Imaging of brain clearance pathways via MRI assessment of the glymphatic system.

Glymphatic clearance dysfunction may play an important role in a variety of neurodegenerative diseases and the progression of ageing. However, in vivo imaging of the glymphatic system is challenging. In this study, we describe an MRI method based on chemical exchange saturation transfer (CEST) of the Angiopep-2 probe to visualize the clearance function of the glymphatic system. We injected rats with Angiopep-2 via the tail vein and performed in vivo MRI at 7 T to track differences in Angiopep-2 signal changes; we then applied the same principles in a bilateral deep cervical lymph node ligation rat model and in ageing rats. We demonstrated the feasibility of Angiopep-2 CEST for visualizing the clearance function of the glymphatic system. Finally, a pathological assessment was performed. Within the model group, the deep cervical lymph node ligation group and the ageing group showed higher CEST signal than the control group. We conclude that this new MRI method can visualize clearance in the glymphatic system.

Does dual antiplatelet therapy increase the risk of haematoma enlargement in the acute stage? A retrospective study of the use of stent-assisted coiling versus coiling alone or balloon-assisted coiling for the treatment of ruptured intracranial aneurysms combined with intracranial haematoma.

This study aims to identify the efficacy and safety of stent-assisted coiling (SAC) treatment of ruptured intracranial aneurysms (RIAs) combined with intracranial haematoma (ICH) compared to coiling alone or balloon-assisted coiling (non-SAC). A retrospective analysis of 54 consecutive patients receiving endovascular therapy from 2014 to 2020 was performed. The data collected included baseline characteristics, angiographic results, perioperative complications, immediate aneurysm occlusion, clinical outcomes, follow-up at discharge and after 6 months, hospitalisation costs, and inpatient length of stay. Patients were categorised into the SAC group and the non-SAC group. Univariate and multivariate logistic regression analyses were used to identify risk factors related to clinical outcomes. Of the 54 patients harbouring RIAs with ICH, 22 (40.74%) and 32 (59.26%) patients were subject to SAC and non-SAC treatments, respectively. Postoperative rebleeding (1 [4.5%] and 3 [9.3%] in SAC and non-SAC groups, respectively, p > 0.05) and Hunt-Hess grade (IV-V) lesions (13.6% vs. 40.6%, p = 0.067) did not differ between the two groups. In total, 10 (45.5%) patients treated with SAC received a Fisher scale score of 0-3 compared with 6 (18.8%) patients treated with non-SAC methods (p = 0.035). Compared with the non-SAC group (7/21.9%), the rate of wide-necked aneurysms was increased in the SAC group (11/50%) (p = 0.031). No differences in poor outcomes (mRS > 2) were noted between the SAC and non-SAC groups (p > 0.05). Multivariate analysis revealed that ischaemic complication events (p = 0.016) represent the only independent risk factor for adverse outcomes, and a trend towards unfavourable clinical outcomes was noted for patients who smoke (p = 0.087). SAC is a safe and efficient treatment for RIAs combined with ICH when dual antiplatelet therapy (DAPT) is used in the perioperative period. In addition, SAC should be preferentially used in wide-neck RIAs. Ischaemic complications are a risk factor for poor clinical outcomes. Given the small sample size and retrospective bias of this study, these findings should be further verified in a study with a larger sample size or a randomised controlled trial (RCT).

Quantitative morphometric changes in vascular mild cognitive impairment patients: early diagnosis of dementia.

Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer's disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.

Angiopep-2, an MRI Biomarker, Dynamically Monitors Amyloid Deposition in Early Alzheimer's Disease.

