fees from Boehringer Ingelheim and grants from Daiichi. HBH reports personal fees from Boehringer Ingelheim, Daiichi Sankyo and Novartis, grants from Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.

Background and Purpose- Besides the established spot sign (SS) in computed tomography angiography (CTA), there is growing evidence that different imaging markers in noncontrast CT offer great value for outcome prediction in patients with intracerebral hemorrhage (ICH). However, it is unclear how the concurrent presence of each sign independently contributes to the predictive power of poor outcome. We, therefore, aimed to clarify the predictive value of 5 recently published noncontrast CT parameters (blend sign, black hole sign, island sign, hematoma heterogeneity, and hypodensities) and the established SS in 1 consecutive series of patients with ICH. Methods- Retrospective study of patients with ICH at 2 German tertiary stroke centers; inclusion criteria were (1) spontaneous ICH and (2) noncontrast CT and CTA performed on admission within 6 hours after onset of symptoms. We defined a binary outcome (good outcome [modified Rankin Scale score of ≤3] versus poor outcome [modified Rankin Scale score of >3]) at discharge. The predictive value of each sign was assessed in univariate and multivariable logistic regression models. Results- Of 201 patients with spontaneous ICH, 28 (13.9%) presented with black hole sign, 38 (18.9%) with blend sign, 120 (59.7%) with hypodensities, 97 (48.3%) with heterogeneous densities, 53 with island sign (26.4%), and 45 (22.4%) with SS. In univariable logistic regression, higher hematoma volume ( P<0.001), intraventricular hemorrhage ( P=0.002), and the presence of black hole sign/blend sign/hypodensities/island sign/SS/heterogeneous density (all P<0.001) on admission CT were associated with poor outcome. Multivariable analysis confirmed intraventricular hemorrhage (odds ratio, 2.20; P=0.025), higher hematoma volume (odds ratio, 1.02 per mL; P<0.019), the presence of hypodensities (odds ratio, 2.47; P=0.018), and SS (odds ratio, 12.22; P<0.001) as independent predictors of poor outcome. Conclusions- This study demonstrates the degree of interaction between 5 recent noncontrast CT imaging markers and SS and their individual contribution for outcome prediction in patients with ICH. Of the CT variables indicating poor outcome SS on CTA and hypodensities were the most reliable outcome predictors.

Besides the established spot sign in computed tomography angiography (CTA), recently investigated imaging predictors of hematoma growth in noncontrast computed tomography (NCCT) suggest great potential for outcome prediction in patients with intracerebral hemorrhage (ICH). Secondary hematoma growth is an appealing target for therapeutic interventions because in contrast to other determined factors, it is potentially modifiable. Even more initial therapy studies failed to demonstrate clear therapeutic benefits, there is a need for an effective patient selection using imaging markers to identify patients at risk for poor outcome and thereby tailor individual treatments for every patient. Hence, this review gives an overview about the current literature on NCCT imaging markers for neurological outcome prediction and aims to clarify the association with the established spot sign. Moreover, it demonstrates the clinical impact of these parameters and gives a roadmap for future imaging research in patients with intracerebral hemorrhage.

Aims: Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH., Methods and Results: We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03)., Conclusion: Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.

Background: Recent studies have suggested that glial fibrillary acidic protein (GFAP) serum concentrations distinguish between intracerebral hemorrhage (ICH) and ischemic stroke (IS) shortly after symptom onset. In this prospective multicenter trial we validated GFAP in an independent patient cohort and assessed the quantitative relationship between GFAP release, bleeding size, and localization., Methods: We included patients with a persistent neurological deficit (NIH Stroke Scale ≥4) suggestive of stroke within 6 h of symptom onset. Blood samples were drawn at hospital admission. GFAP serum concentrations were measured using an electrochemiluminometric immunoassay. Primary endpoint was the final diagnosis established at hospital discharge (ICH, IS, or stroke mimic)., Results: 202 patients were included (45 with ICH, 146 with IS, 11 stroke mimics). GFAP concentrations were significantly higher in ICH than in IS patients [median (interquartile range) 0.16 μg/L (0.04-3.27) vs 0.01 μg/L (0.01-0.01), P <0.001]. A GFAP cutoff of 0.03 μg/L provided a sensitivity of 77.8% and a specificity of 94.2% in distinguishing ICH from IS and stroke mimics [ROC analysis area under the curve 0.872 (95% CI, 0.802-0.942), P <0.001]. GFAP serum concentrations were positively correlated with ICH volume. Lobar ICH volumes were larger and thus associated with higher GFAP concentrations as compared to deep ICH., Conclusions: Serum GFAP was confirmed to be a biomarker indicating ICH in patients presenting with acute stroke symptoms. Very small ICH may be missed owing to less tissue destruction., (© 2016 American Association for Clinical Chemistry.)

