Clinical characteristics and individualized treatment of intracranial aneurysms in young adults: a single-center experience.

This study aimed to investigate the clinical characteristics of intracranial aneurysms in young adults and summarize our treatment experiences. We performed a retrospective review of young patients (15-24 years old) with intracranial aneurysms examined in the Fifth Ward of the Neurosurgery Department of Tianjin Huanhu Hospital between January 2015 and November 2022. Data was reviewed for age, sex, presentation, type and size, treatment modalities, location, postoperative complications, and clinical and imaging outcomes. Among the 23 patients, there were 11 males and 12 females (1:1.09). Their presentations included headache, neurological deficits, aneurysmal subarachnoid hemorrhage, incidental or asymptomatic aneurysm, and traumatic subarachnoid hemorrhage. Twenty-five cases of intracranial aneurysms in 25 patients were identified. The aneurysms were saccular (32%, 8/25), dissecting (52%, 13/25), and fusiform (16%, 4/25) in shape. Treatment modalities included direct clipping, embolization, bypass, trapping, resection, coarctation of internal carotid artery (ICA), and endovascular vessel sacrifice. Of the 25 aneurysms, 16 (64%, 16/25) aneurysms were located in anterior circulation, and 9 (36%, 9/25) were located in the posterior circulation, while multiple aneurysms were identified in two patients. A preoperative magnetic resonance perfusion (MRP) examination was performed in 15 patients with unruptured complex aneurysms, of whom 13/15 (86.67%) showed hypoperfusion. Eighteen (78.26%, 18/23) patients had no postoperative complications, temporary complications occurred in 4 (17.39%, 4/23) patients, and 1 patient died postoperatively. The intracranial aneurysms in young adults (15 ~ 24 years old) are rare. The posterior circulation is more commonly involved than adults, giant and huge aneurysms are frequent, and fusiform and dissecting pathologic features are common. Headache is the most common clinical manifestation. Individualized treatment should be performed, and bypass is an effective treatment for young patients with intracranial aneurysms.

Cerebral revascularization for complex middle cerebral artery aneurysms: surgical strategies and outcomes in a single center.

Cerebral revascularization is the ultimate treatment for a subset of complex middle cerebral artery (MCA) aneurysms. The decision for the revascularization strategy should be made during the treatment process. This study aimed to summarize the revascularization strategies for different types of complex MCA aneurysms and their outcomes. The clinical data of patients with complex MCA aneurysms who underwent cerebral revascularization since 2015 were analyzed retrospectively. The aneurysms were classified according to the location and other main characteristics that affect the selection of surgical modalities. The corresponding surgical modalities and treatment outcomes were summarized. A total of 29 patients with 29 complex MCA aneurysms were treated with cerebral revascularization from 2015 to 2022. Treated aneurysms were located at the prebifurcation segment in 7 patients, bifurcation segment in 12 patients, and postbifurcation segment in 10 patients. Surgical modalities in the prebifurcation segment included four high-flow extracranial-to-intracranial (EC-IC) bypasses with aneurysm trapping or proximal occlusion, two IC-IC bypasses with aneurysm excision, and one combination bypass with aneurysm excision. In the bifurcation segment, surgical modalities included two low-flow EC-IC bypasses with aneurysm excision or trapping, six IC-IC bypasses with aneurysm excision, three combination bypasses with aneurysm excision, and one constructive clipping with IC-IC bypass. In the postbifurcation segment, surgical modalities included nine IC-IC bypasses with aneurysm excision and low-flow EC-IC bypass with aneurysm trapping. The revascularization strategy for prebifurcation aneurysms was determined based on the involvement of lenticulostriate arteries, whereas the strategy for bifurcation aneurysms was determined based on the number of distal bifurcations and the shape of the aneurysm. The location of the aneurysm determined the revascularization strategy for aneurysms in the postbifurcation segments. Angiography demonstrated that aneurysms were completely obliterated in 26 cases and shrank in 3 cases, and all bypasses except one were patent. The mean follow-up period was 47.5 months. Three patients developed hemiplegic paralysis, and one developed transient aphasia postoperatively due to cerebral ischemia. No new neurological dysfunction occurred in the other 25 patients with no recurrence or enlargement of aneurysms during the follow-up. Prebifurcation aneurysms involving the lenticulostriate arteries require proximal occlusion with high-flow bypass. Most of the other aneurysms can be safely excised or trapped by appropriate revascularization strategies according to their location and orientation.

