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Purpose: To determine whether spectral detector CT (SDCT) with a plain non-enhanced monochromatic CT, a water-weighted image after iodine removal, an iodine map, and Mono energetic images changes the diagnosis and classification of intracranial hemorrhage based on single energy CT after endovascular treatment (EVT) for ischemic stroke. Methods: Two readers evaluated single energy and SD CT data collected from 63 patients within one week after EVT. They diagnosed ICH or contrast staining, and graded ICH according to the Heidelberg and Safe Implementation of Thrombolysis in Stroke–Monitoring Study (SITS-MOST) classification. Differences in diagnosis between single energy and SD CT were tested with Pearson's chi-squared test. Diagnostic values of single energy CT were calculated. Interrater agreement was based on Cohen’s Kappa. Results: When spectral data were added to single energy CT, the diagnosis of ICH changed in 8 CT scans (13%): in 4, the diagnosis of ICH was rejected and in 4, initially undetected ICH was diagnosed. In an additional 3 patients, the ICH grade was modified. CT alone had 88% sensitivity, 87% specificity, 88% positive diagnostic value, 87% negative diagnostic value, and 87% overall accuracy for ICH compared to SDCT. Interreader agreement on the presence of ICH was 0.84 (95% CI 0.51–0.86) for spectral CT and 0.84 (95% CI 0.73–0.97) for single energy CT. Conclusion: SD CT after endovascular treatment contributes to the distinction between intracranial hemorrhage and contrast staining.

Background and Objective Clinicians working in intensive care frequently report perceptions of inappropriate care (PIC) situations. Intracerebral haemorrhage (ICH) is associated with high rates of mortality and morbidity. Prognosticating after ICH is complex and may be influenced by clinicians’ subjective impressions and biases, which may, in turn, influence decision making regarding the level of care provided. The aim of this study was to qualitatively explore perceptions of neurocritical care in relation to the expected functional outcome for ICH patients. Design Qualitative study using semi-structured interviews with neurocritical care doctors and nurses. Setting Neurocritical care (NCC) department in a UK neuroscience tertiary referral center. Subjects Eleven neurocritical care nurses, five consultant neurointensivists, two stroke physicians, three neurosurgeons. Intervention None. Measurements and Main Results We conducted 21 semi-structured interviews and identified five key themes: (1) prognostic uncertainty (2) subjectivity of good versus poor outcome (3) perceived inappropriate care (PIC) situations (including for frail elderly patients) (4) challenging nature of decision-making (5) clinician distress. Conclusions Caring for severely affected ICH patients in need of neurocritical care is challenging, particularly with frail elderly patients. Awareness of the challenges could facilitate interventions to improve decision-making for this group of stroke patients and their families, as well as measures to reduce the distress on clinicians who care for this patient group. Our findings highlight the need for effective interdisciplinary shared decision making involving the family, taking into account patients’ previously expressed values and preferences and incorporating these into bespoke care planning.

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.

This study aims at evaluating the importance and its underlying mechanism of the cluster of microRNA-144/451 (miR-144/451) in the models with intracerebral hemorrhage (ICH). A model of collagenase-induced mice with ICH and a model of mice with simple miR-144/451 gene knockout (KO) were used in this study. Neurodeficits and the water content of the brain of the mice in each group were detected 3 days after collagenase injection. The secretion of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), as well as certain biomarkers of oxidative stress, was determined in this study. The results revealed that the expression of miR-451 significantly decreased in the mice with ICH, whereas miR-144 showed no significant changes. KO of the cluster of miR-144/451 exacerbated the neurological deficits and brain edema in the mice with ICH. Further analyses demonstrated that the KO of the cluster of miR-144/451 significantly promoted the secretion of TNF-α and IL-1β and the oxidative stress in the perihematomal region of the mice with ICH. In addition, the miR-144/451's depletion inhibited the regulatory axis' activities of miR-451-14-3-3ζ-FoxO3 in the mice with ICH. In conclusion, these data demonstrated that miR-144/451 might protect the mice with ICH against neuroinflammation and oxidative stress by targeting the pathway of miR-451-14-3-3ζ-FoxO3.