The reliable and dynamic detection of amyloid ß-protein (Aß) deposition using imaging technology is necessary for preclinical Alzheimer's disease (AD), which may significantly improve prognosis. The present study aimed to evaluate the feasibility of applying angiopep-2 (ANG), a chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) biomarker, for monitoring Aß deposition in vivo. ANG exerted a good chemical exchange saturation transfer (CEST) effect and displayed a moderate binding affinity to Aß1-42 in vitro. Six-month-old mice with AD injected with ANG exhibited a significantly enhanced CEST effect than controls in vivo; this effect gradually became more apparent at 8, 10, and 12 months. Spatial learning impairment caused by abundant Aß deposition (representing mild cognitive impairment in AD patients) develops at 12 months in APPswe/PSEN1dE9 (line 85) AD mice. To conclude, the CEST of ANG could display very earlier age-related Aß pathological progress in mice with AD, consistent with immunohistochemistry. ANG has extraordinary potential for clinical transformation as an imaging biomarker to diagnose early AD and track its progress dynamically and nonradiationally.

Combination of Quantitative Susceptibility Mapping and Diffusion Kurtosis Imaging Provides Potential Biomarkers for Early-Stage Parkinson's Disease.

Purpose: This study aimed to detect changes in iron deposition and neural microstructure in the substantia nigra (SN), red nucleus (RN), and basal ganglia of Parkinson's disease (PD) patients at different stages using quantitative susceptibility mapping and diffusion kurtosis imaging to identify potential indicators of early-stage PD. Methods: We enrolled 20 early-stage and 15 late-stage PD patients, as well as 20 age- and sex-matched controls. All participants underwent quantitative susceptibility mapping and diffusion kurtosis imaging to determine magnetic susceptibility (MS), fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) in several brain regions. Results: Compared with the control group, MS and MK values in the SN were significantly increased in the early- and late-stage PD group, whereas MS values in the red nucleus (RN), globus pallidus (GP), and caudate nucleus (CN), FA value in the CN and GP, and MK value in the CN and putamen (PU) were significantly increased in the late-stage PD group. There were positive correlations between MS and MK values in the CN and MS and FA values in the GP. Furthermore, the combination of MS and MK values in the SN provided high accuracy for distinguishing early-stage PD patients from controls. Conclusions: This study identified MS and MK in the SN as potential indicators of early-stage PD.

Mechanical Thrombectomy for M2 Segment Occlusion in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The safety and benefit of mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) patients with M2 segment middle cerebral artery occlusions remain uncertain. OBJECTIVE: To investigate the benefit of mechanical thrombectomy for M2 occlusion compared with M1 occlusion in patients with AIS. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from inception to April 2021 to identify relevant articles. The main results comprised 90-day functional independence (modified Rankin Score from 0-2), successful recanalization (thrombectomy in cerebral infarction [TICI] 2b/3), mortality, and rates of symptomatic intracerebral hemorrhage after using modern thrombectomy devices. Odds ratios (ORs) were generated for binary variants. ReviewManager 5.3 software was used. RESULTS: Ultimately, a total of 14 trials were included, with 3454 participants enrolled. MT for M2 occlusion had a higher rate of 3-month functional independence than M1 occlusion, but the difference was nonsignificant (OR: 1.19, 95% confidence interval [CI]: 0.98 to 1.46). The TICI2b/3 scores (OR: 0.71, 95% CI: 0.58-0.88) in M2 occlusion were remarkably lower than those in M1. The mortality and symptomatic intracerebral hemorrhage rates were comparable between the 2 groups. When comparing M2 and M1 occlusions, we found that there was no significant difference between stent retriever and aspiration in the modified Rankin Score (0-2) after AIS, but aspiration exerted an eminently higher recanalization rate with regard to TICI2b/3 (OR: 0.77, 95% CI: 0.61-0.96). CONCLUSIONS: Compared with M1 occlusion, patients with M2 occlusion treated by MT demonstrated similar clinical outcomes in this study. Moreover, there was no difference between stent retriever and aspiration in treating M2 occlusion in terms of functional independence at 90 days. However, aspiration exerted a conspicuously higher recanalization rate in M2 occlusion than in M1 occlusion.