Analysis of Risk Factors for Vulnerable Plaque Formation and Pathogenic in Carotid Artery.

OBJECTIVES: The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis. MATERIALS AND METHODS: A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders. RESULTS: Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014. CONCLUSIONS: The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.

Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.

BACKGROUND: Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system. RESULTS: Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice. CONCLUSIONS: These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

Feasibility of Simple Linear Measurements to Determine Ventricular Enlargement in Patients With Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: To evaluate the feasibility and reproducibility of linear measurements for determining ventricular enlargement in patients with idiopathic normal pressure hydrocephalus (iNPH) and their correlation to ventricular volume (VV). METHODS: Preoperative brain computed tomography scans were retrospectively evaluated in 36 patients with iNPH. The quantitative markers of Evan index (EI), VV, frontal and occipital horn ratio (FOR), modified cella media index (mCMI), third ventricular width (TVW), temporal horn width (TPH), frontal horn width (FHW), and callosal angle (CA) at the posterior commissure (PC) were independently measured by a neurosurgeon and a radiologist. Intraclass correlation coefficients were calculated to establish inter-rater agreement among the 2 investigators. Pearson correlation coefficients were used to assess the relationship of each linear measurement with total VV. RESULTS: The overall inter-rater agreement among investigators was almost perfect for EI, VV, FOR, mCMI, TVW, substantial for FHW and moderate for TPH, and CA at PC. Pearson correlation coefficients showed excellent correlation between mCMI and VV. Moderate correlation was found between the VV and FHW, TVW, FOR, EI, and CA at PC. Fair correlation was found between the VV and TPH. CONCLUSION: Simple linear measurements could serve as effective alternative to volumetric analysis to determine ventricular size in patients with iNPH. The quantitative marker of mCMI is more reasonable and accurate than EI, FOR, and other simple linear measurements.

Clinical effects of neuroendoscopic hematoma evacuation for hypertensive intracerebral hemorrhage.

OBJECTIVE: To analyze the clinical effects of neuroendoscopic hematoma evacuation for the treatment of hypertensive intracerebral hemorrhage (ICH). METHODS: A total of 80 patients with hypertensive ICH who were admitted to our hospital were included as the subjects of this retrospective study. The patients were assigned into a neuroendoscopic hematoma evacuation group (n=35) and a small bone window craniotomy group (n=45). The post-operative hematoma residues and the clearance rate of the hematoma were compared between the two groups. The intraoperative blood loss, duration of the surgery, and Glasgow Coma Scale (GSC) scores before and after surgery were compared between the two groups. The operation time, intraoperative blood loss, the time consumed to stop bleeding, clearance rate of hematoma, manifestation of complications, and the prognosis 6 months after surgery were analyzed statistically. Self-made questionnaires were used to evaluate the satisfaction degree of patients with their lives and to assess the quality of life after surgery. RESULTS: The operation time, blood loss, and the time consumed to stop bleeding were less in the neuroendoscopic hematoma evacuation group than those in the small bone window craniotomy group (all P<0.05). The GCS scores in the neuroendoscopic hematoma evacuation group were significantly higher than those in the small bone window craniotomy group (P<0.05). The clearance rate of hematoma was higher in the neuroendoscopic hematoma evacuation group than that in the small bone window craniotomy group (P<0.05). CONCLUSION: As compared with small bone window craniotomy for removing hematoma, neuroendoscopic hematoma evacuation showed a better outcome in treating patients with hypertensive ICH. It could improve patients' clinical indications, which is worthy of being widely applied in clinical settings.

Knockdown of circular RNA tousled-like kinase 1 relieves ischemic stroke in middle cerebral artery occlusion mice and oxygen-glucose deprivation and reoxygenation-induced N2a cell damage.

