Search

Background: Stroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood–brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment. Results: Synaptic dysfunction occurs in various ways after stroke and includes the following: damage to neuronal structures, accumulation of pathologic proteins in the cell body, decreased fluidity and release of synaptic vesicles, disruption of mitochondrial transport in synapses, activation of synaptic phagocytosis by microglia/macrophages and astrocytes, and a reduction in synapse formation. Conclusions: This review summarizes the cellular and molecular mechanisms related to synapses and the protective effects of drugs or compounds and rehabilitation therapy on synapses in stroke according to recent research. Such an exploration will help to elucidate the relationship between stroke and synaptic damage and provide new insights into protecting synapses and restoring neurologic function. [ABSTRACT FROM AUTHOR]

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46–12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92–3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions. [ABSTRACT FROM AUTHOR]

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling. [ABSTRACT FROM AUTHOR]

Background and purpose: In ischemic stroke, the impact of short‐ versus long‐term blood glucose level (BGL) on early lesion pathophysiology and functional outcome has not been assessed. The purpose of this study was to directly compare the effect of long‐term blood glucose (glycated hemoglobin [HbA1c]) versus serum BGL on early edema formation and functional outcome. Methods: Anterior circulation ischemic stroke patients who underwent mechanical thrombectomy after multimodal computed tomography (CT) on admission were analyzed. Endpoints were early ischemic cerebral edema, measured by quantitative net water uptake (NWU) on initial CT and functional independence at Day 90. Results: A total of 345 patients were included. Patients with functional independence had significantly lower baseline NWU (3.1% vs. 8.3%; p < 0.001) and lower BGL (113 vs. 123 mg/dL; p < 0.001) than those without functional independence, while HbA1c levels did not differ significantly (5.7% vs. 5.8%; p = 0.15). A significant association was found for NWU and BGL (ß = 0.02, 95% confidence interval [CI] 0.006–0.03; p = 0.002), but not for HbA1c and NWU (ß = −0.16, 95% CI −0.53–0.21; p = 0.39). Mediation analysis showed that 67% of the effect of BGL on functional outcome was mediated by early edema formation. Conclusion: Aggravated early edema and worse functional outcome was associated with elevated short‐term serum BGL, but not with HbA1c levels. Hence, the link between short‐term BGL and early edema development might be used as a target for adjuvant therapy in patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke is a cerebrovascular disease, which is related to DNA damage. Many researches have shown that Ku70 is a key regulator for DNA damage. Here, we aimed to explore Ku70 roles in cerebral ischemic stroke and its potential molecular mechanism. In our study, neural stem cells (NSCs) were induced by oxygen-glucose deprivation/reoxygenation (OGD/R) for constructing cerebral ischemic stroke cell model. CCK8 assay, Brdu/GFP staining, flow cytometry and TUNEL staining were performed to examine cell proliferation, cell cycle and apoptosis, respectively. Relative mRNA and protein levels were detected by quantitative real-time PCR and western blot analysis, respectively. Ku70 positive cells were examined by immunofluorescence staining. Comet assay was employed to determine DNA damage. Animal experiments were performed to assess the effect of transplanting NSCs and Ku70-overexpressed NSCs on neurological deficits, infarct volume, brain edema and blood‒brain barrier (BBB) integrity in middle cerebral artery occlusion (MCAO) model. Our data found that Ku70 expression was decreased in NSCs after OGD/R. Overexpression of Ku70 reduced DNA damage and apoptosis of OGD/R-induced NSCs. Knockdown of Ku70 promoted the activity of ATM/p53. Moreover, KU60019 (ATM-specific inhibitor) reversed the promoting effects of Ku70 silencing on DNA damage and apoptosis in OGD/R-induced NSCs. In animal experiments, transplantation of NSCs-overexpressed Ku70 enhanced cell survival, improved motor function, reduced infarct volume, relieved brain edema and alleviated BBB dysfunction in MCAO mice models. In conclusion, Ku70 overexpression repressed the DNA damage and apoptosis in OGD/R-induced NSCs by regulating ATM/p53 pathway, and transplantation of NSCs-overexpressed Ku70 played neuroprotective effects in MCAO mice models. [ABSTRACT FROM AUTHOR]

Background: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. Methods: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24–31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). Results: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and − 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3–2.2 per 21% ΔCSF). Conclusions: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • This paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH. • Microglia can interact with a wide range of cells, which is important for both disease development and treatment. • We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend. The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood–brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve. [ABSTRACT FROM AUTHOR]

Cerebral ischemia is one reason for death and loss of movement ability of people, which imposes a large and significant cost on the global health system. Niosomes, as useful tools, can increase drug delivery to the brain. The purpose of this research is to investigate the effect of niosomes containing saponin (NS) on stroke- induced damage in the hippocampus of an animal model. The physicochemical characteristics of nanocarriers, such as zeta potential, size, and release test were investigated after the fabrication of thin film method. In this study, Wistar rats were divided into five experimental groups including sham group, stroke group, stroke group with empty niosome injection, stroke group with saponin injection, and stroke group with niosome saponin injection. The study examined various aspects of ischemia including stroke volume, blood-brain barrier (BBB) damage, neurological defects, levels of inflammatory cytokines, and cellular damage in the hippocampus. The findings indicate that NS, with a size of 85.92nm, zeta potential of -34.7 mv, and an entrapment efficiency (EE%) of 85.70% effectively reduced stroke volume, cerebral edema, BBB damage, expression level of TNF-α, and NF-kB genes and inflammation in hippocampal cells. Additionally, NS improved sensory and motor performance in rats. These results demonstrate that NS can mitigate strokeinduced damage in the hippocampus of the rat model by effectively crossing the BBB. [ABSTRACT FROM AUTHOR]

Background: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). Aims: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. Methods: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Results: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201–2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044–1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694–0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002–1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355–0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021–1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613–0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061–2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001–1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004–1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248–0.599). Conclusions: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED. [ABSTRACT FROM AUTHOR]

Background: A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. There is still conflicting evidence whether reperfusion is associated with a lower risk for CED in acute ischemic stroke. Aim: To investigate the association of reperfusion with development of early CED after stroke thrombectomy. Methods: From the SITS-International Stroke Thrombectomy Registry, we selected patients with occlusion of the intracranial internal carotid or middle cerebral artery (M1 or M2). Successful reperfusion was defined as mTICI ⩾ 2b. Primary outcome was moderate or severe CED, defined as focal brain swelling ⩾1/3 of the hemisphere on imaging scans at 24 h. We used regression methods while adjusting for baseline variables. Effect modification by severe early neurological deficits, as indicators of large infarct at baseline and at 24 h, were explored. Results: In total, 4640 patients, median age 70 years and median National Institutes of Health Stroke Score (NIHSS) 16, were included. Of these, 86% had successful reperfusion. Moderate or severe CED was less frequent among patients who had reperfusion compared to patients without reperfusion: 12.5% versus 29.6%, p < 0.05, crude risk ratio (RR) 0.42 (95% confidence interval (CI): 0.37–0.49), and adjusted RR 0.50 (95% CI: 0.44-0.57). Analysis of effect modification indicated that severe neurological deficits weakened the association between reperfusion and lower risk of CED. The RR reduction was less favorable in patients with severe neurological deficits, defined as NIHSS score 15 or more at baseline and at 24 h, used as an indicator for larger infarction. Conclusion: In patients with large artery anterior circulation occlusion stroke who underwent thrombectomy, successful reperfusion was associated with approximately 50% lower risk for early CED. Severe neurological deficit at baseline seems to be a predictor for moderate or severe CED also in patients with successful reperfusion by thrombectomy. [ABSTRACT FROM AUTHOR]

