Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Virtual simulation with AneuShape™ software for microcatheter shaping in intracranial aneurysm coiling: a validation study.

Background: The shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization. Methods: From January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated. Results: Compared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also required more coils for both small (<7 mm) and large (≥7 mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11, p = 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00, p = 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysm obliteration (87.27 vs. 66.00%, p = 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%, p = 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98 min, p < 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy, p < 0.001). Conclusions: Software-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization.

Sleep disorders in the acute phase of coronavirus disease 2019: an overview and risk factor study.

BACKGROUND: Sleep disorders are common during the outbreak of pandemic diseases, and similar disorders are noted in hospitalized COVID-19 patients. It is valuable to explore the clinical manifestations and risk factors for sleep disorders in COVID-19 patients. METHODS: Inpatients with COVID-19 were enrolled. Detailed clinical information was collected, and sleep quality was assessed by PSQI. Patients were divided into a sleep disorder group and a normal group based on a PSQI ≥ 7, and the clinical features were compared between the groups. RESULTS: Fifty-three patients were enrolled, and 47.2% presented sleep disorders. Sleep disorders were associated with older age (> 50), anemia and carbon dioxide retention. Furthermore, factors associated with abnormal component scores of the PSQI were: (1) patients with older age were more likely to have decreased sleep quality, prolonged sleep latency, decreased sleep efficiency, sleep disturbances, and daytime dysfunction; (2) decreased sleep quality and prolonged sleep latency were associated with dyspnea, whereas carbon dioxide retention and more lobes involved in chest CT were associated with prolonged sleep latency; (3) decreased sleep efficiency was more prevalent in patients with anemia. CONCLUSIONS: Sleep disorders were prevalent in patients during the acute phase of COVID-19, and many risk factors (older age, anemia, carbon dioxide retention, the number of lobes involved in chest CT, and dyspnea) were identified. It is important to assess the presence of sleep disorders in patients to provide early intervention.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

GSK-3ß activation accelerates early-stage consumption of Hippocampal Neurogenesis in senescent mice.

Adult hippocampal neurogenesis (AHN) deficits contribute to the progression of cognitive impairments during accelerated senescence, with the mechanistic causes poorly understood. Glycogen synthase kinase-3ß (GSK-3ß) is a critical regulator in prenatal neurodevelopment. The present study aims to study whether and how GSK-3ß regulates AHN during the accelerated senescence. Methods: AHN and AHN-dependent cognition and GSK-3ß were evaluated in 3- and 6-month senescence-accelerated mice prone 8 (SAM-P8) and senescence resistant 1 (SAM-R1) mice, respectively. GSK-3ß was selectively overexpressed in wild-type mice using adeno-associated virus, or knocked-out by crossbreeding with GSK-3ß floxed mice in the neural stem cells (NSCs) of Nestin-Cre mice, or pharmacologically inhibited with SB216763 in SAM-P8 mice. AHN was evaluated by BrdU-, DCX-staining and retrovirus-labeling. Results: AHN transiently increased at 3-month, but dramatically dropped at 6-month of age in SAM-P8 mice with a simultaneous activation of GSK-3ß at 3-month. Selective overexpression of GSK-3ß in hippocampal NSCs of wildtype mice induced long-term AHN deficits due to an accelerated depletion of NSC pool, although it transiently increased the proliferation and survival of the newborn neurons. Pharmacologically inhibiting GSK-3ß by SB216763 efficiently preserved AHN and improved contextual memory in 6-month SAM-P8 mice, while conditional knock-out of GSK-3ß in NSCs impaired AHN. Conclusion: Early-stage activation of GSK-3ß in NSCs impairs AHN by accelerating the depletion of NSC pool, and pharmacological inhibition of GSK-3ß is efficient to preserve AHN during the accelerated aging. These results reveal novel mechanisms underlying the AHN impairments during accelerated senescence and provide new targets for pro-neurogenic therapies for related diseases.

Preliminary Recommendations for Surgical Practice of Neurosurgery Department in the Central Epidemic Area of 2019 Coronavirus Infection.

Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) has posed significant threats to the public health and life in China. Unlike the other 6 identified coronaviruses, the SARS-Cov-2 has a high infectious rate, a long incubation period and a variety of manifestations. In the absence of effective treatments for the virus, it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission. Hereby we focused on the surgical practice in Neurosurgery Department, Tongji Hospital, Wuhan, and drafted several recommendations based on the latest relevant guidelines and our experience. These recommendations have helped us until now to achieve 'zero infection' of doctors and nurses in our department, we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.

Microglia CREB-Phosphorylation Mediates Amyloid-ß-Induced Neuronal Toxicity.

