CT perfusion for predicting intracranial atherosclerotic middle cerebral artery occlusion.

Backgrounds and purpose: Identifying the underlying cause of acute middle cerebral artery occlusion (MCAO) as intracranial atherosclerotic stenosis (ICAS) or embolism is essential for determining the optimal treatment strategy before endovascular thrombectomy. We aimed to evaluate whether baseline computed tomography perfusion (CTP) characteristics could differentiate ICAS-related MCAO from embolic MCAO. Methods: We conducted a retrospective analysis of the clinical and baseline CTP data from patients who underwent endovascular thrombectomy for acute MCAO between January 2018 and December 2022. Core volume growth rate was defined as core volume on CTP divided by onset to CTP time. Multivariate logistic analysis was utilized to identify independent predictors for ICAS-related acute MCAO, and the diagnostic performance of these predictors was evaluated using receiver operating characteristic curve analysis. Results: Among the 97 patients included (median age, 71 years; 60% male), 31 (32%) were diagnosed with ICAS-related MCAO, and 66 (68%) had embolism-related MCAO. The ICAS group was younger (p = 0.002), had a higher proportion of males (p = 0.04) and smokers (p = 0.001), a lower prevalence of atrial fibrillation (AF) (p < 0.001), lower NIHSS score at admission (p = 0.04), smaller core volume (p < 0.001), slower core volume growth rate (p < 0.001), and more frequent core located deep in the brain (p < 0.001) compared to the embolism group. Multivariate logistic analysis identified core volume growth rate (aOR 0.46, 95% CI 0.26-0.83, p = 0.01) as an independent predictor of ICAS-related MCAO. A cutoff value of 2.5 mL/h for core volume growth rate in predicting ICAS-related MCAO was determined from the receiver operating characteristic curve analysis, with a sensitivity of 81%, specificity of 80%, positive predictive value of 66%, and negative predictive value of 90%. Conclusion: Slow core volume growth rate identified on baseline CTP can predict ICAS-related MCAO. Further prospective studies are warranted to confirm and validate these findings.

Maximizing Interlaminar Fracture Toughness in Bidirectional GFRP through Controlled CNT Heterogeneous Toughening.

"Interleaving" is widely used for interlaminar toughening of fiber-reinforced composites, and the structure of interleaving is one of the important factors affecting the toughening efficiency of laminates. Several experiments have demonstrated that compared to continuous and dense structures, toughening layers with structural heterogeneity can trigger multiple toughening mechanisms and have better toughening effects. On this basis, this work further investigates the application of heterogeneous toughening phases in interlaminar toughening of bidirectional GFRP. CNT was selected to construct toughening phases, which was introduced into the interlaminar of composites through efficient spraying methods. By controlling the amount of CNT, various structures of CNT toughening layers were obtained. The fracture toughness of modified laminates was tested, and their toughening mechanism was analyzed based on fracture surface observation. The results indicate that the optimal CNT usage (0.5 gsm) can increase the initial and extended values of interlayer fracture toughness by 136.0% and 82.0%, respectively. The solvent acetone sprayed with CNT can dissolve and re-precipitate a portion of the sizing agent on the surface of the fibers, which improves the bonding of the fibers to the resin. More importantly, larger discrete particles are formed between the layers, guiding the cracks to deflect in the orientation of the toughened layer. This generates additional energy dissipation and ultimately presents an optimal toughening effect.

Long-term recurrence of ischemic events in patients with intracranial atherosclerotic stenosis stratified by symptoms and pathogenesis.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) can cause either transient ischemic attack (TIA) or acute ischemic stroke (AIS). Pathogenesis of ICAS-AIS can be divided into artery-to-artery embolism(A-A), hypoperfusion(HP), and parent-artery atherosclerosis occluding penetrating artery(POPA). However, the prognosis of each type remains uncertain. Our study aimed to investigate potential disparities in the recurrent risk among these four subtypes of symptomatic ICAS. METHODS: From a prospective, single-center cohort study of acute cerebrovascular diseases from January 2017 to November 2021, we recruited 120 ICAS patients and classified them into four groups based on diffusion weighted imaging. Patients were retrospectively followed up for recurrence in December 2022. The primary outcome was recurrent cerebral vascular events (RCVE) in the same territory. RESULTS: Among 120 recruited patients, POPA(33%) was the most common subtype, followed by A-A(32%), HP(29%), and TIA(6%). Cumulative recurrent rate was 31.2% with median months of follow-up as 27(20-45.5). There was no significant difference in the risk of RCVE in the same territory among four subgroups within three months. However, when considering the risk after three months, TIA(57%) had the highest risk of RCVE, followed by A-A(26%), while HP(4%) and POPA(8%) had lower risks (P = 0.001). Cox regression model indicated that symptom and pathogenesis was an independent risk factor for RCVE in long-term prognosis (P = 0.022), after adjusting for a history of hypertension and cerebral infarction. CONCLUSIONS: Distinctive symptoms and pathogenesis of ICAS exhibit varying risks of RCVE in long-term prognosis. The differentiation in recurrent risk may provide valuable insights for guiding secondary prevention strategies.

