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Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their proposed mechanism of action and possible adverse effects, and included information in this review on epidural infusion, sympathetic ganglion block, sympathectomy, pulsed radiofrequency, spinal cord stimulation, dorsal root ganglion stimulation, brain stimulation, transcranial magnetic stimulation, and botulinum toxin injections. Both successful and unsuccessful outcomes have been reported. Although these procedural interventions extend the therapeutic options for erythromelalgia, the evidence for their use is limited. Case reports and small case series comprise most of the evidence. Based on our review, a multidisciplinary approach to management may be needed for patients with erythromelalgia. [ABSTRACT FROM AUTHOR]

Surgery is the mainstay of stroke prevention in patients with symptomatic moyamoya disease (MMD). We present the results of a single-center retrospective study of indirect revascularization surgery for adult MMD, emphasizing angiographic outcomes, including dilation of the superficial temporal artery and formation of new collaterals. A prospectively maintained database of procedures performed for MMD was reviewed. Adult patients treated with indirect revascularization and with long-term angiographic follow-up were included. Preoperative and postoperative angiographic images and baseline and procedural characteristics were analyzed. A Wilcoxon signed-rank test was used to test the hypothesis that the superficial temporal artery increases in diameter postoperatively. We identified 40 hemispheres in 27 patients, of which 35 had a sufficient angiographic follow-up. Bilateral procedures were performed on 16 patients. Most patients were female (72.5%), with a median age of 43 years old. The most common clinical presentation was ischemic stroke in 59.3% of cases. All patients underwent an encephaloduroarteriosynangiosis for treatment. A follow-up angiogram was performed at a median of 13.8 months postoperatively, showing superficial temporal artery (STA)-derived collaterals in 71.4% and collateral ingrowth via the burr holes in 61.8% of cases. Disease progression was evident in 34.3% of hemispheres. The normalized STA diameter was significantly increased postoperatively (2.4 to 3 mm; P < 0.05). A univariate analysis revealed that transdural collaterals and hyperlipidemia may affect collateral ingrowth from the STA, and no other patient- or procedure-related factors, including replacement of the bone flap, impacted on this. A significant increase in STA diameter on follow-up angiography after encephaloduroarteriosynangiosis was found; however, this was not directly associated with STA collateral development. Rates of postoperative transient ischemic attacks were low, and no patients had a new ischemic or hemorrhagic stroke at last follow-up. The presence of transdural collaterals and the absence of hyperlipidemia were associated with STA collateral development on follow-up angiography, but the causality of this finding is unclear. [ABSTRACT FROM AUTHOR]

Looking back at the various advancements in the field of laser and aesthetics in 2023, it can be observed that an increasing number of clinical studies from China are emerging. These changes and developments have been a significant driving force for clinical research in international laser and aesthetics, especially in terms of clinical data and conclusions among Asians, who make up more than 60% of the global population. They also provide opportunities for the development of domestic laser equipment. Laser therapy has shown certain advantages in the treatment of superficial skin diseases and aesthetics, facial rejuvenation and hair removal, pigmentary diseases and tattoos, vascular diseases, superficial tumors, and skin tags. The author has conducted a basic screening and evaluation of the progress in various aspects of the laser field, aiming to provide clinical evidence for current treatment methods. [ABSTRACT FROM AUTHOR]

Training in anastomosis is fundamental in neurosurgery due to the precision and dexterity required. Biological models, although realistic, present limitations such as availability, ethical concerns, and the risk of biological contamination. Synthetic models, on the other hand, offer durability and standardized conditions, although they sometimes lack anatomical realism. This study aims to evaluate and compare the efficiency of anastomosis training models in the intra-extracranial cerebral bypass procedure, identifying those characteristics that enhance optimal microsurgical skill development and participant experience. A neurosurgery workshop was held from March 2024 to June 2024 with 5 vascular techniques and the participation of 22 surgeons. The models tested were the human placenta, the Wistar rat, the chicken wing artery, the nasogastric feeding tube, and the UpSurgeOn Mycro simulator. The scales used to measure these models were the Main Characteristics Score and the Evaluation Score. These scores allowed us to measure, qualitatively and quantitatively, durability, anatomical similarity, variety of simulation scenarios, risk of biological contamination, ethical considerations and disadvantages with specific infrastructure. The human placenta model, Wistar rat model, and UpSurgeOn model were identified as the most effective for training. The human placenta and Wistar rat models were highly regarded for anatomical realism, while the UpSurgeOn model excelled in durability and advanced simulation scenarios. Ethical and cost implications were also considered. The study identifies the human placenta and UpSurgeOn models as optimal for training in intra-extracranial bypass procedures, emphasizing the need for diverse and effective training models in neurosurgery. [ABSTRACT FROM AUTHOR]

Acute rupture and hemorrhage of pediatric brain arteriovenous malformations (AVMs) may lead to cerebral herniation or intractable intracranial hypertension, necessitating emerging surgical interventions to alleviate intracranial pressure. However, there is still controversy regarding the timing of treatment for ruptured AVMs. This study aimed to assess the feasibility of utilizing three-pillar expansive craniotomy (3PEC) at different times during the treatment of pediatric ruptured supratentorial AVMs. A retrospective analysis was conducted on all consecutive cases of acute rupture in supratentorial AVM children who underwent 3PEC at a single institution from 2020 to 2022. General information, clinical characteristics, radiological data, and prognosis were reviewed and analyzed. Thirteen children were included in the analysis. The intracranial pressure of all patients decreased to below 15 mmHg within 10 days. The expansion volume of the cranial cavity of the patients increased by 18.3 cm3 (95% confidence interval, 10.2–26.3; P < 0.001) compared to the hematoma volume. None of the patients required decompressive craniectomy due to intractable intracranial hypertension caused by cerebral swelling. The median waiting period for patients with delayed AVMs treatment was 8 days, during which no rebleeding occurred. Emergency intervention with 3PEC in children experiencing acutely ruptured supratentorial AVMs appears to be feasible. For children requiring delayed management of the AVMs, 3PEC may diminish the risk of rebleeding during the waiting period and shorten the waiting period. [ABSTRACT FROM AUTHOR]