Proton Magnetic Resonance Spectroscopy for Diagnosis of Non-Motor Symptoms in Parkinson's Disease.

Background: The current diagnosis of Parkinson's disease (PD) is mainly based on the typical clinical manifestations. However, 60% dopaminergic neurons have died when the typical clinical manifestations occur. Predictive neurobiomarkers may help identify those PD patients having non-motor disorders or in different stage and achieving the aim of early diagnosis. Up to date, few if any neuroimaging techniques have been described useful for non-movement disorders diagnosis in PD patients. Here, we investigated the alteration of metabolites in PD patients in different stage of PD and non-motor symptoms including sleep, gastrointestinal and cognitive dysfunction, by using the 1H-MRS. Methods: A total of 48 subjects were included between 2017 and 2019: 37 PD (15 men, age 47-82 years) and 11 healthy people (8 men, age 49-74 years). All participants underwent MRI and multi-voxel 1H-MRS examination within 3 days in admission. Six kinds of metabolites, such as creatine (Cr), N-acetyl aspartate/creatine (NAA/Cr), N-acetyl aspartate/choline (NAA/Cho), choline/creatine (Cho/Cr), lipid/creatine (LL/Cr), and myo-Inositol/creatine ratio (mI/Cr) were tested among the PD group and the control groups. Statistical analyses and correlation analyses were performed by using SPSS. The p < 0.05 was considered statistically significant. Results: Compared late PD group with a control group or early group, higher Cr ratio and lower NAA/Cr ratio were observed in the late PD group (p < 0.05). The mI/Cr in the late PD group was also lower than that in the early PD group (p < 0.05). Regarding the relationship between metabolites and NMS, Cho/Cr was higher in the sleep disorder group, whereas mI/Cr was lower in the gastrointestinal dysfunction group in comparison with the non-symptom groups. Moreover, Cr, Cho/Cr, mI/Cr, and LL/Cr were identified to have higher concentrations in the cognitive group in thalamus. Conclusions: Proton magnetic resonance spectroscopy is an advanced tool to quantify the metabolic changes in PD. Three biomarkers (Cr, NAA/Cr, and mI/Cr) were detected in the late stage of PD, suggesting that these markers might be potential to imply the progression of PD. In addition, subgroups analysis showed that MRS of thalamus is a sensitive region for the detection of cognitive decline in PD, and the alteration of neurochemicals (involving Cr, Cho, mI, and LL) may be promising biomarkers to predict cognitive decline in PD.

Low-profile visualized intraluminal support stent for the endovascular treatment of traumatic intracranial internal carotid artery pseudoaneurysms.

Optimal treatment strategies for traumatic intracranial internal carotid artery (ICA) pseudoaneurysms are controversial. The low-profile visualized intraluminal support (LVIS) device is a braided stent with a metal coverage rate between traditional laser cut stents and flow diversion devices. We report here our therapy strategy using the LVIS stent-assisted coiling for treatment of traumatic intracranial ICA pseudoaneurysms. Patients with traumatic intracranial ICA pseudoaneurysms treated by the LVIS stent-assisted coiling in our center between January 2015 and June 2021 were reviewed. The complications, radiographic, and clinical outcomes of these patients were analyzed. A total of 12 patients with 12 pseudoaneurysms were included. The mean maximum aneurysm diameter was 6.2 ± 3.1 mm. Nine patients had a subarachnoid hemorrhage; five patients with Hunt-Hess grade III and four patients with grade IV. All procedures were successfully performed without intraoperative complications. Immediate postoperative angiogram showed that six (50%) aneurysms were Raymond grade 1, four (33.3%) were grade 2, and two (16.7%) were grade 3. Postoperative multiple cerebral infarction occurred in two patients because of vasospasm. Of the ten patients with angiographic follow-up (mean, 29.9 months), two received additional coiling because of recanalization of the pseudoaneurysm, and all aneurysms were completely obliterated at the last examination of the patients. During the clinical follow-up period (mean, 26.8 months), the overall mortality and morbidity were 25% (3/12) and 8.3% (1/12), respectively. LVIS stent-assisted coiling was a feasible approach for the treatment of traumatic ICA pseudoaneurysms.

