Ischemic Stroke and Cerebral Microbleeds: A Two-Sample Bidirectional Mendelian Randomization Study.

INTRODUCTION: Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs. METHODS: The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p < 0.0125 was considered significant, and p values between 0.0125 and 0.05 were considered suggestive of evidence for a potential association. RESULTS: We detected that higher risk of IS [IVW odds ratio (OR) 1.47, 95% confidence interval (CI) 1.04-2.07, p = 0.03] and SVS (IVW OR 1.62, 95% CI 1.07-2.47, p = 0.02) were significantly associated with CMBs. Reverse MR analyses found no significant evidence for a causal effect of CMBs on IS and its subtypes. CONCLUSIONS: Our study provides potential evidence that IS and SVS are causally linked to increased risk of CMBs. Further research is needed to determine the mechanisms of association between IS and CMBs.

A review on surgical treatment options in gliomas.

Gliomas are one of the most common primary central nervous system tumors, and surgical treatment remains the principal role in the management of any grade of gliomas. In this study, based on the introduction of gliomas, we review the novel surgical techniques and technologies in support of the extent of resection to achieve long-term disease control and summarize the findings on how to keep the balance between cytoreduction and neurological morbidity from a list of literature searched. With modern neurosurgical techniques, gliomas resection can be safely performed with low morbidity and extraordinary long-term functional outcomes.

Alarming changes in the global burden of mental disorders in children and adolescents from 1990 to 2019: a systematic analysis for the Global Burden of Disease study.

Mental disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2010. Unpacking how this burden in children and adolescents varies with sex, geographical regions, and ethnicities and how it has changed in the last 3 decades are important to improve the existing public health policies and prevention strategies. The study was conducted using GBD 2019 database. The burden of children and adolescents' (< 20 years old) mental disorders was displayed as prevalence, incidence, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability globally between 1990 and 2019. The number of DALYs in children and adolescents diagnosed with mental disorders was 21.5 million (95% CI: 15.2-29.6 million) in 2019. From 1990 to 2019, the age-standardized rates of DALYs of mental disorders increased from 803.8 per 100,000 (95% CI: 567.7-1104.3 per 100,000) to 833.2 per 100,000 (95% CI: 589.0-1146.1 per 100,000) population. Over the past 30 years, there had been a huge increase in the number of individuals suffering from anxiety disorders, major depressive disorders, and conduct disorders including an alarming increase in the rate of eating disorders such as 24.3% in bulimia nervosa and 17.0% in anorexia nervosa. Globally, 8.8% of children and adolescents have been diagnosed with varieties of mental illnesses, accounting for a heavy disease burden on public health. Besides, the worldwide increasing rates of anxiety disorders, major depressive disorders, and eating disorders have brought considerable challenges to public health undertakings, for which further prevention and treatment countermeasures are urgently needed.

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis.

BACKGROUND: The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed. OBJECTIVE: To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments. METHODS: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis. RESULTS: We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%-99%, I2 = 74.5%), 97% in surgery group (95%CI: 95%-99%, I2 = 18.3%), 87% in endovascular treatment group (95%CI: 80%-93%, I2 = 0.0%), and 68% in radiosurgery group (95%CI: 66%-69%, I2 = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%-2%, I2 = 0.0%), 0% in surgery group (95%CI: 0%-1%, I2 = 0.0%), 4% in endovascular treatment group (95%CI: 0%-8%, I2 = 85.8%), and 3% in radiosurgery group (95%CI: 3%-4%, I2 = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%-4%, I2 = 0.0%), 23% in endovascular treatment group (95%CI: 7%-39%), and 12% in radiosurgery group (95%CI: 12%-13%, I2 = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%-11%, I2 = 94.1%), 20% in surgery group (95%CI: 13%-27%, I2 = 0.0%), 14% in endovascular treatment group (95%CI: 10%-18%, I2 = 64.0%), and 8% in radiosurgery group (95%CI: 7%-9%, I2 = 66.6%). CONCLUSIONS: We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.

Endovascular treatment of blunt injury of the extracranial internal carotid artery: the prospect and dilemma.

The extracranial internal carotid artery (ICA) refers to the anatomic location that reaches from the common carotid artery proximally to the skull base distally. The extracranial ICA belongs to the C1 segment of the Bouthillier classification and is at considerable risk for injury. Currently, the understanding of endovascular treatment (EVT) for blunt injury of the extracranial ICA is limited, and a comprehensive review is therefore important. In this review, we found that extracranial ICA blunt injury should be identified in patients presenting after blunt trauma, including classical dissection, pseudoaneurysm, and stenosis/occlusion. Computed tomography angiography (CTA) is the first-line method for screening for extracranial ICA blunt injury, although digital subtraction angiography (DSA) remains the "gold standard" in imaging. Antithrombotic treatment is effective for stroke prevention. However, routine EVT in the form of stenting should be reserved for patients with prolonged neurological symptoms from arterial stenosis or considerably enlarged pseudoaneurysm. Endovascular repair is now emerging as a favored therapeutic option given its demonstrated safety and positive clinical and radiographic outcomes.