Martorell hypertensive ulcer (MHU) represents a painful, difficult-to-handle condition associated with peri-pheral, subcutaneous arteriolosclerosis caused by chronic hypertensive disease. Betablockers are effective for and widely used to treat hypertensive disease but are reported to exacerbate peripheral vasoconstriction. The effect of betablockers on pre-existing arteriolosclerosis and the course of MHU is, however, unknown. A retrospective study to assess the effect of betablockers on the course and response to treatment of MHU was conducted. Clinical and histopathological data were collected of patients treated for MHU at the authors’ institution between 2014 and 2023 and a side-by-side comparison was performed of patients taking betablockers or not. Analysis focused on MHU severity at presentation, analgesic use, response to therapeutic intervention, and alterations of cutaneous arterioles. The study reports significantly larger ulcers and more frequent use of opioids in patients taking betablockers, while no significant difference was observed in terms of MHU response to treatment. Significantly increased luminal obstruction of peripheral cutaneous arterioles was found in patients taking beta-blockers. Based on these data, betablockers may have a negative effect on the course of MHU and should be carefully assessed in patients with MHU.

Introduction: Reactive angioendotheliomatosis (RAE) is a rare, benign, angioproliferative disorder with poorly understood aetiopathogenesis. It is characterised by vascular occlusion that occurs in patients with coexistent systemic or autoimmune disease. Case Presentation: A 60-year-old female presented with an 8-week history of a painful, non-healing, and non-traumatic ulcer on the left thigh. Her past medical history included smoking, peripheral vascular disease (PVD) and previously treated rectal squamous cell carcinoma. The diagnosis of pyoderma gangrenosum with superimposed cellulitis was considered and treatment with oral antibiotics was initiated. Following failure to improve, a biopsy was undertaken leading to the diagnosis of RAE. The patient was referred for urgent consideration of surgical correction of PVD, but was deemed unsuitable for surgical treatment due to a poor performance status. The patient was treated with conservative measures, but her condition rapidly deteriorated and she passed away a few weeks later. Conclusion: RAE is notorious for mimicking a wide spectrum of diseases. It is an important differential diagnosis to consider in patients with non-healing ulceration and underlying systemic or autoimmune disorders. Our case raises awareness of this rare condition and the mortality that it carries if left untreated. In an attempt to reverse disease progression and mortality, we urge clinicians to attempt surgical correction of PVD even when faced with multiple comorbidities and poor performance status.

Background: Patients with peripheral artery disease (PAD) have 40–70% higher three-year mortality after lower limb amputation compared to non-amputees. In this study, we examined the consequences of delayed treatment for patients with PAD during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study employed a retrospective single-centre cohort design at a large tertiary care hospital. We compared amputees with PAD during the initial COVID-19 outbreak period in 2020 with a control group of amputees from 2019 after a three-year follow-up. Results: In total, 134 amputees with PAD were included due to unsuccessful revascularization (n = 84 in 2020 vs. n = 50 in 2019). Patients in 2020 were significantly younger than those in 2019 (p = 0.01) and mostly admitted with advanced stages of PAD (p < 0.03). The proportion of major limb amputations increased significantly in 2020 (p = 0.03). Non-COVID-19-related deaths among patients in 2020 were more than twice as many as those in 2019, and long-term mortality in 2020 was 49% compared to 39% in 2019 (p = 0.04). Diabetes and renal insufficiency had a significantly negative impact on the survival of amputees with PAD (p < 0.01). Conclusions: Delayed treatment in patients with PAD leads to high long-term mortality risk after amputation, especially in PAD patients with diabetes and renal insufficiency. Therefore, in future pandemics, continuously monitoring patients with PAD will be crucial to prevent delayed treatment and severe short-term and long-term consequences. [ABSTRACT FROM AUTHOR]

