Treatment of conus medullaris arteriovenous malformation: the role of microsurgical treatment.

OBJECTIVE: Conus medullaris arteriovenous malformation (AVM) is rare and challenging to treat. To better define the presentation, prognosis, and optimal treatment of these lesions, the authors present their treatment experiences for conus medullaris AVM. METHODS: Eleven patients with AVM of the conus medullaris were identified between March 2013 and December 2021. Among these patients, 7 who underwent microsurgical treatment were included. Patient data, including age, sex, symptoms at presentation, neurological status, radiological findings, nidus depth (mainly pial lesion vs intramedullary lesion), type of treatment, and recurrence at follow-up, were collected. Postoperative angiography was performed in all patients. Spinal cord function was evaluated using the Frankel grade at the time of admission and 1 year after surgery. RESULTS: All 7 patients presenting with myeloradiculopathy were treated surgically. Four patients (57.1%) underwent endovascular embolization, followed by resection. The other 3 patients underwent microsurgery only. Complete occlusion was confirmed with postoperative angiography in all patients. Of the 3 patients who were nonambulatory before surgery (Frankel grade C), 2 were able to walk after surgery (Frankel grade D) and 1 remained nonambulatory (Frankel grade C) at 1-year follow-up. CONCLUSIONS: Based on the authors' clinical experiences, the results of multimodal treatment for conus medullaris AVM are good, with microsurgical treatment playing an important role. The microsurgical strategy can differ depending on the location of the nidus, and when possible, good results can be expected through microsurgical resection.

Meptyldinocap induces implantation failure by forcing cell cycle arrest, mitochondrial dysfunction, and endoplasmic reticulum stress in porcine trophectoderm and endometrial luminal epithelial cells.

Meptyldinocap is a dinitrophenol fungicide used to control powdery mildew. Although other dinitrophenol pesticides have been found to exhibit reproductive toxicity, studies of meptyldinocaps are scarce. This study investigated the adverse effects of meptyldinocap on porcine trophectoderm (pTr) and porcine endometrial luminal epithelial (pLE) cells, which play crucial roles in implantation. We confirmed that meptyldinocap decreased cell viability, induced apoptosis, and inhibited proliferation by decreasing proliferation-related gene expression and inducing changes in the cell cycle. Furthermore, meptyldinocap treatment caused mitochondrial dysfunction, endoplasmic reticulum stress, and disruption of calcium homeostasis. Moreover, it induces alterations in mitogen-activated protein kinase signaling cascades and reduces the migration ability, leading to implantation failure. Our findings suggest that meptyldinocap reduces the cellular functions of pTr and pLE cells, which are important for the implantation process, and interferes with interactions between the two cell lines, potentially leading to implantation failure. We also propose a mechanism by which the understudied fungicide meptyldinocap exerts its cytotoxicity.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Hexaconazole induces developmental toxicities via apoptosis, inflammation, and alterations of Akt and MAPK signaling cascades.

Hexaconazole is a highly effective triazole fungicide that is frequently applied in various countries to elevate crop productivity. Given its long half-life and high water solubility, this fungicide is frequently detected in the environment, including water sources. Moreover, hexaconazole exerts hazardous effects on nontarget organisms. However, little is known about the toxic effects of hexaconazole on animal development. Thus, this study aimed to investigate the developmental toxicity of hexaconazole to zebrafish, a valuable animal model for toxicological studies, and elucidate the underlying mechanisms. Results showed that hexaconazole affected the viability and hatching rate of zebrafish at 96 h postfertilization. Hexaconazole-treated zebrafish showed phenotypic defects, such as reduced size of head and eyes and enlarged pericardiac edema. Moreover, hexaconazole induced apoptosis, DNA fragmentation, and inflammation in developing zebrafish. Various organ defects, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity, were observed in transgenic zebrafish models olig2:dsRed, fli1:eGFP, and l-fabp:dsRed. Furthermore, hexaconazole treatment altered the Akt and MAPK signaling pathways, which possibly triggered the organ defects and other toxic mechanisms. This study demonstrated the developmental toxicity of hexaconazole to zebrafish and elucidated the underlying mechanisms.

