Peripheral nerve injury (PNI) regeneration involves complex immunoregulatory mechanisms, particularly M2 macrophage‑mediated immunomodulation. Promoting macrophage polarization toward the M2 phenotype represents a potential therapeutic strategy. Exosomes can create favorable microenvironments for tissue regeneration, but their clinical application is often limited by low concentration and purity. Three‑dimensional‑bioprinted exosomes (3D‑Exos) have recently gained attention due to their enhanced concentration and purity. In this study, 3D‑Exos were applied to treat PNI. The regenerative effects of 3D‑Exos were compared with conventionally produced exosomes (2D‑Exos) in vivo. In vitro experiments, RNA sequencing, and miRNA microarray analyses were performed to investigate the underlying mechanisms. The mechanism was further validated in vitro and in vivo. 3D‑Exos significantly enhanced nerve regeneration after PNI and outperformed 2D‑Exos. In vitro studies revealed that 3D‑Exos promoted macrophages polarization toward the M2 macrophages. RNA sequencing indicated that the PI3K/AKT pathway was activated by 3D‑Exos, and miRNA microarray analysis identified miR‑26b‑5p within 3D‑Exos as the key mediator targeting PTEN to activate PI3K/AKT signaling. Subsequently, M2 macrophages facilitated Schwann cell migration, elongation, and myelination, thereby accelerating nerve regeneration. Inhibition of the PI3K/AKT signaling pathway abolished the therapeutic effects of 3D-Exos on nerve regeneration after PNI. This study elucidates a novel mechanism by which 3D‑Exos promote nerve regeneration through reprogramming macrophages polarization via the PI3K/AKT pathway. The work establishes a paradigm‑shifting therapeutic framework that integrates 3D-Exos with immunomodulatory strategies for the treatment of PNI. First demonstration of 3D-Exos as a high-concentration, high-purity therapeutic way to overcome limitations of conventional exosomes applications for PNI. Mechanistic insight into macrophages reprogramming: 3D-Exos drives macrophages polarize into M2 phenotype via PI3K/AKT signaling pathway, fostering an conducive microenvironment critical for SCs myelination, and nerve regeneration. Paradigm-shifting therapeutic framework: Integrates 3D-Exos technology with immunomodulation, establishing a novel crosstalk axis between extracellular vesicles, macrophages, and SCs for functional PNI rehabilitation.
AIMS:This study aimed to investigate the specific mechanism by which angiopoietin-2 (ANGPT2)/Tie2 signaling in macrophages promotes endothelial cell (EC) proliferation in the chronically ischaemic brain (CIB). METHODS:We first analyzed the polarization status of primary Tie2-expressing macrophages (TEMs) and Tie2-overexpressing THP-1-derived macrophages (Tie2-TDMs) following ANGPT2 treatment and detected the expression of representative proangiogenic factors. Subsequently, lysine lactylation (Kla) levels were measured, and chromatin immunoprecipitation (ChIP) assays were performed to explore the downstream activity of ANGPT2/Tie2 signaling. Additionally, in vitro functional assays using human umbilical vein endothelial cells (HUVECs) and in vivo experiments in a rat model of chronic cerebral ischaemia were conducted to confirm the effect of ANGPT2/Tie2-regulated macrophages on angiogenesis. RESULTS:In response to ANGPT2 treatment, the expression of M2 polarization markers and proangiogenic factors increased in TEMs and Tie2-TDMs. Concurrently, LDHA and H3K18la were elevated, and ChIP assays confirmed the regulatory role of ANGPT2/Tie2 signaling in H3K18la-mediated transcriptional regulation. The viability of HUVECs cocultured with Tie2-TDMs was increased. Finally, ANGPT2 overexpression increased M2-polarized TEM infiltration in the CIB; additionally, rats injected with ANGPT2-pretreated TEMs exhibited more prominent EC proliferation. CONCLUSION:ANGPT2/Tie2 induces the H3K18la-mediated M2 polarization of macrophages to facilitate EC proliferation and angiogenesis in the CIB.