Background and objective: Current data on the optimal treatment modality for ruptured anterior communicating artery (AComA) aneurysms are limited. We conducted this multicenter retrospective study to evaluate the safety and clinical outcomes of endovascular treatment (EVT) and microsurgical clipping (MC) for the treatment of ruptured AComA patients. Methods: Patients with ruptured AComA aneurysms were screened from the Chinese Multicenter Cerebral Aneurysm Database. Propensity score matching (PSM) was used to adjust for baseline characteristic imbalances between the EVT and MC groups. The safety outcomes included total procedural complications, procedure-related morbidity/death and remedial procedure for complication. The primary clinical outcome was 2-year functional independence measured by the modified Rankin scale (mRS) score. Results: The analysis included 893 patients with ruptured AComA aneurysms (EVT: 549; MC: 346). PSM yielded 275 pairs of patients in the EVT and MC cohorts for comparison. Decompressive craniectomy being more prevalent in the MC group (19.3% vs. 1.5%, p< 0.001). Safety data revealed a lower rate of total procedural complications (odds ratio [OR] = 0.62, 95% CI 0.39-0.99; p= 0.044) in the EVT group and similar rates of procedure-related morbidity/ death (OR = 0.91, 95% CI 0.48-1.73; p= 0.880) and remedial procedure for complication (OR = 1.35, 95% CI 0.51-3.69, p= 0.657) between the groups. Compared with that of MC patients, EVT patients had a greater likelihood of functional independence (mRS score 0-2) at discharge (OR = 1.68, 95% CI 1.142.50; p = 0.008) and at 2years (OR = 1.89, 95% CI 1.20-3.00; p = 0.005), a lower incidence of 2-year all-cause mortality (OR = 0.54, 95% CI 0.31-0.93; p = 0.023) and a similar rate of retreatment (OR = 1.00, 95% CI 0.23-4.40; p = 1.000). Conclusion: Clinical outcomes after treatment for ruptured AComA aneurysms appear to be superior to those after treatment with MC, with fewer overall procedure-related complications and no increase in the retreatment rate. Additional studies in other countries are needed to verify these findings. [ABSTRACT FROM AUTHOR]

Pure arterial malformations (PAMs) are rare vascular lesions often detected incidentally on brain imaging. They are characterised by a mass of arterial loops containing arteries that are tortuous, overlapping and dilated without any associated arteriovenous shunting. The incidence of PAMs have been rising due to the increasing use of non-invasive angiographic imaging for the diagnosis of neurovascular disorders. This article will present the clinical course of two cases of PAM, both of which demonstrated a stable appearance on surveillance imaging despite the lack of surgical or endovascular intervention. [ABSTRACT FROM AUTHOR]

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated hyaluronic acid (HA) degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between the mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology. [ABSTRACT FROM AUTHOR]

Abstract The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV–V compared with grade I–III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV–V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Introduction: Moya-Moya disease (MMD) is a rare, chronic, and spontaneous steno-occlusive condition that leads to recurrent strokes due to the occlusion of the terminal internal carotid arteries. This article aims to highlight the significance of familial risk for MMD and other vascular disorders among first-degree relatives in Iran. Case Presentation: We report the case of a 55-year-old male who was admitted to our hospital with complaints of transient ischemic attack, left-sided hemiparesis, and decreased vision that occurred during the night. The initial diagnosis was a brain stem stroke. After undergoing digital subtraction angiography, he was diagnosed with MMD. Moya-Moya disease is a rare cause of cerebral stroke and is seldom reported in Iran. The patient was treated conservatively and had a favorable outcome. His family history was notable, with five of his eight siblings having various cardiovascular diseases. Conclusions: These findings may be useful for guiding future genetic studies and preventive counseling, with a focus on the clinical evaluation of serious adverse events. [ABSTRACT FROM AUTHOR]

This article discusses a rare condition called cutaneous collagenous vasculopathy (CCV), which is characterized by the gradual onset of widespread telangiectasias (dilated blood vessels). The condition primarily affects middle-aged females, but there have been only three documented cases in pediatric patients. The article presents a fourth case of pediatric CCV and reviews the features that distinguish it from other similar presentations of telangiectasias. The diagnosis of CCV relies on histology with collagen-specific immunostaining. The etiology of CCV is unclear, but it is postulated that genetic anomalies, underlying systemic diseases, and pharmacologic triggers may play a role. The treatment for CCV is primarily cosmetic, with options such as pulsed dye laser or optimized pulsed light. Further studies are needed to evaluate treatment in both adult and pediatric populations. [Extracted from the article]

Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20–40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV–V compared with grade I–III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV–V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs. [ABSTRACT FROM AUTHOR]

ObjectiveHealthcare disparities are widely described in adults, but barriers affecting access to care for pediatric patients with moyamoya disease (MMD) are unknown. Understanding socioeconomic factors impacting hospital access and outcomes is necessary to address pediatric healthcare disparities.MethodsIn this cross-sectional observational study, the Kids' Inpatient Database was used to identify patients admitted with a primary diagnosis of MMD from 2003 to 2016. Patients ≤ 18 years with a primary diagnosis of MMD based on International Classification of Diseases (ICD) codes were included. Hospital admissions were queried for use of cerebral revascularization based on ICD procedure codes.ResultsQuery of the KID yielded 1449 MMD hospitalizations. After multivariable regression, Hispanic ethnicity (OR 0.52 [95% CI 0.33-0.81], p = 0.004) was associated with lack of surgical revascularization. Private insurance (OR 1.56 [95% CI 1.15-2.13], p = 0.004), admissions at medium- and high-volume centers (OR 2.01 [95% CI 1.42-2.83], p < 0.001 and OR 2.84 [95% CI 1.95-4.14], p < 0.001, respectively), and elective hospitalization (OR 3.37 [95% CI 2.46-4.64], p < 0.001) were positively associated with revascularization. Compared with Caucasian race, Hispanic ethnicity was associated with increased mean (± SEM) length of stay by 2.01 ± 0.70 days (p = 0.004) and increased hospital charges by $24,333.61 ± $7918.20 (p = 0.002), despite the decreased utilization of surgical revascularization. Private insurance was associated with elective admission (OR 1.50 [95% CI 1.10-2.05], p = 0.01) and admission to high-volume centers (OR 1.90 [95% CI 1.26-2.88], p = 0.002). African American race was associated with the development of in-hospital complications (OR 2.52 [95% CI 1.38-4.59], p = 0.003).ConclusionsAmong pediatric MMD hospitalizations, multiple socioeconomic factors were associated with access to care, whether surgical treatment is provided, and whether in-hospital complications occur. These results suggest that socioeconomic factors are important drivers of healthcare disparities in children with MMD and warrant further study.

ObjectivePediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score's generalizability, and expanding its external validity.MethodsA cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale.ResultsA total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods.ConclusionsThe RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.

ObjectiveSporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity.MethodsThe authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples.ResultsThe authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH.ConclusionsThe authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.

Martorell hypertensive ulcer (MHU) represents a painful, difficult-to-handle condition associated with peripheral, subcutaneous arteriolosclerosis caused by chronic hypertensive disease. Betablockers are effective for and widely used to treat hypertensive disease but are reported to exacerbate peripheral vasoconstriction. The effect of betablockers on pre-existing arteriolosclerosis and the course of MHU is, however, unknown. A retrospective study to assess the effect of betablockers on the course and response to treatment of MHU was conducted. Clinical and histopathological data were collected of patients treated for MHU at the authors' institution between 2014 and 2023 and a side-by-side comparison was performed of patients taking betablockers or not. Analysis focused on MHU severity at presentation, analgesic use, response to therapeutic intervention, and alterations of cutaneous arterioles. The study reports significantly larger ulcers and more frequent use of opioids in patients taking betablockers, while no significant difference was observed in terms of MHU response to treatment. Significantly increased luminal obstruction of peripheral cutaneous arterioles was found in patients taking beta-blockers. Based on these data, betablockers may have a negative effect on the course of MHU and should be carefully assessed in patients with MHU. [ABSTRACT FROM AUTHOR]

Background: Cerebral extracranial-intracranial (EC-IC) revascularization technique (superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting) has become the preferred surgical method for the treatment of Moyamoya disease (MMD). We attempted to completely free the two branches of the superficial temporal artery without disconnection. Extracranial and intracranial blood flow reconstruction were then modified by selectively performing a direct bypass technique on one branch and a patch fusion technique on the other of the STA based on the blood flow and the vascular diameter of the intracranial surface blood vessels. Methods: A series of modified STA-MCA bypass surgeries performed consecutively between March 2022 and March 2023 were reviewed and compared to conventional combined bypass surgeries performed during the same period. The following information was collected from all enrolled patients: demographic characteristics, clinical symptoms, and preoperative and postoperative imaging, including Suzuki stage and Matsushima grade. The modified Rankin scale (mRS) was used to assess the changes in neurological status before and after surgery. Results: A total of 41 patients with Moyamoya disease (MMD) who underwent cerebral revascularization were included in this study, of which 30 were conventional revascularization and 11 were modified revascularization. The mean age was 49.91 years, and 18 (43.9%) of the patients were women. The modified group had a lower incidence of cerebral hyperperfusion syndrome (18.2%) than the conventional group (23.3%). After at least 3 months of follow-up, the bypass patency rate remained 100% in the modified group and 93.3% in the conventional group. All patients in the modified group achieved a better Matsushima grade (A + B), with six (54.5%) having an A and five (45.5%) having a B. In contrast, four patients (13.3%) in the conventional group had a Matsushima grade of C. In all, 72.8% of the modified group had postoperative mRS scores of 0 and 1, which was higher than that of the traditional group (63.3%). Conclusion: The improved STA-MCA bypass could provide blood flow to multiple cerebral ischemic areas, reduce excessive blood perfusion, and ensure blood supply to the scalp, with lower complications and better clinical benefits than the traditional combined bypass. [ABSTRACT FROM AUTHOR]

Background: Patients with peripheral artery disease (PAD) have 40–70% higher three-year mortality after lower limb amputation compared to non-amputees. In this study, we examined the consequences of delayed treatment for patients with PAD during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This study employed a retrospective single-centre cohort design at a large tertiary care hospital. We compared amputees with PAD during the initial COVID-19 outbreak period in 2020 with a control group of amputees from 2019 after a three-year follow-up. Results: In total, 134 amputees with PAD were included due to unsuccessful revascularization (n = 84 in 2020 vs. n = 50 in 2019). Patients in 2020 were significantly younger than those in 2019 (p = 0.01) and mostly admitted with advanced stages of PAD (p < 0.03). The proportion of major limb amputations increased significantly in 2020 (p = 0.03). Non-COVID-19-related deaths among patients in 2020 were more than twice as many as those in 2019, and long-term mortality in 2020 was 49% compared to 39% in 2019 (p = 0.04). Diabetes and renal insufficiency had a significantly negative impact on the survival of amputees with PAD (p < 0.01). Conclusions: Delayed treatment in patients with PAD leads to high long-term mortality risk after amputation, especially in PAD patients with diabetes and renal insufficiency. Therefore, in future pandemics, continuously monitoring patients with PAD will be crucial to prevent delayed treatment and severe short-term and long-term consequences.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated hyaluronic acid (HA) degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between the mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Intracranial pial Arteriovenous Fistulas (AVFs) are rare cerebral vascular lesions composed of one or more arterial connections to a single venous channel. We report a 50-year-old patient with a ruptured pial AVF located in an eloquent area. Microsurgery for pial AVF occlusion was proposed with awake craniotomy for motor function and neurological evaluation. Awake craniotomy is a technique that is especially useful for cerebral vascular lesions in eloquent areas, where an occlusion often compromises or suppresses the blood supply, culminating in ischemia with consequent transient or definitive deficits in neurological function.