Preradiosurgery embolization in reducing the postoperative hemorrhage rate for patients with cerebral arteriovenous malformations: a systematic review and meta-analysis.

Few studies have examined the postoperative hemorrhage rate of cerebral arteriovenous malformations (AVMs) treated by embolization prior to stereotactic radiosurgery. The objective of this analysis was to compare the postoperative hemorrhage rate between AVMs treated with and those treated without preradiosurgery embolization. A systematic search of the PubMed and Embase databases was performed with no restriction on the publication period. Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies with sufficient baseline and outcome data. The analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0. Eleven studies comprising 2591 patients were eligible for analysis. There was no significant difference in the postoperative hemorrhage rate between patients who had undergone embolization followed by SRS and those who had undergone SRS alone (OR 1.140, 95% CI 0.851-1.526, p = 0.38). The obliteration rate was significantly lower in the E + SRS group than in the SRS group (OR 0.586, 95% CI 0.398-0.863, p = 0.007). No significant difference in permanent neurological deficits was identified between patients who had undergone embolization followed by SRS and those who had undergone SRS alone (OR 1.175, 95% CI 0.626-2.206, p = 0.616). Available data suggested that preradiosurgery embolization did not reduce the postoperative hemorrhage rate and resulted in a significantly lower obliteration rate than treatment with SRS alone.

Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats.

Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of ELS on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1H MRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1H MRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Adult MD offspring exhibited depression-like behavior. Compared to the control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption (p < 0.05). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1H MRS, hippocampus of MD rats had elevated Glu and glutamate + glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln, γ-aminobutyric acid (GABA), and glutamate + glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1H MRS-identified associations between Glu levels and ELS may guide future clinical studies.

Is Endovascular Treatment Still Good for Ischemic Stroke in Real World?: A Meta-Analysis of Randomized Control Trial and Observational Study in the Last Decade.

BACKGROUND AND PURPOSE: Although endovascular treatment (EVT) for acute ischemic stroke is classified as I evidence, outcomes after EVT in real-world practice appear to be less superior than those in randomized clinical trials (RCTs). Additionally, the effect of EVT is unclear compared with medical treatment (MT) for patients with mild symptoms defined by National Institutes of Health Stroke Scale score <6 or with severe symptoms defined by Alberta Stroke Program Early CT Score <6. METHODS: Literatures were searched in big databases and major meetings from December 6, 2009, to December 6, 2019, including RCTs and observational studies comparing EVT against MT for patients with acute ischemic stroke. Observational studies were precategorized into 3 groups based on imaging data on admission: mild stroke group with National Institutes of Health Stroke Scale score <6, severe stroke group with Alberta Stroke Program Early CT Score <6 or ischemic core ≥50 mL, and normal stroke group for all others. Outcome was measured as modified Rankin Scale score of 0 to 2, mortality at 90 days, and symptomatic intracranial hemorrhage (sICH) at 24 hours. RESULTS: Fifteen RCTs (n=3694) and 37 observational studies (n=9090) were included. EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality in RCTs and normal stroke group, whereas EVT was associated with higher sICH rate in normal stroke group, and no difference of sICH rate appeared between EVT and MT in RCTs. In severe stroke group, EVT was associated with higher modified Rankin Scale 0 to 2 rate and lower mortality, whereas no difference of sICH rate was found. In mild stroke group, there was no difference in modified Rankin Scale 0 to 2 rate between EVT and MT, whereas EVT was associated with higher mortality and sICH rate. CONCLUSIONS: Evidence from RCTs and observational studies supports the use of EVT as the first-line choice for eligible patients corresponding to the latest guideline. For patients with Alberta Stroke Program Early CT Score <6, EVT showed superiority over MT, also in line with the guidelines. On the contrary to the guideline, our data do not support EVT for patients with National Institutes of Health Stroke Scale score <6.