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognised, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P (SP) and its NK1 receptor (NK1R) have been widely studied as a potential therapeutic target. There is evidence that NK1R antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1R has been shown to reduce blood–brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1R has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonists may have some benefit in reducing infection-driven inflammation. However, the NK1R may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. The purpose of this review is to provide a summary of evidence for the involvement of the NK1R in acute CNS inflammation, particularly in the context of traumatic brain injury and stroke. [ABSTRACT FROM AUTHOR]

Background: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. Methods: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl--cotransporter 1; NKCC1) was performed. Results: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. Conclusions: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI. [ABSTRACT FROM AUTHOR]

Cerebral edema can be a consequence of multiple disease processes. Untreated cerebral edema can be fatal, and even with aggressive management, it can be devastating. The objective of this study was to describe the prevalence, underlying causes, and outcomes of cerebral edema in hospitalized children. A retrospective cross-sectional study using the 2016 Kids' Inpatient Database was performed. Children aged one month to 20 years were included. Sample weighting was employed to produce national estimates. Univariate analyses were used to compare those who died and survived. Multivariable logistic regression was performed to assess the influence of demographic variables and etiologic factors on mortality. Cerebral edema was documented in 4903 children of 2,210,263 (2.2 of 1000) discharges. Among children with cerebral edema, males were 57%, white children were 47.9%, and adolescents were 48.9%. The three most common etiologies associated with cerebral edema in this cohort were stroke (21.7%), anoxic injury (21.4%), and central nervous system (CNS) malignancy (16%). The overall hospital mortality rate was 29.4%. The adjusted mortality rate was significantly higher when cerebral edema was associated with anoxic injury (84%). The mortality was lower when cerebral edema was associated with CNS malignancy (9.5%) or diabetic ketoacidosis (DKA) (4.3%). Cerebral edema is uncommon in hospitalized children but has a high mortality. Stroke and anoxic brain injury are the two most common etiologies for cerebral edema in hospitalized children in the United States. Among all etiologies for cerebral edema in children, anoxic brain injury has the highest mortality, whereas DKA has the lowest mortality. [ABSTRACT FROM AUTHOR]

Purpose: Malignant stroke is a life-threatening emergency, with a high mortality rate (1–3). Despite strong evidence showing decreased morbidity and mortality in the adult population, decompressive hemicraniectomy (DCH) has been scarcely reported in the pediatric stroke population, and its indication remains controversial, while it could be a potential lifesaving option. Methods and results: We performed an extensive literature review on pediatric malignant arterial ischemic stroke (pmAIS) and selected 26 articles reporting 97 cases. Gathering the data together, a 67% mortality rate is observed without decompressive therapy, contrasting with a 95.4% survival rate with it. The median modified Rankin score (mRS) is 2.1 after surgery with a mean follow-up of 31.8 months. For the 33% of children who survived without surgery, the mRS is 3 at a mean follow-up of 19 months. As an illustrative case, we report on a 2-year-old girl who presented a cardioembolic right middle cerebral artery stroke with subsequent malignant edema and ongoing cerebral transtentorial herniation in the course of a severe myocarditis requiring ECMO support. A DCH was done 32 h after symptom onset. At the age of 5 years, she exhibits an mRS of 3. Conclusion: Pediatric stroke with malignant edema is a severe condition with high mortality rate if left untreated and often long-lasting consequences. DCH might minimize the vicious circle of cerebral swelling, increasing intracranial pressure and brain ischemia. Our literature review underscores DCH as an efficient therapeutic measure management of pmAIS even when performed after a significant delay; however, long-lasting morbidities remain high. [ABSTRACT FROM AUTHOR]

Background and Purpose: Malignant cerebral edema (MCE) secondary to ischemic stroke is a highly morbid condition. Decompressive craniectomy (DC) is the only treatment for MCE that has been shown to reduce mortality. We examined whether early infarction and/or hypoperfusion in specific topographic regions was predictive of the need for later DC. Methods: A retrospective database of patients evaluated for large vessel occlusion (LVO) stroke at Stanford between 2010 and 2019 was used. Thirty patients with LVO and baseline perfusion MRI who underwent DC were evaluated. Propensity matching based on age, lesion size, and recanalization status was performed on the remaining cohort. Baseline masks of apparent diffusion coefficient (ADC) + Tmax >6 seconds lesions were generated using automated perfusion software. Voxel‐based lesion symptom maping was used to perform logistic regression at each voxel to generate statistical maps of lesion location associated with DC. Hemispheres were combined to increase statistical power. Results: Sixty patients were analyzed. After adjusting for age, lesion size, and recanalization status as covariates, scattered cortical regions, predominately within the temporal and frontal lobe, were mildly to moderately predictive of the need for DC (z‐scores: 2.4‐6.74, p <.01). Conclusions: Scattered temporal and frontal lobe regions on baseline diffusion and perfusion MRI were found to be mildly to moderately predictive of the need for subsequent DC in patients with LVO stroke. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to identify baseline clinical and radiological/procedural predictors and 24‐h radiological predictors for clinical and functional outcomes in stroke patients obtaining complete recanalization in one pass of mechanical thrombectomy (MT) in an optimal baseline and procedural setting. Methods: A retrospective analysis was conducted of prospectively collected data from 924 stroke patients with anterior large vessel occlusion, Alberta Stroke Program Early Computed Tomography (ASPECT) score ≥6 and pre‐stroke modified Rankin Scale score 0, who started MT ≤6 h from symptom onset and obtained first‐pass complete recanalization. A first logistic regression model was performed to identify baseline clinical predictors and a second model to identify baseline radiological/procedural predictors. A third model including baseline clinical and radiological/procedural predictors was performed, and a fourth model including independent baseline predictors from the third model plus 24‐h radiological variables (hemorrhagic transformation [HT] and cerebral edema [CED]). Results: In the fourth model, higher National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.089) and higher ASPECT score (OR 1.292) were predictors of early neurological improvement (ENI) (NIHSS score ≤4 points from baseline or NIHSS score of 0 at 24 h), whereas older age (OR 0.973), longer procedure time (OR 0.990), HT (OR 0.272) and CED (OR 0.569) were inversely associated with ENI. Older age (OR 0.970), diabetes mellitus (OR 0.456), higher NIHSS score (OR 0.886), general anesthesia (OR 0.454), longer onset‐to‐groin time (OR 0.996), HT (OR 0.340) and CED (OR 0.361) were inversely associated with 3‐month excellent functional outcome (mRS score 0–1), whereas higher ASPECT score (OR 1.294) was a predictor of excellent outcome. Conclusions: Higher NIHSS score was a predictor of ENI but inversely associated with 3‐month excellent outcome. Older age, HT and CED were inversely associated with both good outcomes. [ABSTRACT FROM AUTHOR]

The International Journal of Stroke's December issue highlights several important topics in stroke neurology. One of these is reversible cerebral vasoconstriction syndrome (RCVS), a rare condition characterized by the temporary narrowing and dilation of intracranial arteries. RCVS predominantly affects women and is often accompanied by severe headaches. While the radiological appearance of RCVS can be concerning, the majority of patients experience complete or major resolution of symptoms within days to weeks. Another topic discussed is cervical artery dissection (CAD), a common cause of stroke in younger individuals. The risk of recurrent CAD is low, and there are even lower rates of recurrence associated with ischemic events. The issue also explores the timing of anticoagulation after stroke, with studies showing that early initiation of anticoagulation is noninferior to delayed initiation. Additionally, the issue addresses the association between statin use and the risk of intracerebral hemorrhage (ICH), finding no significant association. The risk of expanding cerebral edema (CED) in acute ischemic stroke is lower in patients who undergo successful reperfusion. Finally, the issue highlights the importance of rigor and caution in performing and reporting subgroup analyses in stroke trials. [Extracted from the article]

