Hydroxychloroquine attenuates neuroinflammation following traumatic brain injury by regulating the TLR4/NF-κB signaling pathway.

BACKGROUND: After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood-brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway. METHODS: C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated. RESULTS: HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ. CONCLUSIONS: HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment.

FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages.

BACKGROUND: Resident microglia and macrophages are the predominant contributors to neuroinflammation and immune reactions, which play a critical role in the pathogenesis of ischemic brain injury. Controlling inflammatory responses is considered a promising therapeutic approach for stroke. Recombinant human fibroblast growth factor 21 (rhFGF21) presents anti-inflammatory properties by modulating microglia and macrophages; however, our knowledge of the inflammatory modulation of rhFGF21 in focal cerebral ischemia is lacking. Therefore, we investigated whether rhFGF21 improves ischemic outcomes in experimental stroke by targeting microglia and macrophages. METHODS: C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) and randomly divided into groups that received intraperitoneal rhFGF21 or vehicle daily starting at 6 h after reperfusion. Behavior assessments were monitored for 14 days after MCAO, and the gene expression levels of inflammatory cytokines were analyzed via qRT-PCR. The phenotypic variation of microglia/macrophages and the presence of infiltrated immune cells were examined by flow cytometry and immunostaining. Additionally, magnetic cell sorting (MACS) in combination with fluorescence-activated cell sorting (FACS) was used to purify microglia and macrophages. RESULTS: rhFGF21 administration ameliorated neurological deficits in behavioral tests by regulating the secretion of pro-inflammatory and anti-inflammatory cytokines. rhFGF21 also attenuated the polarization of microglia/macrophages toward the M1 phenotype and the accumulation of peripheral immune cells after stroke, accompanied by a temporal evolution of the phenotype of microglia/macrophages and infiltration of peripheral immune cells. Furthermore, rhFGF21 treatment inhibited M1 polarization of microglia and pro-inflammatory cytokine expression through its actions on FGF receptor 1 (FGFR1) by suppressing nuclear factor-kappa B (NF-κB) and upregulating peroxisome proliferator-activated receptor-γ (PPAR-γ). CONCLUSIONS: rhFGF21 treatment promoted functional recovery in experimental stroke by modulating microglia/macrophage-mediated neuroinflammation via the NF-κB and PPAR-γ signaling pathways, making it a potential anti-inflammatory agent for stroke treatment.

A Multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage (AMPAS): observational registry study.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with very high mortality and morbidity. Our limited knowledge on predictors of long-term outcome in poor-grade patients with aSAH definitively managed comes from retrospective and prospective studies of small case series of patients in single center. The purpose of the AMPAS is to determine the long-term outcomes in poor-grade patients with different managements within different time after aSAH, and identify the independent predictors of the outcome that help guide the decision on definitive management. METHODS/DESIGN: The AMPAS study is a prospective, multicenter, observational registry of consecutive hospitalized patients with poor grade aSAH (WFNS grade IV and V). The aim is to enroll at least 226 poor-grade patients in 11 high-volume medical centers (eg, >150 aSAH cases per year) affiliated to different universities in China. This study will describe poor grade patients and aneurysm characteristics, treatment strategies (modality and time of definitive management), hospitalization complications and outcomes evolve over time. The definitive management is ruptured aneurysm treatment. Outcomes at 3, 6, 12 months after the management were measured using the Glasgow Outcome Scale and the Modified Rankin Scale. DISCUSSION: The AMPAS is the first prospective, multicenter, observational registry of poor grade aSAH with any management. This study will contribute to a better understanding of significant predictors of outcome in poor grade patients and help guide future treatment of the worst patients after aSAH. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TNRC-10001041.

Corrigendum: NmFGF1-regulated glucolipid metabolism and angiogenesis improves functional recovery in a mouse model of diabetic stroke and acts via the AMPK signaling pathway.

[This corrects the article DOI: 10.3389/fphar.2021.680351.].

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

[Analysis of prognostic factors on posterior communicating artery aneurysm caused oculomotor nerve palsy].