Peripheral nerve injury (PNI) is a intractable disease with poor treatment efficacy, it's suggested that ferroptosis is closely related to the occurrence and development of PNI, but more in-depth studies are needed. Puerarin (Pu), an antioxidant from kudzu root, may mitigate PNI, but its mechanism remains unclear. Here, we investigated Pu's role in PNI based on in vivo and in vitro experiments. We found that Pu could promote nerve regeneration after PNI, then we simulated PNI with the classical oxygen-glucose deprivation (OGD) cell injury model to explore the potential mechanism. The RNA sequencing revealed that Pu attenuated OGD-induced injury via ACSL4-dependent ferroptosis, and the molecular docking showed that Pu competitively binds to the ACSL4 active site of arachidonic acid, and the dynamics simulation suggested that the Leu468 and Thr469 were the main sites that Pu binds to ACSL4. Which were further demonstrated by cellular thermal shift assays, microscale thermophoresis, and pull-down assays. Then, in vivo and in vitro assays showed Pu treatment improved nerve morphology, function, and electrophysiology by inhibiting ACSL4-dependent ferroptosis. What's more, loss-of-function study further validated ACSL4's essential role in Pu's neuroprotective effects. In summary, our study demonstrates the role of Pu in promoting PNI recovery via ACSL4-dependent ferroptosis, thus identifying a promising therapeutic strategy for ferroptosis-related diseases.
Objectives:This study aimed to evaluate the effect of the co-administration of metoclopramide and probiotics on enteral feeding tolerance in mechanically ventilated patients after cranial surgery. Methods:From January 2023 to December 2024, a total of 88 patients presenting with acute brain injury and treated by craniocerebral surgery were screened. Of these, 32 were excluded and 56 patients were enrolled and assigned to either the intervention group (n = 32) or the control group (n = 24). Enteral nutrition was initiated within 24 h following nasogastric tube placement. The intervention group received a combined regimen of metoclopramide and probiotics for 3-7 days in addition to the standard enteral nutrition protocol. Feeding complications and functional outcomes were compared between the two groups. Results:Compared to the control group, the intervention group exhibited a statistically significant reduction in total gastric residual volume (GRV) during the first 3 days of gastric tube feeding (103.1 ± 47.8 ml versus 756.3 ± 137.1 ml, P < 0.05). The intervention group demonstrated a significant reduction in vomiting and diarrhea incidence within 7 days (3.1% versus 20.8%; 6.3% versus 25%, all P < 0.05), higher serum albumin levels at 2 weeks (33.1 ± 1.5 g/L versus 31.8 ± 1.5 g/L, P < 0.05), and a shorter hospital stay (17.8 ± 4.1 days versus 23.7 ± 5.1 days, P < 0.05). However, the groups did not differ significantly in 3-month postoperative modified Rankin Scale (mRS) scores (4.2 ± 0.8 versus 4.3 ± 1.0, P > 0.05). Conclusion:The co-administration of metoclopramide and probiotics significantly reduced gastrointestinal intolerance such as gastric retention, vomiting, and diarrhea in mechanically ventilated patients following craniocerebral surgery.
