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A primary intraventricular haemorrhage (PIVH) usually presents with non-localised neurological symptoms since the haematoma is limited to the ventricles. However, it is sometimes associated with focal neurological signs, whose pathophysiologies are not confirmed. Here, we report on a case of PIVH who showed rare manifestations in the acute stage: upward gaze palsy and convergence insufficiency. The CT and MRI showed intraventricular haematoma without evidence of parenchymal haemorrhage, local mass effect around midbrain or hydrocephalus. There had been bilateral papilloedema, and it resolved along with improvement of the ophthalmic symptoms, suggesting a possible causal relation to increased intracranial pressure. The ophthalmic abnormalities suggested injury of the rostral part of the midbrain, especially the region around the dorsal midbrain tectum. It should be known that PIVH is one of the causes of acutely developing upward gaze palsy and convergence insufficiency.

PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is an important signal transduction pathway mediated by enzyme-linked receptors with many biological functions in mammals. This pathway modulates the epigenetic modification of DNA and target gene histones and plays a significant role in regulating biological activity, disease progression, oncogenesis, and cancer progression. PI3K/AKT/mTOR signaling pathway involves and mediates many cellular processes such as nutrient uptake, proliferation, anabolic reactions, and cell survival. Several studies have shown that PI3K/AKT/mTOR has been a promising therapeutic approach to intracerebral hemorrhage (ICH). ICH is characterized by the progressive development of hematoma, which leads to the structural destabilization of the neurons and glial cells, leading to neuronal deformation, further contributing to mitochondrial dysfunction, membrane depolarization, oligaemia, and neurotransmitter imbalance. Partial suppression of cell metabolism and necrosis can occur, depending on the degree of mitochondrial dysfunction. Therefore in the following review, we discuss whether or not the activation of the PI3K/AKT/mTOR signaling pathway could minimize neuronal dysfunction following ICH. We further elaborate the review by discussing the updated pathophysiology of brain hemorrhage and the role of molecular targets in other neurodegenerative diseases. This review provides current approachable disease treatment in various disease states, single and dual PI3K/AKT/mTOR signaling pathway modulators.

A man in his 80s with chronic lymphocytic leukaemia and permanent atrial fibrillation was admitted to our department with the diagnosis of community-acquired pneumonia. He was receiving rivaroxaban 10 mg and was shifted to enoxaparin (1 mg/kg two times per day) during hospitalisation. On the

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy classically thought to be caused by infections through the process of molecular mimicry. We report a case of GBS caused by intracerebral haemorrhage and postulate potential theories for the development of GBS following intracerebral haemorrhage and other non-infectious aetiologies by association. We highlight that GBS is an important differential diagnosis in patients developing generalised paresis following intracerebral haemorrhage.

Background Synovial sarcoma is a soft tissue sarcoma, of uncertain histological origin, usually located near large joints and concerning mainly young adults. Intracranial presentation in the form of metastasis from a primitive body sarcoma has been rarely reported. However, intracranial primitive synovial sarcoma (IPSS) is extremely rare and only a few cases have been reported in the literature. Case description We present the case of a 48-year-old man, with no particular medical history, that was referred to our hospital for severe headache with a normal neurological exam and a CT cerebral scan showing a left frontal lobe hematoma. The initial cerebral CT scan didn’t show any vascular malformation and the body CT scan was negative for a primitive lesion. A close follow-up with a cerebral MRI three months later, demonstrated a T1 enhanced lesion with an important volume progression. The patient underwent a complete surgical removal of this lesion and the first pathology diagnosis was compatible with a meningioma. After further proofreading by an expert and molecular analysis, the diagnosis of monophasic synovial sarcoma was confirmed. Nine months after the first surgery, the follow-up MRI showed the progressive recurrence of the lesion and in this context the patient underwent a second surgery with total resection of the tumor and frontal thin margin excision. Afterwards, the patient was treated with adjuvant radiotherapy, with a good clinical evolution, and till now the follow-up shows no recurrence. Conclusion IPSS is an extremely rare sarcoma, with challenging diagnosis and difficult management. Specific molecular analysis is necessary. Complete resection followed by radiotherapy seem to be the most appropriate therapeutic approach. However, the prognosis is still poor. Our case is even rarer because of the initial presentation as a cerebral hematoma.

Background: Cerebral venous sinus thrombosis is rare and might be overlooked by healthcare providers. It often occurs in the transverse sinuses, superior sagittal sinus, and the vein of Trolard. Sphenoparietal sinus (SPS) and/or superficial middle cerebral vein (SMCV) thrombosis is rare and only 12 cases reported in the literature. Case description: We report a 47-year-old woman with iron deficiency anemia associated with myoma uteri who developed left SPS and SMCV thrombosis. She presented with sudden unconsciousness, right hemiplegia, and aphasia. Brain computed tomography showed subcortical hemorrhages in the left frontal and temporal lobes. Magnetic resonance imaging did not reveal the cause of the bleeding. Although antihypertensive treatment with nicardipine was initiated, she deteriorated into coma the next day and underwent emergency decompressive craniectomy. Thrombosis of the SMCV was identified during surgery. Re-examination of preoperative T2 star-weighted imaging revealed thrombosis of the SPS and SMCV. Conclusion: All but one of the reviewed cases had the thrombosis develop on the left side, which may be attributed to anatomical and brain functional laterality. When an edematous change or cortical hemorrhage of unknown cause is encountered within the perisylvian region, especially on the left side, the possibility of SPS and SMCV thrombosis should be considered.