OBJECTIVE: To study and analyze the factors affecting the recovery of posterior communicating artery aneurysm-induced oculomotor nerve palsy (ONP). METHODS: The clinical and follow-up data of posterior communicating artery aneurysm-induced ONP in 23 patients from May 2005 to May 2009 were retrospectively compared. There were 7 male and 16 female with a mean age of 50.4 years. Among the 23 patients, 13 patients underwent endovascular coiling (endovascular group) and 10 patients underwent surgical clipping (surgical group). RESULTS: Of the patients with 2 year of follow-up, 6 patients recovered completely and 7 patients recovered partially in the endovascular group, compared with 6 patients recovered completely and 4 patients recovered partially in the surgical group (P = 0.407). Compared to the patients with preoperative complete ONP, the rate of complete recovery was higher in the patients with preoperative partial ONP, while the results did not reach the significance (P = 0.095). Patients accepted treatment in 14 days since the onset of symptoms recovered significantly than who accepted treatment after 14 days since the onset of symptoms (P = 0.045). CONCLUSIONS: There is no significant difference in recovery from ONP between endovascular coiling and surgical clipping as treatment for posterior communicating artery aneurysm patients with ONP. Timing of treatment after onset of symptoms is a factor affects the recovery of ONP.

PRMT8 Attenuates Cerebral Ischemia/Reperfusion Injury via Modulating Microglia Activation and Polarization to Suppress Neuroinflammation by Upregulating Lin28a.

Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic stroke-associated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.

Computed tomography angiography based emergency microsurgery for massive intracranial hematoma arising from arteriovenous malformations.

BACKGROUND: Digital subtraction angiography (DSA) and magnetic resonance angiography are the imaging modalities for the detection of intracranial arteriovenous malformations. However, these modalities are time consuming and cannot be used in emergency conditions. Computed tomography angiography (CTA) has also been shown to reliably detect vascular disorders such as cerebral arteriovenous malformations (AVMs). AIMS: The purpose of this study was to evaluate the usefulness CTA in the surgical treatment of AVMs and the hematoma evacuation. PATIENTS AND METHODS: Case records of 18 patients with massive intracranial hematoma secondary to AVMs were retrospectively reviewed. All patients had emergent brain CT and CTA. Follow-up DSA was performed two to three weeks after surgery. The outcome was assessed using Glasgow Outcome Scale (GOS). Results : Emergent CTA demonstrated AVMs and defined the feeding arteries, abnormal vascular nest, and draining veins in all the patients. Fourteen patients underwent hematoma evacuation and total resection of the AVMs, and four patients had hematoma evacuation and a partial resection. Follow-up DSA demonstrated complete resection of AVM in 14/18 patients and partial resection in 4 patients. There were no deaths and none of the patients had rebleeding in the follow up. A GOS scores during follow-up were: GOS 3 in 12 patients, GOS 4 in 4 patients and GOS 2 in 2 patients. CONCLUSIONS: CTA can be a reliable and rapid diagnostic tool for detecting underlying AVM in patients presenting with intracranial hematoma and for the pretreatment planning of emergency craniotomy.

Lin28a attenuates cerebral ischemia/reperfusion injury through regulating Sirt3-induced autophagy.

Cerebral ischemia-reperfusion injury causes damage to local brain tissue and its function, but its specific pathogenesis is still unclear. Autophagy is an important catabolic pathway in eukaryotic cells, which is mainly used to remove damaged intracellular organelles, misfolded long-acting macromolecules and participate in cerebral ischemia-reperfusion injury. Lin28 is a highly conserved RNA-binding protein that plays a role in regulating gene translation, which is important for the growth and maintenance of pluripotent cells. Lin28a has been reported to have a clear protective effect on post-ischemic reperfusion injury of the heart. However, whether Lin28a has an effect on nerve injury after cerebral ischemia-reperfusion needs further study. In this study, we found that the expression of Lin28a was decreased in cerebral ischemia-reperfusion mice model. Upregulation of Lin28a could alleviate the nerve injury caused by ischemia-reperfusion, and promote autophagy of nerve cells. Upregulation of Lin28a reduced nerve cell apoptosis and relieved nerve cell injure induced by oxygen-glucose deprivation/reoxygenation. Lin28a increased the LC3-II levels in nerve cells, suggesting the promotion of autophagy. Mechanism studies indicated that Lin28a promoted autophagy mainly through regulating Sirt3 expression and activating AMPK-mTOR pathway. In conclusion, our study revealed the important role of Lin28a in cerebral ischemia-reperfusion and suggested that Lin28a was a protective factor for cerebral ischemia-induced injury.

NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway.

Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mouse model of T2D stroke. Angiogenesis plays an important role in neuronal survival and functional recovery post-stroke. NmFGF1 promoted angiogenesis in the mouse model of T2D stroke. Furthermore, nmFGF1 reversed the reduction of tube formation and migration in human brain microvascular endothelial cells (HBMECs) cultured in high glucose conditions and treated with oxygen glucose deprivation/re-oxygenation (OGD). Amp-activated protein kinase (AMPK) plays a critical role in the regulation of angiogenesis. Interestingly, we found that nmFGF1 increased the protein expression of phosphorylated AMPK (p-AMPK) both in vivo and in vitro. We found that nmFGF1 promoted tube formation and migration and that this effect was further enhanced by an AMPK agonist (A-769662). In contrast, these processes were inhibited by the application of an AMPK inhibitor (compound C) or siRNA targeting AMPK. Furthermore, nmFGF1 ameliorated neuronal loss in diabetic stroke mice via AMPK-mediated angiogenesis. In addition, nmFGF1 ameliorated glucose and lipid metabolic disorders in our mouse model of T2D stroke without causing significant changes in body weight. These results revealed that nmFGF1-regulated glucolipid metabolism and angiogenesis play a key role in the improvement of functional recovery in a mouse model of T2D stroke and that these effects are mediated by the AMPK signaling pathway.

Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling.

BACKGROUND: Despite advances in the treatment of poor-grade aneurysmal subarachnoid hemorrhage (aSAH), predicting the long-term outcome of aSAH remains challenging, although essential. OBJECTIVE: To predict long-term outcomes after poor-grade aSAH using decision tree modeling. METHODS: This was a retrospective analysis of a prospective multicenter observational registry of patients with poor-grade aSAH with a World Federation of Neurosurgical Societies (WFNS) grade IV or V. Outcome was assessed by the modified Rankin Scale (mRS) at 12 mo, and an unfavorable outcome was defined as an mRS of 4 or 5 or death. Long-term prognostic models were developed using multivariate logistic regression and decision tree algorithms. An additional independent testing dataset was collected for external validation. Overall accuracy, sensitivity, specificity, and area under receiver operating characteristic curves (AUC) were used to assess model performance. RESULTS: Of the 266 patients, 139 (52.3%) had an unfavorable outcome. Older age, absence of pupillary reactivity, lower Glasgow coma score (GCS), and higher modified Fisher grade were independent predictors of unfavorable outcome. Modified Fisher grade, pupillary reactivity, GCS, and age were used in the decision tree model, which achieved an overall accuracy of 0.833, sensitivity of 0.821, specificity of 0.846, and AUC of 0.88 in the internal test. There was similar predictive performance between the logistic regression and decision tree models. Both models achieved a high overall accuracy of 0.895 in the external test. CONCLUSION: Decision tree model is a simple tool for predicting long-term outcomes after poor-grade aSAH and may be considered for treatment decision-making.

Endovascular Coiling versus Surgical Clipping of Very Small Ruptured Anterior Communicating Artery Aneurysms.