The Safety and Efficacy of Endovascular Treatment for Patients With ASPECTS<6 in Anterior Circulation Stroke: A Meta-Analysis and Subgroup Analysis by Imaging Techniques.

BACKGROUND: Endovascular treatment (EVT) is merely recommended as class of recommendation IIb for patients with ASPECTS <6 according to the American Heart Association guideline 2019. In addition, the best determined imaging technique for EVT in patient with ASPECTS<6 remains unknown. The objective of this study was to define the safety and efficacy of EVT for patients with ASPECTS<6 and investigate the superiority between MRI and CT for patient selection. METHODS: A systematic search of PubMed, EMBASE, The Cochrane Library and other additional sources was performed for studies published with no publication period. Our study was conducted corresponding to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRIMA) guidelines. The analysis was performed using the Comprehensive Meta-Analysis (CMA) 2.0. RESULTS: Five studies reporting data from 844 participants were included in our analysis according to the inclusion criteria. Consequently, EVT was associated with statistically significant higher functional independence compared with MT (OR 5.401, 95% CI 3.227-9.041). Whereas EVT was found to be related to lower mortality compared with MT based on eligible data (OR 0.461, 95% CI 0.329-0.647). No significant difference was identified in sICH between EVT and MT (OR 1.075, 95% CI 0.452-2.558). CONCLUSION: According to the results of our study, we suggested that EVT is a preferred therapy in ACS patients with ASPECTS<6 in consideration of efficacy and safety. Furthermore, MRI did not show superiority over CT as no statistical difference was detected in all subgroups.

LncRNAGAS5 sponges miRNA-221 to promote neurons apoptosis by up-regulated PUMA under hypoxia condition.

Objectives: Long noncoding RNAs (lncRNAs) play substantial roles in cerebral ischemia. Growth arrest-specific 5 (GAS5) was reported to be involved in stroke. In the present study, we aimed to investigate the roles of GAS5 in cerebral condition and unveil the underlying mechanism.Method: Transient focal ischemia was induced by intraluminal occlusion of the right Middle cerebral artery occlusion (MCAO) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the volume of cerebral infarction. RT-qPCR was applied to evaluate the level of GAS5 and miR-221. Fluorescence activated Cell Sorting (FACS) and Terminal deoxynucleotidyl transferased (TUNEL)  were used for detection of apoptosis. Western blotting was applied for protein level. Luciferase assay was applied to reveal the underlying relationship between GAS5 and miR-221 or p53-upregulated modulator of apoptosis (PUMA) and miR-221.Results: The results indicated that GAS5 was up-regulated in MCAO rats and in vitro hypoxia cell model while miR-221 expression was decreased in vitro hypoxia cell model. GAS5 promoted cells apoptosis, while miR-221 inhibited cell apoptosis through regulation of PUMA and downstream JNK/H2AX signaling. Moreover, GAS5 and miR-221 have direct interaction and PUMA was the target of miR-221, indicating that GAS5 regulated PUMA through sponging miR-221.Conclusions: the present study revealed that GAS5 aggravated cell apoptosis in hypoxia condition via miR-221/PUMA axis, which may provide potential targets for the treatment of stroke.

Posterior fossa brain arteriovenous malformations : Clinical features and outcomes of endovascular embolization, adjuvant microsurgery and radiosurgery.

