Lower incidence of diabetes mellitus in patients with aneurysmal subarachnoid hemorrhage: a large case-control study with propensity score matching.

Background and purpose: Diabetes mellitus (DM) is a well-established cardiovascular risk factor for atherosclerotic disease; however, its effect on the risk of rupture of intracranial aneurysms remains controversial. Herein, we aimed to perform a case-control study to investigate the relationship between DM and aneurysmal subarachnoid hemorrhage (aSAH). Methods: We retrospectively reviewed the data of patients with ruptured or unruptured aneurysms who were treated between 2013 and 2023. Univariate and multivariate analyses were performed. Propensity score matching (PSM) analysis was conducted to evaluate the relationship between DM and risk of aSAH. Results: A total of 4,787 patients with 5,768 intracranial aneurysms were included. Among them, 2,957 (61.8%) were females, 1765 (36.9%) had ruptured aneurysms, and 531 (11.1%) presented with DM. Female sex, current drinking, and hypercholesterolemia were associated with a higher risk of aSAH, whereas old age, former smoking, and DM were associated with a lower risk of aSAH in multivariate analysis (p < 0.05). The incidence of DM (13.4%, 406/3022) in the unruptured group was higher than that in the ruptured group (7.1%, 125/1765) (odds ratio, 0.55; 95% confidence interval, 0.444-0.680) (p < 0.001). After propensity score matching, 530 patients with DM were successfully matched, and DM was still associated with a lower risk of aSAH (odds ratio, 0.24; 95% confidence interval, 0.185-0.313) (p < 0.001). Conclusion: Patients with aSAH have a lower incidence of DM, however, this case-cohort study could not establish a causal relationship. A prospective and large study with long-term follow-up is warranted to establish a causal relationship.

Microsurgical revascularization of a symptomatic proximal vertebral artery: pilot experiences from a single center.

Background: Vertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA. Methods: Twenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed. Results: Twelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner's syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8-62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported. Conclusion: Microsurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.

Reconstructive endovascular treatment for basilar artery trunk aneurysms: complications and clinical and angiography outcomes.

BACKGROUND: Basilar artery trunk aneurysms (BTAs) are rare intracranial aneurysms. We aim to investigate the procedural complications and clinical and angiographic outcomes of BTAs treated with reconstructive endovascular treatment (EVT). METHODS: We retrospectively reviewed the data of 111 patients with BTAs who underwent reconstructive EVT during 2013-2022. The factors associated with procedural complications and clinical and angiographic outcomes were analyzed. RESULTS: The study included 81 men and 30 women (median age 60 years). Overall, 26 (23.4%) cases presented with subarachnoid hemorrhage and 85 (76.6%) presented with unruptured aneurysms. Periprocedural ischemic and hemorrhagic complications occurred in 29 (26.1%) and 4 (3.6%) cases, respectively. The rate of favorable clinical outcomes was 83.8% (92/111) and the mortality rate was 14.4% (16/111). Angiographic follow-up data were available for 77/95 (81.1%) survivors; 57 (74.0%) and 20 (26%) aneurysms exhibited complete and incomplete obliteration, respectively. Old age, high Hunt and Hess grades (IV-V), hemorrhagic complications, and increased aneurysm size were independent risk factors for unfavorable clinical outcomes (p<0.05). Increased aneurysm size and incomplete aneurysm occlusion on immediate angiography were independent risk factors for incomplete occlusion during follow-up (p<0.05). CONCLUSION: Reconstructive EVTs are a feasible and effective treatment for BTAs but are associated with a high risk of ischemic and hemorrhagic complications and a high mortality rate. Larger aneurysms may predict unfavorable clinical outcomes and aneurysm recurrence during follow-up. Hemorrhagic complications may predict unfavorable clinical outcomes, whereas immediate complete aneurysm occlusion may predict total occlusion during follow-up.

Fluoxetine attenuates apoptosis in early brain injury after subarachnoid hemorrhage through Notch1/ASK1/p38 MAPK signaling pathway.