The efficacy of surgical site suction drain insertion in pterional craniotomy for intracranial cerebral aneurysm.

Objective: We evaluated the role of subgaleal closed suction drains in postoperative epidural hematoma (EDH) and wound complications following pterional craniotomy for cerebral aneurysm. Methods: We reviewed 5,280 pterional craniotomies performed on 5,139 patients between January 2006 and December 2020. A drain was placed subgalealy and tip of drain was positioned between the bone flap and the deep temporalis. 1,637 cases (31%) had a subgaleal suction drain. We analyzed demographic and clinical variables related to EDH requiring evacuation and wound complications in patients with and without drains. Univariate and multivariate logistic regression analyses were performed to determine the associated risk factors. Results: Fourteen cases (0.27%) of EDH requiring evacuation and 30 cases (0.57%) of wound complications were identified. Univariate analysis found that drain insertion, subarachnoid hemorrhage (SAH), and operation time were associated with EDH, while drain insertion, SAH, male gender, older age, and longer operation time were associated with wound complications. Multivariate analysis found no significant association between drain use and EDH (OR=1.62, p=0.402) or wound complications (OR=1.45, p=0.342). Conclusions: Routine use of subgaleal closed suction drains may not be necessary after pterional craniotomy, as drain insertion was not associated with a reduced risk of EDH requiring evacuation or wound complications.

Osthole impairs mitochondrial metabolism and the autophagic flux in colorectal cancer.

BACKGROUND: Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known. HYPOTHESIS/PURPOSE: We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux. STUDY DESIGN: In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system. METHODS: AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses. RESULTS: Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1ß inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNAHisGTG regulated by osthole directly affects the cellular fate of colon cancer cells. CONCLUSION: These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.

Chemical and perfusion markers as predictors of moyamoya disease progression and complication types.

To investigate the association between chemical markers (triglyceride, C-reactive protein (CRP), and inflammation markers) and perfusion markers (relative cerebral vascular reserve (rCVR)) with moyamoya disease progression and complication types. A total of 314 patients diagnosed with moyamoya disease were included. Triglyceride and CRP levels were assessed and categorized based on Korean guidelines for dyslipidemia and CDC/AHA guidelines, respectively. Perfusion markers were evaluated using Diamox SPECT. Cox proportional hazard analysis was performed to examine the relationship between these markers and disease progression, as well as complication types (ischemic stroke, hemorrhagic stroke, and rCVR deterioration). Elevated triglyceride levels (≥ 200) were significantly associated with higher likelihood of end-point events (HR: 2.292, CI 1.00-4.979, P = 0.03). Severe decreased rCVR findings on Diamox SPECT were also significantly associated with end-point events (HR: 3.431, CI 1.254-9.389, P = 0.02). Increased CRP levels and white blood cell (WBC) count were significantly associated with moyamoya disease progression. For hemorrhagic stroke, higher triglyceride levels were significantly associated with end-point events (HR: 5.180, CI 1.355-19.801, P = 0.02). For ischemic stroke, severe decreased rCVR findings on Diamox SPECT (HR: 5.939, CI 1.616-21.829, P < 0.01) and increased CRP levels (HR: 1.465, CI 1.009-2.127, P = 0.05) were significantly associated with end-point events. Elevated triglyceride, CRP, and inflammation markers, as well as decreased rCVR, are potential predictors of moyamoya disease progression and complication types. Further research is warranted to understand their role in disease pathophysiology and treatment strategies.

Pyridaben induces apoptosis and inflammation in bovine mammary epithelial cells by disturbance of calcium homeostasis and upregulation of MAPK cascades.