BACKGROUND: Endovascular coiling of anterior communicating artery (ACoA) aneurysms has evolved dramatically. Ruptured ACoA aneurysms are more likely to be smaller. We aimed to investigate the safety and efficacy of endovascular coiling of very small ruptured ACoA aneurysms compared with surgical clipping. METHODS: We conducted a retrospective analysis of consecutive 111 patients with very small ruptured ACoA aneurysms treated with endovascular coiling or surgical clipping in our single center. Very small aneurysms were defined as aneurysm maximal size ≤3.0 mm. Patients were grouped into coiling and clipping groups. Baseline characteristics, postoperative complications, and clinical outcomes were compared between the 2 groups. RESULTS: Forty-six patients (41.1%) underwent successfully coiling, and 65 patients (58.0%) underwent surgical clipping, including 2 patients who failed coiling and crossed over to surgical clipping. The mean size of the ruptured ACoA aneurysms was 2.6 ± 0.5 mm (range, 1.0-3.0 mm). Patients with smaller aneurysms (P = 0.028) or A1 segment complete configuration (P = 0.009) more often underwent surgical clipping, and patients with A1 segment symmetric configuration more often underwent coiling (P = 0.011). There were not statistically significant differences in intraoperative rupture, early rebleeding, cerebral infarction, and seizure in patients treated with clipping and coiling. Clinical outcomes were similar between the 2 groups. There was no retreatment in both groups. CONCLUSIONS: Patients with very small ruptured ACoA aneurysms can be safely and effectively treated with endovascular coiling. However, smaller ACoA aneurysms still require surgical clipping. A smaller aneurysm size limits the use of endovascular coiling.

Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Risk Factors Affecting Clinical Outcomes in Intracranial Aneurysm Patients in a Multi-Center Study.

Objective: Patients with poor-grade aneurysm subarachnoid hemorrhage (SAH) have commonly been considered to have a poor prognosis. The objective of this study was to investigate the independent risk factors affecting clinical outcomes in intracranial aneurysm patients with poor-grade aneurysm subarachnoid hemorrhage (aSAH) underwent different intervention therapies. Methods: A multicenter observational registry of 324 poor-grade aSAH patients treated at tertiary referral centers from October 2010 to March 2012 were enrolled in this study. The clinical data including patient characteristics on admission and during treatment course, treatment modality, aneurysm size and location, radiologic features, signs of cerebral herniation (dilated pupils), and functional neurologic outcome were collected. Clinical outcomes were assessed via a modified Rankin Scale at 12 months. Multivariate logistic regression models were used to develop prognostic models. The area under the receiver operator characteristic curves (AUC) and Hosmer-Lemeshow tests were used to assess discrimination and calibration. WAP score was developed to predict risk of poor outcome. Results: Older age, female gender, ventilated breathing status, non-reactive pupil response, pupil dilation, lower GCS score, a WFNS grade of V, intraventricular hemorrhage, a higher Fisher grade, a higher modified Fisher grade, and conservative treatment were calculated to be associated with a relatively poor outcome. Multivariate analyses revealed that older age, lower Glasgow coma scale score (GCS), the absence of pupillary reactivity, higher modified Fisher grade, and conservative treatment were independent predictors of poor outcome, showed good discrimination and calibration. Patients with WFNS grade V, older age and non-reactive pupillary reactivity were predicted to have a poor outcome by WAP risk score. Conclusions: A simple WAP risk score had good discrimination and calibration in the prediction of outcome. The risk score can be easily measured and may complement treatment decision-making.

Intracranial Complex Ruptured Aneurysms Coiled with Overlapping Low-Profile Visualized Intraluminal Support Stents: Another Available Option for Complex Ruptured Intracranial Aneurysms.

BACKGROUND: Overlapping stents represent a new paradigm in endovascular interventions, especially for complex and wide-necked aneurysms. The low-profile visualized intraluminal support (LVIS) device is a new generation of self-expanding braided stents recently introduced in China for stent-assisted coiling of intracranial aneurysms. We report several cases of intracranial aneurysms coiled using overlapping LVIS stents to evaluate its efficacy and safety. METHODS: Patients with ruptured intracranial aneurysms treated with double LVIS stents at our center between November 2014 and May 2016 were reviewed. The clinical data and technical results are presented. RESULTS: Ten patients with 15 aneurysms were treated with double LVIS stents, with a 100% technical success rate. No mortality was observed. Immediate angiographic outcome evaluation showed complete occlusion in 13 aneurysms (86.7%) and neck remnants in 2 aneurysms (13.3%). CONCLUSIONS: Double LVIS stents are safe and effective in the treatment of intracranial aneurysms, especially complex aneurysms.

Comparison of Aggressive Surgical Treatment and Palliative Treatment in Elderly Patients with Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after aggressive surgical treatment. METHOD: This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. RESULTS: At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3-5, and palliative treatment were independent predictors of poor prognoses. CONCLUSION: Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.