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4-18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age

ObjectiveWhile the benefit of mechanical thrombectomy (MT) for patients with anterior circulation acute ischemic stroke with large-vessel occlusion (AIS-LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonged. In this study, the authors evaluated safety as well as radiographic and functional outcomes in stroke patients treated with MT via direct carotid puncture (DCP) for prohibitive vascular access.MethodsThe authors retrospectively studied patients from their prospective AIS-LVO database who underwent attempted MT between 2015 and 2018. Patients with prohibitive vascular access were divided into two groups: 1) aborted MT (abMT) after failed transfemoral access and 2) attempted MT via DCP. Functional outcome was assessed using the modified Rankin Scale at 3 months. Associations with outcome were analyzed using ordinal logistic regression.ResultsOf 352 consecutive patients with anterior circulation AIS-LVO who underwent attempted MT, 37 patients (10.5%) were deemed to have prohibitive vascular access (mean age [± SD] 82 ± 11 years, mean National Institutes of Health Stroke Scale [NIHSS] score 17 ± 5, with females accounting for 75% of the patients). There were 20 patients in the DCP group and 17 in the abMT group. The two groups were well matched for the known predictors of clinical outcome: age, sex, and admission NIHSS score. Direct carotid access was successfully obtained in 19 of 20 patients. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 16 (84%) of 19 patients in the DCP group. Carotid access complications included an inability to catheterize the carotid artery in 1 patient, neck hematomas in 4 patients, non-flow-limiting common carotid artery (CCA) dissections in 2 patients, and a delayed, fatal carotid blowout in 1 patient. The neck hematomas and non-flow-limiting CCA dissections did not require any subsequent interventions and remained clinically silent. Compared with the abMT group, patients in the DCP group had smaller infarct volumes (11 vs 48 ml, p = 0.04), a greater reduction in NIHSS score (-4 vs +2.9, p = 0.03), and better functional outcome (shift analysis for 3-month modified Rankin Scale score: adjusted OR 5.2, 95% CI 1.02-24.5; p = 0.048).ConclusionsDCP for emergency MT in patients with anterior circulation AIS-LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates, smaller infarct volumes, and improved functional outcome compared with patients with abMT after failed transfemoral access. DCP should be considered in this patient population.

OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs.

Livedoid vasculopathy (LV) is a thrombo‐occlusive vascular disease with an uncertain aetiology. In addition to cutaneous manifestations, LV patients may develop peripheral neuropathy. This study aimed to examine features of peripheral neuropathy in Chinese LV patients. We retrospectively reviewed and analysed the clinical data of 55 LV patients treated at Peking Union Medical College Hospital and conducted a literature review of peripheral neuropathy in LV patients. The incidence of peripheral neuropathy in our cohort was 12.73%. Among the seven patients with neuropathy, five were women and two were men. Median age at enrollment and disease onset in these patients was 27.29 and 22.57 years, respectively. Mean time from the appearance of cutaneous manifestations to the development of neurological symptoms was 38.67 months. Peripheral neuropathy was generally refractory to treatment, asymmetric in the distal extremities, and slowly progressive. The main symptom was numbness; hypoesthesia and neuromuscular manifestations occurred occasionally. The proportion of patients reporting seasonal worsening of symptoms was significantly higher in LV patients with peripheral neuropathy than in LV patients without neuropathy (P <.05). Peripheral neuropathy is a potential complication of LV. LV patients with peripheral neuropathy require long‐term follow‐up. [ABSTRACT FROM AUTHOR]

ObjectiveThe objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions.MethodsData for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0-2) or poor (mRS score 3-6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0-1 comprised grade 1, 2-3 grade 2, and 4-5 grade 3.ResultsA total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).ConclusionsThe authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

ObjectiveA high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.MethodsBrain AVMs were induced in adult mice in which activin receptor-like kinase 1 (Alk1, a gene that causes AVM) gene exons 4-6 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce Alk1 mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 × 109 [high] or 2 × 109 [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.ResultsCompared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue-positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.ConclusionsUsing mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.

ObjectivePreoperative embolization of brain arteriovenous malformations (AVMs) is performed to facilitate resection, although its impact on surgical performance has not been clearly defined. The authors tested for associations between embolization and surgical performance metrics.MethodsThe authors analyzed AVM cases resected by one neurosurgeon from 2006 to 2017. They tested whether cases with and without embolization differed from one another with respect to patient and AVM characteristics using t-tests for continuous variables and Fisher's exact tests for categorical variables. They used simple and multivariable regression models to test whether surgical outcomes (blood loss, resection time, surgical clip usage, and modified Rankin Scale [mRS] score) were associated with embolization. Additional regression analyses integrated the peak arterial afferent contrast normalized for the size of the region of interest (Cmax/ROI) into models as an additional predictor.ResultsThe authors included 319 patients, of whom 151 (47%) had preoperative embolization. Embolized AVMs tended to be larger (38% with diameter > 3 cm vs 19%, p = 0.001), less likely to have hemorrhaged (48% vs 63%, p = 0.013), or be diffuse (19% vs 29%, p = 0.045). Embolized AVMs were more likely to have both superficial and deep venous drainage and less likely to have exclusively deep drainage (32% vs 17% and 12% vs 23%, respectively; p = 0.002). In multivariable analysis, embolization was not a significant predictor of blood loss or mRS score changes, but did predict longer operating times (+29 minutes, 95% CI 2-56 minutes; p = 0.034) and increased clip usage (OR 2.61, 95% CI 1.45-4.71; p = 0.001). Cmax/ROI was not a significant predictor, although cases with large Cmax/ROI tended to have longer procedure times (+25 minutes per doubling of Cmax/ROI, 95% CI 0-50 minutes; p = 0.051).ConclusionsIn this series, preoperative embolization was associated with longer median resection times and had no association with intraoperative blood loss or mRS score changes.