Mechanical thrombectomy (MT) is recommended in patients with anterior large vessel occlusion from 6 to 24 hours after stroke onset in selected patients with baseline ischemia defined by Alberta stroke program early CT score (ASPECTS) ≥ 6. Recent studies have shown that carefully selected patients with lower ASPECTS 3-5 and even with ASPECTS 0-2 could benefit from MT. A 45-year-old patient was admitted to our emergency department 14 hours after the stroke onset. The neurological assessment revealed severe dysarthria, gaze palsy to the right, and severe left arm and leg palsy. His National Institutes of Health Stroke Scale (NIHSS) score was 10. The emergent brain CT scan showed large right middle cerebral artery territory infarction with right internal carotid artery and right M2 segment occlusion on CT angiography. The ASPECTS was 2. CT perfusion showed a good core/penumbra mismatch ratio in temporal/peri-insular parts and basal ganglia. The MT was performed 14 hours after the stroke onset with a TICI 2b score. The treatment was complicated by the progression of severe brain edema and brain herniation which required emergent decompressive craniectomy. The patient was discharged to the neurorehabilitation center after 26 hospital days with an NIHSS 10. On the last outpatient visit, after three months, the patient scored 5 on NIHHS and 3 on the 3-month Modified Rankin Score. Our patient was successfully treated by MT despite a low ASPECTS and extended time window. Further randomized control trials are necessary to define which subgroup of these patients can benefit from MT. [ABSTRACT FROM AUTHOR]

Background and Purpose: Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated. Methods: Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death. Results: We analyzed 255 patients with 210 baseline CTs, 255 24‐hour CTs, and 81 72‐hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ = –.22) and with CSF ratio and ΔCSF at 24 hours (ρ = –.55/.63) and 72 hours (ρ = –.66/.69), but not with NWU (ρ =.15/.25). Similarly, CSF ratio was correlated with RHV (ρ = –.69/–.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]: 1.95 per 0.1, 95% confidence interval [CI]: 1.52‐2.59) and ΔCSF at 24 hours (OR: 1.87 per 10%, 95% CI: 1.47‐2.49) were associated with malignant edema. Conclusion: CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake. [ABSTRACT FROM AUTHOR]

Malignant acute ischemic stroke (AIS) is characterized by acute neurological deterioration caused by progressive space-occupying brain edema, often occurring in the first hours to days after symptom onset. Without any treatment, the result is often fatal. Despite advances in treatment for AIS, up to 80% of patients with a large hemispheric stroke or cerebellar stroke are at risk of poor outcome. Decompressive surgery can be life-saving in a subgroup of patients with malignant AIS, but uncertainties exist on patient selection, predictors of malignant infarction, perioperative management, and timing of intervention. Although survivors are left disabled, most agree with the original decision to undergo surgery and would make the same decision again. In this narrative review, we focus on the clinical and radiological predictors of malignant infarction in AIS and outline the technical aspects of decompressive surgery as well as duraplasty and cranioplasty. We discuss the current evidence and recommendations for surgery in AIS, highlighting gaps in knowledge, and suggest directions for future studies. Key Points Acute ischemic stroke from occlusion of a proximal intracranial artery can progress quickly to malignant edema, which can be fatal in 80% of patients despite medical management. Decompression surgery is life-saving within 48 hours of stroke onset, but the benefits beyond this time and in the elderly are unknown. Decompressive surgery is associated with high morbidity, particularly in the elderly. The decision to operate must be made after considering the individual's preference and expectations of quality of life in the context of the clinical condition. Further studies are needed to refine surgical technique including value of duraplasty and understand the role monitoring intracranial pressure during and after decompressive surgery. More studies are needed on the pathophysiology of malignant cerebral edema, prediction models including imaging and biomarkers to identify which subgroup of patients will benefit from decompressive surgery. More research is needed on factors associated with morbidity and mortality after cranioplasty, safety and efficacy of implants, and comparisons between them. Further studies are needed to assess the long-term effects of physical disability and quality of life of survivors after surgery, particularly those with severe neurological deficits. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke characterized by high mortality and morbidity rates with no effective treatment. TGF-β/ALK-5 signaling is reported to participated in the regulation of blood-brain barrier (BBB) integrity in the inflammation pain model, the effects of transforming growth factor (TGF)-β1 and the potential mechanisms on BBB after ICH have not been fully elucidated. Herein, we have demonstrated that peripheral administration of TGF-β1 reduces brain edema and ameliorated BBB injury after ICH. Consistent with previous results, TGF-β1 is shown to promote activation of anti-inflammatory microglia and reduce the inflammatory response after ICH. Furthermore, TGF-β1 administration improves long-term outcomes after ICH. Our data suggest that TGF-β1 may be a promising therapeutic agent for ICH. • TGF-β1 attenuates blood-brain barrier damage and promotes long-term neurologic functional outcomes after ICH. • TGF-β1 modulates microglia activation and attenuated neutrophil infiltration after ICH. • TGF-β1 has no effect on the percentages of neutrophils and macrophages in the peripheral blood. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemic stroke is the second major cause of mortality worldwide that results in persisting disability and mental agony. Ischemic stroke is induced by the diminished blood circulation to the brain, which can be due to obstruction by arteriosclerosis, fibromuscular dysplasia, or thrombosis. Triptonide is a diterpene triepoxide, purified out of extracts of Tripterygium wilfordii Hook F, and is an emerging target against, for example, cancers and inflammatory insults. Materials and Methods: Taking this into consideration, this study was designed to analyze the effect of triptonide on ischemic/reperfusion (I/R) cerebral infarction stroke rats. Results: Our study showed that triptonide decreased the infarct volume and brain edema produced by I/R. Moreover, triptonide protected the rats from any neurological deficits, which were analyzed using a five-point scoring system, augmented antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione content, and lowered the activity of acetylcholinesterase. Triptonide also decreased the levels of pro-inflammatory cytokines such as interleukin-1 β (IL-1 β), TNF- α , and IL-6, while it augmented anti-inflammatory cytokines IL-10 and vascular endothelial growth factor. In this study, cerebral infarction stroke rats showed an increase in malondialdehyde levels. Triptonide preserved the normal brain architecture from various neurotoxic effects. Conclusion: Thus, triptonide can be targeted for drug discovery in the future to protect against cerebral infarction stroke. [ABSTRACT FROM AUTHOR]

Background: The optimal strategy for blood pressure management after thrombectomy remains unknown. The primary objective of The Early Intensive Blood Pressure Management after Endovascular Thrombectomy (IDENTIFY) study is to explore the efficacy and safety of early intensive blood pressure management strategies after thrombectomy compared with that of standard management. Methods: The IDENTIFY study is a prospective, randomized, open-label, assessor-blinded multicenter clinical trial. Patients with acute anterior circulation ischaemic stroke who underwent endovascular thrombectomy within 6 h of stroke onset, achieved successful recanalization, and had two consecutive blood pressure readings > 130 mm Hg during the first 6 h after thrombectomy will be enrolled and centrally randomized into intensive or standard management groups in a 1:1 ratio. Continuous blood pressure monitoring will be initiated at the end of thrombectomy, and patients with high blood pressure during the transfer to the wards will also be enrolled. For patients in the intensive management group, the target blood pressure will be < 130 mm Hg, and the use of antihypertensive drugs will be discontinued if systolic blood pressure goes below 110 mm Hg. The target blood pressure for the standard management group will be < 180 mm Hg, and if systolic blood pressure decreases below 140 mm Hg, the use of antihypertensive drugs will be stepwise decreased until the systolic blood pressure reaches 140 mm Hg again or the infusion is discontinued. Patients will have their blood pressure reduced to the target range within 1 h from randomization and maintained until 24 h after thrombectomy with intravenous hypertensive drugs. A sample size of 600 was predicted. The primary outcome will be the rate of dependency (modified Rankin Scale scores 3–6) at 90 days. Secondary outcomes will include intracerebral hemorrhage (either symptomatic or asymptomatic) within 24 h and 7 days, malignant brain oedema, all-cause death, death and severe disability at 90 days, and quality of life at 90 days, which will be measured using the EuroQol-5 Dimensions-5 Level (EQ-5D-5L) and the 36-Item Short Form Health Survey (SF-36). Safety outcomes will include stroke recurrence within 24 h, early neurological deterioration, hypotension within 24 h, death within 7 days after endovascular thrombectomy, and all-cause acute kidney injury. Trial registration chictr.org.cn (identifier: ChiCTR2200057770). Registered March 17, 2022, http://www.chictr.org.cn/edit.aspx?pid=162575&htm=4 [ABSTRACT FROM AUTHOR]