Mechanical thrombectomy; New device; Stroke Trombectomia mecànica; Nou dispositiu; Ictus Trombectomía mecánica; Nuevo dispositivo; Ictus Introduction The ANA™ (Anaconda Biomed) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, ANA allows distal aspiration in combination with a stentretriever (SR) to mobilize the clot into the funnel where it remains copped during extraction. We investigate safety and efficacy of ANA™ in a first-in-man study. Methods Prospective data was collected on 35 consecutive patients treated as first line with ANA™ at a single centre. Outcome measures included per-pass reperfusion scores, symptomatic intracerebral hemorrhage (sICH), NIHSS at day 5, and mRS at 90 days. Results Median NIHSS was 12(9−18). Sites of primary occlusion were: 5 ICA, 15 M1-MCA, 15 M2-MCA. Primary performance endpoint, mTICI 2b-3 within 3 passes without rescue therapy was achieved in 91.4% (n = 32) of patients; rate of complete recanalization (mTICI 2c-3) was 65.7%. First pass complete recanalization rate was 42.9%, and median number of ANA passes 1(IQR: 1−2). In 17.1% (n = 6) rescue treatment was used; median number of rescue passes was 2(1–7), leading to a final mTICI2b-3rate of 94.3% (n = 33). There were no device related serious adverse events, and rate of sICH was 5.7% (n = 2). At 5 days median NIHSS was 1 (IQR 1−6) and 90 days mRS 0−2 was achieved in 60% of patients. Conclusions In this initial clinical experience, the ANA™ device achieved a high rate of complete recanalization with a good safety profile and favourable 90 days clinical outcomes. The study was funded by Anaconda Biomed S.L.

Purpose Timely identification and treatment of intracranial hematomas in patients with brain injury is essential for successful treatment. This study evaluates Infra-scanner as a handy medical screening tool for diagnosing, on-site, cerebral hematomas in patients with head injury. Materials and methods Patients referred to the emergency department of university hospitals with mild to moderate brain trauma, up to 12 h from injury were included. NIR sensors of infra-scan device were placed on the right and left frontal, temporal, peritoneal and occipital parts of the head and light absorption was recorded. Positive or negative cerebral hemorrhage cases were compared with contrast-enhanced CT scan results as the gold standard. Diagnostic parameters of the device and cases related to bleeding were analyzed and reported. Results A total of 300 patients were studied. Sensitivity of the infrasound scanner in the Iranian study population was 94.8 (95% CI: 88% -100) and its specificity was 86.9 (95% CI: 79% -99% 99). Negative predictive value (NPV) was 90.3% and positive predictive value (PPV) was 92.9%. Sensitivity in men (95.7%) (95%CI, 90% -1) was more than women (95% CI, 81% -99%)90%. At the ages of less than 36 years, sensitivity (95.3%) and specificity (87.1%) were more than sensitivity (94.4%) and specificity (86.5%) over 36 years old. If the test had been performed in less than / equal to two hours from trauma, the sensitivity (94.9%) and the specificity (92%) were greater than the sensitivity (94.6%) and the specificity (75%) during when the scan had been performed in more than two hours from trauma. In general, in extra-axial bleeding including EDH, SAH, SDH, the sensitivity was 95.1% and the specificity was 84.5%, while in intra-axial bleeding, including ICH and IVH, the sensitivity was lower (93.9%) and the specificity was 91.7. The sensitivity of the device in detecting bleeding in the occipital lobe (95.8%) was higher than other brain lobes. Conclusion This study shows that Infra-scanner is useful in initial examination and screening of patients with head injury and can be used as an adjunct to a CT scan or when not available and may allow earlier treatment which reduce the secondary damage to the hematoma.

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging. Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017. Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p

Background: We evaluated the effect of persistent hyperglycemia on outcomes in 1000 patients with intracerebral hemorrhage enrolled within 4.5 hours of symptom onset. Methods: We defined moderate and severe hyperglycemia based on serum glucose levels ≥140 mg/dL— Results: In the multivariate analysis, both moderate (odds ratio, 1.8 [95% CI, 1.1–2.8]) and severe (odds ratio, 1.8 [95% CI, 1.2–2.7]) hyperglycemia were associated with higher 90-day death or disability after adjusting for Glasgow Coma Scale score, hematoma volume, presence or absence of intraventricular hemorrhage, hyperlipidemia, cigarette smoking, and hypertension (no interaction between hyperglycemia and preexisting diabetes, P =0.996). Among the patients without preexisting diabetes, both moderate (odds ratio, 1.8 [95% CI, 1.0–3.2]) and severe (odds ratio, 2.0 [95% CI, 1.1–3.7]) hyperglycemia were associated with 90-day death or disability after adjusting for above mentioned potential confounders. Among the patients with preexisting diabetes, moderate and severe hyperglycemia were not associated with 90-day death or disability. Conclusions: Persistent hyperglycemia, either moderate or severe, increased the risk of death or disability in nondiabetic patients with intracerebral hemorrhage. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01176565.

Antithrombotic drugs (ADs) are the mainstay of secondary prevention of thrombotic vascular diseases. Management of patients under long-term treatment with ADs admitted for acute cerebrovascular disease, either ischemic stroke (IS) or intracerebral hemorrhage (ICH), has become a frequent situation that might influence decision-making processes from diagnosis to therapeutic strategies. The aim of this review is to summarize current data from the literature to help clinicians in their decisions for stroke care in patients taking ADs. While a large body of data have made it possible to codify the management of patients presenting IS or ICH under antiplatelet drugs and vitamin K antagonists, the increasing use of direct oral anticoagulants (DOAs) and future development of new antiplatelet drugs raise new problems. Development of rapid assessment tools measuring specific biological activity and reversion agents dedicated to each class of DOAs should make it possible to optimize individual therapeutic strategies. This review highlights the main steps of IS and ICH management from early identification of ADs, and use of dedicated biological assays, to the stepwise strategy to apply revascularization or reversal therapies and finally the resumption of ADs with a focus on individual clinical and radiological characteristics for more personalized care.

Introduction:The purpose of this study was to investigate seasonal variation in stroke incidence using data from a large-scale stroke registry of general population in current Japan., Methods:Shiga Stroke Registry (SSR) is an ongoing population-based registry of stroke that occurred in the Shiga Prefecture in central Honshu, Japan. A total 6,688 cases of first-ever stroke, with onset dates ranging from 1 January 2011 to 31 December in 2013 were included in this study. Incidence rates of first-ever stroke in each season were estimated using the person-year approach and adjusted for age and sex using the Poisson regression models., Results:From 2011 to 2013, we identified a total of 6,688 stroke cases (3,570 men, 3,118 women), of which 4,480 cases had ischemic stroke (2,518 men, 1,962 women), 1,588 had intracerebral hemorrhage (857 men, 731 women) and 563 had subarachnoid hemorrhage (166 men, 397 women). Age- and sex-adjusted incidence rates of total stroke were 151 (95% confidence interval [CI] 144-160, p =, Conclusion:In the present large-scale stroke registry of general population, incidence rates of stroke were highest in winter and lowest in summer in current Japan.