ObjectiveA high level of vascular endothelial growth factor (VEGF) has been implicated in brain arteriovenous malformation (bAVM) bleeding and rupture. However, direct evidence is missing. In this study the authors used a mouse bAVM model to test the hypothesis that elevation of focal VEGF levels in bAVMs exacerbates the severity of bAVM hemorrhage.MethodsBrain AVMs were induced in adult mice in which activin receptor-like kinase 1 (Alk1, a gene that causes AVM) gene exons 4-6 were floxed by intrabasal ganglia injection of an adenoviral vector expressing Cre recombinase to induce Alk1 mutation and an adeno-associated viral vector expressing human VEGF (AAV-VEGF) to induce angiogenesis. Two doses of AAV-VEGF (5 × 109 [high] or 2 × 109 [low]) viral genomes were used. In addition, the common carotid artery and external jugular vein were anastomosed in a group of mice treated with low-dose AAV-VEGF 6 weeks after the model induction to induce cerebral venous hypertension (VH), because VH increases the VEGF level in the brain. Brain samples were collected 8 weeks after the model induction. Hemorrhages in the bAVM lesions were quantified on brain sections stained with Prussian blue, which detects iron deposition. VEGF levels were quantified in bAVM tissue by enzyme-linked immunosorbent assay.ResultsCompared to mice injected with a low dose of AAV-VEGF, the mice injected with a high dose had higher levels of VEGF (p = 0.003) and larger Prussian blue-positive areas in the bAVM lesion at 8 or 9 weeks after model induction (p = 0.002). VH increased bAVM hemorrhage in the low-dose AAV-VEGF group. The overall mortality in the high-dose AAV-VEGF group was 26.7%, whereas no mouse died in the low-dose AAV-VEGF group without VH. In contrast, VH caused a mortality of 50% in the low-dose AAV-VEGF group.ConclusionsUsing mouse bAVM models, the authors provided direct evidence that elevation of the VEGF level increases bAVM hemorrhage and mouse mortality.

The article is a letter to the editor in response to a study on the use of hyaluronidase injection to relieve vascular adverse events (VAEs) caused by non-hyaluronic acid (HA) fillers. The authors of the letter express concerns about the interpretation of the findings in the original study, pointing out assumptions made about the etiology and clinical progression of the diagnosis. They argue that the evidence presented does not sufficiently support the claim of a primary, nonembolic, spastic etiology for VAEs. The authors suggest that further research is needed to clarify the potential role of vasospasm in filler-associated vascular injuries and the effects of hyaluronidase on such etiology. [Extracted from the article]

This review article summarizes the basic principles of vascular anatomy, physiology, diagnostic work-up and treatment for patients with nontraumatic upper extremity vascular disorders. Vascular disorders can be considered vasospastic or occlusive. The most commonly encountered vasospastic condition is Raynaud's Phenomenon secondary to scleroderma. While historically this has been managed medically with vasodilators, more advanced cases can benefit from surgical treatment to improve blood flow and minimize tissue loss, with compelling evidence that earlier surgical intervention can modify disease process and should be considered. Occlusive disease can present as aneurysm or thrombosis and often requires surgical treatment with resection of the occluded segment with or without vascular reconstruction. In advanced atherosclerotic disease or end stage ischemia, arterialization of the venous system can be considered to avoid more proximal amputations. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 may inflict a post‐viral condition known as post‐COVID‐19 syndrome (PCS) or long‐COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID‐19 survivors with PCS versus non‐PCS controls have produced mixed findings. Our review sought to meta‐analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty‐four biomarkers from 23 studies were meta‐analysed. Higher levels of C‐reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02–0.39), D‐dimer (SMD = 0.27; 95% CI: 0.09–0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05–0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02–0.66) were found in COVID‐19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12–0.48) and interleukin‐6 (SMD = 0.30; 95% CI: 0.12–0.49) were also significantly higher in PCS than non‐PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS. [ABSTRACT FROM AUTHOR]

