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Background: The cerebrospinal fluid circulation of patients with intracerebral hemorrhage (ICH) can be blocked by blood clots, resulting in acute hydrocephalus. However, current research on chronic hydrocephalus (CH) is lacking., Methods: A total of 253 patients with ICH combined with coma treated at The Third People's Hospital of Gansu Province after emergency hematoma removal from January 2018 to January 2020 were included. Patients were divided into the CH group (n=48) and the control group (n=205) depending on whether hydrocephalus occurred or not within 3-12 months after operation. The main clinical characteristics of the two groups were compared, and the risk factors for CH were analyzed. Counting data of the two groups were expressed as "n (%)", and multivariate logistic regression analysis was used to explore the risk factors for CH., Results: Compared with the control group, the proportion of patients with modified Graeb score ≥5 points in the CH group increased significantly (52.08% vs. 21.95%, P=0.000). The proportion of patients with preoperative cerebral hernia increased significantly (37.5% vs. 19.51%, P=0.008). The proportion of patients with preoperative obstructive hydrocephalus increased (43.75% vs. 24.39%, P=0.007). The proportion of patients with postoperative subdural effusion increased (41.67% vs. 13.66%, P=0.000). Multivariate logistic regression analysis showed that a modified Graeb score ≥5 points and postoperative subdural effusion were risk factors for the formation of CH in patients with ICH complicated by coma after emergency hematoma removal (P<0.05). The modified Graeb score has diagnostic value for the formation of CH in patients with ICH combined with coma after emergency hematoma removal, and the area under the curve was 0.653 [P=0.001, 95% confidence interval (CI): 0.561-0.744]. There was no significant difference in preoperative neurological deficit score between the control group and the CH group (19.75±3.03 vs. 19.86±3.01, P=0.113). Compared with the control group, the neurological deficit score at 12 months after operation in the CH group was significantly higher (12.73±2.99 vs. 10.64±2.82, P=0.000)., Conclusions: A modified Graeb score >5 points and postoperative subdural effusion are risk factors for the formation of CH in patients with ICH combined with coma after emergency hematoma removal. The formation of CH affects postoperative neurological rehabilitation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-128/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease. [ABSTRACT FROM AUTHOR]

Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment. [ABSTRACT FROM AUTHOR]

• The expressions of RIP3, p-MLKL, AIF and CaMKII increased in a time-dependent manner after ICH. • AIF leaks through the mPTP channel and forms a complex with RIP3 in the cytoplasm. • RIP3-AIF nucleus translocation is primary step of necroptosis. • Inhibition of RIP3/AIF/CaMKII signaling improved neurological functions after ICH. Necroptosis-induced neuronal damage after intracerebral hemorrhage (ICH) has been documented recently. Previous studies have reported that RIP3 and its complex are recognized as central mediators of necroptosis. In this study, the role of RIP3 in the activation of CaMKII and AIF was investigated. We induced ICH in C57BL/6 mice by injecting collagenase IV into the basal ganglia. ICH mice were pretreated with the mPTP inhibitor CsA and the CAMKII inhibitor Kn-93, RIP3 siRNA or RIP3 rAAV. Brain edema and neurobehavior were evaluated. The expression of RIP3, p-MLKL, AIF, and CaMKII proteins was evaluated by western blotting, immunofluorescence (IF) and immunoprecipitation (IP). Significant increases in RIP3, p-MLKL, CaMKII and AIF expression were observed in ICH mice, and RIP3-AIF colocalized in the nucleus. Overexpression of RIP3 by rAAV upregulated AIF expression in both the cytoplasm and nucleus, while CaMKII expression was increased in the cytoplasm. The interaction of RIP3-AIF and RIP3-CaMKII was detected after ICH injury. These complexes were inhibited by CsA with Kn-93 or RIP3 siRNA pretreatment, which reduced brain edema and neurological deficits. Our findings revealed that ICH induced necroptotic neuronal death through the RIP3-CaMKII complex and the RIP3-AIF signaling pathway. Moreover, blockade of mPTP opening could suppress the pathogenesis of necroptosis. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with high morbidity and mortality rates. Oxidative stress and inflammation are important pathological mechanisms of secondary brain injury (SBI) after ICH. Brain and muscle Arnt-like protein 1 (BMAL1), which forms the core component of the circadian clock, was previously shown to be involved in many diseases and to participate in oxidative stress and inflammatory responses. However, the role of BMAL1 in SBI following ICH is unknown. In addition, treatments targeting miR-155 and its downstream signaling pathway may exert a beneficial effect on SBI after ICH, while miR-155 may regulate Bmal1 mRNA stability and translation. Nevertheless, researchers have not clearly determined whetheantagomir-155 upregulates BMAL1 expression and subsequently attenuates ICH-induced brain injury in rats., Methods: After establishing an ICH rat model by injecting