Extracellular accumulation of amyloid-ß (Aß) forming senile plaques is one of the hallmark pathologies in Alzheimer's disease (AD), while the mechanisms underlying the neuronal toxic effect of Aß are not fully understood. Here, we found that intracerebroventricular infusion of the aged Aß42 in mice only induces memory deficit at 24 h but not at 7 days. Interestingly, a remarkably increased CREB (cAMP response element-binding protein) Ser133-phosphorylation (pS133-CREB) with microglial activation was detected at 24 h but not at 7 days after Aß infusion. Aß treatment for 24 h increased pS133-CREB level in microglia of the hippocampal non-granular cell layers with remarkably decreased pS133-CREB immunoreactivity in neurons of the hippocampal granular cell layers, including CA1, CA3, and DG subsets. Inhibition of microglia activation by minocycline or CREB phosphorylation by H89, an inhibitor of protein kinase A (PKA), abolished Aß-induced microglia CREB hyperphosphorylation with restoration of neuronal function and attenuation of inflammatory response, i.e., reduced levels of interleukin-6 (IL6) and pCREB binding of matrix metalloproteinase-9 (MMP9) DNA. Finally, treatment of the primary hippocampal neurons with Aß-potentiated microglia media decreased neuronal GluN1 and GluA2 levels, while simultaneous inhibition of PKA restored the levels. These novel findings reveal that intracerebroventricular infusion of Aß only induces transient memory deficit in mice and the molecular mechanisms involve a stimulated microglial CREB phosphorylation.

Significance of cyclooxygenase-2 elevation in middle cerebral artery for patients with hemorrhagic moyamoya disease.

The etiology and pathogenesis of moyamoya disease (MMD) remain elusive. Some inflammatory proteins, such as cyclooxygenase (COX)-2, are believed to be implicated in the development of MMD. So far, the relationship between COX-2 and MMD is poorly understood and reports on the intracranial vessels of MMD patients are scanty. In this study, tiny pieces of middle cerebral artery (MCA) and superficial temporal artery (STA) from 13 MMD patients were surgically harvested. The MCA and STA samples from 5 control patients were also collected by using the same technique. The expression of COX-2 was immunohistochemically detected and the average absorbance (A) of positively-stained areas was measured. High-level COX-2 expression was found in all layers of the MCA samples from all 5 hemorrhagic MMD patients, while positive but weak expression of COX-2 was observed only in the endothelial layer of the MCA samples from most ischemic MMD patients (6/8, 75%). The average A values of COX-2 in the hemorrhagic MMD patients were substantially higher than those in their ischemic counterparts (t=4.632, P=0.001). There was no significant difference in the COX-2 expression among the "gender" groups, or "radiographic grade" groups, or "lesion location" groups (P>0.05 for all). The COX-2 expression was detected neither in the MCA samples from the controls nor in all STA specimens. Our results suggested that COX-2 was up-regulated in the MCA of MMD patients, especially in hemorrhagic MMD patients. We are led to speculate that COX-2 may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of MMD patients.

Intraoperative neuromonitoring for removal of large vestibular schwannoma: Facial nerve outcome and predictive factors.

BACKGROUND: Preservation of facial nerve (FN) function is one of the major goals for resection of large vestibular schwannoma (VS) (≥ 30 mm). Little is known about the FN outcome and its predictive factors due to limited data. OBJECTIVE: To explore the predictive factors affecting FN outcome following resection of large VS. METHODS: 106 Large VS patients underwent surgical resection from 2010 to 2012 via intraoperative neuromonitoring for FN preservation approach. Postoperative FN function evaluation was conducted at the time points of 3-7th day, 3rd month and at the end of the 2nd year. Correlation between tumor size, intraoperative parameters and FN function were examined. RESULTS: The ratios of total and subtotal resection were 82.1% and 14.2%, respectively. Acceptable FN function was achieved in 78% patients. Patients with good FN function showed much smaller (P < 0.01) VS size than those of poor-FN function patients at 3-7th day, 3rd month and 2nd year. There was a significant correlation between facial motor evoked potential (FMEP) ratios and postoperative FN function at 3-7th day (r = -0.709, P < 0.001) 3rd month (r = -0.709, P< 0.001) and 2nd year (r = -0.750, P < 0.001). Maximal response amplitude (MRA) ratio was a supplementary indicator for train time in predicting both immediate and long-term FN function in patients with large VS. CONCLUSION: Indicative factors of both immediate and long-term postoperative FN function in large VSs include tumor size, intraoperative train time, start to final FMEP ratios and proximal to distal MRA ratios.

Treatment strategies for huge central neurocytomas.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

[Identification and management of intra-operative suspicious tissues in 20 transsphenoidal surgery cases].