OBJECTIVEBrain arteriovenous malformations (bAVMs) are rupture-prone tangles of blood vessels with direct shunting of blood flow between arterial and venous circulations. The molecular and/or cellular mechanisms contributing to bAVM pathogenesis and/or destabilization in sporadic lesions have remained elusive. Initial insights into AVM formation have been gained through models of genetic AVM syndromes. And while many studies have focused on endothelial cells, the contributions of other vascular cell types have yet to be systematically studied. Pericytes are multifunctional mural cells that regulate brain angiogenesis, blood-brain barrier integrity, and vascular stability. Here, the authors analyze the abundance of brain pericytes and their association with vascular changes in sporadic human AVMs.METHODSTissues from bAVMs and from temporal lobe specimens from patients with medically intractable epilepsy (nonvascular lesion controls [NVLCs]) were resected. Immunofluorescent staining with confocal microscopy was performed to quantify pericytes (platelet-derived growth factor receptor-beta [PDGFRβ] and aminopeptidase N [CD13]) and extravascular hemoglobin. Iron-positive hemosiderin deposits were quantified with Prussian blue staining. Syngo iFlow post-image processing was used to measure nidal blood flow on preintervention angiograms.RESULTSQuantitative immunofluorescent analysis demonstrated a 68% reduction in the vascular pericyte number in bAVMs compared with the number in NVLCs (p < 0.01). Additional analysis demonstrated 52% and 50% reductions in the vascular surface area covered by CD13- and PDGFRβ-positive pericyte cell processes, respectively, in bAVMs (p < 0.01). Reductions in pericyte coverage were statistically significantly greater in bAVMs with prior rupture (p < 0.05). Unruptured bAVMs had increased microhemorrhage, as evidenced by a 15.5-fold increase in extravascular hemoglobin compared with levels in NVLCs (p < 0.01). Within unruptured bAVM specimens, extravascular hemoglobin correlated negatively with pericyte coverage (CD13: r = -0.93, p < 0.01; PDGFRβ: r = -0.87, p < 0.01). A similar negative correlation was observed with pericyte coverage and Prussian blue-positive hemosiderin deposits (CD13: r = -0.90, p < 0.01; PDGFRβ: r = -0.86, p < 0.01). Pericyte coverage positively correlated with the mean transit time of blood flow or the time that circulating blood spends within the bAVM nidus (CD13: r = 0.60, p < 0.05; PDGFRβ: r = 0.63, p < 0.05). A greater reduction in pericyte coverage is therefore associated with a reduced mean transit time or faster rate of blood flow through the bAVM nidus. No correlations were observed with time to peak flow within feeding arteries or draining veins.CONCLUSIONSBrain pericyte number and coverage are reduced in sporadic bAVMs and are lowest in cases with prior rupture. In unruptured bAVMs, pericyte reductions correlate with the severity of microhemorrhage. A loss of pericytes also correlates with a faster rate of blood flow through the bAVM nidus. This suggests that pericytes are associated with and may contribute to vascular fragility and hemodynamic changes in bAVMs. Future studies in animal models are needed to better characterize the role of pericytes in AVM pathogenesis.

OBJECTIVERevascularization is indicated in the management of moyamoya disease (MMD), with options that include direct and indirect techniques. Indirect bypass is popular in young children because the diminutive caliber of donors and recipients makes direct bypass difficult. The authors reviewed a series of patients treated with direct superficial temporal artery (STA)–to–middle cerebral artery (MCA) bypass in combination with encephalomyosynangiosis (EMS) in children 3 years or younger to demonstrate feasibility and safety.METHODSA retrospective review of all surgeries for MMD over a 19-year period identified 11 procedures in 6 patients. Surgical results, angiographic outcomes, and clinical outcomes were analyzed.RESULTSPatients had a mean age of 22.4 months. The symptomatic hemisphere was revascularized first, and the contralateral hemisphere was revascularized on average 2.8 months later in 5 patients. All direct bypasses were patent postoperatively and remained patent at late follow-up (mean 4.1 years), with both STA and MCA diameters increasing significantly (n = 5, p < 0.03). At last follow-up (mean follow-up duration, 5.0 years), favorable outcomes (modified Rankin Scale scores 0–2) were observed in 5 of the 6 patients (83%), with 1 dependent patient remaining unchanged postoperatively.CONCLUSIONSDirect STA-MCA bypass in combination with EMS for MMD is feasible and safe in patients 3 years or younger, based on favorable clinical and radiological outcomes in this patient cohort. Direct bypass should be considered when immediate revascularization is needed, without the biological delay associated with indirect bypass.ABBREVIATIONS EDAS = encephaloduroarteriosynangiosis; EMS = encephalomyosynangiosis; MCA = middle cerebral artery; MMD = moyamoya disease; mRS = modified Rankin Scale; STA = superficial temporal artery; TIA = transient ischemic attack.

As the population ages, the question of how to manage brain arteriovenous malformations in the elderly becomes increasingly relevant. Is resection a reasonable option for these patients? In this study, the authors examined the outcomes of surgical patients 60 years or older and found that favorable outcomes were achieved with careful patient selection. Preoperative grading scales were more predictive of outcomes in patients older than 65 years than in those 60-65 years of age.

ObjectiveAlthough numerous arteriovenous malformation (AVM) grading scales consider eloquence in risk assessment, none differentiate the types of eloquence. The purpose of this study was to determine if eloquence subtype affects clinical outcome.MethodsThis is a retrospective review of a prospectively collected clinical database of brain AVMs treated with microsurgery in the period from 1997 to 2017. The only inclusion criterion for this study was the presence of eloquence as defined by the Spetzler-Martin grading scale. Eloquence was preoperatively categorized by radiologists. Poor outcome was defined as a modified Rankin Scale (mRS) score 3-6, and worsening clinical status was defined as an increase in the mRS score at follow-up. Logistic regression analyses were performed.ResultsTwo hundred forty-one patients (49.4% female; average age 33.9 years) with eloquent brain AVMs were included in this review. Of the AVMs (average size 2.7 cm), 54.4% presented with hemorrhage, 46.2% had deep venous drainage, and 17.0% were diffuse. The most common eloquence type was sensorimotor (46.1%), followed by visual (27.0%) and language (22.0%). Treatments included microsurgery alone (32.8%), microsurgery plus embolization (51.9%), microsurgery plus radiosurgery (7.9%), and all three modalities (7.5%). Motor mapping was used in 9% of sensorimotor AVM cases, and awake speech mapping was used in 13.2% of AVMs with language eloquence. Complications occurred in 24 patients (10%). At the last follow-up (average 24 months), 71.4% of the patients were unchanged or improved and 16.6% had a poor outcome. There was no statistically significant difference in the baseline patient and AVM characteristics among the different subtypes of eloquence. In a multivariate analysis, in comparison to visual eloquence, both sensorimotor (OR 7.4, p = 0.004) and language (OR 6.5, p = 0.015) eloquence were associated with poor outcomes. Additionally, older age (OR 1.31, p = 0.016) and larger AVM size (OR 1.37, p = 0.034) were associated with poor outcomes.ConclusionsUnlike visual eloquence, sensorimotor and language eloquence were associated with worse clinical outcomes after the resection of eloquent AVMs. This nuance in AVM eloquence demands consideration before deciding on microsurgical intervention, especially when numerical grading systems produce a score near the borderline between operative and nonoperative management.