BACKGROUND:Paediatric hemorrhagic moyamoya disease (hMMD) is rare, with unclear clinical features and long-term outcomes owing to limited data. We comprehensively evaluated the clinical characteristics, prognosis and optimal treatment strategies for pediatric hMMD. METHODS:We screened paediatric patients with hMMD hospitalised between November 2003 and December 2024. Clinical features, treatments and long-term outcomes were retrospectively analysed. Multivariate logistic regression was used to evaluate risk factors for rebleeding and poor prognosis. RESULTS:During the first decade, hemorrhagic events were rare. However, in the second decade, females experienced hemorrhage at age 13-15 years and males at 10-12 years. Over 1103 patient-years, 96 hemorrhagic events occurred. Before encephaloduroarteriosynangiosis (EDAS), seven rehemorrhage instances occurred among 94 patients over 93.2 patient-years of observation. A modified Rankin Scale score ≥3 on admission independently predicted rehemorrhage (p=0.040; OR 5.280; 95% CI 1.083 to 25.739), while early EDAS (within 3 months of the first hemorrhage) significantly reduced this risk (p=0.043; OR 0.107; 95% CI 0.012 to 0.933). EDAS patients had lower rehemorrhage rates compared with their natural history. Anterior choroidal artery dilation and early-onset and delayed-onset posterior cerebral artery involvement increased postoperative complication risk. Early EDAS reduced postoperative complications (p=0.028; OR 0.219; 95% CI 0.057 to 0.845). CONCLUSION:Although rare, paediatric hMMD carries a high rebleeding rate. The second decade of life may represent the peak period for bleeding in paediatric patients with MMD, necessitating close monitoring. Early EDAS reduces rebleeding and postoperative complications in hMMD. Compared with the natural course, EDAS safely reduces paediatric rehemorrhage.
Peripheral nerve injury (PNI) disrupts nerve function, there has been increasing focus on the role of macrophages in PNI. This study provides a comprehensive analysis of research trends and key topics related to macrophages in the field of PNI. We conducted a search in the Web of Science Core Collection database for studies published between 2000 and 2023 using "macrophages" and "PNI" as keywords. Bibliometric analysis was performed using visualization tools, including VOSviewer, CiteSpace, and GraphPad Prism 8, and others. As of December 31, 2023, a total of 905 relevant publications were identified. In terms of author contributions, Japanese researchers Kiguchi Norikazu and Kishioka Shiroh shared the highest number of publications, each with 15 articles. In terms of journals, Experimental Neurology published the most articles, while the University of Würzburg in Germany emerged as the leading institution in this field, with the highest publication output. Among the 51 countries involved in this research, the United States ranked first, followed by China. The keyword 'exosomes' first appeared in 2021, making it the most recent keyword. Cluster analysis categorized the keywords into four main groups: the role of macrophages in Wallerian degeneration, the role of macrophages in pathological peripheral neuropathic pain, macrophage-derived products after PNI, and role of macrophages in PNI repair and strategies for modulating their function using biomaterials. Macrophages are increasingly crucial in PNI research, and future studies integrating novel approaches may yield innovative therapies for nerve repair.
OBJECTIVE:To compare the postoperative incisional cerebrospinal fluid (CSF) leak rates of closed spinal dysraphism (SD) and identify significant predictors in different age groups. METHODS:We retrospectively collected the data of patients who underwent surgeries of closed SD at our hospital between January 2017 and December 2022. Patients were grouped based on age as preschool children, school children, adolescents, and adults. Pearson's χ2 test, Fisher's exact test, and logistic regression were used to analyze 18 possible predictors of postoperative incisional CSF leak. RESULTS:This retrospective cohort study totally included 1226 patients. Incisional CSF leak rates differed significantly among 4 groups (χ2 = 38.739, P < 0.001) and between preschool children and school children (P = 0.025), adolescents (P < 0.001), and adults (P < 0.001), respectively. Dangerous factor in preschool children was spinal dural repair with a dural substitute (odds ratio [OR] = 21.734, P = 0.038) and surgical site infection (OR = 87.426, P = 0.001), in adolescents was scoliosis/kyphosis (OR = 7.849, P = 0.043), and in adults was wound infection (OR = 8.805, P = 0.016). Using synthetic bone substitute (OR = 0.160, P = 0.049) was protective for school children. CONCLUSIONS:Different age groups show distinct rates and predictors of postoperative incisional CSF leak of closed SD. Realizing and managing the predictors in different ages contributes to reducing postoperative incisional CSF leak and improving surgical outcomes.