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences. [ABSTRACT FROM AUTHOR]

Background: Disparities exist regarding an efficient treatment for stroke. Polyarginines have shown promising neuroprotective properties based on available published studies. Thus, the present study aims to systemically review and analyze existing evidence regarding polyarginine's administration efficacy in animal stroke models. Method: Medline, Scopus, Embase, and Web of Science were systematically searched, in addition to manual search. Inclusion criteria were administrating polyarginine peptides in stroke animal models. Exclusion criteria were previous polyarginine administration, lacking a control group, review articles, and case reports. Data were collected and analyzed using STATA 17.0; a pooled standardized mean difference (SMD) with a 95% confidence interval (CI), meta‐regression, and subgroup analyses were presented. Risk of bias, publication bias, and level of evidence were assessed using SYRCLE's tool, Egger's analysis, and Grading of Recommendations Assessment, Development and Evaluation framework, respectively. Results: From the 468 searched articles, 11 articles were included. Analyses showed that R18 significantly decreases infarct size (SMD = –0.65; 95% CI: –1.01, –0.29) and brain edema (SMD = –1.90; 95% CI: –3.28, –0.51) and improves neurological outcome (SMD = 0.67; 95% CI: 0.44, 0.91) and functional status (SMD = 0.55; 95% CI: 0.26, 0.85) in stroke animal models. Moreover, R18D significantly decreases infarct size (SMD = –0.75; 95% CI: –1.17, –0.33) and improves neurological outcome (SMD = 0.46; 95% CI: 0.06, 0.86) and functional status (SMD = 0.35; 95% CI: 0.16, 0.54) in stroke models. Conclusion: Moderate level of evidence demonstrated that both R18 and R18D administration can significantly improve stroke outcomes in animal stroke models. However, considering the limitations, further pre‐clinical and clinical studies are warranted to substantiate the neuroprotective efficacy of polyarginines for stroke. [ABSTRACT FROM AUTHOR]

Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time. [ABSTRACT FROM AUTHOR]

Bilaterally fixed and dilated pupils in the setting of transtentorial herniation have traditionally been considered a sign of futility. Such patients are often denied life-saving surgery based on the premise that meaningful functional recovery would be extremely unlikely. We sought to determine the survival and functional outcome in a cohort of patients who underwent aggressive medical and surgical management. Charts of all patients managed by a single surgeon over a 42-month period were retrospectively reviewed. Functional outcome was determined using modified Rankin Scale (mRS). Outcome was classified as good (mRS score 0–3), acceptable (mRS score 4), or poor (mRS score 5–6). Patients were 7 men and 2 women with a mean age of 36 years (range, 16–66 years). Etiologies included stroke (4 patients), traumatic brain injury (4 patients), and malignant cerebral edema (1 patient). Preoperative Glasgow Coma Scale scores ranged from 3 to 7, and midline shift was 7–16 mm. All patients received emergency osmotic therapy before decompressive surgery. Time to surgery (from pupillary changes) was <150 minutes for all patients (median 94 minutes; range, 50–148 minutes). At 3 months, 5 patients (55.6%) had recovered, achieving a good (n = 3) or acceptable (n = 2) outcome. The other 4 patients failed to recover and ultimately died of their injury. In well-selected patients with transtentorial herniation and bilaterally fixed and dilated pupils, aggressive and timely medical and surgical management may lead to substantial rates of survival and favorable functional outcome. Preconceived notions of a universally grim prognosis in such patients can lead to self-fulfilling prophecies. [ABSTRACT FROM AUTHOR]

Background and purpose: Oxidative stress and neuroinflammation are the main causes of cerebral ischemia. Saponin with steroid or triterpenoid compounds with a sugar part has strong antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the effect of saponin on cerebral edema, Bax gene expression level, and ischemic neurological defects. Materials and methods: In this experimental study, 24 male Wistar rats were divided into three groups: sham, stroke, and stroke+saponin. Rats in the stroke+saponin group received intravenous injection of saponin (3mg/kg) 30 minutes before cerebral ischemia. Each group was divided into two subgroups: brain edema (n=5) and gene expression level investigation (n=3). Cerebral ischemia was induced by middle cerebral artery occlusion model. After 24 hrs, we investigated neurological deficits resulting from ischemia (Kruskal-Wallis test), the degree of brain edema, and Bax gene expression levels in the cortex, piriform cortex-amygdala, striatum, and hippocampus (one-way ANOVA). Results: Findings indicated a significant decrease in the score of neurological defects resulting from ischemia, the amount of cerebral edema, and the level of Bax gene expression in stroke+saponin group (P<0.05). Conclusion: This study showed that saponin pretreatment in rats with ischemia-reperfusion injury can be effective in reducing the damage caused by cerebral ischemia. [ABSTRACT FROM AUTHOR]

A 44‐year‐old female underwent cranioplasty 6 months after a malignant right MCA stroke. Three hours later, she became unresponsive, with new left‐gaze deviation and right‐side hemiparesis. CT head showed new right MCA hypodensity and diffuse edema. After aggressive medical management, she returned to baseline. A brain MRI showed no stroke. Malignant cerebral edema after uneventful cranioplasty is a rare and often fatal complication related to sudden intracranial negative pressure and altered cerebral autoregulation. This is a rare case in which a patient developed malignant cerebral edema and status epilepticus after cranioplasty and survived. [ABSTRACT FROM AUTHOR]

An editorial is presented on the potential benefits and limitations of adjunctive steroid therapy in acute ischemic stroke patients undergoing endovascular thrombectomy. Topics discussed include the lack of significant efficacy demonstrated in the MARVEL trial, despite some indications of improved survival and potential reduction in pneumonia risk associated with steroid use, prompting further exploration into the role of steroids in stroke management.

Background: Elevated intracranial pressure (ICP) is a serious complication in brain injury. Because of the risks involved, ICP is not monitored in all patients at risk. Noninvasive screening tools to identify patients with elevated ICP are needed. Anisocoria, abnormal pupillary size, and abnormal pupillary light reflex are signs of high ICP, but manual pupillometry is arbitrary and subject to interrater variability. We have evaluated quantitative pupillometry as a screening tool for elevated ICP. Methods: We performed a retrospective observational study of the association between Neurological Pupil index (NPi), measured with the Neuroptics NPi-200 pupillometer, and ICP in patients routinely monitored with invasive ICP measurement in the intensive care unit. We performed a nonparametric receiver operator curve analysis for ICP ≥ 20 mm Hg with NPi as a classification variable. We performed a Youden analysis for the optimal NPi cutoff value and recorded sensitivity and specificity for this cutoff value. We also performed a logistic regression with elevated ICP as the dependent variable and NPi as the independent variable. Results: We included 65 patients with invasive ICP monitoring. A total of 2,705 measurements were analyzed. Using NPi as a screening tool for elevated ICP yielded an area under receiver operator curve of 0.72. The optimal mean NPi cutoff value to rule out elevated ICP was ≥ 3.9. The probability of elevated ICP decreased with increasing NPi, with an odds ratio of 0.55 (0.50, 0.61). Conclusions: Screening with NPi may inform high stakes clinical decisions by ruling out elevated ICP with a high degree of certainty. It may also aid in estimating probabilities of elevated ICP. This can help to weigh the risks of initiating invasive ICP monitoring against the risks of not doing so. Because of its ease of use and excellent interrater reliability, we suggest further studies of NPi as a screening tool for elevated ICP. [ABSTRACT FROM AUTHOR]