Supplemental Digital Content is available in the text., Background and Purpose: We investigated the relation between the ipsilesional corticospinal tract (CST) state and activity of daily living independence in patients with chronic intracerebral hemorrhage. Methods: Fifty-six consecutive patients with unilateral intracerebral hemorrhage and 38 healthy control subjects were recruited for this study. The Motricity index and the modified Barthel index were used to evaluate motor function of the affected extremities and activity of daily living independence, respectively. The diffusion tensor imaging parameter values for fractional anisotropy (FA) and voxel number (VN) of the CST were determined. Ratios of the ipsilesional to the contralesional CST measures were calculated and are presented as the CST-ratio (FA value and VN). Results: The FA value and VN of the ipsilesional CST and the CST-ratio in the patient group were lower than those of the control group (P

Background and Purpose: Hematoma volume (HV) is a significant diagnosis for determining the clinical stage and therapeutic approach for intracerebral hemorrhage (ICH). The aim of this study is to develop a robust deep learning segmentation method for the fast and accurate HV analysis using computed tomography. Methods: A novel dimension reduction UNet (DR-UNet) model was developed for computed tomography image segmentation and HV measurement. Two data sets, 512 ICH patients with 12 568 computed tomography slices in the retrospective data set and 50 ICH patients with 1257 slices in the prospective data set, were used for network training, validation, and internal and external testing. Moreover, 13 irregular hematoma cases, 11 subdural and epidural hematoma cases, and 50 different HV cases into 3 groups (60 mL) were selected to further evaluate the robustness of DR-UNet. The image segmentation performance of DR-UNet was compared with those of UNet, the fuzzy clustering method, and the active contour method. The HV measurement performance was compared using DR-UNet, UNet, and the Coniglobus formula method. Results: Using DR-UNet, the segmentation model achieved a performance similar to that of expert clinicians in 2 independent test data sets containing internal testing data (Dice of 0.861±0.139) and external testing data (Dice of 0.874±0.130). The HV measurement derived from DR-UNet was strongly correlated with that from manual segmentation (R 2 =0.9979; P Conclusions: DR-UNet can segment hematomas from the computed tomography scans of ICH patients and quantify the HV with better accuracy and greater efficiency than the main existing methods and with similar performance to expert clinicians. Due to robust performance and stable segmentation on different ICHs, DR-UNet could facilitate the development of deep learning systems for a variety of clinical applications.

AIM To construct a novel nomogram by integrating computed tomography perfusion (CTP) and clinical parameters for individualised prediction of haemorrhagic transformation (HT) in intravenous thrombolysis (IVT)-treated acute ischaemic stroke (AIS) patients. METHODS Anterior circulation AIS patients who underwent IVT at a single centre from January 2018 to June 2020 were reviewed retrospectively. The CTP parameters of two regions of interest (ROI), the entire perfusion lesion areas, and the infract core areas, were assessed. HT was documented by follow-up CT 24 ± 2 h after IVT. Multivariable logistic regression was conducted by including clinical variables and CTP parameters to identify the independent predictors of HT. A nomogram was developed based on the independent predictors. The discriminative value and calibration of the nomogram were tested by concordance indexes (C-indexes) and calibration plots. Internal validation was performed using fivefold cross-validation. RESULTS The nomogram was generated using the complete data from 341 patients. Seven variables were included in the final nomogram, including: the relative cerebral blood volume (rCBV), permeability surface (PS), and relative PS (rPS) in infract core areas, the relative time to maximum (rTmax) and rPS in entire perfusion lesion areas, the National Institutes of Health Stroke Scale (NIHSS), and atrial fibrillation (AF). The C-indexes were 0.815 and 0.817 for the nomogram and internal validation. The calibration plots showed excellent agreement. CONCLUSION This is the first study establishing a nomogram based on CTP and clinical parameters to predict HT after stroke thrombolysis.

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pThese findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window.Stryker Neurovascular.

AIM To explore the association between haemorrhagic transformation (HT) subtypes and functional outcome in acute ischaemic stroke (AIS) patients with successful recanalization treated by endovascular thrombectomy (EVT). MATERIALS and METHODS Consecutive patients with AIS due to large-vessel occlusion in the anterior circulation, who were treated between January 2015 and June 2019 and achieved successful EVT, were enrolled in this retrospective study. HT was categorized according to the Heidelberg Bleeding Classification. Functional outcome was evaluated using the 90-day modified Rankin Scale (mRS) after stroke onset. Ordinal logistic regression analysis was performed to determine the association of HT subtypes with functional outcomes. RESULTS A total of 243 patients were included for further analysis. Among them, 121 (49.8%) had HT. Ten (4.1%) patients were classified as haemorrhagic infarction (HI) subtype 1, 61 (25.1%) as HI subtype 2, 17 (7.0%) as parenchymal haematoma (PH) subtype 1, and 33 (13.6%) as PH subtype 2. Ordinal logistic regression analysis suggested that HI subtype 2 (adjusted common OR 0.357, 95% CI: 0.192–0.667), PH1 (adjusted common OR 0.254, 95% CI: 0.093–0.696) and PH subtype 2 (adjusted common OR 0.017, 95% CI: 0.006–0.051) were significantly associated with poor functional outcomes. CONCLUSION The present study shows that HI subtype 2, PH subtype 1, and PH subtype 2 are independently associated with poor clinical outcomes in AIS patients with successful recanalization after EVT.