Diagnostic value of CTA and MRA in intracranial traumatic aneurysms.

OBJECTIVE: To investigate the diagnostic value of computerized tomographic angiography (CTA) and magnetic resonance angiography (MRA) for intracranial traumatic aneurysms (TAs). METHODS: CTA and MRA of six patients with intracranial TAs verified by digital subtraction angiography (DSA) and surgery were retrospectively analysed. All patients were examined by nonenhanced computerized tomography (CT) and two by CTA. The source data were reconstructed by volume rendering (VR) and multi-planar reconstruction (MPR) from CTA. Four of them had maximum intensity project (MIP) from MRA. RESULTS: Of the six patients, a total of seven TAs were detected by CTA and MRA examinations. Five cases had only one TA and one case had two TAs. The average diameter was 2.3 cm (1.1-3.3 cm). CTA demonstrated two TAs appeared at the cavernous segment of the internal carotid artery (ICA) and the middle cerebral artery (MCA) respectively. MCA TA was definitely and clearly demonstrated on VR images, whereas VR images failed to depict the cavernous ICA TA, which was detected on MPR images. Two TAs were found irregular saccular shape, irregular margin of parent artery and wide neck on CTA. Four MRA examinations demonstrated five TAs, including the cavernous segment ICA TAs (2 cases), the supraclinoid segment ICA TA (1 case), and the cavernous segment associated with opposite side of the petrosal segment ICA TA (1 case). In a cavernous ICA TA, MRA only revealed aneurysm body, whereas aneurysm neck and distal segment of the parent artery were not revealed. In the remaining cases, MRA clearly depicted aneurysm body and parent artery, whereas the neck was not displayed. ICA TAs showed irregular capsule-like high signal intensity on MRA images. Four TAs exhibited irregular distal segment of the parent artery. TAs at the supraclinoid segment or MCA failed to find fracture signs on nonenhanced CT. CONCLUSIONS: Both CTA and MRA examinations are the effective non-invasive method of imageology for diagnosing intracranial TAs, while CTA is more eligible for diagnosing TAs after nonenhanced CT has demonstrated skull base fractures.

Predicting intraprocedural rupture and thrombus formation during coiling of ruptured anterior communicating artery aneurysms.

BACKGROUND: Intraprocedural rupture and thrombus formation are serious complications during coiling of ruptured intracranial aneurysms, and they more often occur in patients with anterior communicating artery (ACoA) aneurysms. OBJECTIVE: To identify independent predictors of intraprocedural rupture and thrombus formation during coiling of ruptured ACoA aneurysms. METHODS: Between January 2008 and February 2015, 254 consecutive patients with 255 ACoA aneurysms were treated with coiling. We retrospectively reviewed intraoperative angiograms and medical records to identify intraprocedural rupture and thrombus formation, and re-measured aneurysm morphologies using CT angiography images. Multivariate logistic regression models were used to determine independent predictors of intraprocedural rupture and thrombus formation. RESULTS: Of the 231 patients included, intraprocedural rupture occurred in 10 (4.3%) patients, and thrombus formation occurred in 15 (6.5%) patients. Patients with smaller aneurysms more often experienced intraprocedural rupture than those with larger aneurysms (3.5±1.3 mm vs 5.7±2.3 mm). Multivariate analysis showed that smaller ruptured aneurysms (p=0.003) were independently associated with intraprocedural rupture. The threshold of aneurysm size separating rupture and non-rupture groups was 3.5 mm. Multivariate analysis showed that a history of hypertension (p=0.033), aneurysm neck size (p=0.004), and parent vessel angle (p=0.023) were independent predictors of thrombus formation. The threshold of parent vessel angle separating thrombus and non-thrombus groups was 60.0°. CONCLUSIONS: Ruptured aneurysms <3.5 mm were associated with an increased risk of intraprocedural rupture, and parent vessel angle <60.0°, wider-neck aneurysms, and a history of hypertension were associated with increased risk of thrombus formation during coiling of ruptured ACoA aneurysms.

