Targeting the multifaceted roles of mitochondria in intracerebral hemorrhage and therapeutic prospects.

Intracerebral hemorrhage (ICH) is a severe, life-threatening subtype of stoke that constitutes a crucial health and socioeconomic problem worldwide. However, the current clinical treatment can only reduce the mortality of patients to a certain extent, but cannot ameliorate neurological dysfunction and has a high recurrence rate. Increasing evidence has demonstrated that mitochondrial dysfunction occurs in the early stages of brain injury and participates in all stages of secondary brain injury (SBI) after ICH. As the energy source of cells, various pathobiological processes that lead to SBI closely interact with the mitochondria, such as oxidative stress, calcium overload, and neuronal injury. In this review, we discussed the structure and function of mitochondria and the abnormal morphological changes after ICH. In addition, we discussed recent research on the involvement of mitochondrial dynamics in the pathological process of SBI after ICH and introduced the pathological variations and related molecular mechanisms of mitochondrial dysfunction in the occurrence of brain injury. Finally, we summarized the latest progress in mitochondrion-targeted agents for ICH, which provides a direction for the development of emerging therapeutic strategies targeting the mitochondria after ICH.

Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes: Insight From the BP-TARGET Trial.

BACKGROUND AND PURPOSE: To assess the association between systolic blood pressure change (ΔSBP) at different time intervals after successful reperfusion with radiographic and clinical outcomes. METHODS: This is a post hoc analysis of the BP-TARGET multicenter trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy). ΔSBP was defined as end of procedure SBP minus mean SBP at different time intervals (15-60 minutes, 1-6 hours, and 6-24 hours postprocedure). The primary outcome was the poor functional outcome (90-day modified Rankin Scale score 3-6). RESULTS: We included a total of 267 patients (130 in the intensive treatment group). Compared with patients with favorable outcome, patients with poor outcome had lower ΔSBP (less SBP reduction) at all times intervals. After adjusting for potential confounders including baseline SBP, both ΔSBP15-60M and ΔSBP6-24H were associated with lower odds of poor outcome (adjusted odds ratio per 5 mm Hg SBP reduction, 0.89 [95% CI, 0.81-0.99], and adjusted odds ratio 0.82 [95% CI, 0.73-0.92], respectively). Concerning safety outcomes, patients with intraparenchymal hemorrhage had lower ΔSBP at all time intervals. ΔSBP15-60M was associated with lower odds of any intraparenchymal hemorrhage (adjusted odds ratio per 5 mm Hg SBP reduction 0.91 [95% CI, 0.83-0.99]). Conversely, ΔSBP was not associated with mortality or neurological deterioration at any time interval. CONCLUSIONS: After successful reperfusion, ΔSBP had a linear relationship with poor outcome and the risk of poor outcome was higher with less reduction from the baseline SBP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03160677.

A single-cell atlas of the normal and malformed human brain vasculature.

Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.

Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage.

BACKGROUND: The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). METHODS: A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6 h from onset (T0) and at 7 days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90 days was the outcome of interest, and predictors were explored with multivariable logistic regression. RESULTS: A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90 days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0 ml/100 g/min, p < .001, and median CBV change -0.5 vs. -0.4 ml/100 g, p = .010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1 ml/100 g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15-1.55), p < .001; OR for 0.1 ml/100 g CBV reduction: 1.67, 95% CI 1.18-2.35, p = .004). The presence of CBF < 20 ml/100 g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08-5-54, p = .032). CONCLUSION: Perihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.

Machine Learning Models Prognosticate Functional Outcomes Better than Clinical Scores in Spontaneous Intracerebral Haemorrhage.

OBJECTIVE: This study aims to develop and compare the use of deep neural networks (DNN) and support vector machines (SVM) to clinical prognostic scores for prognosticating 30-day mortality and 90-day poor functional outcome (PFO) in spontaneous intracerebral haemorrhage (SICH). MATERIALS AND METHODS: We conducted a retrospective cohort study of 297 SICH patients between December 2014 and May 2016. Clinical data was collected from electronic medical records using standardized data collection forms. The machine learning workflow included imputation of missing data, dimensionality reduction, imbalanced-class correction, and evaluation using cross-validation and comparison of accuracy against clinical prognostic scores. RESULTS: 32 (11%) patients had 30-day mortality while 177 (63%) patients had 90-day PFO. For prognosticating 30-day mortality, the class-balanced accuracies for DNN (0.875; 95% CI 0.800-0.950; McNemar's p-value 1.000) and SVM (0.848; 95% CI 0.767-0.930; McNemar's p-value 0.791) were comparable to that of the original ICH score (0.833; 95% CI 0.748-0.918). The c-statistics for DNN (0.895; DeLong's p-value 0.715), and SVM (0.900; DeLong's p-value 0.619), though greater than that of the original ICH score (0.862), were not significantly different. For prognosticating 90-day PFO, the class-balanced accuracies for DNN (0.853; 95% CI 0.772-0.934; McNemar's p-value 0.003) and SVM (0.860; 95% CI 0.781-0.939; McNemar's p-value 0.004) were better than that of the ICH-Grading Scale (0.706; 95% CI 0.600-0.812). The c-statistic for SVM (0.883; DeLong's p-value 0.022) was significantly greater than that of the ICH-Grading Scale (0.778), while the c-statistic for DNN was 0.864 (DeLong's p-value 0.055). CONCLUSION: We showed that the SVM model performs significantly better than clinical prognostic scores in predicting 90-day PFO in SICH.

Fatal cerebral hemorrhage in a patient with thrombotic thrombocytopenic purpura with a normal platelet count during treatment with caplacizumab.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy with a severe mortality and morbidity. Caplacizumab has recently been approved in the Netherlands as a new therapeutic option in patients with life-threatening organ failure due to aTTP. We describe the case of a 50 year old patient with aTTP who was referred to our hospital for treatment with caplacizumab. After undergoing treatment with plasmapheresis, prednisolone, rituximab and caplacizumab, her platelet count recovered and she was ready to be discharged. Unfortunately, before discharge she developed a fatal intra-cerebral hemorrhage. Fatal hemorrhage as an adverse event of caplacizumab has not been described before. Up to now there is no evidence-based treatment for caplacizumab induced heavy bleeding.

Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

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.

Dynamic Process of Secondary Pulmonary Infection in Mice With Intracerebral Hemorrhage.

Stroke is a common central nervous system disease in clinical practice. Stroke patients often have infectious complications, such as pneumonia and infections of the urinary tract and gastrointestinal tract. Although it has been shown that translocation of the host gut microbiota to the lungs and immune dysfunction plays a vital role in the development of infection after ischemic stroke, the occurrence and mechanism of pulmonary infection at different time points after hemorrhagic cerebral remain unclear. In this study, the changes in the immune system and intestinal barrier function in mice during disease development were investigated at 1 day (M 1 d), 3 days (M 3 d) and 7 days (M 7 d) following hemorrhagic stroke to clarify the mechanism of secondary pulmonary infection. The experimental results revealed that after hemorrhagic stroke, model mice showed increased brain damage from day 1 to 3, followed by a trend of brain recovery from day 3 to 7 . After hemorrhagic stroke, the immune system was disturbed in model mice. Significant immunosuppression of the peripheral immune system was observed in the M 3 d group but improved in the M 7 d group. Staining of lung tissues with hematoxylin and eosin (H&E) and for inflammatory factors revealed considerable disease and immune disorders in the M 7 d group. Stroke seriously impaired intestinal barrier function in mice and significantly changed the small intestine structure. From 1 to 7 d after stroke, intestinal permeability was increased, whereas the levels of markers for intestinal tight junctions, mucus and immunoglobulin A were decreased. Analysis based on 16S rRNA suggested that the microflora in the lung and ileum was significantly altered after stroke. The composition of microflora in lung and ileum tissue was similar in the M 7d group, suggesting that intestinal bacteria had migrated to lung tissue and caused lung infection at this time point after hemorrhagic stroke. In stroke mice, the aggravation of intestinal barrier dysfunction and immune disorders after intracerebral hemorrhage, promoted the migration of enteric bacteria, and increased the risk of pneumonia poststroke. Our findings reveal the dynamic process of infection after hemorrhagic stroke and provide clues for the optimal timing of intervention for secondary pulmonary infection in stroke patients.

Mathematical modeling of the hematocrit influence on cerebral blood flow in preterm infants.

Premature birth is one of the most important factors increasing the risk for brain damage in newborns. Development of an intraventricular hemorrhage in the immature brain is often triggered by fluctuations of cerebral blood flow (CBF). Therefore, monitoring of CBF becomes an important task in clinical care of preterm infants. Mathematical modeling of CBF can be a complementary tool in addition to diagnostic tools in clinical practice and research. The purpose of the present study is an enhancement of the previously developed mathematical model for CBF by a detailed description of apparent blood viscosity and vessel resistance, accounting for inhomogeneous hematocrit distribution in multiscale blood vessel architectures. The enhanced model is applied to our medical database retrospectively collected from the 254 preterm infants with a gestational age of 23-30 weeks. It is shown that by including clinically measured hematocrit in the mathematical model, apparent blood viscosity, vessel resistance, and hence the CBF are strongly affected. Thus, a statistically significant decrease in hematocrit values observed in the group of preterm infants with intraventricular hemorrhage resulted in a statistically significant increase in calculated CBF values.