Intracranial post-clipping residual or recurrent aneurysms: Current status and treatment options (Review).

Following the clipping of intracranial aneurysms, post-clipping residual or recurrent aneurysms (PCRRAs) can occur. In recent years, the incidence of PCRRAs has increased due to a prolonged follow-up period and advanced imaging techniques. However, several aspects of intracranial PCRRAs remain unclear. Therefore, the present study performed an in-depth review of the literature on PCRRAs. Herein, a summary of PCRRAs that can be divided into the following two categories is presented: i) Those occurring after the incomplete clipping of an aneurysm, where the residual aneurysm regrows into a PCRRA; and ii) those occurring after the complete clipping of an aneurysm, in which a de novo aneurysm occurs at the original aneurysm site. Currently, digital subtracted angiography remains the gold standard for the imaging diagnosis of PCRRAs as it can eliminate metallic clip artifacts. Intracranial symptomatic PCRRAs should be actively treated, particularly those that have ruptured. A number of methods are currently available for the treatment of intracranial PCRRAs; these mainly include re-clipping, endovascular treatment (EVT) and bypass surgery. Currently, re-clipping remains the most effective method used to treat PCRRAs; however, it is a very difficult procedure to perform. EVT can also be used to treat intracranial PCRRAs. EVT methods include coiling (stent- or balloon-assisted) and flow-diverting stents (or coiling-assisted). Bypass surgery can be selected for difficult-to-treat, complex PCRRAs. On the whole, following appropriate treatment, the majority of intracranial PCRRAs achieve a high occlusion rate and a good prognosis.

Imaging characteristics and endovascular treatment strategy for cerebellar arteriovenous malformations.

Cerebellar arteriovenous malformations (CAVMs) have increased probabilities of rupture and bleeding compared with arteriovenous malformations (AVMs) in other locations of the brain. Endovascular treatment (EVT) for CAVMs is difficult; as the angioarchitecture of CAVMs is complex, EVT may be associated with complications, due to the involvement of crucial structures, such as the brainstem. The present study aimed to determine the efficacy of EVT for CAVMS. For this purpose, 33 cases of CAVMs treated with EVT from January, 2015 to January, 2020 were retrospectively analyzed. The 33 patients were aged 8 to 73 years (mean age, 40.4±17.8 years) and 21 were female (63%, 21/33). Rupture and bleeding occurred in 29 patients (87.9%, 29/33). Among the 33 CAVM cases, 15 (45.5%, 15/33) were fed by a single artery, and 18 (54.5%, 18/33) were fed by multiple arteries. In total, 27 patients (81.8%, 27/33) had superficial vein drainage alone. Among the 33 cases, 15 were complicated by 16 aneurysms, including 14 prenidal aneurysms and 2 intranidal aneurysms. Among the 33 cases, the nidus of the CAVM (87.9%, 29/33) was treated with Onyx™ casting in 29 patients: 8 cases (27.6%, 8/29) had an embolization volume of <1/3 of the nidus, 11 cases had a volume of 1/3-2/3 of the nidus (37.9%, 11/29) and 10 cases had a volume >2/3 of the nidus (34.5%, 10/29). Among the EVT complications, there were 3 cases (9.1%, 3/33) of intraoperative and post-operative bleeding, which resulted in two deaths (on the 1st and 7th days). The length of hospital stay was 10.7±5.4 days. In total, 27 patients (81.7%, 27/33) had a Glasgow Outcome Scale (GOS) score of 5 at discharge. On the whole, the present study demonstrates that overall, EVT is a feasible treatment for CAVM and may be used to obtain acceptable therapeutic effects.

Weighted gene co-expression network analysis identified six hub genes associated with rupture of intracranial aneurysms.

Intracranial aneurysms (IAs) are characterized by localized dilation or ballooning of a cerebral artery. When IAs rupture, blood leaks into the space around the brain to create a subarachnoid hemorrhage. The latter is associated with a higher risk of disability and mortality. The aims of this study were to gain greater insight into the pathogenesis of ruptured IAs, and to clarify whether identified hub genes represent potential biological markers for assessing the likelihood of IA progression and rupture. Briefly, the GSE36791 and GSE73378 datasets from the National Center of Biotechnology Information Gene Expression Omnibus database were reanalyzed and subjected to a weighted gene co-expression network analysis to test the association between gene sets and clinical features. The clinical significance of these genes as potential biomarkers was also examined, with their expression validated by quantitative real-time PCR. A total of 14 co-expression modules and 238 hub genes were identified. In particular, three modules (labeled turquoise, blue, and brown) were found to highly correlate with IA rupture events. Additionally, six potential biomarkers were identified (BASP1, CEBPB, ECHDC2, GZMK, KLHL3, and SLC2A3), which are strongly associated with the progression and rupture of IAs. Taken together, these findings provide novel insights into potential molecular mechanisms responsible for IAs and they highlight the potential for these particular genes to serve as biomarkers for monitoring IA rupture.