Predictors of hemodynamic instability during and persistent after carotid artery stenting.

OBJECTIVES: The risk factors for post-carotid artery stenting severe hemodynamic instability remain elusive. This study aimed to identify the predictors of severe hemodynamic instability during and persisted after carotid artery stenting. MATERIALS AND METHODS: Consecutive patients who underwent carotid artery stenting for extracranial carotid artery stenosis at a single-center between September 2018 and July 2021 were retrospectively assessed. The predictive factors of severe hemodynamic instability intraoperation and post-operation were analyzed. RESULTS: Among the 139 patients included, 63 experienced severe hemodynamic instability, with 45 and 18 cases occurring intra and postoperatively, respectively. Persistent was observed in 21 patients. Smoke exposure (odds ratio [OR], 2.38; p=0.039), carotid bifurcation stenosis (OR, 0.91; p=0.018), and large-diameter balloon (>4 mm) dilatation (OR, 11.95; p<0.001) were identified as independent risk factors for hemodynamic instability at any stage of carotid artery stenting. Intraoperatively, large-diameter balloon (>4 mm) dilatation was associated with an increased risk of hemodynamic instability occurrence (OR, 4.67; p=0.01), whereas general anesthesia (OR, 0.19; p=0.001) and a longer distance from the stenosis to the carotid bifurcation (OR, 0.89; p=0.01) were negatively associated with hemodynamic instability. Furthermore, smoking exposure (OR, 3.73; p=0.03), large diameter balloon dilatation (OR, 6.12; p=0.032), distance from stenosis to bifurcation (OR, 0.85; p=0.047) and long-stent (40 mm) implantation (OR, 0.84 [95% confidence interval, 0.74-0.95]; p=0.007) could independently predict persistent hemodynamic instability. CONCLUSION: Patients with a smoking history, lesions near the carotid bulb, or dilatation using a large-diameter balloon were most likely to suffer severe hemodynamic instability. General anesthesia can protect against severe hemodynamic instability only intraoperatively. Long-term stent implantation may reduce persistent hemodynamic instability.

Corrigendum: Impaired Glymphatic Transport Kinetics Following Induced Acute Ischemic Brain Edema in a Mouse pMCAO Model.

[This corrects the article DOI: 10.3389/fneur.2022.860255.].

A Comparison of Different Endovascular Treatment for Vertebral Artery Origin Stenosis.

OBJECTIVE: To compare the safety and efficacy of stenting with drug-eluting stent (DES), stenting with bare mental stent (BMS), and angioplasty alone with drug-coated balloon (DCB) in patients with symptomatic vertebral artery origin stenosis (VAOS) who did not respond to aggressive medical management. METHODS: We performed a retrospective analysis of consecutive patients with symptomatic VAOS who underwent endovascular treatment between December 2018 and November 2021 at our institution. The main outcome compared were technical success, perioperative complications, residual stenosis, stroke recurrence, progression of residual stenosis, and restenosis. RESULTS: A total of 46 patients were included: 29 were stented with DES, 12 were stented with BMS, and 5 received angioplasty alone with DCB. Technical success was achieved in 100%, 100%, and 60%, respectively (P = 0.008). Residual stenosis was 10.8%, 20.2%, and 51.2%, respectively (P < 0.001). Perioperative complications occurred only in 1 case in the DES group (P = 1.00). During a mean follow-up of 14.1 months, stroke recurrence rate was 6.9%, 16.7%, and 0% respectively (P = 0.73). Absolute progression of residual stenosis was 10.1%, 34.9%, and -8.0%, respectively (P < 0.001). Restenosis rate was 6.9%, 50.0%, and 20.0%, respectively (P = 0.007). CONCLUSIONS: In patients with symptomatic VAOS who did not respond to aggressive medical management, stenting with DES shows superiority in the lowering the restenosis rate compared with stenting with BMS. Angioplasty alone with DCB is associated with the slowest progression of stenosis in spite of moderate residual stenosis.

Impaired Glymphatic Transport Kinetics Following Induced Acute Ischemic Brain Edema in a Mouse pMCAO Model.