Different Effects of Hematoma Expansion on Short-Term Functional Outcome in Basal Ganglia and Thalamic Hemorrhages.

PURPOSE: To investigate the impact of hematoma expansion (HE) on short-term functional outcome of patients with thalamic and basal ganglia intracerebral hemorrhage. METHODS: Data of 420 patients with deep intracerebral hemorrhage (ICH) that received a baseline CT scan within 6 hours from symptom onset and a follow-up CT scan within 72 hours were retrospectively analyzed. The poor functional outcome was defined as modified Rankin score (mRS) > 3 at 30 days. Receiver operating characteristic (ROC) curves for relative and absolute growth of HE were generated and compared. Multivariable logistic regression models were used to analyze the impact of HE on the functional outcome in basal ganglia and thalamic hemorrhages. The predictive values for different thresholds of HE were calculated, and correlation coefficient matrices were used to explore the correlation between the covariables. RESULTS: Basal ganglia ICH showed a higher possibility of absolute hematoma growth than thalamic ICH. The area under the curve (AUC) for absolute and relative growth of thalamic hemorrhage was lower than that of basal ganglia hemorrhage (AUC 0.71 and 0.67, respectively) in discriminating short-term poor outcome with an AUC of 0.59 and 0.60, respectively. Each threshold of HE independently predicted poor outcome in basal ganglia ICH (P < 0.001), with HE > 3 ml and > 6 ml showing higher positive predictive values and accuracy compared to HE > 33%. In contrast, thalamic ICH had a smaller baseline volume (BV, 9.55 ± 6.85 ml) and was more likely to initially involve the posterior limb of internal capsule (PLIC) (85/153, 57.82%), and the risk of HE was lower without PLIC involvement (4.76%, P = 0.009). Therefore, in multivariate analysis, the effect of thalamic HE on poor prognosis was largely replaced by BV and the involvement of PLIC, and the adjusted odds ratios (ORs) of HE was not significant (P > 0.05). CONCLUSION: Though HE is a high-risk factor for short-term poor functional outcome, it is not an independent risk factor in thalamic ICH, and absolute growth is more predictive of poor outcome than relative growth for basal ganglia ICH.

Perihematomal Edema After Intracerebral Hemorrhage: An Update on Pathogenesis, Risk Factors, and Therapeutic Advances.

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.

Shock index predicts up to 90-day mortality risk after intracerebral haemorrhage.

BACKGROUND: Shock index (SI - heart rate/systolic blood pressure) has been studied as a measure of haemodynamic status. We aimed to determine whether SI measures within 72 h of admission were associated with adverse outcomes in intracerebral haemorrhage (ICH). METHODS: Patients were drawn from the Virtual International Stroke Trials Archive-Intracerebral Haemorrhage (VISTA-ICH). Multivariable Cox regressions modelled the relationship between SI (on admission, 24, 48, 72 h) and mortality (at 3-, 7-, and 90-days), 90-day incident pneumonia and cardiovascular events (MACE). Ordinal logistic regressions modelled the relationship between SI and 90-day modified Rankin Scale (mRS). RESULTS: 979 patients were included. Baseline SI was not associated with mortality. 24 h SI > 0.7 was associated with 7-day mortality (hazard ratio (95% confidence interval) = 3.14 (1.37-7.19)). 48 h and 72 h SI > 0.7 were associated with 7-day (4.23 (2.07-8.66) and 3.24 (1.41-7.42) respectively) and 90-day mortality (2.97 (1.82-4.85) and 2.05 (1.26-3.61) respectively). SI < 0.5 at baseline, 48 h and 72 h was associated with decreased pneumonia risk. 24 h and 48 h SI > 0.7was associated with increased MACE risk. 48 h and 72 h SI > 0.7 was associated with increased odds of higher 90-day mRS. CONCLUSION: Higher-than-normal SI subsequent to initial encounter was associated with higher post-ICH mortality at 3, 7, and 90 days. Lower-than-normal SI was associated with a decreased risk of incident pneumonia.

O-GlcNAcase inhibitor has protective effects in intracerebral hemorrhage by suppressing the inflammatory response.