BACKGROUND: Posterior fossa brain arteriovenous malformations (PFbAVM) are relatively rare brain disorders but have a high risk of hemorrhage. Endovascular embolization to reduce the lesion size before treatment may improve the outcome of PFbAVM. The purposes of this study were to identify risk factors associated with hemorrhage in PFbAVM and to assess clinical outcomes in patients receiving initial endovascular embolization. MATERIAL AND METHODS: From 1999 to 2013 a total of 63 patients with PFbAVMs were treated (31 males and 32 females, 14.1 % of all AVM cases). A retrospective examination of patient demographics, clinical presentation, angiographic features, treatment modalities, complications and outcomes was carried out. The re-hemorrhage rate, obliteration rate and modified Rankin scale (MRS) were used as measures of outcome. RESULTS: Of the 63 PFbAVM patients 54 (85.7 %) exhibited hemorrhage and 15 had confirmed aneurysms. The cerebellar location (P = 0.007) and deep venous drainage (P = 0.012) were independent predictors of hemorrhage in multivariate analyses. The mean estimated devascularization was 46.9 % (range 10-100 %) in the 20 patients (31.7 %) treated by endovascular embolization. The 16 patients with residual niduses were further treated by radiosurgery, microsurgery or embolization. Complete obliteration was attained in 12 patients (67 %) while 2 (5.7 %) were left with persisting neurological deficits and 1 had a re-hemorrhage 3 years later (annual rate of 4.6 %). Favorable outcome (MRS ≤ 2) was obtained in the 20 patients receiving initial endovascular embolization (P = 0.039 versus preoperative MRS). CONCLUSION: Cerebellar location and deep venous drainage are predictors of hemorrhage in PFbAVM. Adjuvant endovascular embolization is useful and safe for PFbAVM prior to microsurgery or radiosurgery.

Comparison of polyvinyl alcohol copolymer with detachable balloons for the embolisation of direct carotid cavernous fistula: a single-centre experience.

OBJECTIVES: To characterise the safety, efficacy and cost of direct carotid-cavernous fistula (CCF) treatment using polyvinyl alcohol copolymer or detachable balloons. METHODS: We reviewed retrospectively patients with direct CCFs treated with either a detachable balloon or polyvinyl alcohol copolymer at our hospital from 2005 to 2015 and identified 94 patients with 105 CCFs. All patients had follow-up angiograms. The CCF occlusion rate, procedure complication rate, treatment expense and operation time were recorded. RESULTS: With a mean of 5.4 months of angiographic follow-up, the complete occlusion rate and recanalisation rate of the polyvinyl alcohol copolymer group was not significantly different from that of the detachable balloon group. The treatment expense was much higher and the operation time was much longer in the polyvinyl alcohol copolymer group than the detachable balloon group (P < 0.001). CONCLUSIONS: Embolisation of CCF with polyvinyl alcohol copolymer is as safe and effective as detachable balloon but has a much higher cost and longer operation time. KEY POINTS: • Carotid-cavernous fistula results from a damaged carotid artery. • Detachable balloons have been used with success for many years. • Some reported excellent outcomes after embolisation with polyvinyl alcohol copolymer. • Treatment expense is much higher in the polyvinyl alcohol copolymer group.

Multidisciplinary Care of Unruptured Brain Arteriovenous Malformations to Improve Symptomatic Headache and the Onset, Progression, and Outcomes of Unruptured Brain Arteriovenous Malformations.