autologous blood, the time course of changes in levels of the BMAL1 protein after ICH was analyzed. Subsequently, this study was designed to investigate the potential role and mechanisms of BMAL1 in SBI following ICH using lentiviral overexpression and antagomir-155 treatments., Results: BMAL1 protein levels were significantly decreased in the ICH group compared to the sham group. Genetic overexpression of BMAL1 alleviated oxidative stress, inflammation, brain edema, blood-brain barrier injury, neuronal death, and neurological dysfunction induced by ICH. On the other hand, we observed that inhibiting miRNA-155 using antagomir-155 promoted the expression of BMAL1 and further activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to attenuate brain injury after ICH., Conclusions: These results reveal that BMAL1 serves as a neuroprotective agent in ICH and upregulation of BMAL1 attenuates ICH-induced SBI. Therefore, BMAL1 may be a promising therapeutic target for SBI following ICH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-1863). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Iron has a key role in the activation of the autophagic pathway in rats with intracerebral hemorrhage (ICH), and hepcidin has the ability to reduce brain iron in ICH-rats. We therefore hypothesized that hepcidin might be able to inhibit autophagy by reducing iron in an ICH brain. Here, we investigated the effects of Ad-hepcidin and/or hepcidin peptide on autophagic activities in ICH models in vitro and in vivo. We demonstrated that ad-hepcidin and hepcidin peptide both inhibited hemin-induced increase in LC3-II/LC3-I conversion ratio and reversed the reduction in p62 content in cortical neurons in vitro. We also showed that ad-hepcidin inhibited ICH-induced increase in LC3-II/LC3-I conversion ratio and reversed ICH-induced reduction in p62 content in the brain cortex of rats in vivo. Based on these findings plus previous data on the effects of ad-hepcidin and/or hepcidin peptide on iron contents in ICH models, we suggested that hepcidin-induced inhibition of autophagy might be mediated via reducing iron in hemin-treated neurons in vitro and ICH-rat brain in vivo. • Hepcidin inhibits LC3-II/LC3-I conversion ratio increase in ICH models in vitro and in vivo. • Hepcidin reverses the reduction in p62 content in ICH models in vitro and in vivo. • Inhibition of autophagy by hepcidin might be mediated by reducing iron in ICH models. [ABSTRACT FROM AUTHOR]

Background: Microglia plays a vital role in neuroinflammation, contributing to the pathogenesis of intracerebral hemorrhage (ICH)-induced brain injury. Mesenchymal stem cells (MSCs) hold great potential for treating ICH. We previously revealed that MSCs ameliorate the microglial pyroptosis caused by an ischemic stroke. However, whether MSCs can modulate microglial pyroptosis after ICH remains unknown. This study aimed to investigate the neuroprotective effects of hypoxia-preconditioned olfactory mucosa MSCs (OM-MSCs) on ICH and the possible mechanisms., Methods: ICH was induced in mice via administration of collagenase IV. At 6 h post-ICH, 2-4×10 5 normoxic/hypoxic OM-MSCs or saline were intracerebrally administered. To evaluate the neuroprotective effects, the behavioral outcome, apoptosis, and neuronal injury were measured. Microglia activation and pro-inflammatory cytokines were applied to detect neuroinflammation. Microglial pyroptosis was determined by western blotting, immunofluorescence staining, and transmission electron microscopy (TEM)., Results: The two OM-MSC-transplanted groups exhibited significantly improved functional recovery and reduced neuronal injury, especially the hypoxic OM-MSCs group. Hypoxic OM-MSCs attenuated microglial activation as well as the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Moreover, we found that hypoxia-preconditioned OM-MSCs ameliorated pyroptosis by diminishing the levels of pyroptosis-associated proteins in peri-hematoma brain tissues, decreasing the expression of the microglial nod-like receptor family protein 3 (NLRP3) and caspase-1, and reducing the membrane pores on microglia post-ICH., Conclusions: Our study showed that hypoxic preconditioning augments the therapeutic efficacy of OM-MSCs, and hypoxia-preconditioned OM-MSCs alleviate microglial pyroptosis in the ICH model., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2590). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Prostaglandin E1 (PGE1) exerts various pharmacological effects such as membrane stabilization, anti-inflammatory functions, vasodilation, and platelet aggregation inhibition. We have previously demonstrated that PGE1 has a beneficial impact on patients suffering from intracerebral hemorrhage (ICH). The related mechanism underlying PGE1's beneficial effect on ICH treatment needs further exploration., Methods: The present study elucidates the mechanism of PGE1 on ICH treatment using a neuronal apoptosis model in vitro . The mouse primary cortical neurons were pretreated with different concentrations of PGE1, followed by the treatment with hemin, the main catabolite in whole blood, to mimic the clinical ICH., Results: Comparing with the vehicle-treated group, PGE1 prevented cultured cortical neurons from the accumulation of inhibited intracellular levels of reactive oxygen species (ROS), amelioration of mitochondrial membrane potential, and hemin-induced apoptosis. The reduction of ROS and apoptosis were associated with the up-regulation of Heme oxygenase-1 (HO-1) expression. Knockdown of nuclear transcription factor erythroid 2-related factor (Nrf2) by siRNA attenuated the upregulation of HO-1 as well as the protective effect of PGE1., Conclusions: Our work suggests that the Nrf2/HO-1 molecular pathway may play a crucial role in treating ICH patients with PGE1 and may represent novel molecular targets, resulting in discovering new drugs for ICH treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5839). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial., Objective: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications., Methods: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials., Results: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence., Conclusions: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Background: To explore the mechanisms of raw rhubarb and wine-processed rhubarb treatment in a rat model of intracerebral hemorrhage (ICH)., Methods: After adapting to their environment, 30 male Wistar rats were divided into 5 treatment groups: blank control group (CK) (normal saline), sham operation group (SICH) (normal saline), ICH model group (ICH) (normal saline), ICH + raw rhubarb enema group (RO) (raw rhubarb 3.60 g/kg), and ICH + wine-processed rhubarb enema group (WRO) (wine-processed rhubarb 3.60 g/kg). The rhubarb enema (once a day) was given since 3 days before ICH treatment, and was consistently given until 12 hours, 24 hours, 3 days, and 7 days post operation. Serum oxidative stress and inflammatory markers were detected by ELISA, and differences between raw rhubarb and wine-processed rhubarb treatment in ICH rats were screened by proteomics and metabolomics., Results: Both rhubarb treatments effectively improved oxidative stress and inflammatory responses. After ICH, the proteins and metabolites in the brain tissue were significantly altered. Compared with raw rhubarb, wine-processed rhubarb had a better protective effect by dysregulating amino acid metabolism in the ICH model., Conclusions: Our study provides a basis for further research into the mechanisms of rhubarb treatment from different processing technologies, and promotes the application of rhubarb as a therapeutic approach to ICH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7831). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: To observe the effect of acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) on NLRP3 inflammatory corpuscle in rats with intracerebral hemorrhage (ICH), and to explore the action mechanism of acupuncture on promoting the recovery of neural function in rats with ICH., Methods: Forty SPF six-week-old male SD rats were randomly divided into a sham operation group, a model group, a non-acupoint group and an acupuncture group, 10 rats in each group. The rats in the model group, non-acupoint group and acupuncture group were intervened with autologous blood injection to prepare ICH model, while the rats in the sham operation group were only intervened with operation but not injection with autologous blood. About 3 hours after the establishment of the model, the rats in the acupuncture group were intervened with acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7), once every 12 hours, for 7 days; the rats in the non-acupoint group were intervened with acupuncture at the non-acupoint [parallel to the "Baihui" (GV 20), 1 cm next to the midline] on the affected side, and other treatment was the same as the acupuncture group. At the end of the intervention, the composite nerve function score of each group was evaluated; the histomorphology of the hemorrhage penumbra was observed by HE staining; the expression of NLRP3 inflammatory corpuscle in the brain was detected by immunohistochemistry; the relative protein expression levels of NLRP3, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in brain were detected by the method of Western blot., Results: Seven days into intervention, compared with the sham operation group, each item score and total score of composite nerve function in the model group were significantly reduced ( P <0.01, P <0.05). There was edema and karyopyknosis in brain neuron as well as necrocytosis and inflammatory cell infiltration in the model group. Compared with the model group and the non-acupoint group, the total score of composite nerve function and the scores of symmetrical movement of limbs (LS) and proprioception of tentacles (VP) in the acupuncture group were increased ( P <0.01, P <0.05), and the cell necrosis and inflammatory cell infiltration were relieved. Compared with the sham operation group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the model group were increased ( P <0.01); compared with the model group and the non-acupoint group, NLRP3 inflammatory corpuscle expression and the relative protein expression levels of NLRP3, IL-1β and IL-18 in brain tissue in the acupuncture group were reduced ( P <0.01)., Conclusion: Acupuncture at "Baihui" (GV 20) through "Qubin" (GB 7) could downregulate the expression of NLRP3, IL-1β and IL-18 in the brain tissue of ICH rats, inhibit the inflammatory response, and promote the recovery of neural function.