Bilaterally fixed and dilated pupils (BFDP) in the setting of transtentorial herniation due to a space-occupying lesion have traditionally been considered a sign of futility. As a result, such patients may be denied life-saving decompressive surgery, resulting in very high mortality rates. We sought to determine the survival rate and functional outcomes in patients with transtentorial herniation and BFDP following emergency decompressive surgery. This was a systematic review of MEDLINE, Embase, Cochrane, and Google Scholar databases, using a combination of 15 prespecified keywords, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology. Individual patient data were extracted, pooled, and analyzed. Twenty-two studies totaling 503 patients were included. Study designs were as follows: prospective cohort (n = 1), retrospective cohort (n = 15), and case report (n = 6). Nearly two thirds of patients (67.7%) were male. The mean age was 41 years (range = 3–82). The median preoperative Glasgow coma scale was 3 (range = 3–6). Nearly two thirds (66.9%) underwent surgical decompression within 2 hours of pupillary changes. The mean follow-up was 7 months (range = 1–40). Two thirds (67%) died. Among survivors, 50.5% had severe disability (Glasgow outcome scale = 2–3), while 49.5% had a good outcome (Glasgow outcome scale 4–5), representing 17% of the whole population. Given the methodological limitations, the prognostic value of age, Glasgow coma scale, and time to surgery could not be determined. The literature suggests a rate of favorable recovery approaching 17% following decompressive surgery in patients with transtentorial herniation and BFDP, secondary to space-occupying lesions. In the setting of stroke or trauma, the clinical finding of BFDP should not be solely relied on as an indicator of futility. Prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) dysfunction, characterized by degradation of BBB junctional proteins and increased permeability, is a crucial pathophysiological feature of acute ischemic stroke. Dysregulation of multiple neurovascular unit (NVU) cell types is involved in BBB breakdown in ischemic stroke that may be further aggravated by reperfusion therapy. Therefore, therapeutic co-targeting of dysregulated NVU cell types in acute ischemic stroke constitutes a promising strategy to preserve BBB function and improve clinical outcome. However, methods for simultaneous isolation of multiple NVU cell types from the same diseased central nervous system (CNS) tissue, crucial for the identification of therapeutic targets in dysregulated NVU cells, are lacking. Here, we present the EPAM-ia method, that facilitates simultaneous isolation and analysis of the major NVU cell types (endothelial cells, pericytes, astrocytes and microglia) for the identification of therapeutic targets in dysregulated NVU cells to improve the BBB function. Applying this method, we obtained a high yield of pure NVU cells from murine ischemic brain tissue, and generated a valuable NVU transcriptome database (https://bioinformatics.mpi-bn.mpg.de/SGD%5fStroke). Dissection of the NVU transcriptome revealed Spp1, encoding for osteopontin, to be highly upregulated in all NVU cells 24 h after ischemic stroke. Upregulation of osteopontin was confirmed in stroke patients by immunostaining, which was comparable with that in mice. Therapeutic targeting by subcutaneous injection of an anti-osteopontin antibody post-ischemic stroke in mice resulted in neutralization of osteopontin expression in the NVU cell types investigated. Apart from attenuated glial activation, osteopontin neutralization was associated with BBB preservation along with decreased brain edema and reduced risk for hemorrhagic transformation, resulting in improved neurological outcome and survival. This was supported by BBB-impairing effects of osteopontin in vitro. The clinical significance of these findings is that anti-osteopontin antibody therapy might augment current approved reperfusion therapies in acute ischemic stroke by minimizing deleterious effects of ischemia-induced BBB disruption. [ABSTRACT FROM AUTHOR]

Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel in the brain, called ischemic stroke and hemorrhagic stroke, respectively. Stroke is more common in men than women. Atrial fibrillation, hypertension, kidney disease, high cholesterol and lipids, genetic predisposition, inactivity, poor nutrition, diabetes mellitus, family history and smoking are factors that increase the risk of stroke. Restoring blood flow by repositioning blocked arteries using thrombolytic agents or endovascular therapy are the most effective treatments for stroke. However, restoring circulation after thrombolysis can cause fatal edema or intracranial hemorrhage, and worsen brain damage in a process known as ischemia–reperfusion injury. Therefore, there is a pressing need to find and develop more effective treatments for stroke. In the past, the first choice of treatment was based on natural compounds. Natural compounds are able to reduce the symptoms and reduce various diseases including stroke that attract the attention of the pharmaceutical industry. Nowadays, as a result of the numerous studies carried out in the field of herbal medicine, many useful and valuable effects of plants have been identified. The death-associated protein kinase (DAPK) family is one of the vital families of serine/threonine kinases involved in the regulation of some biological functions in human cells. DAPK1 is the most studied kinase within the DAPKs family as it is involved in neuronal and recovery processes. Dysregulation of DAPK1 in the brain is involved in the developing neurological diseases such as stroke. Natural products can function in a variety of ways, including reducing cerebral edema, reducing brain endothelial cell death, and inhibiting TNFα and interleukin-1β (IL-1β) through regulating the DAPK1 signal against stroke. Due to the role of DAPK1 in neurological disorders, the aim of this article was to investigate the role of DAPK1 in stroke and its modulation by natural compounds. [ABSTRACT FROM AUTHOR]