BACKGROUND: Symptomatic headaches attributed to unruptured brain arteriovenous malformations (ubAVMs) are very common and affect patients' quality life, but multidisciplinary care of ubAVMs to improve symptomatic headache remains unclear. OBJECTIVE: The objective is to identify the features of symptomatic headaches, and to obtain headache outcomes following multidisciplinary care of ubAVMs, as well as provide background on the natural history of ubAVMs. STUDY DESIGN: The features of symptomatic headaches and headache outcomes were analyzed in a large cohort of cases after multidisciplinary care of ubAVMs. We have also provided information on the natural history of ubAVMs. SETTING: This study was conducted at the Department of Neurosurgery of Zhujiang Hospital where 336 patients from 1998 to 2014 were reviewed by a multidiscipline team. Only 124 patients were eligible. METHODS: The demographics, clinical features, imaging features, and headache details of eligible patients were reviewed. An 11-point pain scale score was used to assess symptomatic headaches before, during, and after treatment. The headache outcomes, death or stroke, and adverse functional outcomes (modified Rankin Scale score = 2, mRS = 2) were assessed following multidisciplinary care of ubAVMs. RESULTS: Twenty-three (56.1%) of 41 patients had migraine-like headaches located in occipital lobe (P < 0.001), while forty (63.5%) of 63 patients had tension-type-like headaches located in frontotemporal lobe (P < 0.001). For patients with tension-type-like or all types of headache, headache improvement differed between the multidisciplinary group and medical group (87.8% vs. 31.8%, P < 0.001; 85.7% vs. 40.7%, P < 0.001). The risk of death or stroke did not differ between multidisciplinary group and medical group (P = 0.393), whereas the risk of adverse functional outcome (mRS = 2) differed significantly by long-time follow-up (23.0% vs.10.0%, P = 0.022). LIMITATIONS: This study provides the initial experience to support multidisciplinary care for ubAVMs to improve symptomatic headaches and patients' quality life, but based on the retrospective study with inherent limitations, larger samples and multi-center trials are needed on this interesting issue. CONCLUSIONS: Occipital ubAVM is more likely to present with migraine-like headache, while frontotemporal ubAVM tends to present with tension-type-like headache. The effectiveness of multidisciplinary care for ubAVM to improve headache has been shown, but the natural history of ubAVM patients with headache remains unclear.Key Words: Unruptured brain arteriovenous malformations, headache, headache improvement, natural history.

Baicalein Attenuates Neurological Deficits and Preserves Blood-Brain Barrier Integrity in a Rat Model of Intracerebral Hemorrhage.

Previous studies have demonstrated that baicalein has protective effects against several diseases, which including ischemic stroke. The effect of baicalein on the blood-brain barrier (BBB) in intracerebral hemorrhage (ICH) and its related mechanisms are not well understood. We aimed to investigate the mechanisms by which baicalein may influence the BBB in a rat model of ICH. The rat model of ICH was induced by intravenous injection of collagenase IV into the brain. Animals were randomly divided into three groups: sham operation, vehicle, and baicalein group. Each group was then divided into subgroups, in which the rats were sacrificed at 24 and 72 h after ICH. We assessed brain edema, behavioral changes, BBB leakage, apoptosis, inducible nitric oxide synthase (iNOS), zonula occludens (ZO)-1, Mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). Treatment with baicalein reduced brain water content, BBB leakage, apoptosis, and neurologic deficits, compared with vehicle. Baicalein also decreased ICH-induced changes in the levels of iNOS but increased the levels of ZO-1. The protective effect of baicalein on the BBB in ICH rats was possibly invoked by attenuated p-38 MAPK and JNK phosphorylation, and decreased activation of the NF-κB signaling pathway, which may have suppressed gene transcription, including iNOS, and eventually decreased formation of peroxynitrite (ONOO-). Our results suggest that baicalein exerts a protective effect on BBB disruption in the rat model of ICH. The likely mechanism is via inhibition of MAPKs and NF-κB signaling pathways, leading to decreased formation of iNOS and ONOO-, thereby improving neurological function.

Fistula and Infratentorial Location, Characteristics That Contribute to Cerebral Arteriovenous Malformations, Lead to the Formation of Associated Aneurysms in Patients.