Pyridaben is a widely used pyridazinone insecticide used to protect crops against insects and mites. The toxicity of pyridaben has been reported in mice, zebrafish, the human reproductive system, nervous system, and respiratory system. Pyridaben can also be ingested by dairy cattle through feed. However, the toxicity of pyridaben in cattle has not been investigated on. Thus, this study focuses on demonstrating the toxicity of pyridaben in the bovine mammary glands and with the generation milk in the bovine mammary epithelial cells, as it is crucial to the continuance of the amount and the quality of the milk produced. We started by analyzing the intracellular toxicity along with the impact of pyridaben on the cell cycle distribution and the transcription of associated genes. Pyridaben treatment induced cell cycle arrest accompanied the disruption in G1 and S phases with imbalanced cytosolic and mitochondrial calcium ion homeostasis, and caused a destruction of mitochondrial membrane potential. This eventually led to apoptosis of MAC-T cells. We also investigated in the impact that pyridaben has on MAPK signaling proteins, where phosphorylation of ERK1/2, JNK, and p38 were upregulateed. Moreover, examination of the effect of pyridaben in the inflammatory genes revealed hyperactivation of the inflammatory gene transcription. This is the first research to assess the negative outcomes that pyridaben could impose on dairy cattle and milk production.

Alteration in Effects of Endometriosis on Fecundity According to Pregnancy Experience in Mouse Model.

This study is aimed at identifying variations in the effect of endometriosis on fecundity in a mouse model based on prior pregnancy experience. Endometriosis is one of the most prevalent gynecological diseases and is known to impact female fecundity adversely. In this study, an endometriosis mouse model was established by allografting uterine horn tissue using Pelch's method. The effect of endometriosis on fecundity was confirmed in primiparous and multiparous female mice. As fecundity indicators, the pregnancy rate, number of litters, pregnancy period, and survival rate of the pups were investigated. As a result of the experiment, the pregnancy rate decreased, and the pregnancy period tended to be shorter in primiparous female mice. However, there was no significant change in the multiparous mice. In addition, it has been established that correlations exist between the size of lesions and certain fecundity indicators of the lesion, even among primiparous and multiparous females with endometriosis. The study attempted to demonstrate a link between pregnancy experience and fecundity changes caused by endometriosis by experimentally reproducing clinical results using mouse models. These results suggest strategies for identifying several pathophysiological characteristics of endometriosis.

Fraxetin reduces endometriotic lesions through activation of ER stress, induction of mitochondria-mediated apoptosis, and generation of ROS.

BACKGROUND: Fraxetin, a phytochemical obtained from Fraxinus rhynchophylla, is well known for its anti-inflammatory and anti-fibrotic properties. However, fraxetin regulates the progression of endometriosis, which is a benign reproductive disease that results in low quality of life and infertility. HYPOTHESIS/PURPOSE: We hypothesized that fraxetin may have therapeutic effects on endometriosis and aimed to elucidate the underlying mechanisms of mitochondrial function and tiRNA regulation. STUDY DESIGN: Endometriotic animal models and cells (End1/E6E7 and VK2/E6E7) were used to identify the mode of action of fraxetin. METHODS: An auto-implanted endometriosis animal model was established and the effects of fraxetin on lesion size reduction were analyzed. Cell-based assays including proliferation, cell cycle, migration, apoptosis, mitochondrial function, calcium efflux, and reactive oxygen species (ROS) were performed. Moreover, fraxetin signal transduction was demonstrated by western blotting and qPCR analyses. RESULTS: Fraxetin inhibited proliferation and migration by inactivating the P38/JNK/ERK mitogen-activated protein kinase (MAPK) and AKT/S6 pathways. Fraxetin dissipates mitochondrial membrane potential, downregulates oxidative phosphorylation (OXPHOS), and disrupts redox and calcium homeostasis. Moreover, it triggered endoplasmic reticulum stress and intrinsic apoptosis. Furthermore, we elucidated the functional role of tiRNAHisGTG in endometriosis by transfection with its inhibitor. Finally, we established an endometriosis mouse model and verified endometriotic lesion regression and downregulation of adhesion molecules with inflammation. CONCLUSION: This study suggests that fraxetin is a novel therapeutic agent that targets mitochondria and tiRNAs. This is the first study to demonstrate the mechanisms of tiRNAHisGTG with mitochondrial function and cell fates and can be applied as a non-hormonal method against the progression of endometriosis.