Subarachnoid hemorrhage (SAH) is a severe brain condition associated with a significantly high incidence and mortality. As a consequence of SAH, early brain injury (EBI) may contribute to poor SAH patient outcomes. Apoptosis is a signaling pathway contributing to post-SAH early brain injury and the diagnosis of the disease. Fluoxetine is a well-studied serotonin selective reuptake inhibitor (SSRI). However, its role in apoptosis has not been clearly understood. The present investigation assessed the effects of Fluoxetine in apoptosis and the potential Notch1/ASK1/p38 MAPK signaling pathway in EBI after SAH. Adult C57BL/6 J mice were subjected to SAH. Study mice (56) were randomly divided into 4 groups: the surgery without SAH (sham (n = 8), SAH+ vehicle; (SAH+V) (n = 16), surgery+ Fluoxetine (Fluox), (n = 16) and SAH+ Fluoxetine (n = 16). Various parameters were investigated 12, 24, 48, and 72 h after induction of SAH. Western blot analysis, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, Immunohistochemistry (IHC), and flow cytometry were carried out in every experimental group. According to the findings, the SAH downregulated NOTCH1 signaling pathway, Jlk6 inhibited Notch1, Notch1 inactivation increased apoptotic protein expression and suppressed Bax, and cytochrome C. Fluoxetine reversed the effects of notch1 inhibition in SAH. The Neuroprotective Fluoxetine effects involved suppression of apoptosis post-SAH. In summary, early Fluoxetine treatment significantly attenuates apoptosis and the expression of apoptosis-related proteins after 72 h post-SAH. Fluoxetine may ameliorate early brain injury after subarachnoid hemorrhage through anti-apoptotic effects and Notch1/ASK1/p38 MAPK signaling pathway.

Treatment of early brain injury after subarachnoid hemorrhage in the rat model by inhibiting p53-induced ferroptosis.

Post-subarachnoid hemorrhage (SAH) survivors experience severe neurological disability. Previous studies implicate that ferroptosis is involved in SAH. Ferroptosis is an iron-dependent form of regulated cell death caused by the accumulation of lipid peroxidation. However, the role and the mechanism of ferroptosis in SAH are still uncertain and need further study. Thus, we investigated the effect of ferroptosis on early brain injury (EBI) after SAH and further clarified its mechanism. The results showed ferroptosis characteristics appeared in the cerebral cortex of rats with SAH after 24 h. However, ferroptosis could be rescued by Ferrostatin-1 (Fer-1). Treatment with Fer-1 could increase SLc7a11 and GPx4, and alleviated damage-associated molecular pattern molecules and inflammatory cytokines. Similarly, blood-brain barrier impairment, brain edema, behavioral deficits and neuronal damage were reduced by inhibiting ferroptosis. More importantly, the p53 inhibitor pifithrin-α could significantly block cortical SAH-induced ferroptosis. Collectively, these results indicated that ferroptosis aggravated EBI after SAH was partly dependent on p53, and inhibiting ferroptosis might be an effective therapeutic target for EBI.

Aneurysm Wall Enhancement in Unruptured Intracranial Aneurysms: A Histopathological Evaluation.

Background Unruptured intracerebral aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging scans may be a promising predictor for rupture-prone intracerebral aneurysms. However, the pathophysiology of AWE remains unclear. To this end, the association between AWE and histopathological changes was assessed in this study. Methods and Results A total of 35 patients with 41 unruptured intracerebral aneurysms who underwent surgical clipping were prospectively enrolled. A total of 27 aneurysms were available for histological evaluation. The macroscopic and microscopic features of unruptured intracerebral aneurysms with and without enhancement were assessed. The microscopic features studied included inflammatory cell invasion and vasa vasorum, which were assessed using immunohistochemical staining with CD68, CD3, CD20, and myeloperoxidase for the former and CD34 for the latter. A total of 21 (51.2%) aneurysms showed AWE (partial AWE, n=7; circumferential AWE, n=14). Atherosclerotic and translucent aneurysms were identified in 17 and 14 aneurysms, respectively. Aneurysm size, irregularity, and atherosclerotic and translucent aneurysms were associated with AWE on univariate analysis (P<0.05). Multivariate logistic regression analysis showed that atherosclerosis was the only factor significantly and independently associated with AWE (P=0.027). Histological assessment revealed that inflammatory cell infiltration, intraluminal thrombus, and vasa vasorum were significantly associated with AWE (P<0.05). Conclusions Though AWE on vessel wall magnetic resonance imaging scans may be associated with the presence of atherosclerotic lesions in unruptured intracerebral aneurysms, inflammatory cell infiltration within atherosclerosis, intraluminal thrombus, and vasa vasorum may be the main pathological features associated with AWE. However, the underlying pathological mechanism for AWE still needs to be further studied.

