Middle meningeal artery embolization (MMAE) has shown efficacy for chronic subdural hematoma (cSDH), but optimal patient selection and timing (pre-, post-surgical, or standalone) remain unclear. This study evaluated the impact of volume, and embolization timing on outcomes at discharge and follow-up. The study included 135 patients undergoing MMAE; only those with complete radiological data were analyzed. To reduce baseline clinical bias, patients were stratified into quartiles (Q) based on preoperative hematoma volume. Changes in functional status were assessed by calculating the difference in modified Rankin Scale (mRS) score between admission and discharge (ΔmRSa➝d), as well as between admission and follow-up (ΔmRSa➝f). The entire cohort was divided into three groups based on the timing of MMAE: pre-surgical, post-surgical and standalone. At admission, mRS distribution differed across quartiles (p = 0.005), with better functional status more common in Q1 and higher mRS (≥ 3) increasing in larger volumes. At discharge, outcomes varied by embolization timing (p < 0.001). Stand-alone treatment was associated with greater clinical stability, especially in Q1, while improvement increased with hematoma volume in the pre-surgical group. The post-surgical group showed a milder pattern of severity compared to the pre-surgical group. The same trends were observed at follow-up. On multivariable analysis, admission mRS was the strongest predictor of poor outcome (mRS ≥ 3) (OR 6.209, p < 0.001), with age also significant (OR 1.078, p = 0.027). Preoperative hematoma volume was the only independent predictor of reoperation (OR 1.017, p = 0.017). Discharge outcome was mainly driven by admission mRS and age, while preoperative hematoma volume was associated with reoperation risk. In patients with lower hematoma burden (Q1-Q2), stand-alone MMAE showed greater early functional stability than pre- or post-surgical strategies.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular disorder characterized by multisystem arteriovenous malformations (AVMs). Still, the influence of demographic factors and specific pathogenic variants on systemic and cerebrovascular involvement remains incompletely defined. We retrospectively included 142 patients with genetically confirmed HHT diagnosis. Systemic and neurovascular data were collected for each patient and stratified by age and sex. Then, we conducted univariate analyses for genotype-phenotype correlations after adjusting for age and sex. Afterwards, the significant associations were tested in multivariable logistic regression models to verify confounding effects. Hepatic AVMs and gastrointestinal bleeding increased significantly with age, whereas neurological manifestations showed no age dependency. In multivariable analysis for hepatic AVMs, increasing age was independently associated with hepatic involvement (p = 0.037), while ENG (p = 0.035) was associated with a lower likelihood of hepatic AVMs compared to ACVRL1. For brain AVMs, age, ENG gene, and variant truncation status were independent predictors, and the ACVRL1 c.277 C > T (p.Arg93*) mutation showed an independent association (p = 0.035). In HHT, age and gene-level effects are robust predictors of systemic AVM involvement, whereas mutation-specific associations remain difficult to evaluate. Larger multicenter studies are needed to validate variant-level risk and support personalized surveillance strategies.

The EARLYDRAIN trial demonstrated the efficacy of lumbar drainage (LD) in aneurysmal subarachnoid hemorrhage (aSAH) but did not differentiate between patients requiring dual drainage [LD plus external ventricular drainage (EVD)] versus single-catheter management. The purpose of this study was to investigate the safety and additive efficacy of simultaneous double drainage (EVD + LD) compared with isolated EVD in patients with high-grade aSAH, stratifying by actual device usage. This secondary analysis stratified 254 EARLYDRAIN trial participants on the basis of daily intensive care unit (ICU) device records. To minimize selection bias, the isolated LD cohort (n = 43), characterized by significantly milder admission severity (mean Glasgow Coma Scale (GCS) 13.3, p < 0.001), was excluded from efficacy models. The primary analysis compared simultaneous double drainage (n = 92) vs. isolated EVD (n = 119). Multivariable logistic regression models were adjusted for age, Hunt–Hess grade, modified Fisher grade, and total cerebrospinal fluid (CSF) drainage volume. Double drainage and isolated EVD groups were well balanced for admission GCS (p = 0.672) and intraventricular hemorrhage prevalence (p = 0.355). Suspected infection rates were similar (47.8