Objective To develop and validate a nomogram for predicting the risk of venous thromboembolism in critically ill patients with primary intracerebral hemorrhage. Methods Patients ≥18 years old with primary intracerebral hemorrhage were screened within 24 hours of onset from January 2019 to April 2021. Univariate and multivariate logistic regression analyses were performed to screen out independent predictors that were significantly associated with venous thromboembolism. A nomogram was constructed based on the results of a multivariate regression analysis. Discrimination and calibration were used to evaluate performance of the nomogram. A decision curve analysis was used to assess its clinical utility. Results This study enrolled 369 patients. The nomogram included 3 predictors from the regression analysis: D-dimer, National Institutes of Health Stroke Scale score, and Glasgow Coma Scale score on admission. The area under the receiver operating characteristic curve was 0.794, indicating good discrimination of the nomogram. The nomogram demonstrated calibration curves with slight deviation from the ideal predictions. Decision curve analysis showed that the prediction nomogram was clinically useful. Conclusions This nomogram comprising D-dimer, National Institutes of Health Stroke Scale score and Glasgow Coma Scale score on admission can accurately predict the risk of venous thromboembolism in critically ill patients with intracerebral hemorrhage.

Objective To develop and validate a radiomics-clinical nomogram for the prediction of short-term prognosis in patients with deep intracerebral hemorrhage (DICH) on admission. Methods A total of 326 patients with DICH (development cohort = 187; testing cohort = 81; validation cohort = 58) were retrospectively included. Radiomics features were extracted from computed tomography (CT) images and optimal features were selected using least absolute shrinkage and selection operator regression. A radiomics score (R-score) was developed using the optimal features. Univariate and multivariate analyses were used to determine independent risk factors for poor outcomes at 30 days. A radiomics-clinical (R-C) nomogram was developed and validated in the three cohorts. Receiver operating characteristic curve (ROC), calibration curve and decision curve analyses were conducted to evaluate the performances of the R-C nomogram. Results Only 4 of 396 radiomics features were selected to develop R-scores. Age, onset-to-CT time, Glasgow Coma Scale score, midline shift and R-score were detected as independent predictors of poor prognosis of DICH. The R-C nomogram was developed by the independent predictors and showed acceptable discrimination with areas under ROCs of 0.80, 0.79 and 0.70 in the development, testing and validation cohorts, respectively. The R-C nomogram showed good agreement between the predicted probability and the actual probability (all P > 0.05) and clinical applicability in each cohort. Conclusions The R-C nomogram is a stable and effective tool for predicting the short-term prognosis of DICH, which may help clinicians perform individual risk assessments and make decisions for patients with DICH.

Background Hemorrhage rates of conservatively managed brainstem cavernous malformations (BSCMs) vary widely in the literature. We aimed to elucidate the reason for the variation and to add the results of our experience of BSCMs management over the past decade. Methods We performed a review of consecutive patients with BSCMs referred to our department in the period 2006–2018. A hemorrhagic event was defined as a radiographically verified intralesional and extralesional hemorrhage. Both retrospective and prospective hemorrhage rates were calculated based on the patient age in years, counted either from birth or from the time of initial presentation until the last contact (or until surgical resection). In addition, we retrieved and reviewed publications with a clear definition of hemorrhagic event and a detailed description of BSCM hemorrhage rate. Results In total, 118 patients with BSCMs were reviewed, and 78 patients (mean age on admission 45.9 years) were included in the final analysis. The retrospective and prospective hemorrhage rates were 1.9% (95% confidence interval 1.6%–2.3%) per year and 11.9% (95% confidence interval 7.5%–17.8%), respectively. The retrospective hemorrhage rate in the literature review ranged from 1.9% to 6.8% per year with a median value of 3.8%, whereas the prospective hemorrhage rate ranged between 4.1% and 21.5%, with a median value of 10.2%. Conclusions The reported hemorrhage rates are calculated in 2 different ways. In our patient cohort, both the retrospective and prospective hemorrhage rates were in accordance with those in the literature. The long-term hemorrhage rate lies between the prospective and retrospective rate.

Granulocyte colony-stimulating factor (G-CSF) has been reported to exert a protective effect against secondary brain damage, but the underlying mechanisms remain unknown. We explored the ability of G-CSF to protect the brain from injury in a rat autologous blood-induced model of intracerebral hemorrhage (ICH), with a special focus on the anti-inflammation effect. An ICH was induced in 8-week-old male rats by an infusion of autologous blood, and the rats were then randomly assigned to five treatment groups: sham, ICH, and ICH+ low-dose (25 µg/kg), middle-dose (50 µg/kg), and high-dose (75 µg/kg) G-CSF. We then evaluated the levels of brain inflammation-related genes and proteins. The levels of tumor-necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA increased between days 1 and 14 post-ICH, with the highest expression on day 3. These changes were rectified by G-CSF in a dose-dependent manner. At day 3 post-injury, an elevation of the nuclear factor-kappa B (NF-κB) p65 protein level and a reduction of the inhibitor of NF-κB alpha (IκBα) protein level were observed; G-CSF treatment exerted a beneficial effect on both protein expressions. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were increased; these changes were rectified by the highest dose of G-CSF. The brain-protecting effects of G-CSF are likely to be attributable, at least in part, to attenuation of the TNF-α, IL-6, iNOS, and COX-2 expressions induced by NF-κB activation in the brain tissues of this autologous blood-induced ICH rat model.

Background and Purpose: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. Methods: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. Results: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8–13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%–99.1%) and 79.0% (95% CI, 54.4%–94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912–1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. Conclusions: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: 3618210420, 2217698.

To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 hours.A retrospective cohort study was made covering the period 2015-2017.An adult Intensive Care Unit (ICU).Epidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD.A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD 24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD 24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD 24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups.Early BD (24 h) was associated to GCS 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation.

A 47-year-old woman with history of seizure disorder (semiology of seizure unknown), not well controlled with antiepileptic drugs since last 30 years presented with 1-year history of intermittent throbbing headache. On the day prior to admission, she experienced worst headache, followed by loss of consciousness. On regaining consciousness, she had neck pain without any focal neurological deficit, but examination was marked by positive meningeal signs. She had history of oral ulceration, photosensitivity and small joints pain for which no medical consultancy was sought until. Following relevant investigations, this case came out to be moyamoya angiopathy secondary to underlying systemic lupus erythematosus. She was put on immunosuppressive and immunomodulator as per recommendations. Among neurological symptoms, headache improved dramatically without any further seizure recurrence till the 6 months of follow-up.