Background: Cerebral edema forms immediately after blood flow interruption in ischemic stroke, which largely increased the death and disability. The glymphatic (glial-lymphatic) pathway is a major regulator of the brain liquid dynamics and homeostasis. This study aimed to investigate the transport kinetics of the glymphatic system after the appearance of ischemic edema. Methods: In this study, a coated filament was attached to the left middle cerebral artery (MCA) of mice to establish a mouse model of permanent middle cerebral artery occlusion with an intact blood-brain barrier (BBB). The glymphatic function was then quantified using contrast-enhanced MRI (11.7T) by employing an injection of gadobenate dimeglumine (BOPTA-Gd) into the cisterna magna of mice. We then evaluated the expression and polarization of aquaporin-4 (AQP4) as a proxy for the physiological state of the glymphatic system. Results: Our results revealed a positive correlation between the signal intensity in T1-weighted images and the corresponding apparent diffusion coefficient (ADC) values in the cortex, striatum, and periventricular zone, suggesting that impaired glymphatic transport kinetics in these regions is correlated to the cytotoxic edema induced by the occlusion of MCA. Furthermore, the increased depolarization of AQP4 in the parenchyma perivascular space (PVS) was consistent with glymphatic failure following the induced early cerebral ischemic edema. Conclusions: Glymphatic transport kinetics were suppressed between the onset of cytotoxic edema and the disruption of the BBB, which correlated with the diminishing ADC values that vary based on edema progression, and is associated with depolarization of AQP4 in the parenchyma PVSs.

Human induced pluripotent stem cells derived from a patient with a mutation of FBN1c.1858C > T (p. Pro620Ser).

Mutation of FBN1 has certain relation with the incidence of cranial cervical artery dissection. Our study reprogrammed human induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMC) of a patient with a mutation of FBN1c.1858C > T (p. Pro620Ser). The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Besides, it has normal karyotype and could differentiate into mesoderm, endoderm and neuronal layers. We also identified it has the same specific mutation with our patient.

Dl-3-n-Butylphthalide Alleviates Demyelination and Improves Cognitive Function by Promoting Mitochondrial Dynamics in White Matter Lesions.

White matter lesions (WMLs) are a type of cerebrovascular disorder accompanied by demyelination and cognitive decline. Dl-3-n-butylphthalide (D1-NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases, although the function of DI-NBP on WML is still not clear. This study aims to investigate whether DI-NBP affects cognitive function and ameliorates demyelination in a model of WML. The bilateral carotid artery stenosis (BCAS) mouse model and in vitro brain slice cultures with low glucose and low oxygen (LGLO) treatment were adopted. The Dl-NBP was administered intragastrically for 28 days after BCAS or added at a dose of 50 µm for 48 h after LGLO. Spatial learning and memory were evaluated by an eight-arm radial maze. Demyelination was detected using a TEM. Mitochondrial dynamics were assessed by time-lapse imaging in the cultured brain slices. The function of the synapse was evaluated by the patch clamp technique. In BCAS mice, obvious demyelination and cognitive decline were observed, while both were significantly relieved by a high-dose D1-NBP treatment (100 mg/kg). Along with demyelination, mitochondrial accumulation in the axons was significantly increased in the BCAS mice model, but with the treatment of a high-dose D1-NBP, mitochondrial accumulation was mitigated, and the anterograde/retrograde transport of mitochondria was increased. Following the improved anterograde/retrograde transport of mitochondria, the synapse activity was significantly upregulated while the reactive oxygen species (ROS) generation was remarkably decreased in the cultured brain slices. In addition, we identified syntaphilin (SNPH) as the downstream target of D1-NBP. The overexpression of SNPH mediated the effects of D1-NBP in mitigating axonal mitochondrial accumulation. In conclusion, the D1-NBP treatment significantly relieved demyelination and improved spatial learning and memory in the WML model by promoting mitochondrial dynamics. These neuroprotective effects of D1-NBP were mediated by inhibiting the mitochondrial arching protein, SNPH, which provided a potential therapeutic target for WML.

Sequential tirofiban infusions combined with endovascular treatment may improve outcomes in acute ischemic stroke - a meta-analysis.