Induction of SPARC on Oxidative Stress, Inflammatory Phenotype Transformation, and Apoptosis of Human Brain Smooth Muscle Cells Via TGF-ß1-NOX4 Pathway.

Secreted protein acidic and rich in cysteine (SPARC) has a close association with inflammatory response and oxidative stress in tissues and is widely expressed in intracranial aneurysms (IAs), especially in smooth muscle cells. Therefore, it is inferred that SPARC might be involved in the formation and development of IAs through the inflammatory response pathway or oxidative stress pathway. The aim of this study is to investigate the pathological mechanism of SPARC in oxidative stress, inflammation, and apoptosis during the formation of IAs, as well as the involvement of TGF-ß1 and NOX4 molecules. Human brain vascular smooth muscle cells (HBVSMCs) were selected as experimental objects. After the cells were stimulated by recombinant human SPARC protein in vitro, the ROS level in the cells was measured using an ID/ROS fluorescence analysis kit combined with fluorescence microscope and flow cytometry. The related protein expression in HBVSMCs was measured using western blotting. The mitochondrial membrane potential change was detected using a mitochondrial membrane potential kit and laser confocal microscope. The mechanism was explored by intervention with reactive oxygen scavengers N-acetylcysteine (NAC), TGF-ß1 inhibitor (SD-208), and siRNA knockout. The results showed that SPARC upregulated the expression of NOX4 through the TGF-ß1-dependent signaling pathway, leading to oxidative stress and pro-inflammatory matrix behavior and apoptosis in HBVSMCs. These findings demonstrated that SPARC may promote the progression of IAs.

SPARC induces phenotypic modulation of human brain vascular smooth muscle cells via AMPK/mTOR-mediated autophagy.

Secreted protein acidic and rich in cysteine (SPARC) was widely expressed in VSMCs of human IAs and could reduce the capability of self-repair. This indicates that SPARC may play a role in the promotion of IAs formation and progression, but the mechanism remains unclear. In this study, we further investigated whether SPARC could induce phenotypic modulation of Human Brain Vascular Smooth Muscle Cells (HBVSMCs) and sought to elucidate the role of SPARC-mediated autophagy involved in it. The results demonstrated that SPARC inhibited the expression of contractile genes in HBVSMCs and induced a synthetic phenotype. More importantly, SPARC significantly up-regulated multiple proteins including autophagy marker microtubule-associated protein light chain 3-II (LC3-II), Beclin-1, and autophagy-related gene 5(ATG5). Furthermore, SPARC could promote p62 degradation. The autophagy inhibitor 3- methyladenine (3-MA) significantly blocked SPARC-induced phenotypic modulation of HBVSMCs. We further sought to elucidate the molecular mechanism involved in SPARC-induced autophagy, and found that SPARC could activate the AMPK/mTOR signaling pathway in HBVSMCs. AMPK could be pharmacologically inhibited by Compound C (CC), which significantly decreased the phosphorylation of AMPK into p-AMPK, increased the phosphorylation of mTOR into p-mTOR, and decreased LC3-II, Beclin-1 and ATG5 levels. This suggested that activated AMPK/ mTOR signaling is related to SPARC-mediated autophagy. These results indicated that SPARC plays a role in the phenotypic modulation of HBVSMCs through autophagy activation by AMPK/mTOR signaling pathway.

Application of fluorescein sodium in breast cancer brain-metastasis surgery.

OBJECTIVE: Surgical resection serves an important role in the multidisciplinary treatment of cerebral metastases (CMs). Conventional white-light, microsurgical, and circumferential stripping of CMs is standard neurosurgical procedure, but is associated with a high recurrence rate. Based on this outcome, there is an urgent need for a new surgical strategy, such as fluorescence-guided resection, for CMs, in order to achieve total removal. METHODS: A retrospective study was carried out in 38 patients clinically and pathologically diagnosed with breast cancer brain metastasis at three medical centers from May 2012 to June 2016. The study comprised group 1 (fluorescein-guided surgery) and group 2 (standard microsurgery). In group 1, 5 mg/kg of fluorescein sodium was injected intravenously after an allergy test and before general anesthesia for 17 patients. A yellow 560 filter was employed for microsurgical tumor resection. Group 2 consisted of 21 patients for whom fluorescein was not administered. RESULTS: Surgical outcomes were assessed concerning the extent of resection and Karnofsky performance status. Gross total resection was achieved in these patients, with high fluorescence markedly enhancing tumor visibility. The extent of resection had a powerful influence on performance status. Overall survival after CM was 24.1 months in patients given fluorescein and was 22.8 months in the nonfluorescein group. CONCLUSION: Fluorescein-guided surgery is a simple, safe, and practical method to resect breast cancer brain metastasis, and leads to a higher proportion of resection compared to common microsurgery. This offers a tremendous advantage when navigating a tiny tumor, and improves the quality of life of patients with CM.