Objective:To evaluate the efficacy and safety of flow diverter (FD) devices in the treatment of basilar artery aneurysms, and to assess their clinical outcomes and associated complications. Methods:A retrospective analysis was conducted on 30 patients with basilar artery aneurysms treated with FD devices at our institution between 2020 and 2024. Patient demographics, aneurysm characteristics, intraoperative and postoperative imaging, and clinical follow-up data were collected. Statistical analysis was performed to assess treatment efficacy and complication rates. Results:Among the 30 patients, 20 were male (66.7%) and 10 were female (33.3%), with a median age group of 65-69 years. The majority of aneurysms were located in the basilar artery trunk (70%), while 30% were basilar apex aneurysms. All procedures were technically successful (success rate: 100%). The mean aneurysm diameter was 10.6 ± 4.9 mm. The mean follow-up period was 12.9 months. Imaging follow-up demonstrated a complete or near-complete aneurysm occlusion rate of 86.7%; occlusion rates for the Tubridge and Pipeline Flex devices were 83.3 and 88.9%, respectively, with no statistically significant difference between the two devices (p > 0.05). Treatment-related complications occurred in 4 cases (13.3%), all presenting as transient ischemic symptoms, with no cases of permanent severe neurological deficits. 93.3% of patients (28/30) achieved an excellent functional outcome (mRS score of 0-1), and all patients (100%) had a functional outcome of mRS 0-2. Conclusion:In this retrospective cohort, FD treatment for basilar artery aneurysms was associated with a high rate of complete or near-complete occlusion (86.7%) and a favorable safety profile, as evidenced by the low rate of complications (13.3%, all transient). The clinical outcomes were excellent, with 93.3% of patients achieving an mRS of 0-1. The Tubridge and Pipeline devices demonstrated comparable efficacy and safety outcomes in this study, although the small sample size and non-randomized design preclude definitive conclusions regarding superiority or equivalence. Our findings indicate that rigorous preoperative antiplatelet management and meticulous operative technique are critical for these results. This study supports the consideration of FDs for BAAs in carefully selected patients, but further large-scale, prospective studies are warranted to confirm long-term durability and optimize patient selection.
Approximately half of patients with chronic ischemic cerebrovascular disease (CICD) exhibit poor revascularization. Metallothionein 2 A (MT2A) has a high affinity for metal ions and is potentially capable of chelating toxic copper ions to alleviate the impairment of angiogenesis. Therefore, we hypothesized that MT2A could promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions during copper overload (CPO). We first collected dura matter (DM) samples from CICD patients and examined the expression of cuproptosis-related genes (DLAT, FDX1, and SDHB) to confirm the inhibitory effect of CPO on angiogenesis. Then, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of elesclomol and CuCl2 to determine the optimal concentration for inducing CPO. HUVEC activity and mitochondrial structure and function were detected to explore the ability of MT2A to alleviate CPO-induced damage. Finally, a rat model of 2-vessel occlusion plus encephalo-myo-synangiosis (2VO + EMS) with CPO was established to test the proangiogenic effect of MT2A through the copper–mitochondria regulatory mechanism in chronically ischemic brains. Compared with those from Matsushima grade A patients, DM samples from Matsushima grade C patients presented significantly greater DLAT and FDX1 expression and significantly lower SDHB expression. The optimal drug concentration for inducing CPO was subsequently determined, and in vitro experiments revealed that HUVEC activity was significantly decreased in the CPO group under hypoxic culture, accompanied by increased DLAT oligomerization, decreased SDHB expression, increased HSP70 expression. Moreover, significantly more common mitochondrial aberrations and significantly lower mitochondrial activity were detected in the CPO group compare with the control group. Additionally, MT2A overexpression alleviated CPO-induced mitochondrial dysfunction and cytotoxicity, improving HUVEC viability. In vivo, a CPO rat model was established, and CPO inhibited cerebral angiogenesis in 2VO + EMS model rats. Moreover, significantly greater CD31 expression, less DLAT accumulation, more mitochondria, and fewer mitochondrial abnormalities were observed in the CPOMT2A+ group than in the CPO group, accompanied by significantly improved cerebral blood perfusion and cognitive function. MT2A can promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions and rescuing CPO-induced mitochondrial dysfunction.