Ischemic stroke (IS) is an essential contributor to the neurological morbidity and mortality throughout the world. The significance of circular RNA tousled-like kinase 1 (circTLK1) in IS has been documented. This study set out to explore the mechanism of circTLK1 in IS. Middle cerebral artery occlusion (MCAO) mouse models in vivo and oxygen-glucose deprivation and reoxygenation (OGD/R) cell models in vitro were first established, followed by evaluation of infarct volume and neurological impairment, and cell viability and apoptosis. The expression patterns of circTLK1, miR-26a-5p, phosphatase and tensin homolog (PTEN), insulin-like growth factor type 1 receptor (IGF-1 R), and glucose transporter type 1 (GLUT1) were detected by RT-qPCR and Western blotting. Co-localization of circTLK1 and miR-26a-5p in N2a cells was tested by fluorescence in situ hybridization assay. The binding relationships among circTLK1, PTEN, and miR-26a-5p were verified by dual-luciferase assay and RNA pull-down. circTLK1 and PTEN were highly expressed while miR-26a-5p was under-expressed in IS models. circTLK1 knockdown decreased infarct volume and neurological impairment in MCAO mouse models and relieved OGD/R-induced neuronal injury in vitro. circTLK1 and miR-26a-5p were co-located in the N2a cell cytoplasm. circTLK1 regulated PTEN as a sponge of miR-26a-5p. PTEN positively regulated IGF-1 R and GLUT1 expressions. miR-26a-5p inhibitor annulled the repressive effects of circTLK1 silencing on OGD/R-induced neuronal injury. sh-PTEN partially annulled the effects of the miR-26a-5p inhibitor on OGD/R-induced neuronal injury. In conclusion, circTLK1 knockdown relieved IS via the miR-26a-5p/PTEN/IGF-1 R/GLUT1 axis. These results may provide a new direction to IS potential therapeutic targets.

Long non-coding RNA GAS5 retards neural functional recovery in cerebral ischemic stroke through modulation of the microRNA-455-5p/PTEN axis.

OBJECTIVE: Cerebral ischemic stroke (IS) threatens the daily life of individuals, with high mortality. Emerging studies have deciphered the independent roles of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5), microRNA (miR)-455-5p and phosphatase and tensin homolog (PTEN) in IS, but the understanding of their integrated function is in its infancy. Therefore, this study focusing on the GAS5/miR-455-5p/PTEN axis was initiated. METHODS: Middle cerebral artery occlusion (MCAO) models were established by the suture method. GAS5, miR-455-5p and PTEN expression was detected in rat brain tissues after MCAO. Rats were injected with sh-GAS5 or miR-455-5p agomir before MCAO modeling. A neurobehavioral evaluation was conducted, and oxidative stress injury, apoptosis and mitochondrial function were detected in brain tissues of IS rats. The relationships between GAS5 and miR-455-5p, and between miR-455-5p and PTEN were verified. PC12 cells were transfected with sh-GAS5 or miR-455-5p mimic under oxygen and glucose deprivation/reoxygenation (OGD/R) conditions to evaluate cell viability and apoptosis. RESULTS: GAS5 and PTEN expression levels were elevated and miR-455-5p expression was reduced in brain tissues of MCAO rats and OGD/R-induced PC12 cells. GAS5 downregulation or miR-455-5p upregulation improved neurobehavior, attenuated apoptosis and oxidative injury, and relieved mitochondrial damage in brain tissues of IS rats. Silencing GAS5 or restoring miR-455-5p minimized OGD/R-induced cell damage. MiR-455-5p downregulation antagonized the effects of GAS5 inhibition on IS. CONCLUSION: This work elucidates that GAS5 downregulation upregulates miR-455-5p to repress PTEN expression, in turn attenuating IS, which may broaden the horizon of IS treatment.

[Application of continuous monitoring of intracranial pressure and brain oxygen partial pressure in the treatment of patients with severe craniocerebral injury].