Prognostic factors for olfactory groove meningioma with nasal cavity extension.

OBJECTIVES: Meningioma recurrence remains a significant issue. No study has described the relationship between the clinical features and prognosis of communicating meningioma that primarily originates from the olfactory groove. The aim of the study was to identify prognostic factors of communicating olfactory groove meningiomas that could be stratified according to their risk of recurrence. RESULTS: A Simpson grade one or two resection was achieved. Complications with cerebrospinal rhinorrhoea occurred in two patients: one required reoperation, and the other was managed successfully with external drainage of lumbar cistern. There were 5 known clinical recurrences within the median follow-up of more than 5 years. The median 5-year recurrence-free survival for patients was 88.4%. Factors such as gender, tumour size, T2 signal and the hyperostotic bone had no significant effect on recurrence-free survival. However, recurrence was activated by oedema range, hyperostosis, dural tail sign and tumor texture (p < 0.05). Interestingly, female patients with the disease were younger than males at diagnosis, and the difference was statistically significant ( p = 0.013). CONCLUSIONS: Based on these features of communicating olfactory groove meningiomas, different strategies may be adopted for the follow-up and subsequent treatment. Due to the relatively uncommon incidence, more investigations into the clinical behaviour of this entity are crucial. PATIENTS AND METHODS: A retrospective study of 43 patients harbouring olfactory groove meningiomas invading the ethmoid or nasal cavity was conducted at three medical centers from 2000 to 2010. The records were reviewed for clinical presentations, imaging studies, surgical observation, histological features and follow-up.

Different clinical characteristics between perimesencephalic subarachnoid hemorrhage and diffuse subarachnoid hemorrhage with negative initial angiography.

AIM: The purpose of this study was to compare the different clinical features, outcome and treatment strategies in patients with perimesencephalic SAH (p-SAH) and diffuse SAH (d-SAH). MATERIAL AND METHODS: 83 patients with spontaneous SAH and negative initial cerebral angiography were retrospectively reviewed. RESULTS: There were 49 patients with p-SAH and 34 with d-SAH. The patients with d-SAH were likely to be hypertensive and smoking and have elevated cholesterol and lactate dehydrogenase and White blood cells. 95.9% of patients with p-SAH had a Hunt&Hess grade of I-II, whereas 73.5% of patients with d-SAH had Grade I-II, 9 patients had Grade III-IV. All patients with p-SAH had a modified Fisher scale of 1-2 and a favorable outcome, whereas 47 % and 8.8% of the patients with d-SAH had a score of 1-2 and had a poor prognosis, respectively. Hydrocephalus, clinical vasospasm, re-bleeding and pneumonia were common in patients with d-SAH. CONCLUSION: The initial bleeding pattern was associated with the initial clinical condition and outcome, and d-SAH might lead to a worse clinical course and outcome and might have a high risk of complications. Repeated DSA is recommended to exclude aneurysm in patients with d-SAH, whereas CT angiography was enough in patients with p-SAH.

Expression of ß-amyloid precursor protein in refractory epilepsy.

ß-amyloid precursor protein (ß-APP), also known as Aß peptide, has a key role in the pathogenesis of Alzheimer's disease, and is also likely to be involved in the development of refractory epilepsy. The mechanism behind the association between ß-APP and refractory epilepsy remains to be elucidated. The aim of the present study was to examine the levels of APP mRNA and ß-APP protein in patients with refractory epilepsy. Tissue samples were obtained from patients with chronic pharmacoresistant epilepsy who underwent surgery. Levels of APP mRNA and ß-APP protein in epileptic temporal lobe and hippocampal tissue were assessed using quantitative polymerase chain reaction, immunohistochemistry and immunofluorescence. The expression levels of protein significantly increased in the temporal cortex and the hippocampus of the patients with epilepsy. ß-APP may thus contribute to the pathogenesis of refractory epilepsy.

Intradiploic hemangioma with repeated hemorrhage in a child with hemophilia.