ObjectiveThe pathogenesis of dural arteriovenous fistulas (DAVFs) remains poorly defined. Prior studies on thrombophilia as a risk factor for DAVF development are limited by small sample sizes and poor generalizability.MethodsIn this longitudinal observational study, all patients with intracranial DAVFs evaluated at the University of California, San Francisco from December 1994 through April 2014 were identified. After obtaining patient consent, 3 thrombophilic mutations, factor V Leiden (rs6025), MTHFR (rs1801133), and prothrombin G20210A, were genotyped. The authors evaluated the association of thrombophilia status (presence of any thrombophilic mutation) and clinical and angiographic characteristics using either a 2-sample t-test or Fisher's exact test.ResultsA total of 116 patients with diagnosed intracranial DAVFs were included in the study. Twenty-five (22%) patients met criteria for thrombophilia. Focal neurological deficits tended to occur more frequently in the thrombophilia group (78% vs 57%, p = 0.09). Angiographic characteristics of DAVFs, including high-risk venous flow pattern, multiplicity of DAVF, and the presence of venous sinus thrombosis, did not differ significantly between the 2 groups but tended to be more common in the thrombophilic than in the nonthrombophilic group.ConclusionsThis study is one of the largest of thrombophilia and DAVF to date. The frequency of mutations associated with thrombophilia in this study was higher than that in the general population.

Objective: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). The authors of this study evaluate how applying noninvasive transauricular vagus nerve stimulation (taVNS) can target this deleterious inflammatory response following SAH and reduce the rate of radiographic vasospasm., Methods: In this prospective, triple-blinded, randomized controlled trial, 27 patients were randomized to taVNS or sham stimulation. Serial blood and CSF samples were collected every 3 days to quantify inflammatory markers. Radiographic cerebral vasospasm severity and functional outcomes (modified Rankin Scale scores) were analyzed., Results: No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than in the sham-treated group (p < 0.001). In the taVNS group, tumor necrosis factor-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); interleukin-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%). Patients treated with taVNS had significant improvement in modified Rankin Scale scores from admission to first follow-up (p = 0.014), unlike patients in the sham-treated group (p = 0.18). The taVNS group had a significantly lower rate of discharge to a skilled nursing facility or hospice (p = 0.04)., Conclusions: taVNS is a noninvasive method of neuro- and systemic immunomodulation. This trial supports the finding that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.

Objective: The complex mix of factors, including hemodynamic forces and wall remodeling mechanisms, that drive intracranial aneurysm growth is unclear. This study focuses on the specific regions within aneurysm walls where growth occurs and their relationship to the prevalent hemodynamic conditions to reveal critical mechanisms leading to enlargement., Methods: The authors examined hemodynamic models of 67 longitudinally followed aneurysms, identifying 88 growth regions. These regions (of enlargement) were pinpointed through alignment and distance mapping between baseline and follow-up models. Aneurysm wall subdivisions were created based on saccular anatomy and flow-related characteristics, which were used to assess local hemodynamics. The distribution of growing regions across these subdivisions was then studied and stratified by aneurysm location and morphology to reveal distinct growth patterns. Statistical significance was evaluated using the Kruskal-Wallis and Mann-Whitney tests., Results: Growth predominantly occurred in the body (p < 0.0001) of aneurysms, with anterior communicating artery (ACom) (p < 0.0001) and lateral (p = 0.002) aneurysms showing a significantly greater tendency for growth in this region. In comparison, middle cerebral artery (MCA) (p < 0.0001) and bifurcation (p = 0.0001) aneurysms demonstrated growth in both the dome and the body. Notable differences in growth distribution across saccular regions included ACom versus MCA (neck, p = 0.038), bifurcation versus lateral (neck, p = 0.008), and so forth. The central flow region saw the most growth (p < 0.0001); although not significant, ACom (p = 0.196) and lateral (p = 0.218) aneurysms showed a tendency for growth in inflow and central zones, while MCA (p = 0.001) and bifurcation (p < 0.0001) aneurysms were more likely to grow in the central flow region., Conclusions: Two primary mechanisms seem to influence aneurysm growth: high-flow impingement jets in the neck, body, and inflow zones leading to wall degeneration/thinning, mainly in ACom aneurysms; and slow, oscillatory flow conditions in the dome and central flow zones promoting wall remodeling/thickening, mainly in MCA aneurysms. This latter mechanism is also observed as secondary flows in ACom aneurysms. These findings emphasize the need to understand the distinct and sometimes concurrent mechanisms of aneurysm growth, advocating for targeted monitoring and interventions that mitigate rupture risks by considering the unique hemodynamic environments within different aneurysm regions and locations.