Background: Intracerebral hemorrhage (ICH) is a major cause of death and disability globally. As a type of secondary injury after ICH, treatment for cell death can promote the recovery of neurological function. Methods: Among all the cell death, neuronal necroptosis has recently been demonstrated of significance in the pathogenesis of ICH. However, the administration of drugs against necroptosis has many limitations. Results: In the present study, we found that metformin, a first-line medication for the treatment of type 2 diabetes, can effectively inhibit neuronal necroptosis after ICH by activating the AMPK related pathway, thereby significantly improving neurological function scores and reducing brain edema. Conclusion: These results will provide a new perspective for future research in necroptosis.

Background Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra-early stroke (≤ 6 hours). Our meta-analysis updated the evidence on its safety and benefits in acute stroke. Methods We searched major electronic databases for randomised trials comparing transdermal GTN vs placebo/control in acute stroke. Primary outcomes were mortality, 90-day modified Rankin Scale (mRS) and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilisation and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were; ICH vs ischemic stroke; minor (NIHSS ≤ five) vs major (NIHSS > five) ischemic stroke; ischemic stroke with vs without thrombolysis; prehospital vs non prehospital settings; time from stroke to randomization ≤ six vs > six hours and high vs low overall RoB studies. Results 7 eligible primary trials enrolled 5363 patients. GTN reduced systolic BP [mean difference (MD) -4.74; 95% CIs -6.03 to -3.45 mmHg] and diastolic BP (MD -2.94; 95% CIs -3.74 to -2.13 mmHg) 24 hours post treatment but did not affect 4-10-day mortality [relative risk (RR) 1.11; 95% CIs 0.82 to 1.49], 90-day mortality [RR 0.96; 95% CIs 0.77 to 1.19] and 90-day mRS >2 (RR 0.98; 95% CIs 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. Conclusions Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra-early stroke (≤ 6 hours).

Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P

Although the assessment of nutrition is essential for stroke patients, detailed associations between nutritional status at admission, subsequent complications, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH) are unclear. We aimed to elucidate these associations using the Controlling Nutritional Status (CONUT) score. Consecutive patients with acute ICH were investigated. Nutritional status was evaluated using the CONUT score, calculated from the serum albumin level, lymphocyte count, and total cholesterol level. Subsequent complications, such as hemorrhage expansion (HE) during the acute stage and aspiration pneumonia during hospitalization, were evaluated. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. Of the 721 patients, 49 had HE, 111 had aspiration pneumonia, and 409 had poor outcomes. Patients with HE had significantly lower total cholesterol levels than those without HE. Patients with aspiration pneumonia had significantly lower albumin levels, lower lymphocyte counts, and higher CONUT scores than those without aspiration pneumonia. Patients with poor outcomes had significantly lower albumin levels, lower lymphocyte counts, lower total cholesterol levels, and higher CONUT scores than those with good outcomes. Multivariable logistic analysis showed that higher CONUT scores were independently associated with poor outcome (odds ratio, 1.28; 95% confidence interval, 1.09-1.49; P = 0.002) after adjusting for baseline characteristics, HE, and aspiration pneumonia. Each component of CONUT was a useful predictor of subsequent complications. Malnutrition, determined using the CONUT score, was independently associated with poor outcomes in patients with ICH after adjusting for these complications.

Introduction: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). Methods: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013–June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. Results: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). Discussion/Conclusion: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Background and Purpose: Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades. Methods: We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression. Results: Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27–2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%; P Conclusions: Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.

Background The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor TRAF6. TRAF6 interacts with NLRP3 to promote the activation of NLRP3 inflammasome. However, the role of MST4 in neuroinflammation after intracerebral hemorrhage (ICH) and how it interacts with NLRP3 inflammasome remain unclear. Methods Mice were administered MST4 AAV four weeks before collagenase-induced ICH. ICH mice received either hesperadin (MST4 selective inhibitor), or MCC950 (NLRP3 inflammasome selective inhibitor). Neurological deficits and brain water content were assessed. Western blot and immunofluorescence were performed to evaluate the proteins content and localization in MST4/NLRP3 signaling pathway. Results The expression of endogenous MST4 and NLRP3 was increased after ICH compared to sham group. MST4 and NLRP3 were respectively colocalized in microglia. Upregulation of MST4 gene inhibited the activation of NLRP3 inflammasome, the release of IL-1β and TNF-α, and significantly improved brain edema and neurological deficits. Hesperadin pretreatment inhibited the expression of MST4 and increased the expression of NLRP3 inflammasome-mediated proteins, which aggravated neurological deficits and cerebral edema. MCC950 markedly alleviated neurological deficits and brain edema but had no effect on the expression of MST4 protein. Conclusions MST4 alleviates inflammatory progression and brain injury in ICH mice possibly by inhibiting NLRP3 inflammasome activation.

Background Triggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH). Methods Serum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome. Results As compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively. Conclusion Serum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Hypertension and cerebral amyloid angiopathy (CAA) are the most common causes of primary ICH, but the mechanism of hemorrhage in both conditions is unclear. Although fibrinoid necrosis and Charcot-Bouchard aneurysms (CBAs) have been postulated to underlie vessel rupture in ICH, the role and significance of CBAs in ICH has been controversial. First described as the source of bleeding in hypertensive hemorrhage, they are also one of the CAA-associated microangiopathies along with fibrinoid necrosis, fibrosis and "lumen within a lumen appearance." We describe clinicopathologic findings of CBAs found in 12 patients out of over 2700 routine autopsies at a tertiary academic medical center. CBAs were rare and predominantly seen in elderly individuals, many of whom had multiple systemic and cerebrovascular comorbidities including hypertension, myocardial and cerebral infarcts, and CAA. Only one of the 12 subjects with CBAs had a large ICH, and the etiology underlying the hemorrhage was likely multifactorial. Two CBAs in the basal ganglia demonstrated associated microhemorrhages, while three demonstrated infarcts in the vicinity. CBAs may not be a significant cause of ICH but are a manifestation of severe cerebral small vessel disease including both hypertensive arteriopathy and CAA.