Effects of Cetrorelix on Ovary and Endometrium Prior to Anti-PD-L1 Antibody in Murine Model.

BACKGROUND: Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration. METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. RESULTS: Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. CONCLUSION: Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PD-L1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.

Bifenox compromises porcine trophectoderm and luminal epithelial cells in early pregnancy by arresting cell cycle progression and impairing mitochondrial and calcium homeostasis.

Bifenox is a widely used herbicide that contains a diphenyl ether group. However its global usage, the cell physiological effects that induce toxicity have not been elucidated. In this study, the effect of bifenox was examined in porcine trophectoderm and uterine epithelial cells to investigate the potential toxicity of the implantation process. To uncover the toxic effects of bifenox, cell viability and apoptosis following treatment with bifenox were evaluated. To investigate the underlying cellular mechanisms, mitochondrial and calcium homeostasis were investigated in both cell lines. In addition, the dysregulation of cell signal transduction and transcriptional alterations were also demonstrated. Bifenox reduced cell viability and significantly increased the number of cells arrested at the sub-G1 stage. Moreover, bifenox depolarized the mitochondrial membrane and upregulated the calcium flux into the mitochondria in both cell lines. Cytosolic calcium flux increased in porcine trophectoderm (pTr) cells and decreased in porcine luminal epithelium (pLE) cells. In addition, bifenox activated the mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways. Furthermore, bifenox inhibited the expression of retinoid receptor genes, such as RXRA, RXRB, and RXRG. Chemokine CCL8 was also downregulated at the mRNA level, whereas CCL5 expression remained unchanged. Overall, the results of this study suggest that bifenox deteriorates cell viability by arresting cell cycle progression, damaging mitochondria, and controlling calcium levels in pTr and pLE cells. The present study indicates the toxic potential of bifenox in the trophectoderm and luminal epithelial cells, which can lead to implantation disorders in early pregnancy.

Superficial temporal artery interposition bypass for the treatment of complex intracranial aneurysms: Flexible and creative options for flow preservation bypass.

PURPOSE: Flow-preservation bypass is a treatment option for complex intracranial aneurysms (IAs) that cannot be managed with microsurgical clipping or endovascular treatment. Various bypass methods are available, including interposition grafts such as the radial artery or saphenous vein. Size discrepancy, invasiveness, and procedure complexity must be considered when using interposition grafts. We describe our experience of treating complex IAs using a superficial temporal artery (STA) interposition bypass. METHODS: We retrospectively reviewed the medical records and operative videos of all patients who were treated for complex IAs at our center from January 2009 to December 2021 using cerebral revascularization. Clinical, radiological, and surgical findings of the cases that underwent STA interposition bypass were investigated. RESULTS: Seventy-six bypass procedures were performed of which seven (9.2%) complex IAs were managed using STA interposition bypass. Of these 5 cases were of anterior cerebral artery, 1 of middle cerebral artery, and 1 of posterior inferior cerebellar artery aneurysm. There were no postoperative ischemic complications. Revision surgery for postoperative pseudomeningocele was performed in one case. The long-term bypass patency rate was 85.7% (6 out of 7) and good long-term aneurysm control was achieved in all cases, with a mean follow-up of 64 months. CONCLUSIONS: When treating complex IAs, creative revascularization strategies are needed in selective cases for favorable outcomes. STA interposition graft bypass which can reduce the size discrepancy between the donor and recipient may be a less invasive, flexible, and practical option for treating complex IAs.

Deep geometric learning for intracranial aneurysm detection: towards expert rater performance.