Background: Intracranial atherosclerotic stenosis (ICAS) is a leading cause of ischemic stroke, particularly in the anterior circulation. Understanding the underlying stroke mechanisms is essential for guiding personalized treatment strategies. This study proposes an integrated framework that combines CT perfusion imaging, vascular anatomical features, computational fluid dynamics (CFD), and machine learning to classify stroke mechanisms based on the Chinese Ischemic Stroke Subclassification (CISS) system. Methods: A retrospective analysis was conducted on 118 patients with intracranial atherosclerotic stenosis. Key indicators were selected using one-way ANOVA with nested cross-validation and visualized through correlation heatmaps. Optimal thresholds were identified using decision trees. The classification performance of six machine learning models was evaluated using ROC and PR curves. Results: Time to Maximum (Tmax) > 4.0 s, wall shear stress ratio (WSSR), pressure ratio, and percent area stenosis were identified as the most predictive indicators. Thresholds such as Tmax > 4.0 s = 134.0 mL and WSSR = 86.51 effectively distinguished stroke subtypes. The Logistic Regression model demonstrated the best performance (AUC = 0.91, AP = 0.85), followed by Naive Bayes models. Conclusions: This multimodal approach effectively differentiates stroke mechanisms in anterior circulation ICAS and holds promise for supporting more precise diagnosis and personalized treatment in clinical practice.
BACKGROUND AND OBJECTIVES:Although plenty of evidence supports the effectiveness of sacral neuromodulation (SNM) in improving urination and defecation, few studies concerned its effect on the patients with spinal dysraphism (SD). This study aimed to evaluate the effects of SNM on SD-induced neurogenic bladder and bowel dysfunction. METHODS:We prospectively followed the patients with SD who underwent SNM in our department from May 2019 to June 2024. Fusion images of sacrococcygeal computed tomography and magnetic resonance sacral plexus nerve images were used as essential references for preoperative evaluation and intraoperative implantation. Patient's subjective improvement by ≥50% from baseline was defined as implantation procedure success. Among the included patients, urodynamics, urinary ultrasonography, daily urination frequency, daily urine leakage, and neurogenic bowel dysfunction score were compared before and after SNM and between unilateral and bilateral SNM. RESULTS:A total of 44 patients were included, of whom 97.73% reported improved symptoms and 47.73% achieved implantation procedure success. SNM significantly improved the average postvoid residual volume, maximum cystometric capacity, bladder compliance, daily urination frequency, daily urine leakage, and neurogenic bowel dysfunction score. We found a significantly higher success rate in the patients stimulated bilaterally compared with those stimulated unilaterally but no intergroup differences against age (between minors and adults), sex, lower urinary tract symptoms, and intestinal symptoms. Bilateral SNM performed significantly better in improving postvoid residual volume, daily urination frequency, and daily urine leakage than unilateral SNM. No SNM-related complications were reported during follow-up. CONCLUSION:SNM can improve urination and defecation in the patients with SD safely and effectively. We strongly recommend fusion imaging of sacrococcygeal computed tomography and magnetic resonance sacral plexus imaging as a valuable and promising technique for preoperative evaluation and intraoperative implantation. A flexible implantation strategy involving electrode location and number helps achieve ideal modulation effects in the patients with SD.