INTRODUCTION:Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder marked by mucocutaneous telangiectasias, recurrent epistaxis, and visceral arteriovenous malformations (AVMs). Neurologic risks include brain AVMs and hemorrhagic stroke. Several rare genetic and sporadic syndromes ("HHT-like" syndromes) share overlapping vascular features, complicating diagnosis. Differentiating these conditions is essential for accurate neurovascular risk assessment. METHODS:A comprehensive literature review (PubMed, Scopus, Embase, Google Scholar; 1990-2025) targeted cerebrovascular manifestations of HHT and related syndromes. Key entities included Wyburn-Mason syndrome, Cobb syndrome, Klippel-Trénaunay syndrome (KTS), neurofibromatosis type 1 (NF1), PHACE(S) syndrome, capillary malformation-AVM (CM-AVM), Parkes Weber syndrome (PWS), juvenile polyposis/HHT overlap (JP-HHT), HHT type 5 (BMP9/GDF2), PTEN hamartoma tumor syndrome (PHTS), and blue rubber bleb nevus syndrome (BRBNS). Data on gene variants, lesion types, neuroimaging, stroke risk, and neurologic outcomes were synthesized. RESULTS:High-flow cerebrovascular malformations similar to HHT are prominent in Wyburn-Mason syndrome, CM-AVM, and PWS, conferring a substantial hemorrhagic stroke risk. NF1 and PHACE(S) primarily feature occlusive arteriopathies linked to ischemic events. KTS, BRBNS, and PHTS predominantly show low- or mixed-flow anomalies with lower CNS hemorrhagic risk but increased thrombotic complications. JP-HHT carries added gastrointestinal cancer risk via SMAD4 variants, while HHT type 5 often presents incompletely. Genetic testing and tailored neuroimaging are critical for differentiation. CONCLUSIONS:Although many syndromes mimic HHT, few combine mucosal telangiectasias, high-flow AVMs, and recurrent hemorrhage. Integrating clinical, imaging, and genetic data enables precise diagnosis, risk stratification, and personalized management.

BACKGROUND:Arteriovenous malformation (AVM) recurrence after complete surgical resection is a rare but significant clinical event. The underlying mechanisms and factors that predict recurrence remain incompletely defined. METHODS:We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We included case series reporting on AVM recurrence following an angiographically documented complete resection. Data on initial clinical presentation, patients' demographics, AVM features, and patterns of recurrence were extracted and analyzed. RESULTS:We included 15 studies with a total of 1287 patients in our meta-analysis. The overall estimated recurrence rate was 5.4%. Hemorrhagic presentation appeared as a major predictor: in fact, 94% of recurrences occurred in patients with a prior rupture, corresponding to a 7.3% (95% CI, 0.049-0.098) recurrence rate within this high-risk subgroup. Ruptured AVMs were associated with 4-fold higher odds of recurrence compared with unruptured AVMs (odds ratio, 4.072 [95% CI, 1.492-11.113]). Younger age was also found to be a key factor, with pediatric patients accounting for 89% of all recurrences. Deep venous drainage was associated with a nearly 5-fold increased risk of recurrence (odds ratio, 4.96 [95% CI, 1.801-13.662]), while eloquent brain location was not found as a statistically significant predictor. The mean time to recurrence was 39.6 (95% CI, 27.80-51.41) months, while follow-ups varied among patients. CONCLUSIONS:Hemorrhagic presentation, younger age, and deep venous drainage demonstrated to be significant predictors of AVM recurrence after complete resection, whereas vascular aging appears protective. In older individuals, proangiogenic mediators (VEGF [vascular endothelial growth factor], HIF-1 [hypoxia-inducible factor-1] α, eNOS [endothelial nitric oxide synthase], and MMPs [matrix metalloproteinases]) are downregulated via aging-related pathways, limiting neovascularization and making recurrence biologically less likely. These findings underscore the need for prolonged, risk-adapted surveillance protocols, particularly for high-risk pediatric patients who present with hemorrhage.

Cavernous malformations (CMs) are vascular lesions that can lead to seizures or hemorrhage. Although pregnancy involves hormonal and circulatory changes that might influence CM behavior, whether it increases the risk of bleeding is unclear. We performed a systematic review using PubMed/MEDLINE and Scopus of published reports describing pregnant women diagnosed with cerebral or spinal CMs. The study question was framed using the PEO strategy, with pregnant women with cavernous angioma as the population, hemorrhage as the exposure, and clinical outcomes as the endpoints. The search was updated to July 12th, 2025 with no time restrictions. This review followed the PRISMA 2020 guidelines. Thirty-two studies were selected accounting for 94 patients. Most lesions were localized in the brainstem and supratentorial regions. Among patients that were symptomatic during gestation, hemorrhage occurred in 70.9