Preoperative and postoperative predictors of long-term outcome after endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have received endovascular treatment. Endovascular treatment of poor-grade aSAH, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade aSAH. METHODS A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade aSAH. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mRS) score at 12 months, and poor outcome was defined as an mRS score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model's discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration. RESULTS At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mRS score of 4, 6 (4.4%) had an mRS score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI 0.80-0.92, p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI 0.81-0.93, p < 0.001). Both models had good calibration (p = 0.941 and p = 0.653, respectively). CONCLUSIONS Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade aSAH. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade aSAH with ruptured wide-neck aneurysms. ▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I.

Stent-assisted coiling versus coiling alone of poor-grade ruptured intracranial aneurysms: a multicenter study.

INTRODUCTION: Endovascular coiling is a valid treatment option for poor-grade ruptured aneurysms. However, little is known about stent-assisted coiling of poor-grade aneurysms. OBJECTIVE: To compare the safety and efficacy of stent-assisted coiling with coiling alone for poor-grade aneurysms. METHODS: Using multicenter data on poor-grade aneurysms, we performed a retrospective analysis of 131 consecutive patients treated with endovascular coiling within 14 days after ictus. Patients were split into two groups: stent-assisted coiling and coiling alone. Baseline characteristics, immediate angiographic results, perioperative complications, and clinical outcomes were compared between the two groups. RESULTS: Twenty-three (17.6%) patients were treated with stent-assisted coiling and 108 (82.4%) with coiling alone. There were no statistically significant differences in patient age, sex, clinical grade, Fisher grade, modified Fisher grade, aneurysm location, and size between the stent-assisted coiling and coiling alone groups. Intraprocedural aneurysm rupture, procedure-related ischemic complication, external ventricular drainage-related hemorrhagic complication, and symptomatic vasospasm did not differ between the two groups. Immediate angiographic results and clinical outcomes at discharge and at 6 and 12 months did not differ between the groups. Aneurysm rebleeding occurred in 4 (17.4%) patients after stent-assisted coiling compared with 2 (1.9%) patients after coiling alone (p<0.007). Multivariate analysis showed that incomplete aneurysm occlusion was independently associated with aneurysm rebleeding (p=0.016), and there was a trend toward aneurysm rebleeding after stent-assisted coiling (p=0.051). CONCLUSIONS: Stent-assisted coiling of poor-grade aneurysms is feasible and safe compared with coiling alone. However, the hemorrhagic complication and aneurysm rebleeding may not be negligible.

Variation in Patient Characteristics and Outcomes Between Early and Delayed Surgery in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: There is no consensus regarding the optimal timing for surgery for poor-grade aneurysmal subarachnoid hemorrhage. OBJECTIVE: To retrospectively evaluate variation in patient characteristics and outcomes between early and delayed surgery groups. METHODS: Poor-grade aneurysmal subarachnoid hemorrhage was defined as a World Federation of Neurosurgical Societies grade of IV or V after resuscitation. Early surgery was defined as surgery performed within 72 hours of ictus, and delayed surgery was defined as surgery after 72 hours. Outcomes were assessed by modified Rankin score. The mean time of follow-up was 12.5 ± 3.4 months. RESULTS: Of the 118 patients included in the study, 80 (68%) underwent early surgery and 38 (32%) underwent delayed surgery. Patients with brain herniation (P < .001) and a lower Fisher grade (P = .02) more often underwent early surgery. Patients in the early group more often underwent decompressive craniectomy (P < .001). Postoperative complications and length of hospital stay did not differ, and outcomes were similar between the 2 groups. Forty (34%) patients had an excellent outcome (modified Rankin score 0-1). Multivariate analysis showed a slight trend toward an excellent outcome in the early surgery group. Younger age, World Federation of Neurosurgical Societies grade IV after resuscitation, and middle cerebral artery aneurysms were independent predictors of an excellent outcome. CONCLUSION: Although patients with brain herniation and a lower Fisher grade were more likely to undergo early surgery, there was a slight trend toward an excellent outcome in the early surgery group. Patients with a younger age, World Federation of Neurosurgical Societies grade IV after resuscitation, and middle cerebral artery aneurysms were more likely to experience an excellent outcome.