Multiple neuronal injury pathways are activated during cerebral ischemia and reperfusion (I/R). This study was designed to decrease potential neuronal injuries by using both transcranial direct current stimulation (tDCS) polarities in cerebral ischemia and its following reperfusion period. Ninety rats were randomly divided into six groups. In the sham group, rats were intact. In the I/R group, global cerebral I/R was only induced. In the I/R + c-tDCS and I/R + a-tDCS groups, cathodal and anodal currents were applied, respectively. In the I/R + c/a-tDCS, cathodal current was used in the cerebral ischemia and anodal in the reperfusion. In the I/R + a/c-tDCS group, cathodal and anodal currents were applied in the I/R, respectively. Hippocampal tissue was used to determine the levels of IL-1β, TNF-α, NOS, SOD, MDA, and NMDAR. Hot plate and open field tests evaluated sensory and locomotor performances. The cerebral edema was also measured. Histological assessment was assessed by H/E and Nissl staining of the hippocampal CA1 region. All tDCS modes significantly decreased IL-1β and TNF-α levels, especially in the c/a-tDCS. All tDCS caused a significant decrease in MDA and NOS levels while increasing SOD activity compared to the I/R group, especially in the c/a-tDCS mode. In the c-tDCS and a/c-tDCS groups, the NMDAR level was significantly decreased. The c/a-tDCS group improved sensory and locomotor performances more than other groups receiving tDCS. Furthermore, the least neuronal death was observed in the c/a-tDCS mode. Using two different polarities of tDCS could induce more neuroprotective versus pathophysiological pathways in cerebral I/R, especially in c/a-tDCS mode. Highlights: Multiple pathways of neuronal injury are activated in cerebral ischemia and reperfusion (I/R). Using tDCS could modulate neuroinflammation and oxidative stress pathways in global cerebral I/R. Using c/a-tDCS mode during cerebral I/R causes more neuroprotective effects against neuronal injuries of cerebral I/R. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage remains the deadliest form of stroke worldwide, inducing neuronal death through a wide variety of pathways. Therapeutic hypothermia is a robust and well-studied neuroprotectant widely used across a variety of specialties. Aims: This review summarizes results from preclinical and clinical studies to highlight the overall effectiveness of therapeutic hypothermia to improve long-term intracerebral hemorrhage outcomes while also elucidating optimal protocol regimens to maximize therapeutic effect. Summary of review: A systematic review was conducted across three databases to identify trials investigating the use of therapeutic hypothermia to treat intracerebral hemorrhage. A random-effects meta-analysis was conducted on preclinical studies, looking at neurobehavioral outcomes, blood brain barrier breakdown, cerebral edema, hematoma volume, and tissue loss. Several mixed-methods meta-regression models were also performed to adjust for variance and variations in hypothermia induction procedures. Twwenty-one preclinical studies and five human studies were identified. The meta-analysis of preclinical studies demonstrated a significant benefit in behavioral scores (ES = −0.43, p = 0.02), cerebral edema (ES = 1.32, p = 0.0001), and blood brain barrier (ES = 2.73, p ≤ 0.00001). Therapeutic hypothermia was not found to significantly affect hematoma expansion (ES = −0.24, p = 0.12) or tissue loss (ES = 0.06, p = 0.68). Clinical study outcome reporting was heterogeneous; however, there was recurring evidence of therapeutic hypothermia-induced edema reduction. Conclusions: The combined preclinical evidence demonstrates that therapeutic hypothermia reduced multiple cell death mechanisms initiated by intracerebral hemorrhage; yet, there is no definitive evidence in clinical studies. The cooling strategies employed in both preclinical and clinical studies were highly diverse, and focused refinement of cooling protocols should be developed in future preclinical studies. The current data for therapeutic hypothermia in intracerebral hemorrhage remains questionable despite the highly promising indications in preclinical studies. Definitive randomized controlled studies are still required to answer this therapeutic question. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and long-term disability worldwide. Astrocytes structurally compose tripartite synapses, blood–brain barrier, and the neurovascular unit and perform multiple functions through cell-to-cell signaling of neurons, glial cells, and vasculature. The crosstalk of astrocytes and other cells is complicated and incompletely understood. Here we review the role of astrocytes in response to ischemic stroke, both beneficial and detrimental, from a cell–cell interaction perspective. Reactive astrocytes provide neuroprotection through antioxidation and antiexcitatory effects and metabolic support; they also contribute to neurorestoration involving neurogenesis, synaptogenesis, angiogenesis, and oligodendrogenesis by crosstalk with stem cells and cell lineage. In the meantime, reactive astrocytes also play a vital role in neuroinflammation and brain edema. Glial scar formation in the chronic phase hinders functional recovery. We further discuss astrocyte enriched microRNAs and exosomes in the regulation of ischemic stroke. In addition, the latest notion of reactive astrocyte subsets and astrocytic activity revealed by optogenetics is mentioned. This review discusses the current understanding of the intimate molecular conversation between astrocytes and other cells and outlines its potential implications after ischemic stroke. "Neurocentric" strategies may not be sufficient for neurological protection and recovery; future therapeutic strategies could target reactive astrocytes. [ABSTRACT FROM AUTHOR]

• OECs display prominent total-antioxidant, proliferative, and migratory capacity compared with human brain microvascular endothelial cells (HBMECs). • OECs can incorporate into the vascular network with HBMECs and form a functional blood–brain barrier (BBB). • Exogenous addition of OECs repairs the integrity and function of an in vitro model of human BBB. • Intravenous administration of OECs to rats subjected to middle cerebral artery occlusion effectively decreased brain edema volume in the ipsilateral brain hemisphere. • Exogenous addition of OECs attenuated ischemia-evoked oxidative stress and apoptosis on HBMECs. We have previously reported that outgrowth endothelial cells (OECs) restore cerebral endothelial cell integrity through effective homing to the injury site. This study further investigates whether treatment with OECs can restore blood–brain barrier (BBB) function in settings of ischemia-reperfusion injury both in vitro and in vivo. An in vitro model of human BBB was established by co-culture of astrocytes, pericytes, and human brain microvascular endothelial cells (HBMECs) before exposure to oxygen-glucose deprivation alone or followed by reperfusion (OGD±R) in the absence or presence of exogenous OECs. Using a rodent model of middle cerebral artery occlusion (MCAO), we further assessed the therapeutic potential of OECs in vivo. Owing to their prominent antioxidant, proliferative, and migratory properties, alongside their inherent capacity to incorporate into brain vasculature, treatments with OECs attenuated the extent of OGD±R injury on BBB integrity and function, as ascertained by increases in transendothelial electrical resistance and decreases in paracellular flux across the barrier. Similarly, intravenous delivery of OECs also led to better barrier protection in MCAO rats as evidenced by significant decreases in ipsilateral brain edema volumes on day 3 after treatment. Mechanistic studies subsequently showed that treatment with OECs substantially reduced oxidative stress and apoptosis in HBMECs subjected to ischemic damages. This experimental study shows that OEC-based cell therapy restores BBB integrity in an effective manner by integrating into resident cerebral microvascular network, suppressing oxidative stress and cellular apoptosis. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is a triad of hyperglycemia, metabolic acidosis and ketosis. It is a life-threatening complication of diabetes mellitus (DM) that can lead to death without appropriate treatment. DKA with stroke increases morbidity and mortality in the intensive care unit (ICU). A 37-year-old male was brought to the emergency department with sudden onset of weakness for the past two days. He had been diagnosed with type 2 DM five years earlier, but it was poorly controlled. On examination, his Glasgow Coma Scale was within normal limits. Laboratory and radiological investigations revealed severe hyperglycemia, metabolic acidosis, and brain stem infarct. He required intubation and was admitted to the ICU with a diagnosis of DKA and cerebellar and brain stem infarct. The patient succumbed to death despite 13 days of ICU management. DKA can precipitate a cerebellar and brain stem infarct, but it can be fatal despite extreme management in the ICU. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this preliminary study is to evaluate the efficacy and safety of the Enterprise stent for intracranial atherosclerotic disease (ICAD) in patients who presented with acute stroke due to vessel steno-occlusion and in patients with symptomatic disease despite optimum medical management. Materials and Methods: A retrospective data analysis was performed on 15 consecutive patients who were treated with Enterprise stenting for recanalization of symptomatic intracranial steno-occlusive arteries due to underlying ICAD. Their clinical and radiological data were reviewed to evaluate procedural results, periprocedural and postprocedural complications, and clinical outcome. Results: Enterprise stents were deployed as a rescue method in 15 patients for recanalization of steno-occlusion. All patients achieved final modified thrombolysis in cerebral infarction (mTICI) score improvement (53.3% with a mTICI score from 0 to 2b or 3, 46.7% with a mTICI score from 1 to 3). Two postprocedural complications (1 symptomatic intracranial hemorrhage and 1 severe brain edema, 13.3%) occurred among 15 patients. Among 12 patients with acute ischemic stroke (AIS), 6 patients (50%) had improvement in their National Institute of Health Stroke Scale of more than 4 at discharge. Seven patients (58.3%) had a good functional outcome with 3-month modified Rankin Score (mRS)≤2, and mortality occurred (mRS=6) in 2 patients (16.7%). None of the 10 AIS and 3 transient ischemic attack patients experienced further ischemic events attributable to the treated steno-occlusion during the follow-up period (ranged from 4 to 36 months, median 12 months). Conclusion: This retrospective study suggests that Enterprise stenting can effectively and safely achieve recanalization in symptomatic steno-occlusive intracranial arteries. [ABSTRACT FROM AUTHOR]