Background and Purpose: We aimed to determine whether dual-energy CT (DECT) follow-up can differentiate contrast staining (CS) from intracranial hemorrhage (ICH) in stroke patients treated with intravenous thrombolysis (IVT), who had undergone acute stroke imaging using CT angiography (CTA), and CT perfusion (CTP). Materials and Methods : Between November 2012 and January 2018, 168 patients at our comprehensive stroke center underwent DECT follow-up within 36 h after IVT and acute CTA with or without CTP but did not receive intra-arterial imaging or treatment. Two independent readers evaluated plain monochromatic CT (pCT) alone and compared this with a second reading of a combined DECT approach using pCT and water- and iodine-weighted images, establishing and grading the ICH diagnosis, per Heidelberg and Safe Implementation of Treatments in Stroke Monitoring Study (SITS-MOST) classifications. Results: On pCT alone within 36 h, 31/168 (18.5%) patients had findings diagnosed as ICH. Using combined DECT (cDECT) changed ICH diagnosis to "CS only" in 3/168 (1.8%) patients, constituting 3/31 (9.7%) of cases with initially pCT-diagnosed ICH. These three cases had pCT diagnoses of one SAH, one minor, and one more extensive petechial hemorrhage (hemorrhagic infarction types 1 and 2), respectively. pCT alone had a 100% sensitivity, 98% specificity, 90% positive predictive value (PPV), 100% negative predictive value (NPV), and 98% accuracy for any ICH, compared to the cDECT. Inter-reader agreement for ICH classification using pCT compared to DECT was weighted kappa 0.92 (95% CI 0.87-0.98) vs. 0.91 (0.85-0.95). Conclusion: Compared to pCT, DECT within 36 h after IV thrombolysis for acute ischemic stroke, changes the radiological diagnosis of post-treatment ICH to "CS only" in a small proportion of patients. Studies are warranted of whether the altered radiological reports have an impact on patient management, for example initiation timing of antithrombotic secondary prevention., (Copyright © 2020 Almqvist, Almqvist, Holmin and Mazya.)