A 62-year-old man with a past medical history of uncontrolled hypertension, tobacco abuse, and type 2 diabetes mellitus (DM) presented to the emergency department due to worsening confusion over the last 24 hours as reported by a friend. A CT brain without contrast was obtained, which demonstrated a bilateral intracerebral hemorrhage (ICH). Spontaneous bilateral intracerebral hemorrhage is an exceedingly rare condition with only 30-40 reported cases. This patient had a non-traumatic ICH, without focal neurological deficits on presentation. The patient had no complications while hospitalized despite the imaging findings. Clinicians should keep a broad differential similar to causes of spontaneous non-traumatic unilateral ICH, including uncontrolled hypertension, tumor mass, coagulopathies, and vasculopathies. Although brain CT is the most appropriate study in the acute setting, MRI is the gold standard for definitive diagnosis and should be performed urgently to further characterize the lesions. Clinicians should be aware of non-traumatic ICH complications, which include aspiration pneumonia, quadriparesis, hemiparesis, and recurrent stroke. Management is supportive mainly by reducing risk factors for complications, including blood pressure control, aspiration precautions, reversing coagulopathies, frequent neurological checks, and consultation with multiple disciplines such as neurosurgery or neurointerventional radiology.

Objective Hypertension is the commonest cause of acute spontaneous intracerebral hemorrhage (ICH) which is life-threatening with a poor prognosis. The aim of this study is to evaluate the prognosis and blood pressure monitoring and control in patients presented by acute spontaneous ICH. Methods One hundred and fifty patients presented by acute spontaneous ICH were classified according to the modified Rankin Scale (mRS) score after discharge to 70 patients with better outcomes (mRS = 0–2) while 80 patients with poor outcome (mRS = 3–6). Independent factors that were significantly related to prognosis were assessed by multivariate logistic regression. Spearman’s correlation of the blood pressure monitoring in the acute ICH and the outcome was investigated. Results Systolic blood pressure at the onset of ICH was higher in the unfavorable outcome group (P = 0.009). Diastolic blood pressure 1 h after admission, systolic blood pressure 6 h after admission, and the systolic blood pressure 24 h after admission to hospital were lower in the favorable outcome group (P = 0.005, P = 0.007 and 0.01, respectively). The independent variables related to favorable outcomes were younger age patients (P = 0.004), better level of consciousness at admission to hospital (P = 0.0001), and lower systolic blood pressure 6 h after admission to hospital (P = 0.005), decreased volume of hematoma (P = 0.05), supratentorial ICH (P = 0.02), and absence of intraventricular hemorrhage (P = 0.02). Conclusions Proper control and monitoring of the blood pressure in acute intracerebral hemorrhage must be initiated immediately especially in the first 6 h after hospitalization. Trial registration ClinicalTrials.gov ID: NCT04191863 'Retrospectively registered'

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.

Background The neuroprotective effects of neuroserpin (NSP) have been well documented in both patients and animal models with cerebral ischemia; however, have never been investigated in hemorrhagic stroke. The aim of this study is to verify the neuroprotection of NSP in the non-tPA-induced intracerebral hemorrhage (ICH) mouse model. Methods C57BL/6J male mice (n = 198) were involved in this study. ICH models were established with infusion of autologous blood into the brain parenchyma. We then detected NSP expression in ICH brains by morphological methods and western blotting analysis. We measured the brain water content and detected blood-brain barrier (BBB) permeability to verify the neuroprotective effects of NSP. Results We found that NSP protein expression was upregulated in ICH models, with a peak at 48 h after ICH induction. NSP local administration reduced the brain edema and the BBB permeability in ICH models. The neurological deficits were also ameliorated. Thus, the neuroprotection of NSP in ICH state was confirmed. Additionally, we also found that the distribution pattern of occludin-expressing cells was obviously changed by the ICH procedure but partly recovered after NSP administration. This finding indicated that protecting and/or repairing the injured vascular endothelial cells may be a potential mechanism involved in NSP neuroprotection, which needs further verification. Conclusions Our results supported the fact that NSP may be considered as a potential therapy for ICH for the neuroprotective effects including amelioration of the edema. Electronic supplementary material The online version of this article (10.1186/s12883-017-0976-1) contains supplementary material, which is available to authorized users.

In many cerebral grey matter structures including the neocortex, spreading depolarization (SD) is the principal mechanism of the near-complete breakdown of the transcellular ion gradients with abrupt water influx into neurons. Accordingly, SDs are abundantly recorded in patients with traumatic brain injury, spontaneous intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage (aSAH) and malignant hemispheric stroke using subdural electrode strips. SD is observed as a large slow potential change, spreading in the cortex at velocities between 2 and 9 mm/min. Velocity and SD susceptibility typically correlate positively in various animal models. In patients monitored in neurocritical care, the Co-Operative Studies on Brain Injury Depolarizations (COSBID) recommends several variables to quantify SD occurrence and susceptibility, although accurate measures of SD velocity have not been possible. Therefore, we developed an algorithm to estimate SD velocities based on reconstructing SD trajectories of the wave-front's curvature center from magnetic resonance imaging scans and time-of-SD-arrival-differences between subdural electrode pairs. We then correlated variables indicating SD susceptibility with algorithm-estimated SD velocities in twelve aSAH patients. Highly significant correlations supported the algorithm's validity. The trajectory search failed significantly more often for SDs recorded directly over emerging focal brain lesions suggesting in humans similar to animals that the complexity of SD propagation paths increase in tissue undergoing injury., Highlights • An algorithm has been developed to estimate spreading depolarization (SD) velocities in neurocritical care. • The algorithm is based on reconstructing SD trajectories of the wave-front's curvature center. • It utilizes MRI scans and time-of-SD-arrival-differences between subdural electrode pairs. • Variables indicating SD susceptibility correlated with algorithm-estimated SD velocities. • The findings establish the opportunity to exploit the SD velocity as part of the multimodal assessment in neurocritical care.