OBJECTIVE: Because the formation of associated aneurysms (AAs) related to the characteristics of cerebral artriovenous malformations (cAVMs) is poorly recognized, the purpose of this study was to identify the responsible characteristics of cAVMs related to the formation of AAs and to identify patients with responsible characteristics related to the formation of AAs through the analysis of the outcomes of these patients after treatment. METHODS: This study was performed to analyze the baseline characteristics of patients with cAVMs and AAs. The recurrent AA and residual size of cAVMs were used to evaluate the outcomes of patients after treatment. At the same time, the ROC curve was measured to gauge the relationship between the residual size of cAVMs and recurrent AAs in eligible patients. RESULTS: Fifty (15.0%) patients with cAVMs and AA were confirmed; these patients had twice the hazard of hemorrhage as patients with only isolated cAVMs. An infratentorial location (P < 0.001) and fistula (P = 0.002) were independent predictors of the formation of AAs. After a mean 22.7 months follow-up, 2 patients developed recurrent AAs, and the annual recurrence rate for patients with responsible characteristics was 17.6%, but for all patients was 7.2%. The ROC curve showed that patients, specifically patients with responsible characteristics, the residual size of the cAVM was closely related to recurrent AA (area = 0.89, 95% confidence interval 0.81-0.97, P = 0.023, cut-off value = 82.5%). CONCLUSIONS: Patients with cAVMs and AA who harbor a fistula or an infratentorial location tend to form AAs. To prevent recurrent AAs and decrease the subsequent risk of hemorrhage, complete obliteration of cAVMs or retrograding over 80% size of cAVMs is recommended.

Endovascular treatment of cerebellar arteriovenous malformations: management of associated aneurysms first or later.

The purpose of this study was to determine the safety and effectiveness of cerebellar arteriovenous malformations (AVMs) embolization and find out the suitable methods to manage associated aneurysms. Medical records of all patients between 1997 and 2014 with a diagnosis of cerebellar AVMs were retrospectively reviewed. Univariable and multivariable logistic analysis were used to assess AVMs characteristics to calculate for the risk of hemorrhage. Endovascular treatment was the main treatment measure to manage the AVMs and associated aneurysms. Of 142 patients, 115 (81.0 %) presented with hemorrhage and 42 (29.6 %) with associated aneurysms. A significant association with cerebellar AVMs hemorrhage was found for small size, prenidal aneurysms, and deep venous drainage in the univariable and multivariable analysis. Associated aneurysms were treated firstly in 41 patients except for 1 patient with 2 prenidal and 2 intranidal aneurysms. The special case was dealt with AVMs and 2 intranidal aneurysms first and angiography showed that the 2 prenidal associated aneurysms disappeared with time. Hemorrhage appeared in 13/142 patients (9.2 %) during the follow-up period, none of which was with associated aneurysms. Endovascular treatment can be a feasible way for treating cerebellar AVMs. Intranidal associated aneurysms should be treated first. Prenidal associated aneurysms can be treated later depending on the angioarchitecture of AVMs.

Comparison between Solitaire™ AB and Enterprise stent-assisted coiling for intracranial aneurysms.

The aim of the present study was to analyze the feasibility, rate of procedure-related complications and midterm angiographic follow-up outcomes using the Enterprise (EP) and Solitaire™ AB (ST) stents in the stent-assisted coiling of intracranial aneurysms. In total, 81 patients with 90 aneurysms were included in the study, with the aim to treat 43 aneurysms with the EP stent (47.8%) and 47 aneurysms with the ST stent (52.2%). The 90 aneurysms were successfully stented and subsequently coiled; however, in four patients undergoing treatment with the EP stent, the stent was not navigable; thus, treatment with the ST stent was employed (EP, n=39, 43.3%; ST, n=51, 56.7%). Of the 90 aneurysms, 44 cases were ruptured aneurysms, with 74 located in the anterior circulation and 16 located in the posterior circulation. The stenting success rate of the ST stent was significantly higher compared with the EP stent. However, no statistically significant differences were observed with regard to the packing density, complete occlusion, progressive occlusion, recurrence rate, procedure-related complications, in-stent stenosis and stent migration rates between the two groups. In conclusion, the two common medical devices used for intracranial aneurysms are relatively safe and effective for the treatment of intracranial aneurysms. However, due to the higher stenting success rate of the ST stent, this medical devise was demonstrated to be more flexible and feasible compared with the EP stent.