BACKGROUND: Intracerebral hemorrhage (ICH) is aggravated by immune cells that participate in the inflammatory response from the blood-brain barrier (BBB). O-Glycosylation has been reported to regulate the inflammatory response in the central nervous system but its cerebral protective effects remain unknown. Therefore, this study was carried out to investigate the protective effects of O-GlcNAcylation in a murine model of ICH and the possible mechanisms involved. METHODS: The effects of O-GlcNAcylation on hematoma and edema formation were tested using pathological and dry/wet weight methods, whereas its effects on neural function were determined using neurologic tests. The effect of O-GlcNAcylation on BBB integrity was determined by Evans blue dye extrusion. Flow cytometry was used to quantify the immune cells in the central nervous system. Immunofluorescence was used to detect the protective effect of O-GlcNAcylation in ICH. RESULTS: The hematoma volume was significantly lower in the prevention and treatment groups than in the control group after ICH induction, indicating that O-GlcNAcylation had reduced the formation of cerebral hematoma in ICH. In the prevention and treatment groups, the modified neurological severity score, corner turn test and rotating rod test results were improved and the BBB integrity was better than that in the control group. O-GlcNAcylation also regulated the microglia, neutrophils and other central nervous system immune cells after ICH, effectively reducing the inflammatory response. CONCLUSIONS: O-GlcNAcylation played an important role in suppressing the inflammatory response, enhancing the BBB integrity and reducing edema after ICH.

Tranexamic Acid for Adult Patients with Spontaneous Intracerebral Hemorrhage: A Systematic Review with Meta-analysis.

BACKGROUND: The effects of tranexamic acid on spontaneous intracerebral hemorrhage in reducing hematoma expansion and mortality as well as its role in thromboembolic complications and in the improvement of functional outcomes remain substantially uncertain. OBJECTIVE: The objective of this systematic review was to evaluate the efficacy and safety of tranexamic acid in patients with spontaneous intracerebral hemorrhage. METHODS: Several databases were searched from inception up to 20 June, 2021. We included randomized controlled trials that compared tranexamic acid with placebo or no treatment for the management of intracerebral hemorrhage. The primary outcomes were hematoma expansion and 90-day mortality. The secondary outcomes were hemorrhagic volume change, thromboembolic complications, and functional outcomes. RESULTS: Overall, six trials with 2800 patients were included in this meta-analysis. Tranexamic acid was associated with a reduced risk of hematoma expansion (relative risk 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.03, I2 = 0%, six trials with 2800 participants) and a lessening of hematoma volume change (mean difference - 1.28, 95% CI - 2.44 to - 0.12; p = 0.03; I2 = 0%, four trials with 2626 participants), without a corresponding higher rate of major thromboembolic complications (relative risk 1.20, 95% CI 0.85-1.69; p = 0.80; I2 = 0%, five trials with 2759 participants). The present analysis also demonstrated that tranexamic acid had no effect on reducing 90-day mortality (relative risk 1.02, 95% CI 0.88-1.19; p = 0.80; I2 = 0%, five trials with 2770 participants). CONCLUSIONS: In adults with spontaneous intracerebral hemorrhage, tranexamic acid reduced the risk of intracerebral hemorrhage growth compared with the control. The effects on 90-day mortality remained inconclusive. Further studies should report death within 24 h and death due to bleeding whenever possible.

Activation of Frizzled-7 attenuates blood-brain barrier disruption through Dvl/ß-catenin/WISP1 signaling pathway after intracerebral hemorrhage in mice.

BACKGROUND: Destruction of blood-brain barrier (BBB) ​​is one of the main mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Frizzled-7 is a key protein expressed on the surface of endothelial cells that controls vascular permeability through the Wnt-canonical pathway involving WNT1-inducible signaling pathway protein 1 (WISPI). This study aimed to investigate the role of Frizzled-7 signaling in BBB preservation after ICH in mice. METHODS: Adult CD1 mice were subjected to sham surgery or collagenase-induced ICH. Frizzled-7 activation or knockdown was performed by administration of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) by intracerebroventricular injection at 48 h before ICH induction. WISP1 activation or WISP1 knockdown was performed to evaluate the underlying signaling pathway. Post-ICH assessments included neurobehavior, brain edema, BBB permeability, hemoglobin level, western blot and immunofluorescence. RESULTS: The brain expressions of Frizzled-7 and WISP1 significantly increased post-ICH. Frizzled-7 was expressed in endothelial cells, astrocytes, and neurons after ICH. Activation of Frizzled-7 significantly improved neurological function, reduced brain water content and attenuated BBB permeability to large molecular weight substances after ICH. Whereas, knockdown of Frizzled-7 worsened neurological function and brain edema after ICH. Activation of Frizzled-7 significantly increased the expressions of Dvl, ß-Catenin, WISP1, VE-Cadherin, Claudin-5, ZO-1 and reduced the expression of phospho-ß-Catenin. WISP1 knockdown abolished the effects of Frizzled-7 activation on the expressions of VE-Cadherin, Claudin-5 and ZO-1 at 24 h after ICH. CONCLUSIONS: Frizzled-7 activation potentially attenuated BBB permeability and improved neurological deficits after ICH through Dvl​​/ß-Catenin/WISP1 pathway. Frizzled-7 may be a potential target for the development of ICH therapeutic drugs.