Intraosseous hemangioma is an uncommon benign vascular tumor, which is most frequently found in middle-aged female patients. The clinical course is usually insidious and the outcome excellent after total resection. The authors report a case of a calvarial hemangioma in a child with hemophilia who experienced a catastrophic postoperative hematoma and discuss the mechanism, clinical features, and treatment of this condition.

Lack of association between GSTM1 and GSTT1 polymorphisms and brain tumour risk.

OBJECTIVE: Glutathione S-transferases (GSTs) are important enzymes that are involved in detoxification of environmental carcinogens. Molecular epidemiological studies have been conducted to investigate the association between GSTM1 and GSTT1 homozygous deletion polymorphisms and brain tumours but results have been conflicting. The aim of this study was to clarify this problem using a meta-analysis. METHODS: A total of 9 records were identified by searching the PubMed and Embase databases. Fixed- and random-effects models were performed to estimate the pooled odds ratios. RESULTS: No significant association was found between the GSTM1 and GSTT1 homozygous deletion polymorphisms and risk of brain tumours, including glioma and meningioma. Similar negative results were also observed in both population-based and hospital-based studies. CONCLUSION: These findings indicate that the GSTM1 and GSTT1 polymorphisms may not be related to the development of brain tumours.

Pure spinal epidural cavernous hemangioma.

BACKGROUND: Pure epidural cavernous hemangiomas without bony involvement are rare, representing 4% of all spinal epidural tumors. Most of these are case reports and are easily misdiagnosed. METHODS: Herein nine patients (male:female, 5:4, average age: 51 years) with symptomatic pure epidural spinal cavernous hemangioma between 2005 and 2011 were treated, and the clinical, radiological, and pathological records, treatment, and prognosis were discussed. RESULTS: All patients experienced a slowing progressive clinical course, except for one with intralesional hemorrhage. Clinical manifestations included back or radiating pain, sensorimotor deficits, and sphincters disturbance. Eight lesions were isointense on T1- and hyperintense on T2-weighted images with homogenously strongly enhancement and one was mixed signal with heterogeneous enhancement because of intratumoral hemorrhage. Hemilaminotomoy or laminotomy was performed and total resection was achieved. All patients experienced a gradual neurological improvement with no recurrence. CONCLUSIONS: Spinal epidural cavernous hemangioma is a benign vascular malformation that should be excluded in the diagnosis of epidural lesion. Total surgical resection is recommended and usually results in a good prognosis.

A spinal epidural dumbbell cellular schwannoma in an infant.

Intraspinal schwannoma is a rare neoplasm in pediatric patients; cellular schwannoma is an unusual histological subtype of schwannoma. A six-month-old infant with an epidural dumbbell cellular schwannoma presented with progressive weakness of his arms and legs. A spinal MRI revealed an epidural mass from C5 to T4, and a complete surgical resection was achieved after laminotomy and facetectomy. The patient experienced a gradual neurological improvement and was still healthy without recurrence at the latest follow-up. The diagnosis of cellular schwannoma was confirmed on immunohistological examination.

Symptomatic Rathke cleft cyst.

Rathke cleft cysts (RCC) are uncommon intrasellar lesions. Although their clinical manifestations, radiological features and treatment are frequently reported, controversy remains as a result of their rarity. We reviewed the preoperative clinical manifestations, neurological examination findings, visual acuity and fields, endocrinological function, radiographic study findings, surgical and pathological records, and prognosis of 45 patients with RCC (21 males, 24 females, average age: 47 years) admitted to our department between January 2002 and January 2011. The most common clinical manifestations included headaches, and visual and hormonal disturbances. Most RCC were intrasellar with a suprasellar extension. The most common MRI patterns were hypointense on T1-weighted and hyperintense on T2-weighted images, isointense on T1-weighted and hyperintense on T2-weighted images, and hyperintense on T1-weighted and hyperintense on T2-weighted images. Aspiration and biopsy of the cyst wall were performed in most patients. Most patients experienced improved headaches and visual disturbance, but the hormonal disturbance rarely returned to normal, especially in those patients with a serious preoperative hormonal disturbance. The recurrence rate was 14%, which was associated with the extent of cyst removal, inflammation and rim enhancement, as well as the surgical approach. Aspiration and biopsy of the cyst wall still seems to be an effective treatment for most RCC for its low morbidity and good prognosis. Conservative treatment and close follow-up may be suitable for small cysts with subtle clinical manifestations.