The graphical abstract indicates that NDRG2 negatively regulates GLT1 expression in astrocytes following hemorrhage-related stimulation and that downregulation of astrocytic NDRG2 promotes the interstitial glutamate clearance, thus alleviating glutamate neurotoxicity after OxyHb induction. Our findings suggest a novel mechanism for the regulation of GLT1 in astrocytes through the NDRG2/NF-κB pathway and provide a potential therapeutic target for astrocytes after hemorrhagic brain injury. • NDRG2 deletion mitigates the secondary brain injury after ICH. • NDRG2 inhibition astrocytes-drived neurotoxicity following OxyHb stimulation. • NDRG2 negatively regulates astrocytic GLT1 via NF-κB p65 signaling. N-myc downstream-regulated gene 2 (NDRG2), a newly identified astrocytic stress response gene, is involved in the regulation of astrocytic morphology and function, and has been indicated to be a potential therapeutic target for some central nervous system (CNS) diseases. However, the role of NDRG2 in intracerebral hemorrhage (ICH) remains unknown. Here, we reported that NDRG2 suppression exerted neuroprotection effect against hemorrhagic brain injury in ICH mice and in oxyhemoglobin (OxyHb)-treated cells. Ndrg2 knockout (Ndrg2 −/−) mice exhibited reduced hematoma volume and neuronal apoptosis in perihematoma although Ndrg2 deficiency showed little effect on the initial hematoma volume after ICH induction by collagenase injection. Moreover, contrary to the increase in NDRG2 expression after ICH, the expression of glutamate transporter 1 (GLT1) in astrocytes was dramatically decreased in WT (Ndrg2 +/+) mice, while which could be more maintained in Ndrg2 knockout mice following ICH. Furthermore, in terms of the mechanism of epigenetic regulation of GLT1 by NDRG2, the results showed that NDRG2 directly interacted with NF-κB, and inhibited the nuclear import and DNA binding activity of the NF-κB p65 subunit after OxyHb treatment in primary astrocytes, decreasing GLT1 transcription and impairing glutamate uptake. Overall, our findings indicate that NDRG2 plays a key role in the pathology of ICH by regulating astrocytic GLT1 expression; thus suppressing NDRG2 may be a potential therapeutic target for ICH. [ABSTRACT FROM AUTHOR]

Objectives: Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH., Patients and Methods: This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months., Results: The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p =  0.087). Gender did not affect PTSD symptom development, (t = 1.34, p =  0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01)., Conclusion: Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: For patients hospitalized after acute ischemic stroke (AIS), the preadmission comorbidities, level of consciousness (LOC), age and neurologic deficit (PLAN) score can help to identify those who may have a poor outcome. Implementing the PLAN score in other types of stroke may also have predictive value. Our study aimed to evaluate the PLAN score's prognostic accuracy in predicting 1-year mortality and severe disability after intracerebral hemorrhage (ICH)., Methods: We analyzed data found in the China National Stroke Registry (CNSR) of 2,453 hospitalized patients in 132 urban Chinese hospitals, diagnosed with ICH from September 2007 to August 2008. The outcomes analysis included 30-day mortality, modified Rankin Scale score (mRS) of 5-6 at discharge, and 1-year mortality. Univariate and multivariate analysis was performed, and we calculated consistency statistics (C statistic). We evaluated the PLAN score performance using area under the curve (AUC) calculations., Results: We found that the 30-day mortality was 12.6%, the frequency of a mRS 5-6 at discharge was 20.6%, and 1-year mortality was 21.9%. The PLAN score had good predictive value in 30-day mortality (C statistic, 0.82), death or severe dependence at discharge (0.84), and 1-year mortality (0.82)., Conclusions: In patients hospitalized for ICH, the 30-day mortality, death or severe dependence at discharge and 1-year mortality can be predicted by the PLAN score. Similarly to patients hospitalized after AIS, the PLAN score can help to identify patients likely to have poor outcomes following hospitalization for ICH., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The localization of arteriovenous malformations (AVMs) intraoperatively in the setting of an acute intracerebral hemorrhage (ICH) is crucial to avoid damage of delicate vascular structures that may even further exacerbate the bleed. Currently, surgical mapping using preoperative angiographic is the standard of practice. We report the use of intraoperative ultrasound for the diagnosis and localization of an AVM in the case of a 61-year-old female with reported iodine contrast allergy and previous severe reaction, in a setting with limited resources, without other imaging options or timely transfer to another facility readily available. Immediate surgical care was warranted to avoid further deterioration of the patient; intraoperative diagnosis and localization of the suspected underlying lesion were done using ultrasound. The ultrasound display showed tubular anechoic intertwined structures that demonstrated bidirectional flow, which is suggestive of an AVM. The intraoperative diagnosis allowed the surgeon to avoid an inadvertent approach to the vascular malformation nidus or vessels, which could have further complicated the case. We believe that intraoperative ultrasound may be valuable for the neurosurgeons today in many settings. Despite the fact that this case occurred in a scenario with limited resources and no other imaging method (such as magnetic resonance imaging (MRI), magnetic resonance angiography (MRA)) available, we advise readers not to rely solely on intraoperative ultrasound., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Bertani et al.)