Background Leukoaraiosis is a type of lesion characterized by tissue rarefaction or myelin pallor resulting from axons loss and gliosis. Synthetic magnetic resonance imaging (MRI) could yield quantitative T1, T2, proton density (PD) values of leukoaraiosis in addition to information on the volume of the lesion. Purpose To investigate the feasibility of quantifying leukoaraiosis using synthetic MRI and to explore the association between leukoaraiosis and cerebral small vascular diseases and cerebral atherosclerosis. Material and Methods Patients with acute ischemic stroke were enrolled in this study. All participants underwent a conventional T2-weighted image, brain volume, CUBE fluid attenuated inversion recovery, and synthetic MRI acquisition using a 3.0-T MR system. A time-of-flight magnetic resonance angiography was also obtained. We evaluated the T1, T2, PD values and leukoaraiosis volume. Results Analysis of the leukoaraiosis volume ratios demonstrated a positive association with T2 values, a negative association with T1 values, and no association with PD values. Leukoaraiosis volume ratios were independently correlated with age ( P < 0.001), lacunes ( P = 0.022), and cerebral microbleeds ( P = 0.010). A statistical association was found between both age ( P < 0.001) and lacunes ( P = 0.047) and leukoaraiosis T2 values. Conclusion Synthetic MRI may enhance the evaluation of leukoaraiosis, in addition to providing information on its volume. Leukoaraiosis may represent a type of cerebral small vascular disease rather than cerebral atherosclerosis and may share the same pathological mechanism as lacunes and cerebral microbleeds.

BACKGROUND Previous studies demonstrating the association between renal functions and cerebral small vessel diseases have usually focused on white matter hyperintensity in the general population or lacunar stroke patients. This study aimed to investigate the effects of renal function on imaging markers of cerebral small vessel disease and etiologic subtypes of stroke in patients with acute ischemic stroke or transient ischemic attack. MATERIALS AND METHODS A total of 356 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to the Stroke Unit and underwent brain magnetic resonance imaging were evaluated. Demographic data, vascular risk factors, stroke etiology, estimated glomerular filtration rate and severity of cerebral small vessel disease markers, and total cerebral small vessel disease burden were evaluated. RESULTS There was a significant inverse correlation between estimated glomerular filtration rate and total number of lacunes, periventricular and deep subcortical Fazekas scores, grade of enlarged perivascular spaces in the centrum semiovale, lobar and total cerebral microbleeds, and total cerebral small vessel disease burden. Impaired renal function was an independent risk factor for the presence of lacunes, deep cerebral microbleeds, and increased total burden. Renal function impairment and periventricular white matter hyperintensities were significantly associated with the etiologic subgroup of small vessel occlusion. The results were still significant after the exclusion of patients below 50 years of age. CONCLUSION Our results indicate that there is a relationship between renal function impairment and increased total burden, as well as acute ischemic stroke/transient ischemic attack due to small vessel occlusion.

BACKGROUND Perihematomal edema (PHE) following primary intracranial hemorrhages (ICHs) affects the patient outcome. Also, serum biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) have been associated with ICHs outcome. We aimed to investigate the association between these biomarkers and PHE in ICH patients. METHODS In this cross-sectional study, patients with primary ICH between January 2020 and August 2020 were evaluated. All participants underwent spiral brain computed tomography scans upon admission, and 48 to 72 hours later and quantification of initial hematoma volume was performed. Serum level of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), GFAP, and S100B on admission were measured by enzyme-linked immunosorbent assays. Acute clinical outcome was assessed by the modified-Rankin scale, National Institute of Health Stroke Scale (NIHSS), and ICH score. RESULTS Thirty-seven ICH patients (21 patients with a favorable outcome and 16 unfavorable) were studied. Compared with survival patients, nonsurvivor patients showed a higher serum level of MMP-9, VEGF, GFAP, and S100B (P

PURPOSE OF REVIEW Blood pressure management in acute stroke has long been a matter of debate. Epidemiological data show that high blood pressure is associated with death, disability and early stroke recurrence, whereas the pathophysiological rationale for ensuring elevated blood pressure in order maintain adequate cerebral perfusion remains a pertinent argument, especially in ischaemic stroke. RECENT FINDINGS The European Stroke Organisation Guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage provide recommendations for the appropriate management of blood pressure in various clinical acute stroke settings. SUMMARY In this narrative review, we provide specific updates on blood pressure management in ICH, blood pressure management in the setting of reperfusion therapies for ischaemic stroke, and the evidence for the use of induced hypertension in patients with acute ischaemic stroke in the light of the recent guidelines.

Recently, the efficacy of middle meningeal artery (MMA) embolization for chronic subdural hematoma (cSDH) in the elderly has been reported. However, no previous reports of MMA embolization for cSDH in children with ventricular assist devices (VAD) have been published. Here, we report a case of MMA embolization for cSDH in a child with VAD. A 15-month-old female was diagnosed with dilated cardiomyopathy at 7 months old. Soon, a VAD was inserted, and anticoagulant and antiplatelet therapy was started. Bilateral cSDH was observed at 15 months, and, 2 months later, an acute exacerbation of the right cSDH necessitated intracerebral hemorrhage removal. Afterwards, increased intracranial pressure occurred due to a contralateral subdural hematoma but, 4 months after intracerebral hemorrhage removal, CT showed new hemorrhaging in the left cSDH. MMA embolization was then conducted to prevent rebleeding in the hematoma. Selective angiography of the left MMA demonstrated stains of hematoma capsules from the frontal and parietal branches, which were embolized using liquid embolic material. During the procedure, the material migrated into the intracranial vessels via an undetected transdural anastomosis. Postoperatively, no new neurological abnormalities, including hemiparesis, were observed. Two months later, CT showed a decrease in hematoma size. MMA embolization for cSDH in pediatric patients with VAD may be effective, if vigilance is maintained against transdural anastomoses.