BACKGROUND: Early detection of intracranial aneurysms (IAs) is crucial for patient outcomes. Typically identified on angiographic scans such as CT angiography (CTA) or MR angiography (MRA), the sensitivity of experts in studies on small IAs (diameter <3 mm) was moderate (64-74.1% for CTAs and 70-92.8% for MRAs), and these figures could be lower in a routine clinical setting. Recent research shows that the expert level of sensitivity might be achieved using deep learning approaches. METHODS: A large multisite dataset including 1054 MRA and 2174 CTA scans with expert IA annotations was collected. A novel modality-agnostic two-step IA detection approach was proposed. The first step used nnU-Net for segmenting vascular structures, with model training performed separately for each modality. In the second step, segmentations were converted to vascular surface that was parcellated by sampling point clouds and, using a PointNet++ model, each point was labeled as an aneurysm or vessel class. RESULTS: Quantitative validation of the test data from different sites than the training data showed that the proposed approach achieved pooled sensitivity of 85% and 90% on 157 MRA scans and 1338 CTA scans, respectively, while the sensitivity for small IAs was 72% and 83%, respectively. The corresponding number of false findings per image was low at 1.54 and 1.57, and 0.4 and 0.83 on healthy subject data. CONCLUSIONS: The proposed approach achieved a state-of-the-art balance between the sensitivity and the number of false findings, matched the expert-level sensitivity to small (and other) IAs on external data, and therefore seems fit for computer-assisted detection of IAs in a clinical setting.

Mass Effect After Flow Diversion for Unruptured Large and Giant Cavernous or Paraclinoid Internal Carotid Artery Aneurysm.

OBJECTIVE: The mass effect associated with large or giant intracranial aneurysms is difficult for traditional endovascular treatment. This study investigated whether flow diverters can relieve the aneurysmal mass effect caused by aneurysmal compression symptoms. METHODS: Fifty-five patients with unruptured large and giant intracranial aneurysms treated by a flow diverter at our institution from January 2014 to February 2022 were retrospectively evaluated. RESULTS: In this study, 53 patients were included. Initially, 27 patients (51.9%), including 10 with compressive optic neuropathy, 12 with third nerve palsy, 2 with facial hyperesthesia, and 11 with sixth nerve palsy, were symptomatic. The symptom duration was shorter in the improved group (n = 2.2 ± 4.0 vs. n = 3.1 ± 3.9, P = 0.49). Thrombus formation following the flow diversion procedure was typically observed on magnetic resonance imaging (MRI) performed immediately and was not significantly associated with symptomatic improvement (OR = 0.395; 95% CI (0.058-2.698), P = 0.343). However, symptomatic improvement was seen in most patients when the aneurysm size decreased on MRI. A reduction in the aneurysm size on the MRI at the 3-month follow-up was correlated with symptomatic improvement in the multivariate analysis (OR = 0.08, 95% CI (0.013-0.485), P < 0.05). CONCLUSIONS: A flow diverter might help alleviate compression symptoms caused by large or giant intracranial aneurysms. Shrinkage of the aneurysm within 3 months postoperatively and a shorter duration of symptoms contribute to the favorable outcomes of mass effect. Ultimately, prompt treatment is crucial for improving symptomatic intracranial artery aneurysms.

Treatment of Dural Arteriovenous Fistula with Intradural Draining Vein at the Craniocervical Junction: Case Series with Special Reference to the Anatomical Considerations.