Objectives: Up to 10% of acute ischemic stroke (AIS) patients can die in the first 30 days. Older age and a higher National Institutes of Health Stroke Scale (NIHSS) score are associated with transition to comfort measures only (CMO) in AIS. There are insufficient data on specific stroke etiology, infarct location, or vascular territory for the association of AIS with the use of CMO. We therefore evaluated the clinical and imaging factors associated with utilization of CMO and their outcomes. Methods: AIS patients seen in an academic comprehensive stroke center in the United States between July 1, 2015, and June 30, 2016, were subgrouped based on the use of CMO orders (CMO vs. non-CMO) during hospitalization. Clinical, laboratory, and imaging data were analyzed. Multivariable logistic regression analysis was performed, adjusting for pertinent covariates. Results: The study consisted of 296 patients, 27 (9%) patients were transitioned to CMO. Compared with non-CMO patients, those with CMO were older (mean ± standard deviation: 66 ± 15 vs. 75 ± 11 years, p = 0.002). Hemorrhagic transformation of AIS was more likely in CMO (17% vs. 41%, p = 0.0030) compared with non-CMO patients. On multivariate analysis, severe stroke measured by the NIHSS score (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 1.1–1.4), infarction of the insular cortex (OR = 12.9; 95% CI = 1.4–118.4), and presence of cerebral edema with herniation (OR = 9.4; 95% CI = 2.5–35.5) were associated with transition to CMO. Conclusions: The presence of severe stroke, infarction of the insular cortex, and cerebral edema with herniation were associated with utilization of CMO in AIS. Impairment of multiple neurological functions served by the insular cortex could play a role in transition to CMO. [ABSTRACT FROM AUTHOR]

The role of cerebral pressure autoregulation (CPA) in brain injury and disorders has gained increased interest. The CPA is often disturbed as a consequence of acute brain injury, which contributes to further brain damage and worse outcome. Specifically, in severe traumatic brain injury, CPA disturbances predict worse clinical outcome and targeting an autoregulatory-oriented optimal cerebral perfusion pressure threshold may improve brain energy metabolism and clinical outcome. In aneurysmal subarachnoid hemorrhage, cerebral vasospasm in combination with distal autoregulatory disturbances precipitate delayed cerebral ischemia. The role of optimal cerebral perfusion pressure targets is less clear in aneurysmal subarachnoid hemorrhage, but high cerebral perfusion pressure targets are generally favorable in the vasospasm phase. In acute ischemia, autoregulatory disturbances may occur and autoregulatory-oriented blood pressure (optimal mean arterial pressure) management reduces the risk of hemorrhagic transformation, brain edema, and unfavorable outcome. In chronic occlusive disease such as moyamoya, the gradual reduction of the cerebral circulation leads to compensatory distal vasodilation and the residual CPA capacity predicts the risk for cerebral ischemia. In spontaneous intracerebral hemorrhage, the role of autoregulatory disturbances is less clear, but CPA disturbances correlate with worse clinical outcome. Also, in community-acquired bacterial meningitis, CPA dysfunction is frequent and correlates with worse clinical outcome, but autoregulatory management is yet to be evaluated. In this review, we discuss the role of CPA in different types of brain injury and disease, the strengths and limitations of the monitoring methods, the potentials of autoregulatory management, and future directions in the field. [ABSTRACT FROM AUTHOR]

Aims: To explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis. Methods: We analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3‐month death and major disability (modified Rankin Scale (mRS) score of 3–6). The secondary outcomes were 3‐month mortality (mRS score of 6), moderate‐severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively. Results: Elevated DBIL pre‐thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595–6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre‐thrombolysis showed the similar results (OR 2.185; 95% CI 1.111–4.298; p for trend = 0.047), while IBIL pre‐thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974–3.687; p for trend = 0.090). Multivariable‐adjusted spline regression model showed a positive linear dose‐response relationship between DBIL pre‐thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre‐thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084–0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001–0.024). Increased DBIL post‐thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184–4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066–0.453) and IDI (95% CI) = 0.025 (0.008–0.043). Conclusion: Increased DBIL pre‐thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches. [ABSTRACT FROM AUTHOR]

The application of decompressive craniectomy (DC) is thoroughly documented in the management of brain edema, particularly following traumatic brain injury. However, an increasing amount of concern is developing among the universal medical community as regards the application of DC in the treatment of other causes of brain edema, such as subarachnoid hemorrhage, cerebral hemorrhage, sinus thrombosis and encephalitis. Managing stroke continues to remain challenging, and demands the aggressive and intensive consulting of a number of medical specialties. Middle cerebral artery (MCA) infarcts, which consist of 1-10% of all supratentorial infarcts, are often associated with mass effects, and high mortality and morbidity rates. Over the past three decades, a number of neurosurgical medical centers have reported their experience with the application of DC in the treatment of malignant MCA infarction with varying results. In addition, over the past decade, major efforts have been dedicated to multicenter randomized clinical trials. The present study reviews the pertinent literature to outline the use of DC in the management of malignant MCA infarction. The PubMed database was systematically searched for the following terms: 'Malignant cerebral infarction', 'surgery for stroke', 'DC for cerebral infarction', and all their combinations. Case reports were excluded from the review. The articles were categorized into a number of groups; the majority of these were human clinical studies, with a few animal experimental clinical studies. The surgical technique involved was DC, or hemicraniectomy. Other aspects that were included in the selection of articles were methodological characteristics and the number of patients. The multicenter randomized trials were promising. The mortality rate has unanimously decreased. As for the functional outcome, different scales were employed; the Glasgow Outcome Scale Extended was not sufficient; the Modified Rankin Scale and Bathel index, as well as other scales, were applied. Other aspects considered were demographics, statistics and the very interesting radiological ones. There is no doubt that DC decreases mortality rates, as shown in all clinical trials. Functional outcome appears to be the goal standard in modern-era neurosurgery, and quality of life should be further discussed among the medical community and with patient consent. [ABSTRACT FROM AUTHOR]

Traumatic acute subdural hematoma (aSDH) is associated with a high mortality rate caused by post-operative cerebral infarction. Recently, brain natriuretic peptide (BNP) was considered a reliable biomarker in the acute phase of traumatic brain injuries. We therefore aimed in this study to analyze BNP levels on admission, identify the predictors of their elevation, and assess the relationship between BNP and the risk of post-operative cerebral infarction. Patients with isolated, unilateral, traumatic aSDH who were admitted to our department between July 2017 and May 2020 were enrolled in this study. On admission, cranial computer tomography (CCT) and BNP sampling were simultaneously performed. Additionally, the time between head trauma and BNP sampling (TTS) was assessed. Admission radiographic variables included hematoma volumes, midline shift, and degree of brain edema. Cerebral infarction was detected on postoperative CCT. In total, 130 patients were included in this study. Surgical treatment was performed in 82.3% (n = 107) of cases. The multiple regression analysis showed that larger hematoma volumes (p = 0.032) and advanced age (p = 0.005) were independent predictors of elevated BNP when TTS <24 h. The binomial logistical regression analysis identified BNP with a cutoff value of <29.4 pg/mL (TTS = 3–12 h, adjusted odds ratio [aOR] = 16.5, p = 0.023) as an independent predictor of post-operative cerebral infarction. Elevated BNP levels in the first 24 h post-trauma were related to larger hematoma volumes and advanced age. Further, an increased risk of post-operative cerebral infarction was identified in patients with lower BNP levels in the post-traumatic period 3–12 h. [ABSTRACT FROM AUTHOR]