OBJECTIVE: To determine appropriate protocols for the identification and management of intra operative suspicious tissues during transsphenoidal surgery. METHODS: Clinical data and pathological reports of 20 patients with intra-operative suspicious tissues during transsphenoidal surgeries were analyzed retrospectively. The methods for discriminating between adenoma and normal pituitary tissues were reviewed. RESULTS: The postoperative pathological reports revealed that adenoma and normal pituitary tissues coexisted in 9 samples, while 5 samples were identified as normal pituitary tissues, 2 as adenoma tissues, and 4 as other tissues. Adenomas were distinguished from normal pituitary tissues on the basis of intra-operative appearance, texture, blood supply and possible existence of boundary. CONCLUSION: If decisions are difficult to made during surgeries from the appearance of the suspicious tissues, pathological examinations are advised as a guidance for the next steps.

Inhibition of EGFR/MAPK signaling reduces microglial inflammatory response and the associated secondary damage in rats after spinal cord injury.

BACKGROUND: Emerging evidence indicates that reactive microglia-initiated inflammatory responses are responsible for secondary damage after primary traumatic spinal cord injury (SCI); epidermal growth factor receptor (EGFR) signaling may be involved in cell activation. In this report, we investigate the influence of EGFR signaling inhibition on microglia activation, proinflammatory cytokine production, and the neuronal microenvironment after SCI. METHODS: Lipopolysaccharide-treated primary microglia/BV2 line cells and SCI rats were used as model systems. Both C225 and AG1478 were used to inhibit EGFR signaling activation. Cell activation and EGFR phosphorylation were observed after fluorescent staining and western blot. Production of interleukin-1 beta (IL-1 ß) and tumor necrosis factor alpha (TNF α) was tested by reverse transcription PCR and ELISA. Western blot was performed to semi-quantify the expression of EGFR/phospho-EGFR, and phosphorylation of Erk, JNK and p38 mitogen-activated protein kinases (MAPK). Wet-dry weight was compared to show tissue edema. Finally, axonal tracing and functional scoring were performed to show recovery of rats. RESULTS: EGFR phosphorylation was found to parallel microglia activation, while EGFR blockade inhibited activation-associated cell morphological changes and production of IL-1 ß and TNF α. EGFR blockade significantly downregulated the elevated MAPK activation after cell activation; selective MAPK inhibitors depressed production of cytokines to a certain degree, suggesting that MAPK mediates the depression of microglia activation brought about by EGFR inhibitors. Subsequently, seven-day continual infusion of C225 or AG1478 in rats: reduced the expression of phospho-EGFR, phosphorylation of Erk and p38 MAPK, and production of IL-1 ß and TNF α; lessened neuroinflammation-associated secondary damage, like microglia/astrocyte activation, tissue edema and glial scar/cavity formation; and enhanced axonal outgrowth and functional recovery. CONCLUSIONS: These findings indicate that inhibition of EGFR/MAPK suppresses microglia activation and associated cytokine production; reduces neuroinflammation-associated secondary damage, thus provides neuroprotection to SCI rats, suggesting that EGFR may be a therapeutic target, and C225 and AG1478 have potential for use in SCI treatment.

[The relative analysis of clinical endocrine features and pathological types of pituitary microadenomas].

OBJECTIVES: To study the relationship between the clinical presentation, endocrinal findings and pathological types in patients with pituitary microadenomas, so as to improve the accuracy of clinical diagnosis and choose the best therapy strategy before the operation. METHODS: From January 2007 to June 2009, the clinical data of 94 patients who were surgically removed pituitary microadenomas were obtained, including the clinical presentation, endocrinal findings and pathological diagnosis. The analysis was accomplished with Chi-square test. RESULTS: Hormonal symptoms were found in 86 patients (91.5%), it occurred more frequently in immunopositive patients (85/92, 92.4%) than in immunonegative patients (1/2, 50.0%) (P < 0.05). The coincidence of hormonal symptoms and immunohistochemistry diagnosis was 71.7%; 88.9% patients had the symptoms of amenorrhea, galactorrhea and sexual function diseases in prolactin (PRL) positive group and 28.1% patients had the symptoms of gigantism or acromegaly in growth hormone (GH) positive group. The coincidence of endocrinal findings and immunohistochemistry diagnosis was 69.0%; 87.7% patients had high level of blood PRL in PRL positive group and 21.9% patients had high level of blood GH in GH positive group. CONCLUSIONS: There is an obvious relationship between the clinical presentation, endocrinal findings and pathological diagnosis in patients with pituitary microadenomas, which may contribute to the clinical diagnosis and treatment of pituitary secreting microadenomas.