PURPOSE OF REVIEW Direct oral anticoagulants (DOAC) are the mainstay of anticoagulant therapy for stroke prevention in patients with nonvalvular atrial fibrillation. Persistent uncertainties remain in different areas, and this review discusses current dilemmas based on selected studies. RECENT FINDINGS Optimal timing of DOAC initiation after a recent ischaemic stroke in patients with atrial fibrillation is currently unknown and subject of ongoing randomized controlled trials. Ischaemic stroke despite anticoagulant therapy in patients with atrial fibrillation is frequent, constitutes heterogeneous causes (competing stroke cause, medication error and cardioembolism despite anticoagulation) and optimal treatment is currently unknown. Thorough etiological work-up is justified. Recent randomized controlled trials found no beneficial effect of DOAC therapy in unselected patients with embolic stroke of undetermined source (ESUS). Currently ongoing trials targeting subgroup of ESUS patients with additional atrial cardiopathy will provide novel data. Cerebral mircobleeds combined in a novel risk score (MICON score) provide good predictive value to stratify the risk of intracranial haemorrhage in patients taking anticoagulants. Use of DOAC after intracerebral haemorrhage in patients with atrial fibrillation is subject of ongoing trials. SUMMARY There are still significant uncertainties in anticoagulant management in patients with stroke. Ongoing trials will soon provide novel data to improve management of these patients.

Several vaccines have been approved worldwide for the prevention of morbidity and mortality against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of these vaccines has raised concerns regarding their adverse effects. Herein, we report the first case of intracerebral hemorrhage (ICH) due to vasculitis after the first dose of mRNA vaccine (BNT162b2, Pfizer/BioN-Tech). Although this case cannot demonstrate a direct relationship between COVID-19 vaccination and vasculitis, the clinical and histological features of this patient are highly consistent with the adverse effects of COVID-19 vaccine.

Purpose Hospital-acquired pneumonia (HAP) is becoming a serious problem in China, especially caused by multi-drug resistant (MDR), which is a risk factor for poor prognosis of intracranial cerebral hemorrhage (ICH). We investigate the risk factors for HAP among patients with ICH and study the antibiotic use and medical costs of MDR infection. Methods We performed a retrospective, case–control, parallel study in Xiangya Hospital. Patients included in this study and diagnosed with basal ganglia hemorrhage were admitted between January 2017 and December 2019. Results Univariate analysis discovered some personal risk factors including gender (p = .002), age (p = .023), and underlying conditions such as diabetes (p = .036), coronary heart disease (p = .009), and renal insufficiency (p = .001). Invasive medical operations including endotracheal intubation, tracheotomy, ventilator use, lumbar puncture, urinary catheter insertion, and peripherally inserted central catheter (PICC) (p

ObjectiveTo summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH).MethodsA prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults 6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect.ResultsOf 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6–5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth.InterpretationOverall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent.PROSPERO registration numberCRD42019141136.

BACKGROUND Cerebral hemorrhage secondary to cerebral embolism after mechanical thrombectomy is characterized by high morbidity, disability and mortality. If the patient also has severe pulmonary embolism (PE) at the same time, the treatment becomes more complex. This report describes the treatment strategy for a patient with PE and cerebral hemorrhage secondary to cerebral embolism after mechanical thrombectomy. CASE SUMMARY A 70-year-old woman presented to our emergency department with right-sided hemiplegia and mixed aphasia of 2.5 h duration. She was diagnosed with left cerebral embolism, left internal carotid artery occlusion, PE and left calf intramuscular vein thrombosis. Following mechanical thrombectomy, brain magnetic resonance imaging showed cerebral infarction with basal ganglia hemorrhage. We observed changes in cerebral hemorrhage on serial monitoring of brain computed tomography and adjusted the dose of anticoagulant drugs. After 3 wk of treatment, the patient’s neurological and respiratory symptoms significantly improved, and a favorable prognosis was obtained. CONCLUSION Anticoagulation could be a potential option for PE accompanied by hemorrhagic transformation of an ischemic infarct.

Objective To evaluate the clinicoradiologic characteristics of hemorrhagic meningiomas (HMs) that are missed or misdiagnosed on radiologic imaging studies. Methods Clinical and radiologic data from 6 patients with HM who were initially misdiagnosed were collected and recorded respectively. In addition, we performed a literature review for misdiagnosed HM and summarized the results. Results Five of the 6 patients with misdiagnosed HM were female, and 1 was male. Both computed tomography (CT) and magnetic resonance imaging were performed in 4 patients, and CT alone was performed in 2. On CT, the HM was heterogeneously hyperdense in 5 patients and isodense in 1 patient. In all 4 patients who underwent magnetic resonance imaging, the HM was mixed iso- and hypointense on T1-weighted imaging and heterogeneously hyperintense on T2-weighted imaging. Marked heterogeneous contrast enhancement was observed in 2 patients, strong rim enhancement in 1, and peripheral enhancement in 1. The dural tail sign was seen in only 1 patient. The initial radiologic misdiagnoses were subdural hematoma (n = 1), malignant glioma (n = 1), ruptured arterial aneurysm (n = 1), metastasis (n = 2), and uncertain (n = 1). In the literature review, 22 cases of HM diagnostic error were collected. The main misdiagnoses were subdural hematoma (27.3%), traumatic hematoma (13.6%), vascular anomaly (13.6%), malignant glioma (4.5%), and metastasis (4.5%). Conclusions Our study showed that in patients with HM with inadequate imaging evaluation, a small tumor associated with massive hematoma and atypical imaging features was more likely to be misdiagnosed.

An invasive aspergillosis (IA) primarily occurs among immunocompromised patients. Recently with an influenzae infection prevalently spreading, influenzae-associated invasive aspergillosis (IAIA) has been reported occasionally. By contrast, neuroleptic malignant syndrome (NMS) occurs rarely in psychiatric patients who are treated with Olanzapine. We report a 43 years old male with psychiatric disorder who had developed IAIA followed by NMS and cerebral hemorrhage as the result of aspergillus invasion to cerebral vessels. He had also super-infection of COVID-19, 13 months later to be saved completely after invasive mechanical respiratory supports. From clinical aspects, we would emphasize that it is of importance to find earlier co-occurrence of IAIA patients with cerebral hemorrhage due to secondary infectious vasculopathy of IA.