Rheumatoid vasculitis (RV) occurs in patients with long-standing rheumatoid arthritis (RA) or high levels of immunological factors and can result in devastating cardiovascular (CV) events. Here we report a case of a 38-year-old male who presented with hypertensive emergency and intracerebral hemorrhage (ICH). In the literature, a few observational studies have indicated the association of RA with hypertension; however, little evidence exists supporting a direct relationship between RA and ICH. In this case, we attempted to evaluate the complex relationship between all of these factors and found that early detection and treatment of RA may be beneficial in reducing ICH; however, large studies in the future are warranted to validate our observation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To examine clinical factors, including established electroencephalography (EEG) consensus recommendations, that may influence EEG-prescription in critically-ill intracerebral hemorrhage (ICH) patients in the neurointensive care unit., Methods: Retrospective analysis of 330 ICH patients admitted to a neurointensive care unit at an academic medical center between 01/2013-12/2015. We compared EEG prescription patterns with current EEG consensus recommendations, and employed univariate and multivariable logistic regression modeling to determine clinical variables associated with EEG ordering., Results: Seventy-eight (41%) of 190 subjects underwent EEG in accordance with EEG-consensus guidelines, demonstrating an overall accuracy (probability that EEG prescription aligned with EEG consensus recommendations) of 64.6% (95%-CI59.1-69.7). Factors independently associated with EEG ordering included fulfillment of EEG consensus recommendations, lower admission Glasgow Coma Scale (GCS), and presence of clinical seizures. The unadjusted and adjusted C-statistics for fulfillment of consensus recommendations was 0.74 (95%-CI 0.69-0.80) and 0.85 (95%-CI 0.81-0.90), respectively. Among 83 subjects undergoing EEG (25.2%), EEG findings informed clinical decision-making in 50 patients (60%)., Conclusions: EEG appeared underused in ICH, since <50% of patients who fulfilled guideline criteria underwent EEG. Prescription of EEG was related to factors beyond those included in consensus recommendations. Validation of our findings and their association with outcome is required., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Experimental animal model studies have shown neuroprotective properties of magnesium. We assessed the relationship between admission magnesium and admission stroke severity and 3-month clinical outcomes in patients with acute intracerebral hemorrhage (ICH)., Methods: The present study included 323 patients with acute ICH who were prospectively identified. Demographic characteristics, lifestyle risk factors, National Institute of Health Stroke Scale (NIHSS) score, hematoma volumes, and other clinical features were recorded at baseline for all participants. Patients were divided into three groups based on the admission magnesium levels (T1: <0.84; T2: 0.84-0.91; T3: ≥0.91 mmol/L). Clinical outcomes were death, poor functional outcome (defined by modified rankin ccale [mRS] scores 3-6) at 3 months., Results: After 3-month follow-up, 40 (12.4%) all-cause mortality and 132 (40.9%) poor functional outcome were documented. Median NIHSS scores for each tertile (T1 to T3) were 8.0, 5.5, and 6.0, and median hematoma volumes were 10.0, 8.05, and 12.4 ml, respectively. There was no significant association between baseline NIHSS scores (P=0.176) and hematoma volumes (P=0.442) in T3 and T1 in multivariable linear regression models. Compared with the patients in T1, those in T3 were associated with less frequency of all-cause mortality [adjusted odds ratio (OR), 0.10; 95% confidence interval (CI), 0.02-0.54; P-trend=0.010] but not poor functional outcome (adjusted OR, 1.80; 95%CI, 0.71-4.56; P-trend=0.227) after adjustment for potential confounders., Conclusion: Elevated admission serum magnesium level is associated with lower odds of mortality but not poor functional outcome at 3 months in patients with acute ICH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences in patients' characteristics, management and outcome at discharge and 90 days after PIVH., Methods: Consecutive patients with PIVH from a single center in China were enrolled over a 7- year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and outcomes were examined. The logistic regression models were used in the study to identify the predictors of poor outcome., Results: In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p = 0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001), harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission compared with men. There were no differences between female and male patients regarding the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI, 0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment, the gender specific independent predictors for unfavorable outcome were higher with a Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women, and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus (OR = 0.17; 95% CI, 0.03-0.86) in men., Conclusion: Women with PIVH exhibit some distinctive baseline features compared with men. The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus in men., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and purpose The pathogenesis of brain injury after intracerebral hemorrhage is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue.In recent years, there has been a greater research interest into the various inflammatory biomarkers and growth factors that are secreted during intracerebral hemorrhage. The biomarkers investigated in this study are tumor necrosis factor alpha (TNF alpha), C-reactive protein (CRP), homocysteine (Hcy), and vascular endothelial growth factor (VEGF). The aim of this study was to further investigate the effects of these biomarkers in predicting the acute severity outcome of intracerebral hemorrhage (ICH). Methods We conducted a retrospective chart review of patients with spontaneous ICH with TNF alpha, CRP, VEGF, and Hcy levels drawn on admission. Forty-two patients with spontaneous ICH with at least one of the above labs were included in the study. Primary outcomes included death, Glasgow Coma Scale (GCS) on admission, early neurologic decline (END), and hemorrhage size. Secondary outcomes included GCS on discharge, ICH score, functional outcome risk stratification scale of intracerebral hemorrhage (FUNC score), change in hemorrhage size, need for surgical intervention, and length of intensive care unit (ICU) stay. Results Forty-two patients with spontaneous intracerebral hemorrhage (ICH) were analyzed, 12 patients (28.5%) required surgical intervention, and four patients (9.5%) died. Only low VEGF serum values were found to predict mortality. TNF alpha, CRP, Hcy, and VEGF levels in our patients with ICH were not found to predict early neurologic decline and were not correlated with GCS on admission, initial hemorrhage size, change in hemorrhage size, need for surgical intervention, ICH score, FUNC score, midline shift, and length of ICU stay. CRP and Hcy were elevated in 58% and 31% of patients tested, respectively. GCS on admission and ICH score were significantly associated with mortality. Conclusion After careful statistical review of the data obtained from this patient population, only low VEGF values were found to be a significant predictor of mortality. However, elevated CRP and Hcy levels were associated with a non-significant trend in hemorrhage size and mortality suggesting that CRP and Hcy-lowering therapies may decrease hemorrhagic stroke risk and severity., Competing Interests: The authors have declared that no competing interests exist.

Hypertension (HTN) is the most common cause of non-traumatic ICH, yet echocardiography, which can stage hypertensive heart disease (HHD), is not part of the routine evaluation of patients with ICH. Previous studies have shown that angiotensin converting enzyme inhibitors and angiotensin receptor blockers are associated with regression of left ventricular hypertrophy (LVH) and reversal of myocardial fibrosis. Improvement in these architectural changes in the heart has been shown to improve outcomes and prevent major adverse cardiac events, including stroke. Obtaining echocardiography on ICH patients routinely could help to access the prevalence of HHD and to tailor antihypertensive regimens in this high risk group of patients. Further study is required to determine whether angiotensin directed therapies provide optimal secondary prevention in ICH patients with HHD. [ABSTRACT FROM AUTHOR]

A 17-year-old woman was urgently transported to our hospital due to consciousness disturbance. A blood examination revealed intracerebral hemorrhage, WBC 233,800/l, blasts 93%, and disseminated intravascular coagulation. The results of bone-marrow aspiration indicated acute myeloid leukemia (M2 in FAB classification) with t (7;11) (p15;p15) and the resulting chimeric gene NUP98-HOXA9 and with FLT3-ITD. Following hematoma evacuation, induction therapy was initiated and the leukocytes in the cerebrospinal fluid observed in the spinal drainage were monitored. Because they increased on days 5 and 9 after the completion of induction therapy, intrathecal chemotherapy (IT) was performed; this finally contributed to controlling AML in the central nervous system (CNS), together with the restoration of normal hematopoiesis. Subsequently, after complete molecular remission with consolidation therapies containing high-dose cytarabine, a bone-marrow transplantation with a myeloablative regimen was conducted from a 1-allele mismatched sibling donor. Finally, the patient was discharged without major sequela on day 228 after the first visit. The management of CNS disease in AML with intracerebral hemorrhage remains unclear. Our case suggests that IT at the appropriate time based on the monitored number of cerebrospinal fluid leukocytes could be useful in controlling AML in the CNS after intracerebral hemorrhage.