BACKGROUND:The optimal management of symptomatic vertebral artery in-stent restenosis or occlusion (SVISRO) after stent-assisted angioplasty (SAA) at the vertebral artery origin remains unclear. This study aimed to investigate the efficacy of vertebral artery reconstruction surgery (VRS) surgery among SVISRO patients. METHODS:A retrospective study was conducted to analyze the clinical data for SVISRO patients admitted to the Third Affiliated Hospital of Sun Yat-sen University between May 2011 and November 2021. The stroke recurrence and stroke-free rates during the follow-up (FU) period and the patients' neurological statuses at the last FU were compared between a VRS group and an intensive medical therapy (IMT) group. RESULTS:Sixty-two SVISRO patients with an average age of 60.1 ± 8.3 years and an average FU duration of 67.6 ± 32.5 months were studied. The VRS group had significantly fewer stroke recurrences than the IMT group did (5.7% vs. 25.9%, p = 0.034). A 154-month stroke-free rate of 73.8% (95% CI, 24.5% to 93.7%) was observed in the VRS group, whereas the IMT group had a stroke-free rate of 33.9% (95% CI, 17.3% to 75.0%). The hazard ratio (log-rank) between the two groups was 0.234 (95% CI, 0.063-0.871; p = 0.048). The modified Rankin scale score for the VRS group was significantly better than that for the IMT group at the final FU (p = 0.032). CONCLUSIONS:In patients with SVISRO secondary to SAA, VRS targeting the extracranial vertebral artery (V1-V2) appears to reduce stroke recurrence, increase the stroke-free rate and improve neurological status.
Postoperative collateral formation (PCF) in patients with moyamoya disease (MMD) who underwent Encephaloduroarteriosynangiosis (EDAS) is often used as an index to evaluate the effectiveness of surgery. However, it has not been studied whether PCF can predict long-term outcomes in MMD patients. Our study aimed to determine the relationship between PCF and long-term prognosis and stroke events in adult patients with MMD. The authors reviewed 246 hemispheres of 123 patients who underwent EDAS surgery at our hospital between January 2017 and December 2018. Multivariate logistic regression analysis showed that poor PCF (OR 4.094, 95
Endothelial cell glycolysis plays a novel and significant role in Schwann cells and peripheral nerve injury repair, which represents an emerging and important area of research. Glycolysis in endothelial cells is a conserved and tightly regulated biological process that provides essential energy (ATP) and intermediates by ultimately converting glucose into lactate. This metabolic pathway is crucial for maintaining the normal function of endothelial cells. During peripheral nerve injury repair, endothelial cell glycolysis influences the function of Schwann cells and the efficiency of nerve regeneration. Beyond glycolysis, endothelial cells also secrete various factors, including growth factors and extracellular vesicles, which further modulate Schwann cell activity and contribute to the repair process. This review will summarize the role of endothelial cell glycolysis in Schwann cell function and peripheral nerve injury repair, aiming to provide new insights for the development of novel strategies for peripheral nerve injury treatment.
The triglyceride-glucose (TyG) index is related to various cardiovascular diseases, but its relationship with stroke and all-cause mortality (ACM) in individuals with coronary artery disease (CAD) is still not well understood. This research sought to analyze the interaction between the TyG index and the occurrence of stroke and ACM in CAD participants. The dataset was derived from the National Health and Nutrition Examination Survey (NHANES), with 809 CAD patients included from 1999 to 2018. TyG index was determined by ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Findings showed that heightened TyG index values were markedly associated with a greater risk of stroke; a U-shaped interconnection was detected between the TyG index and stroke risk, with the threshold at 8.14. Individuals with a TyG index exceeding this threshold exhibited a markedly higher rate of stroke occurrence. Additionally, a J-shaped correlation was observed between the TyG index and ACM, with the threshold at 9.25, above which the risk of death increased. These findings indicate that the TyG index could act as a practical indicator for predicting stroke and ACM among CAD patients, particularly when considering threshold values.