In this meta-analysis, we explored whether tirofiban could safely improve outcomes when combined with endovascular therapy in acute ischemic stroke with large vessel occlusion. We searched the PubMed, EMBASE, Web of Science, and The Cochrane Library databases from January 2000 to October 2019 for relevant RCTs/non-RCTs. A total of 13 trials involving 2584 patients, of whom 893 (34.5%) received tirofiban, were ultimately included in the meta-analysis. The results suggested that tirofiban improved patient independence at 90 days (51.2% vs 42.4%; OR 1.26; p =0.02) without increasing the risk of symptomatic intracranial hemorrhage (OR 1.01; p =0.96) or mortality (OR 0.86; p =0.09). There was no association between the use of tirofiban and recanalization rate (OR 1.35; p =0.11). Subgroup analysis showed that a loading dose followed by maintenance doses, but not a single dose, of tirofiban increased favorable 90-day functional outcomes (OR 1.49; p =0.0008). Moreover, low maintenance doses may be more effective than high maintenance doses (OR 1.41; p =0.02). These results suggest that adjunctive tirofiban treatment administered as a loading dose followed by low-dose maintenance may improve functional outcomes of endovascular therapy in acute ischemic stroke.

Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Mitigate Trained Immunity in the Brain.

Trained immunity was recently discovered in innate immune cells and shown to facilitate the clearance of pathogens at the time of occurrence of the second insult. However, it exacerbates several aspects of neuropathologies, and proper therapy is needed to rectify this abnormal immune reaction. Mesenchymal-stem cells (MSCs) exhibit a distinct capability for brain repair but are associated with safety concerns. Extracellular vesicles derived from MSCs are a promising alternative therapy. In this study, we used lipopolysaccharides to activate trained immunity in the brain and examined the therapeutic potential of MSC-derived extracellular vesicles in mitigating the trained-immunity-induced exacerbated neuropathology. We found that MSC-derived extracellular vesicles showed comparable effects to those of MSCs in the mitigation of trained immunity in the brain. Moreover, the administration of MCS-derived extracellular vesicles mitigated the aggregated inflammatory responses in the acute stage of stroke and alleviated the trained-immunity-induced increased load of amyloid-ß in APP/PS1 mice. We further investigated the molecular machinery of MSC-derived extracellular vesicles and found that IL-10 is important for the mediation of the therapeutic potential of MSC-derived extracellular vesicles toward the alleviation of trained immunity. Our study indicates that extracellular-vesicle-based regenerative strategies might be useful to mitigate trained immunity in the brain.

Collateral grade of the Willis' circle predicts outcomes of acute intracranial internal carotid artery occlusion before thrombectomy.

BACKGROUND AND PURPOSE: Endovascular mechanical thrombectomy (EVMT) shows significant promise in improving acute ischemic stroke (AIS) with proximal artery occlusion, but outcomes have been variable. We explored the patients treated by thrombectomy to investigate the association between a favorable clinical outcome of EVMT in intracranial internal carotid artery occlusion (iICAO) and a set of predictors. METHODS: A total of 38 iICAO patients treated by EVMTs were analyzed. Primary collateral grades (PCG) at baseline based on the integrity of Willis' circle were categorized into three degrees. The favorable outcomes, measured by modified Rankin scale (mRS), were defined as ≤2 at 90 days. The reperfusion was one of the most important confounders, defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b. The other risk factors included demographic characteristics, vascular risk factors, stroke severity, procedural EVMT, and PCG at baseline was adjusted to reveal the association with favorable outcomes. RESULTS: Of 38 iICAO patients, 65.8% (25 in 38) achieved reperfusion. However, only 31.6% (12/38) achieved favorable outcomes at 90 days. With a PCG3, 61.5% of them achieved favorable outcomes, while only 37.5% of those with PCG2 and PCG1 achieved favorable outcomes (p = .003). In multivariable logistic regression, PCG was revealed as a predictor for favorable outcomes (OR 5.278, p = .019) after adjusting the reperfusion and other factors. CONCLUSIONS: The PCG based on the integrity of Willis' circle might be an underlying predictor of the prognosis of AIS in patients with iICAO after EVMT. The function of intact anterior communicating artery (AcoA) and ipsilateral posterior communicating artery (PcoA) in favoring prognosis of the iICAO patients might need to be validation in future study.

Tirofiban facilitates the reperfusion process during endovascular thrombectomy in ICAS.