BACKGROUND: Dural arteriovenous fistulas at the craniocervical junction (CCJ DAVFs) are a rare vascular disease. Endovascular treatment (EVT) and microsurgery are the primary treatment modalities for CCJ DAVFs. However, incomplete treatment or complications may occur after treatment because of the anatomical complexity. OBJECTIVE: We analyzed the neurosurgical treatment experiences of CCJ DAVFs to recommend suitable classification and treatment options. METHODS: CCJ DAVFs were anatomically classified into three types according to the feeding arteries and their relationships with the anterior spinal (ASAs) and lateral spinal arteries (LSAs). Type 1 was fed by the radiculomeningeal artery from the vertebral artery and was not associated with the ASA or LSA. Type 2 was fed by the radiculomeningeal artery, and the radicular artery supplied the LSA near the fistula point. Type 3 had the characteristics of type 1 or type 2 CCJ DAVFs, except the ASA also contributed to the fistula. RESULTS: There were 5, 7, and 4 cases of type 1, type 2, and type 3 CCJ DAVFs, respectively. EVT was attempted in 12 patients, of whom only 1 (type 1) was completely cured without complications. Nine cases had residual lesions after EVT, and two had spinal cord infarction due to occlusion of the LSA. Fourteen patients underwent microsurgical treatment. In all 14 cases, CCJ DAVFs were completely obliterated after microsurgery. CONCLUSION: In cases of type 1 CCJ DAVF, both microsurgical treatment and EVT may be considered. However, for type 2 and 3 CCJ DAVFs, microsurgery may be a superior treatment modality.

Aquaporin-4 Deficiency is Associated with Cognitive Impairment and Alterations in astrocyte-neuron Lactate Shuttle.

Cognitive impairment refers to notable declines in cognitive abilities including memory, language, and emotional stability leading to the inability to accomplish essential activities of daily living. Astrocytes play an important role in cognitive function, and homeostasis of the astrocyte-neuron lactate shuttle (ANLS) system is essential for maintaining cognitive functions. Aquaporin-4 (AQP-4) is a water channel expressed in astrocytes and has been shown to be associated with various brain disorders, but the direct relationship between learning, memory, and AQP-4 is unclear. We examined the relationship between AQP-4 and cognitive functions related to learning and memory. Mice with genetic deletion of AQP-4 showed significant behavioral and emotional changes including hyperactivity and instability, and impaired cognitive functions such as spatial learning and memory retention. 18 F-FDG PET imaging showed significant metabolic changes in the brains of AQP-4 knockout mice such as reductions in glucose absorption. Such metabolic changes in the brain seemed to be the direct results of changes in the expression of metabolite transporters, as the mRNA levels of multiple glucose and lactate transporters in astrocytes and neurons were significantly decreased in the cortex and hippocampus of AQP-4 knockout mice. Indeed, AQP-4 knockout mice showed significantly higher accumulation of both glucose and lactate in their brains compared with wild-type mice. Our results show that the deficiency of AQP-4 can cause problems in the metabolic function of astrocytes and lead to cognitive impairment, and that the deficiency of AQP4 in astrocyte endfeet can cause abnormalities in the ANLS system.

Quantification of motion during microvascular anastomosis simulation using machine learning hand detection.

OBJECTIVE: Microanastomosis is one of the most technically demanding and important microsurgical skills for a neurosurgeon. A hand motion detector based on machine learning tracking technology was developed and implemented for performance assessment during microvascular anastomosis simulation. METHODS: A microanastomosis motion detector was developed using a machine learning model capable of tracking 21 hand landmarks without physical sensors attached to a surgeon's hands. Anastomosis procedures were simulated using synthetic vessels, and hand motion was recorded with a microscope and external camera. Time series analysis was performed to quantify the economy, amplitude, and flow of motion using data science algorithms. Six operators with various levels of technical expertise (2 experts, 2 intermediates, and 2 novices) were compared. RESULTS: The detector recorded a mean (SD) of 27.6 (1.8) measurements per landmark per second with a 10% mean loss of tracking for both hands. During 600 seconds of simulation, the 4 nonexperts performed 26 bites in total, with a combined excess of motion of 14.3 (15.5) seconds per bite, whereas the 2 experts performed 33 bites (18 and 15 bites) with a mean (SD) combined excess of motion of 2.8 (2.3) seconds per bite for the dominant hand. In 180 seconds, the experts performed 13 bites, with mean (SD) latencies of 22.2 (4.4) and 23.4 (10.1) seconds, whereas the 2 intermediate operators performed a total of 9 bites with mean (SD) latencies of 31.5 (7.1) and 34.4 (22.1) seconds per bite. CONCLUSIONS: A hand motion detector based on machine learning technology allows the identification of gross and fine movements performed during microanastomosis. Economy, amplitude, and flow of motion were measured using time series data analysis. Technical expertise could be inferred from such quantitative performance analysis.