This study aimed to develop and validate a nomogram model for predicting cerebral infarction risk after superficial temporal artery–middle cerebral artery (STA-MCA) bypass in patients with intracranial atherosclerotic stenosis (ICAS). Patients with ICAS who received STA-MCA bypass were enrolled in this study. The independent risk factors for post bypass infarction were identified using univariate and multivariate logistic regression analyses. A nomogram model was developed and subsequently evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Eventually, 316 patients with ICAS were included in the study. Diabetes, smoking, and high triglyceride and total cholesterol levels were identified as the independent risk factors, and a nomogram model was developed. The model achieved areas under the curve (AUCs) of 0.88 (95
OBJECTIVE:In adult patients with moyamoya disease (MMD), insufficient postoperative collateral formation is usually seen after combined bypass surgery. The arachnoid membrane, a critical anatomical barrier between extracranial and intracranial vascular systems, has an unclear role in postoperative angiogenesis. The aim of this study was to investigate whether intraoperative arachnoid membrane opening enhances angiogenesis in adult patients undergoing combined bypass surgery for MMD. METHODS:This multicenter, prospective, randomized controlled trial (Membrane Opening to Promote Angiogenesis in Adult MMD [MOPOAM]) was conducted across 8 institutions in China. Between June 2022 and August 2023, 104 patients diagnosed with MMD through digital subtraction angiography were randomly assigned to two groups: one group underwent arachnoid opening (n = 51), while the other group had arachnoid preservation (n = 53). The primary endpoint was the rate of good angiogenesis (Matsushima grade A and B) assessed 6-12 months postoperatively, and the secondary endpoint was the incidence of surgical complications within 1 month postsurgery. RESULTS:All 104 patients completed the study. The rate of good angiogenesis was 54.9% in the arachnoid opening group and 64.2% in the arachnoid preservation group, with no significant difference between groups (OR 1.470, 95% CI 0.669-3.229; p = 0.337). Postoperative complications were observed in 2 patients (3.9%) in the arachnoid opening group and in 5 patients (9.4%) in the arachnoid preservation group, showing no significant difference (OR 2.552, 95% CI, 0.472-13.796; p = 0.276). No significant association between arachnoid opening procedures and functional recovery (assessed by modified Rankin Scale scores) was found during the 6- to 12-month follow-up period (p = 0.831). CONCLUSIONS:In adults with MMD, arachnoid membrane opening during combined bypass surgery did not significantly improve postoperative angiogenesis rates or increase perioperative complications.
BACKGROUND Intracranial aneurysms (IAs) coexisting with chronic-phase cerebral infarction (CI) present unique therapeutic challenges. Antiplatelet therapy for infarction increases bleeding risks during aneurysm treatment, whereas delayed intervention may raise rupture risks. Flow diverters (FDs) have transformed IA management, but evidence regarding their safety and efficacy in patients with concomitant chronic CI remains scarce. CASE REPORT A 56-year-old man presented with slurred speech and right-sided weakness caused by subacute CI in the left basal ganglia. Imaging identified a small, unruptured IA (2.50×1.74×1.54 mm) in the left internal carotid artery ophthalmic segment. The aneurysm was asymptomatic, without corresponding neurological deficits or headaches. Dual antiplatelet therapy (DAPT: aspirin 100 mg/day and clopidogrel 75 mg/day) and atorvastatin (20 mg/day) were initiated on Day 1. By Day 25 (chronic infarction phase, ≥21 days post-onset, with stabilized neurological symptoms), an FD (Pipeline™ Flex, 4.25×16 mm; Medtronic, USA) was implanted. Postoperatively, DAPT was maintained for 6 months to mitigate FD-related thromboembolic risk and prevent CI recurrence, after which single antiplatelet therapy (aspirin 100 mg/day) was continued. Follow-up at 12 and 36 months demonstrated complete aneurysm obliteration and full recovery of motor and speech functions without recurrent ischemia or hemorrhage. CONCLUSIONS FD implantation was safely performed and resulted in favorable outcomes for an unruptured IA in a patient with chronic-phase CI. Appropriate timing during the chronic phase and individualized antiplatelet management appeared to balance infarction control and aneurysm occlusion. Further research is warranted to determine broader applicability of these findings.