Basilar dolichoectasia with intermural hematoma accompanied by cerebral microbleeds and white matter hyperintensities: A case report.

RATIONALE: The clinical manifestations of basilar dolichoectasia (BD) are variable. The diagnosis is based on imaging measurements. Digital subtraction angiography displays only the dilated vascular lumen and lacks visualization of the arterial wall. High-resolution Magnetic resonance imaging (MRI) can identify intramural hematoma; therefore, it may be more suitable for the imaging evaluation of BD. However, most of the existing literature pertaining to BD lacks vascular wall assessment. PATIENT CONCERNS: A 65-year-old Chinese man perceived weakness of the left upper and lower limb, double vision, dizziness, nausea, and vomiting was admitted to the emergency department. Fifteen years prior to this admission, he began taking levamlodipine besylate inconsistently for hypertension, but the level of blood pressure control was uncertain. The patient's father had a family history of hypertension. DIAGNOSES: An emergency axial computed tomography scan of the brain showed basilar artery (BA) dilation. Computed tomography angiography further indicated a maximum BA diameter of 38.94 mm. The length was >182 mm. MRI revealed acute infarctions of the right medulla oblongata and pons. Meanwhile, the patient had evidence of cerebral small vessel disease, including cerebral microbleeds and white matter hyperintensities. Whole-exome sequencing eliminated significant genetic variations consistent with clinical phenotypes. BD and intramural hematoma were further confirmed by high-resolution MRI of the arterial wall. INTERVENTIONS: Atorvastatin was admitted according to the results of the high-resolution MRI of the arterial wall. Benidipine hydrochloride was selected as a long-term anti-hypertensive drug. OUTCOMES: The patient had no symptoms of neurological damage during 3-month follow-up. LESSONS: Current evidence shows that BD has no obvious correlation with atherosclerosis. BA dissection and uncontrolled hypertension may be important factors in the progression of BD. BD-related stroke is likely to recur, and there are no standard secondary prevention measures. BD is often accompanied by cerebral microbleeds, and bleeding risk must be assessed during secondary prevention. When the BA diameter is greater than 10 mm, anti-platelet medication should be used with caution, blood pressure should be strictly controlled, and endovascular treatment should be considered.

Incident stroke in patients with Alzheimer's disease: systematic review and meta-analysis.

Vascular mechanisms are increasingly recognized in the pathophysiology of Alzheimer's disease (AD), but less is known about the occurrence of stroke in AD patients. We aimed to quantify the risk of stroke in patients with AD and compare the incidence rates (IR) of stroke in individuals without AD. Systematic search of Embase and MEDLINE between 1970 and 2020. Inclusion criteria: reports with ≥ 50 patients with non-familial AD, which reported the occurrence of stroke (all types) and/or ischemic stroke and/or intracerebral hemorrhage (ICH) during follow-up. Meta-analyses of pooled data using random-effects model were performed. IR were calculated for each study. Incidence rate ratios (IRR) were calculated for studies presenting a control-group without AD. Among 5109 retrieved studies, 29 (0.6%) fulfilled the inclusion criteria, reporting a total of 61,824 AD patients. In AD patients the IR were 15.4/1000 person-years for stroke (all types), 13.0/1000 person-years for ischemic stroke and 3.4/1000 person-years for ICH. When compared to controls without AD, incidence rate for ICH in AD patients was significantly higher (IRR = 1.67, 95%CI 1.43-1.96), but similar for ischemic stroke. Incident stroke is not a rare event in AD population. AD is associated with an increased risk of intracerebral hemorrhage which warrants further clarification.

Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2.

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post-randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH-2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14-1.50) but not with hematoma expansion, while HR-ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01-1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01-1.3). Every 10-bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR-ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR-ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR-ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01176565.

Association of Satellite Sign with Postoperative Rebleeding in Patients Undergoing Stereotactic Minimally Invasive Surgery for Hypertensive Intracerebral Haemorrhage.

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.