Clipping of Unruptured Anterior Choroidal Artery Aneurysms Together with Small Branches: Safety Confirmation Using Intraoperative Indocyanine Green Video-Angiography and Intraoperative Neurophysiological Monitoring.

BACKGROUND: In treating anterior choroidal artery (AChA) aneurysms, preserving the AChA main trunk is of course necessary to prevent postoperative ischemic complications. However, in practice, complete occlusions are often limited by small branches. OBJECTIVE: We aimed to demonstrate that even in cases where complete occlusion of the AChA aneurysm is complex due to small branches, complete occlusion can be safely achieved using indocyanine green video-angiography and intraoperative neurophysiological monitoring (IONM). METHODS: We performed a retrospective review of all unruptured AChA aneurysms surgically treated at our institution from 2012 to 2021. All available surgical videos were reviewed to find AChA aneurysms clipped with small branches; clinical and radiological data were collected for these cases. RESULTS: Among 391 cases of unruptured AChA aneurysms treated surgically, 25 AChA aneurysms were clipped with small branches. AChA-related ischemic complications occurred in 2 cases (8%) without retrograde indocyanine green filling to the branches. These 2 cases had changes in IONM. There were no ischemic complications in the remaining cases with retrograde indocyanine green filling to the branches and no change in IONM. During an average follow-up of 47 months (12-111 months), a small residual neck was observed in 3 cases (12%) and recurrence or progression of the aneurysm was observed in only 1 case (4%). CONCLUSIONS: The surgical treatment of AChA aneurysms carries the risk of devastating ischemic complications. Even in cases where complete clip ligation seems impossible due to small branches associated with AChA aneurysms, complete occlusion can be safely achieved using indocyanine green video-angiography and IONM.

Efficacy of Acetylcysteine and Selenium in Aneurysmal Subarachnoid Hemorrhage Patients: A Prospective, Multicenter, Single Blind Randomized Controlled Trial.

BACKGROUND: Subarachnoid hemorrhage (SAH) patients have oxidative stress results in inflammation, tissue degeneration and neuronal damage. These deleterious effects cause aggravation of the perihematomal edema (PHE), vasospasm, and even hydrocephalus. We hypothesized that antioxidants may have a neuroprotective role in acute aneurysmal SAH (aSAH) patients. METHODS: We conducted a prospective, multicenter randomized (single blind) trial between January 2017 and October 2019, investigating whether antioxidants (acetylcysteine and selenium) have the potential to improve the neurologic outcome in aSAH patients. The antioxidant patient group received antioxidants of acetylcysteine (2,000 mg/day) and selenium (1,600 µg/day) intravenously (IV) for 14 days. These drugs were administrated within 24 hours of admission. The non-antioxidant patient group received a placebo IV. RESULTS: In total, 293 patients were enrolled with 103 patients remaining after applying the inclusion and exclusion criteria. No significant differences were observed in the baseline characteristics between the antioxidant (n = 53) and non-antioxidant (n = 50) groups. Among clinical factors, the duration of intensive care unit (ICU) stay was significantly shortened in patients who received antioxidants (11.2, 95% confidence interval [CI], 9.7-14.5 vs. 8.3, 95% CI, 6.2-10.2 days, P = 0.008). However, no beneficial effects were observed on radiological outcomes. CONCLUSION: In conclusion, antioxidant treatment failed to show the reduction of PHE volume, mid-line shifting, vasospasm and hydrocephalus in acute SAH patients. A significant reduction in ICU stay was observed but need more optimal dosing schedule and precise outcome targets are required to clarify the clinical impacts of antioxidants in these patients. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004628.