Background and Purpose: Significant early hematoma growth in patients with intracerebral hemorrhage is an independent predictor of poor functional outcome. Recently, the novel blend sign (BS) has been introduced as a new imaging sign for predicting hematoma growth in noncontrast computed tomography. Another parameter predicting increasing hematoma size is the well-established spot sign (SS) visible in computed tomographic angiography. We, therefore, aimed to clarify the association between established SS and novel BS and their values predicting a secondary neurological deterioration., Methods: Retrospective study inclusion criteria were (1) spontaneous intracerebral hemorrhage confirmed on noncontrast computed tomography and (2) noncontrast computed tomography and computed tomographic angiography performed on admission within 6 hours after onset of symptoms. We defined a binary outcome (secondary neurological deterioration versus no secondary deterioration). As secondary neurological deterioration, we defined (1) early hemicraniectomy under standardized criteria or (2) secondary decrease of Glasgow Coma Scale of >3 points, both within the first 48 hours after symptom onset., Results: Of 182 patients with spontaneous intracerebral hemorrhage, 37 (20.3%) presented with BS and 39 (21.4%) with SS. Of the 81 patients with secondary deterioration, 31 (38.3%) had BS and SS on admission. Multivariable logistic regression analysis identified hematoma volume (odds ratio, 1.07 per mL; P≤0.001), intraventricular hemorrhage (odds ratio, 3.08; P=0.008), and the presence of BS (odds ratio, 11.47; P≤0.001) as independent predictors of neurological deterioration., Conclusions: The BS, which is obtainable in noncontrast computed tomography, shows a high correlation with the computed tomographic angiography SS and is a reliable predictor of secondary neurological deterioration after spontaneous intracerebral hemorrhage., (© 2016 American Heart Association, Inc.)

Purpose: This study aimed to evaluate the effectiveness and safety of the NeVaTM stent retriever as first- and second-line device for mechanical thrombectomy in acute ischemic stroke. Methods: In this retrospective single-center study, all consecutive patients that underwent mechanical thrombectomy with NeVaTM stent retriever as first- or second-line device due to intracranial vessel occlusion with acute ischemic stroke between March and November 2022 were included. Results: Thirty-nine patients (m=18, f=21) with a mean age of 69.9 ± 13.3 years were treated with the NeVaTM stent retriever. NeVaTM stent retriever was used as first-line device in 24 (61.5%) of patients and in 15 (38.5%) as second-line device. First-pass rate (≥mTICI 2c) of NeVaTM stent retriever was both 66.7% when used as first- or second-line device. Final recanalization rate including rescue strategies was 92.3% for ≥mTICI2c and 94.9% for ≥mTICI2b. No device-related minor or major adverse events were observed. A hemorrhage was detected in 33.3% of patients at 24h post-thrombectomy dual-energy CT, of which none was classified as symptomatic intracerebral hemorrhage. NIHSS and mRS improved significantly at discharge compared to admission (p<0.05). Conclusion: The NeVaTM stent retriever has a high effectivity and good safety profile as first- and second-line device for mechanical thrombectomy in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Introduction: In patients with spontaneous intracerebral hemorrhage (ICH), several non-contrast computed tomography (NCCT) markers and the spot sign (SS) in computed tomography (CT) angiography (CTA) have been established for the prediction of hematoma growth and neurological outcome. However, the prognostic value of these markers in patients under oral anticoagulation (ORAC) is unclear. We hypothesized that outcome prediction by these imaging markers may be significantly different between patients with and without ORAC. Therefore, we aimed to investigate the predictive value of NCCT markers and SS in patients with ICH under ORAC. Methods: This is a retrospective study of the database for patients with ICH at a German tertiary stroke center. Inclusion criteria were (1) patients with ICH, (2) oral anticoagulation within the therapeutic range, and (3) NCCT and CTA performed on admission within 6 h after onset of symptoms. We defined a binary outcome: modified Rankin Scale (mRS) ≤ 3 = good outcome versus mRS > 3 = poor outcome at discharge. The predictive value of each sign was assessed in uni- and multivariable logistic regression models. Results: Of 129 patients with ICH under ORAC, 76 (58.9%) presented with hypodensities within the hematoma in admission NCCT, 64 (52.7%) presented with an irregular shape of the hematoma, 60 (46.5%) presented with a swirl sign, 49 (38.0%) presented with a black hole sign, and 46 (35.7%) presented with a heterogeneous density of the hematoma. Moreover, 44 (34.1%) patients had a satellite sign, in 20 (15.5%) patients, an island sign was detected, 18 (14.0%) patients were blend-sign positive, and 14 (10.9%) patients presented with a CTA spot sign. Inter-rater agreement was very high for all included characteristics between the two readers. Multivariable logistic regression analysis identified the presence of black hole sign (odds ratio 10.59; p < 0.001), swirl sign (odds ratio 14.06; p < 0.001), and satellite sign (odds ratio 6.38; p = 0.011) as independent predictors of poor outcome. Conclusions: The distribution and prognostic value of several NCCT markers and CTA spot sign in ICH patients under ORAC is comparable to those with spontaneous ICH, even though these parameters are partly based on coagulant status. These findings suggest that a similar approach can be used for further research regarding outcome prediction in ICH patients under ORAC and those with spontaneous ICH. [ABSTRACT FROM AUTHOR]