OBJECTIVE: To investigate the effects of continuous monitoring intracranial pressure (ICP) and brain oxygen partial pressure (PbtO2) on the prognosis of patients with severe craniocerebral injury. METHODS: A prospective randomized controlled trial was conducted. Seventy patients with severe craniocerebral injury with a Glasgow coma score (GCS) 4-8 admitted to the neurosurgical intensive care unit (NICU) of the People's Hospital of Inner Mongolia Autonomous Region from January 2017 to May 2020 were enrolled, and they were divided into ICP monitoring group and ICP+PbtO2 monitoring group by random number table. Patients in ICP monitoring group received ICP monitoring and were given traditional treatment of controlling ICP and cerebral perfusion pressure (CPP), the therapeutic target was ICP < 20 mmHg (1 mmHg = 0.133 kPa) and CPP > 60 mmHg. Patients in ICP+PbtO2 monitoring group were given ICP and PbtO2 monitoring at the same time, and oxygen flow was adjusted on the basis of controlling ICP and CPP to maintain the PbtO2 > 20 mmHg, and the therapeutic target of ICP and CPP was the same as the ICP monitoring group. ICP and PbtO2 values were recorded during monitoring in the two groups, the results of CPP, GCS and arterial blood gas analysis were recorded, and the prognosis at 3 months and 6 months after injury was compared by Glasgow outcome scale (GOS) score between the two groups. GOS score > 3 was considered as good prognosis. Kaplan-Meier survival curve was drawn, and the 3-month and 6-month cumulative survival rates of the two groups were analyzed. Linear regression analysis was used to further evaluate the relationship between PbtO2 and GOS score. RESULTS: Finally, a total of 70 patients with severe craniocerebral injury were enrolled in the analysis, 34 patients received ICP combined with PbtO2 monitoring and guided therapy, and 36 patients received ICP monitoring alone. The average ICP of ICP+PbtO2 monitoring group was significantly lower than that of ICP monitoring group (mmHg: 13.4±3.2 vs. 18.2±8.3, P < 0.01). Although the CPP in both groups was great than 60 mmHg, the average CPP of ICP+PbtO2 monitoring group was significantly higher than that of ICP monitoring group (mmHg: 82.1±10.5 vs. 74.5±11.6, P < 0.01). No significant difference was found in average GCS score or arterial partial pressure of carbon dioxide (PaCO2) between the ICP+PbtO2 monitoring group and ICP monitoring group [GCS score: 5.3±2.3 vs. 5.2±2.2, PaCO2 (mmHg): 33.5±4.8 vs. 32.6±5.2, both P > 0.05]. The average arterial partial pressure of oxygen (PaO2) of ICP+PbtO2 monitoring group was obviously higher than that of ICP monitoring group (mmHg: 228.4±93.6 vs. 167.3±81.2, P < 0.01). Compared with the ICP monitoring group, the good outcome rates of 3 months and 6 months after injury in the ICP+PbtO2 monitoring group were significantly higher (3 months: 67.6% vs. 38.9%, 6 months: 70.6% vs. 41.7%, both P < 0.05). Kaplan-Meier survival curve showed that the 3-month and 6-month cumulative survival rates of ICP+PbtO2 monitoring group were significantly higher than those of ICP monitoring group (3 months: 85.3% vs. 61.1%, Log-Rank test: χ2 = 5.171, P = 0.023; 6 months: 79.4% vs. 55.6%, Log-Rank test: χ2 = 4.511, P = 0.034). Linear regression analysis showed that PbtO2 was significantly correlated with GOS score at 3 months and 6 months after injury in patients with severe craniocerebral injury (r values were 0.951 and 0.933, both P < 0.01). CONCLUSIONS: PbtO2 compared with ICP monitoring guiding therapy is valuable in improving the prognosis of patients with severe craniocerebral injury. It can improve the prognosis at 3-6 months after injury.

Downregulation of KLF13 through DNMT1-mediated hypermethylation promotes glioma cell proliferation and invasion.

BACKGROUND: Recent evidence indicates that Kruppel-like factor 13 (KLF13) has critical roles in regulating cell differentiation, proliferation and may function as a tumor suppressor. However, its role in glioma progression is poorly understood. METHODS: Public database was used to explore the expression and prognostic value of KLF13 in glioma. Cell proliferation and invasion assays were used to explore the role of KLF13. Bisulfite sequencing and ChIP assay were used to determine the methylation of KLF13 promoter in glioma and the regulation of KLF13 by DNMT1. RESULTS: We found that KLF13 inhibited glioma cell proliferation and invasion, which could be reversed by AKT activation. DNMT1-mediated hypermethylation was responsible for downregulation of KLF13. Knocking down of DNMT1 restored KFL13 expression and inhibited cell proliferation and invasion as well. Patients with high expression of KLF13 might have a better prognosis. CONCLUSION: KLF13 suppressed glioma aggressiveness and the regulation of KLF13 could be a potential therapeutic target.

Acute histopathological responses and long-term behavioral outcomes in mice with graded controlled cortical impact injury.

While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point™-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term (14-28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage, as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.