The aim of the present study was to assess the use of tirofiban injections for rescue therapy following artery reocclusion due to intra-luminal thrombosis during endovascular thrombectomy in patients with acute ischemic stroke (AIS). A total of seven cases of patients treated with adjunctive tirofiban injections following failed endovascular thrombectomy due to instant intra-luminal thrombosis were retrospectively assessed. A Solitaire stent was used as the primary thrombectomy device in all patients. Tirofiban was injected intra-arterially via a temporarily deployed Solitaire stent with continuous intravenous infusion for the subsequent 24 h; half of the conventionally recommended dose was employed. Outcome measures included angiographic reperfusion (mTICI), symptomatic intracranial hemorrhage, mortality and functional independence at 90 days (modified Rankin Scale, 0-2). Six patients had occlusions in the middle cerebral artery and one patient had occlusions in the basilar artery. Of the seven patients, five exhibited successful reperfusion (mTICI 2b-3) and achieved functional independence following 90 days. Reperfusion failed in the remaining two patients, who succumbed within 90 days of therapy. No intracranial or extracranial hemorrhage cases were identified. The results of the present study suggest that tirofiban facilitates reperfusion and ameliorates long-term prognosis in patients with AIS undergoing endovascular thrombectomy, and may be safe for those receiving intravenous tissue plasminogen activator therapy.

Aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder with recurrent short partial transverse myelitis and favorable prognosis: Two new cases.

Understanding the characteristics of neuromyelitis optica spectrum disorder (NMOSD) with recurrent short partial transverse myelitis (SPTM), which is very rare, contributes to the differential diagnosis of multiple sclerosis (MS). We present two Chinese aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD cases who had at least twice SPTM during 4 and 6 years of follow-up, respectively. Their SPTMs have been mild and responded well to corticosteroids just like in the case of MS. The findings highlight the need of searching for serum AQP4-IgG (cell-based assay strongly recommended) in patients with recurrent SPTM and suggest that those patients may have a mild acute attack phase and favorable long-term prognosis.

Attitudes toward the American nutrition guidelines for the critically ill patients of Chinese intensive care physicians.

Nutrition therapy is essential for the management of critically ill patients. Some guidelines have been published to standardize and optimize the nutrition therapy. However, there are still many controversies in nutrition practice and there is a gap between guidelines and clinical nutrition therapy for patients in intensive care units (ICUs). This study aimed to assess attitudes and beliefs toward nutrition therapy of Chinese intensive care physicians by using the American guidelines as a surrogate. A questionnaire was sent to 45 adult ICUs in China, in which surveyed physicians were asked to rate their attitudes toward the American guidelines. A total of 162 physicians from 45 ICUs returned the questionnaires. Physicians were categorized into groups according to their professional seniority, hospital levels and whether they were members of Chinese Society for Parenteral and Enteral Nutrition (CSPEN). Overall, 94% of the respondents thought that nutrition therapy for critically ill patients was very important, and 80% mentioned that they used the American guidelines. There was diversity of opinion on the recommendations pertaining to nutrition assessment, supplemental parenteral nutrition and cutoff values for gastric residual volume, negative or neutral attitudes about these recommendations were 43%, 59% and 41%, respectively. Members of CSPEN were more likely to select a greater strength of recommendation than non-members. In conclusion, the overall attitudes of Chinese intensive care physicians toward the American guidelines were positive. Nevertheless, given the great guideline-practice gap, nutrition-focused education is warranted for many intensive care physicians in China.

Delayed admission to ICU does not increase the mortality of patients post neurosurgery.

Increasing shortage of intensive care resources is a worldwide problem. While routine postoperative admission to the intensive care unit (ICU) of patients undergoing neurosurgery is a long established practice for many hospitals. Therefore, some neurosurgical patients have to be cared in post anesthesia care unit (PACU) before ICU admission during high ICU occupancy. The aim of this study was to compare the outcome of neurosurgical patients immediately admitted to the ICU post operation with those who were required to wait for ICU bed in PACU and managed by anesthesiologists before ICU admission. All adult neurosurgical patients admitted to our ICU between January 2010 and July 2013 were retrospectively analyzed. Recorded data included demographic data, surgical categories, end time of operation, operation hours, postoperative complication, hospital/ICU length of stay and cost, Glasgow coma score (GCS) on ICU discharge and ICU mortality. A total of 989 neurosurgical patients were evaluated. Nine hundred thirty-seven (94.7%) patients were immediately admitted and 52 (5.3%) patients had delayed ICU admission. Median PACU waiting hours was 4.3 h (interquartile range: 2.0-10.2 h). Delayed ICU admission post neurosurgery was highly associated with the end time of operation (p = 0.019) and high ICU occupancy (p < 0.0001). Average GCS on ICU discharge was higher in immediately admitted group (13.0 ± 3.5 vs. 11.4 ± 4.5, p = 0.012). However, delayed admission to ICU post neurosurgery was not associated with prolonged ICU length of stay, increased ICU mortality, increased postoperative complication and hospital/ICU cost (all p > 0.05). Thus, an algorithm for appropriate disposition of neurosurgical patients is warranted so as to balance the quality of care and control of scarce intensive resources.