OBJECTIVE The objective of this study was to describe the clinical and neuroradiological characteristics of a cohort of preterm infants who had undergone external ventricular drain insertion as a temporary measure to treat posthemorrhagic ventricular dilatation. In addition, the authors investigated the factors predicting permanent shunt dependency. METHODS The authors retrospectively reviewed the medical records of a cohort of preterm infants who had undergone external ventricular drain insertion at Gaslini Children’s Hospital (Genoa, Italy) between March 2012 and February 2018. They also analyzed clinical characteristics and magnetic resonance imaging data, including diffusion- and susceptibility-weighted imaging studies, which were obtained before both catheter insertion and removal. RESULTS Twenty-eight infants were included in the study. The mean gestational age was 28.2 ± 2.7 weeks, and the mean birth weight was 1209 ± 476 g. A permanent ventriculoperitoneal shunt was inserted in 15/28 (53.6%) infants because of the failure of external ventricular drainage as a temporary treatment option. Compared with the shunt-free group, the shunt-dependent group had a significantly lower gestational age (29.3 ± 2.3 vs 27.2 ± 2.7 weeks, p = 0.035) and tended toward a lower birth weight (p = 0.056). None of the clinical and neuroradiological characteristics significantly differed between the shunt-free and shunt-dependent groups at the time of catheter insertion. As expected, ventricular parameters as well as the intraventricular extension of intracerebral hemorrhage, as assessed using the intraventricular hemorrhage score, were reportedly higher in the shunt-dependent group than in the shunt-free group before catheter removal. CONCLUSIONS External ventricular drainage is a reliable first-line treatment for posthemorrhagic hydrocephalus. However, predicting its efficacy as a unique treatment remains challenging. A lower gestational age is associated with a higher risk of posthemorrhagic hydrocephalus progression, suggesting that the more undeveloped the mechanisms for the clearance of blood degradation products, the greater the risk of requiring permanent cerebrospinal fluid diversion, although sophisticated MRI investigations are currently unable to corroborate this hypothesis.

Objective Occlusion of ventriculoperitoneal shunts placed after intraventricular hemorrhage occurs frequently. The objective of this study was to develop a hemorrhagic hydrocephalus model to assess the ability of an oscillating microactuator within the ventricular catheter (VC) to prevent shunt obstruction. Methods An in vitro hydrocephalus model with extreme risk of shunt obstruction was created. Phosphate-buffered saline, blood, and thrombin were driven through ventriculoperitoneal shunts for 8 hours. Five VCs were fitted with a microactuator and compared with 5 control VCs. The microactuator was actuated by an external magnetic field for 30 minutes. Pressure within the imitation lateral ventricle was measured. Results In the 5 control shunts, 6 obstructions developed (3 VC, 3 valve-distal catheter) compared with 1 obstruction (VC) in the 5 microactuator shunts. In the control and microactuator groups, the median volume exiting the shunts in 8 hours was 30 mL versus 256 mL. Median time to reach an intraventricular pressure of 40 mm Hg (13.8 minutes vs. >8 hours), median total time >40 mm Hg (6.2 hours vs. 0.0 hours), and median maximum pressure (192 mm Hg vs. 36 mm Hg) were significantly improved in the microactuator group (P Conclusions In addition to protecting the VC, the microactuator appeared to prevent hematoma obstructing the valve or distal catheter, resulting in a much longer duration of low intraventricular pressures. A microactuator activated by placing the patient's head in an external magnetic field could reduce shunt obstructions in hemorrhagic hydrocephalus.

Intracerebral hemorrhage (ICH) remains a common and debilitating form of stroke. This neurological emergency must be diagnosed and treated rapidly yet effectively. In this article, we review the medical, surgical, repair, and regenerative treatment options for managing ICH. Topics of focus include the management of blood pressure, intracranial pressure, coagulopathy, and intraventricular hemorrhage, as well as the role of surgery, regeneration, rehabilitation, and secondary prevention. Results of various phase II and III trials are incorporated. In summary, ICH patients should undergo rapid evaluation with neuroimaging, and early interventions should include systolic blood pressure control in the range of 140 mmHg, correction of coagulopathy if indicated, and assessment for surgical intervention. ICH patients should be managed in dedicated neurosurgical intensive care or stroke units where continuous monitoring of neurological status and evaluation for neurological deterioration is rapidly possible. Extravasation of hematoma may be helpful in patients with intraventricular extension of ICH. The goal of care is to reduce mortality and enable multimodal rehabilitative therapy.

Background Cerebrovascular diseases associated with SARS-CoV-2 are being increasingly reported in the literature as the coronavirus disease 2019 (COVID-19) pandemic continues. However, a case-based retrospective analysis of the literature about SARS-CoV-2-cerebrovascular disease (SCVD) is not yet well established. Thus, we reviewed the literature on SCVD covering a comprehensive range of topics spanning the clinical features, mechanism, treatment, and outcomes of patients with SCVD. Methods We searched PubMed® and included single-case reports and case series with full text in English that reported original data of patients with CVD and a confirmed recent SARS-CoV-2 infection. Clinical data were extracted. Results We included all 51 articles indexed in PubMed® that were published between January 1, 2020, and June 20, 2020. The selected studies reported a total of 167 cerebrovascular events including ischemic stroke, cerebral hemorrhage, subarachnoid hemorrhage, and cerebral venous thrombosis in patients with confirmed COVID-19. The detailed demographic and clinical characteristics of patients with CVD are summarized. Conclusion This summary of patient characteristics may help clinicians better anticipate SCVD outcomes and complications in their COVID-19 patients.

Background: In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. Methods: APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7–90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2·5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. Findings: Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73–83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21–74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1·9 years (IQR 1·0–3·1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12·6% [95% CI 6·7–21·5]) and in 12 (24%) allocated to avoid anticoagulation (11·9% [95% CI 6·2–20·8]; adjusted hazard ratio 1·05 [95% CI 0·48–2·31]; p=0·90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. Interpretation: Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Funding: Dutch Heart Foundation (grant 2012T077).