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.

Developmental venous anomaly (DVA) is the most common, benign, congenital vascular malformation of the brain and mostly an incidental finding on imaging. The exact etiology of DVA is unknown but thought to be due to medullary vein thrombosis during embryonic venous development. DVA is generally asymptomatic although associated neurologic deficits and seizures have been described. Several reports of DVA causing neurovascular compression, obstructive hydrocephalus, venous infarction, and intracerebral hemorrhage (ICH) have been described. In this report, we discuss a patient with fluctuating neurological symptoms found to have multiple DVA, predominantly draining into the deep venous system. To the best of our knowledge, DVAs leading to simultaneous ischemic stroke, intracerebral hemorrhage, and seizures are not reported in the literature. We reviewed the relevant literature and discussed the epidemiology and clinical and radiological characteristics of DVA.

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.

Cell death is deeply involved in pathophysiology of brain injury after intracerebral hemorrhage (ICH). Necroptosis, one of the recently discovered forms of cell death, plays an important role in various diseases, including ICH. Previous studies have suggested that a considerable number of neurons undergoes necroptosis after ICH. However, necroptosis of microglia after ICH has not been reported to date. The present study demonstrated for the first time that necroptosis occurred in the microglia surrounding the hematoma after ICH in C57 mice, and melatonin, a hormone that is predominantly synthesized in and secreted from the pineal gland, exerted a neuroprotective effect by suppressing this process. When we further explored the potential underlying mechanism, we found that melatonin inhibits RIP3-mediated necroptosis by regulating the deubiquitinating enzyme A20 (also known as TNFAIP3) expression after ICH. In summary, we have demonstrated the role of microglial necroptosis in the pathogenesis of ICH. More importantly, A20 was identified as a novel target of melatonin, which opens perspectives for future research.

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. Keywords: Endoscopic treatment, Hypertension, Intracerebral hemorrhage (ICH), Hematoma evacuation

The effectiveness of current management of critically ill stroke patients depends on rapid assessment of the type of stroke, ischemic or hemorrhagic, and on a patient's general clinical status. Thrombolytic therapy with recombinant tissue plasminogen activator (r-tPA) is the only effective treatment for ischemic stroke approved by the Food and Drug Administration (FDA), whereas no treatment has been shown to be effective for hemorrhagic stroke. Furthermore, a narrow therapeutic window and fear of precipitating intracranial hemorrhage by administering r-tPA cause many clinicians to avoid using this treatment. Thus, rapid and objective assessments of stroke type at admission would increase the number of patients with ischemic stroke receiving r-tPA treatment and thereby, improve outcome for many additional stroke patients. Considerable literature suggests that brain-specific protein biomarkers of glial [i.e. S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP)] and neuronal cells [e.g., ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), αII-spectrin breakdown products SBDP120, SBDP145, and SBDP150, myelin basic protein (MBP), neurofilament light chain (NF-L), tau protein, visinin-like protein-1 (VLP 1), NR2 peptide] injury that could be detected in the cerebrospinal fluid (CSF) and peripheral blood might provide valuable and timely diagnostic information for stroke necessary to make prompt management and decisions, especially when the time of stroke onset cannot be determined. This information could include injury severity, prognosis of short-term and long-term outcomes, and discrimination of ischemic or hemorrhagic stroke. This chapter reviews the current status of the development of biomarker-based diagnosis of stroke and its potential application to improve stroke care.

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.