An acute reduction in plasma osmolality causes rapid uptake of water by astrocytes but not by neurons, whereas both cell types swell as a consequence of lost blood flow (ischemia). Either hypoosmolality or ischemia can displace the brain downwards, potentially causing death. However, these disorders are fundamentally different at the cellular level. Astrocytes osmotically swell or shrink because they express functional water channels (aquaporins), whereas neurons lack functional aquaporins and thus maintain their volume. Yet both neurons and astrocytes immediately swell when blood flow to the brain is compromised (cytotoxic edema) as following stroke onset, sudden cardiac arrest, or traumatic brain injury. In each situation, neuronal swelling is the direct result of spreading depolarization (SD) generated when the ATP-dependent sodium/potassium ATPase (the Na+/K+ pump) is compromised. The simple, and incorrect, textbook explanation for neuronal swelling is that increased Na+ influx passively draws Cl− into the cell, with water following by osmosis via some unknown conduit. We first review the strong evidence that mammalian neurons resist volume change during acute osmotic stress. We then contrast this with their dramatic swelling during ischemia. Counter-intuitively, recent research argues that ischemic swelling of neurons is non-osmotic, involving ion/water cotransporters as well as at least one known amino acid water pump. While incompletely understood, these mechanisms argue against the dogma that neuronal swelling involves water uptake driven by an osmotic gradient with aquaporins as the conduit. Promoting clinical recovery from neuronal cytotoxic edema evoked by spreading depolarizations requires a far better understanding of molecular water pumps and ion/water cotransporters that act to rebalance water shifts during brain ischemia. [ABSTRACT FROM AUTHOR]

Background: Ischemic water uptake in acute stroke is a reliable indicator of lesion age. Nevertheless, inter-individually varying edema progression has been observed and elevated water uptake has recently been described as predictor of malignant infarction. Aims: We hypothesized that early-elevated lesion water uptake indicates accelerated "tissue clock" desynchronized with "time clock" and therefore predicts poor clinical outcome despite successful recanalization. Methods: Acute middle cerebral artery stroke patients with multimodal admission-CT who received successful thrombectomy (TICI 2b/3) were analyzed. Net water uptake (NWU), a quantitative imaging biomarker of ischemic edema, was determined in admission-CT and tested as predictor of clinical outcome using modified Rankin Scale (mRS) after 90 days. A binary outcome was defined for mRS 0–4 and mRS 5–6. Results: Seventy-two patients were included. The mean NWU (SD) in patients with mRS 0–4 was lower compared to patients with mRS 5–6 (5.0% vs. 12.1%; p < 0.001) with similar time from symptom onset to imaging (2.6 h vs. 2.4 h; p = 0.7). Based on receiver operating curve analysis, NWU above 10% identified patients with very poor outcome with high discriminative power (AUC 0.85), followed by Alberta Stroke Program Early CT Score (ASPECTS) (AUC: 0.72) and National Institutes of Health Stroke Scale (NIHSS) (AUC: 0.72). Conclusions: Quantitative NWU may serve as an indicator of "tissue clock" and pronounced early brain edema with elevated NWU might suggest a desynchronized "tissue clock" with real "time clock" and therefore predict futile recanalization with poor clinical outcome. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore the association of serum level of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and its related inflammatory biomarkers (hypoxia inducible factor-1α, cathepsin B, caspase-1 and matrix metalloproteinase-9) with malignant brain edema (MBE) in patients with acute ischemic stroke.Methods: We prospectively enrolled patients with acute ischemic stroke admitted < 24 h from onset of symptoms. Brain CT was performed on admission and blood samples were collected. Repeated brain CT/MRI was performed < 7 days of admission to identify the presence of MBE, defined as neurological deterioration with imaging signs of midline shift or compressed basal cisterns. Logistic regression analysis was performed to assess the association between inflammatory biomarkers and MBE, adjusted for age and National Institutes of Health Stroke Scale (NIHSS).Results: 200 patients (69.3 ± 14.3 years; male 55 %) were included for analysis, of whom 26 patients developed MBE (median time from stroke onset to MBE 32.5 h). Compared with patients without MBE, those with MBE had higher level of serum concentration of NLRP3 (median time from onset to blood collection 3 h, 1.85 ng/ml vs. 1.11 ng/ml, P = 0.026). NLRP3 level was positively correlated with NIHSS on admission (Spearman ρ = 0.18, P = 0.01) and the association between NLRP3 and MBE was attenuated (OR 1.47, 95 % CI 0.88-2.46, P = 0.138) after adjusting for age and NIHSS. There was no significant difference in other biomarkers between MBE and non-MBE groups.Conclusions: There was a trend of association between a higher level of serum concentration of NLRP3 and an increased risk of MBE after ischemic stroke, possibly confounded by the severity of stroke, which is worth further validation in large cohort studies. [ABSTRACT FROM AUTHOR]

Background Decompressive craniectomy (DC) has become the definitive surgical procedure to manage a medically intractable rise in intracranial pressure. DC is a life-saving procedure resulting in lower mortality but also higher rates of severe disability. Although technically straightforward, DC is accompanied by many complications. It has been reported that complications are associated with worse outcome. We reviewed a series of patients who underwent DC at our department to establish the incidence and types of complications. Methods We retrospectively evaluated the incidence of complications after DC performed in 135 patients during the time period from January 2013 to December 2018. Postoperative complications were evaluated using clinical status and CT during 6 months of follow-up. In addition, the impact of potential risk factors on the incidence of complications and the impact of complications on outcome were assessed. Results DC was performed in 135 patients, 93 of these for trauma, 22 for subarachnoid hemorrhage, 13 for malignant middle cerebral artery infarction, and 7 for intracerebral hemorrhage. Primary DC was performed in 120 patients and secondary DC in 15 patients. At least 1 complication occurred in each of 100 patients (74%), of which 22 patients (22%) were treated surgically. The following complications were found: edema or hematoma of the temporal muscle (34 times), extracerebral hematoma (33 times), extra-axial fluid collection (31 times), hemorrhagic progression of contusions (19 times), hydrocephalus (12 times), intraoperative malignant brain edema (10 times), temporal muscle atrophy (7 times), significant intraoperative blood loss (6 times), epileptic seizures (5 times), and skin necrosis (4 times). Trauma (p = 0.0006), coagulopathy (p = 0.0099), and primary DC (p = 0.0252) were identified as risk factors for complications. There was no significant impact of complications on outcome. Conclusions The incidence of complications following DC is high. However, we did not confirm a significant impact of complications on outcome. We emphasize that some phenomena are so frequent that they can be considered a consequence of primary injury or natural sequelae of the DC rather than its direct complication. [ABSTRACT FROM AUTHOR]

Introduction: The clinical factors predisposing to ischemic stroke in reversible cerebral vasoconstriction syndrome (RCVS) are unclear. In this observational cross-sectional study, we aimed to evaluate the risk factors and clinical outcomes associated with the development of ischemic stroke in patients with RCVS. Methods: We utilized the Nationwide Readmissions Database 2016–2017 to identify all hospitalizations with RCVS, with or without acute ischemic stroke. Independent predictors of and clinical outcomes associated with ischemic stroke were analyzed using logistic regression. Results: Among 1065 hospitalizations for RCVS (mean ± SD age 49.0 ± 16.7 years, female 69.7%), 267 (25.1%) had ischemic stroke. Patients with ischemic stroke were more likely to have hypertension (OR 2.33, 95% CI 1.51–3.60), diabetes (OR 1.81, 95% CI 1.11–2.98), and tobacco use (OR 1.64, 95% CI 1.16–2.33) and were less likely to have a history of migraine (OR 0.56, 95% CI 0.35–0.90). Ischemic stroke was associated with higher odds of cerebral edema (OR 3.15, 95% CI 1.31–7.57) and respiratory failure (OR 2.39, 95% CI 1.28–4.44). Patients with ischemic stroke also had longer hospital stay by a mean duration of 6.7 days, P < 0.001, higher hospital charges by a mean of $72,961, P < 0.001, and a higher likelihood of not being discharged to home (OR 3.57, 95% CI 2.39–5.33). They had higher in-hospital mortality rate; however, the difference was not statistically significant. Conclusion: Ischemic stroke affects nearly 25% of patients with RCVS and is associated with adverse clinical outcomes. RCVS patients with cerebrovascular risk factors might have a higher predisposition for developing ischemic lesions during the disease process. [ABSTRACT FROM AUTHOR]