Brain arteriovenous malformation with transdural blood supply: Current status.

Arterial blood supply to a brain arteriovenous malformation (BAVM) is mainly derived from the internal carotid artery (ICA) and vertebral basilar artery (VBA) system. However, in certain cases, arteries supplying the meninges may also contribute to the blood supply of the BAVM, resulting in the formation of a BAVM with transdural blood supply (TBS). To review the current status of BAVM with TBS, a literature search was performed in the PubMed database. Articles were screened for relevance and suitability of data. According to recent studies, the mechanisms by which TBS to a BAVM forms are mainly classified into the congenital and acquired type. BAVM with TBS is common in elderly patients and is characterized by intracranial hemorrhage, epilepsy, chronic headache and increased intracranial pressure. Digital subtraction angiography is the gold standard for diagnosing BAVM with TBS. Superselective angiography is also important. Treatments for BAVM with TBS include surgical resection, endovascular treatment (EVT), stereotactic radiosurgery and combined treatment. Surgical resection is difficult to perform. EVT has become the major therapy for treating BAVM with TBS due to its low procedural invasiveness. Combination of surgical resection and EVT may be a good option. In addition, stereotactic radiosurgery is frequently used as a complementary treatment to surgical and endovascular interventions. The prognosis of BAVM with TBS is not favorable, as the defect involves a complex arterial supply system.

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage.

BACKGROUND/AIMS: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381) on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB) by targeting leucine-rich repeat C4 protein (LRRC4) through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. METHODS: Rat models of CLB and middle cerebral artery occlusion (MCAO) were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA) to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), nerve growth factor (NGF) and neurite outgrowth inhibitor -A (Nogo-A), Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF). RESULTS: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1ß, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group), while BrdU-positive cell number, contents of NGF and IL-10, and expression of SDF-1, CXCR4, pERK, Slit2 and VEGF in brain tissues were decreased (those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO + miR-381 mimic + AMD3100 group). The results in the CLB + MCAO + mimic group were opposite of those in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups. CONCLUSION: Taken together, we concluded that up-regulation of miR-381 promoted nerve injury repair in acute cerebral ischemia rats after CLB by negatively regulating LRRC4 through activating the SDF-1/CXCR4 signaling pathway.

Remote Multiple Intraparenchymal Hemorrhages Following Aneurysmal Clipping of the Anterior Communicating Artery: A Case Report and Literature Review.

Remote intraparenchymal hemorrhage after clipping of a ruptured aneurysm is rare. The pathogenesis is variable, and the therapeutic strategies remain controversial, because the natural history is unclear. Here we report a woman with subarachnoid hemorrhage (SAH), who had an aneurysm of the anterior communicating artery identified by computed tomography angiography (CTA). A 51-year-old women, who was in a good preoperative condition without movement disorders before operation, went on to exhibit left hemiparesis after aneurysmal clipping as she recovered from anesthesia in the operating room. CT images performed immediately after surgery showed that two intraparenchymal hemorrhages were present contralateral to the site of the operation. After conservative treatment, the patient recovered, but still displayed a movement disorder in the left limb. SAH induced-vasospasm, defective vascular autoregulation, excessive drainage of the cerebrospinal fluid, a change in the intracranial pressure after craniotomy, and brain shift may contribute to the pathogenesis of remote hemorrhage after surgery.

Research Progress of Moyamoya Disease in Children.

During the onset of Moyamoya disease (MMD), progressive occlusion occurs at the end of the intracranial internal carotid artery, and compensatory net-like abnormal vessels develop in the skull base, generating the corresponding clinical symptoms. MMD can affect both children and adults, but MMD in pediatric patients exhibits distinct clinical features, and the treatment prognoses are different from adult patients. Children are the group at highest risk for MMD. In children, the disease mainly manifests as ischemia, while bleeding is the primary symptom in adults. The pathogenesis of MMD in children is still unknown, and some factors are distinct from those in adults. MMD in children could result in progressive, irreversible nerve functional impairment, and an earlier the onset corresponds to a worse prognosis. Therefore, active treatment at an early stage is highly recommended. The treatment methods for MMD in children mainly include indirect and direct surgeries. Indirect surgeries mainly include multiple burr-hole surgery (MBHS), encephalomyosynangiosis (EMS), and encephaloduroarteriosynangiosis (EDAS); direct surgeries mainly include intra- and extracranial vascular reconstructions that primarily consist of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. Indirect surgery, as a treatment for MMD in children, has shown a certain level of efficacy. However, a standard treatment approach should combine both indirect and direct procedures. Compared to MMD in adults, the treatment and prognosis of MMD in children has higher clinical significance. If the treatment is adequate, a satisfactory outcome is often achieved.