Cerebrovascular autoregulation may be dysfunctional after acute intracerebral hemorrhage (ICH). This disruption in autoregulation can potentially result in secondary neurological damage that may present as an intracranial hemorrhage at locations distant from the primary site of hemorrhage. We discuss a case of 68-year-old female who presented with acute left hemiparesis from a spontaneous right frontal ICH. Magnetic resonance imaging (MRI) was negative for any other blooming artifact. Her weakness was improving, but after 72 hours from admission, she had an acute change in her mental status and was found to have a new left frontal ICH distant from the primary hemorrhage. Cerebral dysregulation following spontaneous ICH may predispose patients with risk factors, such as chronic hypertension, to a secondary spontaneous ICH distant from initial ICH. Recognizing this phenomenon can guide the management of acute ICH., Competing Interests: The authors have declared that no competing interests exist.

Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy ( p  = 0.042) and showed tendency for improving functional recovery ( p  = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage., Competing Interests: The authors declare no conflicts of interest.

Hypertensive intracerebral hemorrhage (ICH) is still a highlighting global issue. Endoscopic evacuation as a minimally invasive treatment became an alternative other than conventional craniotomy and catheter drainage for ICH. However, there is no unified indication or standardized procedure on endoscopic treatment of ICH. Here we explored the literature and gathered information from different studies, to review the background, technical points, and existing problems of endoscopic treatment for ICH.

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain., Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management., Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries., Predictors: Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively)., Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms., Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity)., Limitations: Generalizability issues arising from a clinical trial population., Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disease of proven genetic origin affecting 0.3-0.5% of the general population. It is characterized by abnormally enlarged and leaky capillaries, which predispose to seizures, focal neurological deficits and intracerebral hemorrhage. Causative loss-of-function mutations have been identified in 3 genes, KRIT1 (CCM1), CCM2 and PDCD10 (CCM3). While providing new options for the development of pharmacological therapies, recent advances in knowledge of the functions of these genes have clearly indicated that they exert pleiotropic effects on several biological pathways. Recently, we found that defective autophagy is a common feature of loss-of-function mutations of the 3 known CCM genes, and underlies major phenotypic signatures of CCM disease, including endothelial-to-mesenchymal transition and enhanced ROS production, suggesting a unifying pathogenetic mechanism and reconciling the distinct therapeutic approaches proposed so far. In this invited review, we discuss autophagy as a possible unifying mechanism in CCM disease pathogenesis, and new perspectives and avenues of research for disease prevention and treatment, including novel potential drug repurposing and combination strategies, and identification of genetic risk factors as basis for development of personalized medicine approaches.

Background: Cerebral venous thrombosis developing after surgical or endovascular obliteration of arteriovenous fistula (AVF) is a rare but devastating complication that has not been adequately reported. Case Description: Two patients presenting with AVF (1 pial, 1 dural) and large venous pouches were successfully treated by surgical and endovascular means and were neurologically intact postoperatively. Rapid neurologic deterioration was seen on postoperative day 5 in the first patient and postoperative day 2 in the second patient. Both patients had massive cerebral venous thromboses on brain imaging and surgical exploration. One patient died and the other was severely disabled. Conclusion: Rapid occlusion of a high-flow AVF resulting in significant venous stasis can precipitate thrombosis of the venous system distal to the fistulous point. In the presence of large venous pouches and significant venous stasis, strict therapeutic anticoagulation may be required to prevent cerebral venous thrombosis. Therapeutic anticoagulation, though feasible following endovascular treatment, may prove particularly challenging after open surgical interventions given the risk of hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Background: The authors report a case of lateral posterior choroidal artery pseudoaneurysm that caused a spontaneous thalamic hemorrhage. The case supports obtaining computed tomographic angiography (CTA) even in seemingly routine cases of hypertensive hemorrhage and demonstrates a possibly unreported type of aneurysm causing thalamic hemorrhage. Case Description: A 60-year-old man with a history of hypertension presented with a spontaneous right thalamic hemorrhage, and CTA showed a focus of contrast inside the hematoma. One month later, the patient was well but a CTA showed that the hematoma had resolved but that there was enlargement of the contrast-enhancing lesion in the thalamus. Catheter angiography showed an aneurysm of the lateral posterior choroidal artery. This was excised via an occipital interhemispheric supratentorial subcallosal approach. The patient recovered fully and returned to work 3 months later. Conclusion: The case shows the need to carefully review CTA after ICH, even in cases of seemingly typical hypertensive ICH. [ABSTRACT FROM AUTHOR]