Traumatic subarachnoid hemorrhage (SAH) is the second most frequent intracranial hemorrhage and a common radiologic finding in computed tomography. This study aimed to estimate the risk of mortality in adult trauma patients with traumatic SAH concurrent with other types of intracranial hemorrhage, such as subdural hematoma (SDH), epidural hematoma (EDH), and intracerebral hemorrhage (ICH), compared to the risk in patients with isolated traumatic SAH. We searched our hospital&rsquo, s trauma database from 1 January, 2009 to 31 December, 2018 to identify hospitalized adult patients &ge, 20 years old who presented with a trauma abbreviated injury scale (AIS) of &ge, 3 in the head region. Polytrauma patients with an AIS of &ge, 3 in any other region of the body were excluded. A total of 1856 patients who had SAH were allocated into four exclusive groups: (Group I) isolated traumatic SAH, n = 788, (Group II) SAH and one diagnosis, n = 509, (Group III) SAH and two diagnoses, n = 493, and (Group IV) SAH and three diagnoses, n = 66. One, two, and three diagnoses indicated occurrences of one, two, or three other types of intracranial hemorrhage (SDH, EDH, or ICH). The adjusted odds ratio with a 95% confidence interval (CI) of the level of mortality was calculated with logistic regression, controlling for sex, age, and pre-existing comorbidities. Patients with isolated traumatic SAH had a lower rate of mortality (1.8%) compared to the other three groups (Group II: 7.9%, Group III: 12.4%, and Group IV: 27.3%, all p &lt, 0.001). When controlling for sex, age, and pre-existing comorbidities, we found that Group II, Group III, and Group IV patients had a 4.0 (95% CI 2.4&ndash, 6.5), 8.9 (95% CI 4.8&ndash, 16.5), and 21.1 (95% CI 9.4&ndash, 47.7) times higher adjusted odds ratio for mortality, respectively, than the patients with isolated traumatic SAH. In this study, we demonstrated that compared to patients with isolated traumatic SAH, traumatic SAH patients with concurrent types of intracranial hemorrhage have a higher adjusted odds ratio for mortality.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. MATERIALS AND METHODS: Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not (P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage. CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.

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.

Stroke is a major cause of neurological disability and death in industrialized nations. Therapeutic hypothermia has been shown to protect the brain from ischemia, stroke, and other acute neurological insults at the laboratory level. It has been shown to improve neurological outcome in certain clinical settings including anoxic brain injury due to cardiac arrest and hypoxic-ischemic neonatal encephalopathy. Hypothermia seems to affect multiple aspects of brain physiology and it is likely that multiple mechanisms underlie its protective effect. Understanding the events that occur in the ischemic brain during hypothermia might help lead to an understanding of how to protect the brain against acute injuries.

Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH) and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins.

Objectives We aimed to investigate the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood cells in spontaneous intracerebral hemorrhage (ICH) patients and to analyze its clinical significance. Design and methods Tim-3 expression on peripheral immunocytes from ICH patients and healthy volunteers was measured by flow cytometry. The correlation between Tim-3 expression and the clinical indices was estimated using linear regression. Results Tim-3 expressions on peripheral CD3+ T cells and CD8+ T cells in ICH patients are significantly downregulated, while Tim-3 expressions on CD14+ monocytes and CD16+CD56+ NK cells are increased. Furthermore, Tim-3 expression on peripheral CD8+ T cells was negatively correlated with the inflammatory response, the disease severity and the outcome of ICH patients. However, there was no relationship between Tim-3 expression and blood glucose concentration. Conclusions Altered expression of Tim-3 might play an important role in the pathogenesis of ICH, demonstrating that Tim-3 might be a novel candidate molecule for prognosis evaluation of ICH patients., Highlights • Tim-3 expression on peripheral blood cells in ICH patient was dysregulated. • Tim-3 expression on CD8+ T cells negatively correlated with the disease severity. • Tim-3 expression on CD8+ T cells negatively correlated with the patients' outcome.

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.

Markku Kaste ja Filip Scheperjans työryhmän jäsenenä. 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 90, 60-90, and 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. Am J Kidney Dis. 68(1): 94-102. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.

Background: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. Methods: Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. Results: Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19–2.84; current use OR 2.23, CI 1.37–3.62; heavy use OR 2.48, CI 1.50–4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). Conclusion: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.

Lacunar infarction, white matter hyperintensities (WMH), deep cerebral microbleeds (dCMB), and deep intracerebral hemorrhage (ICH) are increasingly recognized as manifestations of a common underlying vasculopathy, encompassed by the term "cerebral small-vessel disease" (CSVD). Epidemiologic studies have found robust associations of the individual aspects of CSVD with aging and hypertension; however, heritability estimates and the disproportionate burden of CSVD in underrepresented minorities suggest that genetic factors contribute substantially to CSVD risk. Here we present the rationale for studying these phenotypes as part of a spectrum of CSVD, review aspects of genetic study design, summarize current knowledge of genetic contribution to CSVD, and discuss the next steps required to translate these genetic discoveries into therapies for this devastating disease. Genetic studies were identified using PubMed. Regions achieving genome-wide significance in association studies, meta-analyses of candidate gene studies, and studies of genes associated with Mendelian conditions exhibiting CSVD phenotypes have been summarized.