Hereditary Hemorrhagic Telangiectasia (HHT) exhibits marked phenotypic heterogeneity. Although gene–organ associations are well established for visceral involvement, predictors of cerebrovascular malformations (CVMs), particularly brain arteriovenous malformations (bAVMs), remain incompletely defined. This study aimed to investigate genotype–phenotype correlations and identify predictors of bAVMs in a genetically confirmed HHT cohort. We conducted a retrospective analysis of 142 Caucasian patients with genetically confirmed HHT. Clinical manifestations were systematically assessed and correlated with the mutated gene (ENG, ACVRL1, and SMAD4), variant type (truncating vs. non-truncating), and protein domain location. Multivariable logistic regression was performed to identify independent predictors of bAVMs. The cohort included 83 (58.5

Cerebral cavernous malformations (CCMs) are vascular lesions frequently presenting with seizures on presentation. Studies have widely analyzed topography as a determinant of epileptogenesis. However, the association between lesion volumetry and epileptic risk remains poorly investigated, as no objective volumetric thresholds have been established to stratify seizure risk. We conducted a multicentric case–control study including 230 adult patients with CCMs. Patients were grouped according to their initial presentation: seizure (n = 75) versus non-seizure (n = 155). We calculated the volumes of the lesions using the ABC/2 method and categorized them into quartiles. Subsequently, we run a multivariate logistic regression assessing independent predictors of epilepsy, adjusting for demographic, clinical, and radiological factors. We also estimated the diagnostic accuracy of lesion volume thresholds (> 11.9 mm3, > 80 mm3, > 300 mm3). Lesion volume was significantly associated with epileptic risk. Lesions ≥ 80 mm3 were shown to have higher odds of seizures on presentation (OR 86.4, 95

Bioresorbable flow diverters (BRFDs) are emerging as next-generation alternatives to permanent metallic stents for intracranial aneurysm flow diversion. These devices aim to provide temporary flow diversion that scaffolds aneurysm healing and then dissolves, potentially reducing chronic foreign-body risks. We performed a systematic review (PRISMA methodology) updated to August 2025 to assess BRFD technology and performance. Seventeen studies (2013–2025) met inclusion criteria, describing 27 prototype BRFDs. Devices varied widely in material and design. Many were fully polymeric (typically poly–L-lactic acid or polycaprolactone) or used biodegradable metals (FeMnN), often in polymer–metal hybrid configurations. Approximately 30

BACKGROUND:Managing patients with multiple intracranial aneurysms remains challenging, both for identifying the ruptured aneurysm in the acute phase and for deciding whether to treat unruptured bystanders later. As traditional risk scores rely largely on aneurysm size, this study used an intrapatient matched design to better assess the anatomical determinants of rupture beyond patient-specific factors. METHODS:A retrospective analysis was conducted on 55 patients harboring a total of 136 intracranial aneurysms. To inherently control systemic risk factors, the ruptured index aneurysm was directly compared against the unruptured bystanders within the same individual. A generalized linear mixed model was utilized to evaluate morphological predictors of rupture. RESULTS:After adjusting for topography, absolute dome width emerged as a strong independent predictor of intrapatient rupture (odds ratio [OR] 1.56, 95% confidence interval [CI]: 1.12-2.18, P = 0.008), alongside the macroscopic presence of blebs (OR 7.27, 95% CI: 1.65-32.06, P = 0.009). Conversely, the size ratio and neck size lost their statistical significance (P = 0.697 and P = 0.567, respectively). Topographically, aneurysms located at the anterior and posterior communicating arteries exhibited the highest propensity for rupture (74% and 69%, overall effect P = 0.002), with significantly higher odds of rupture compared to the middle cerebral artery baseline (OR 9.83 and OR 8.99, respectively). CONCLUSIONS:The propensity for aneurysm rupture within the same patient is associated with a combination of absolute volumetric growth (width) and focal morphological instability (blebs). Topographically, high-flow bifurcations such as anterior communicating artery and posterior communicating artery carry the highest risk. The decision-making process for treating unruptured bystander aneurysms should comprehensively integrate both absolute size thresholds and local wall irregularities.

BACKGROUND:Delayed cerebral ischemia (DCI) remains a major morbidity and mortality problem following aneurysmal subarachnoid hemorrhage (SAH). Advancements in neurocritical care permit a slow but accurate identification of patients at high risk for DCI. Machine learning models are now emerging as tools for DCI prediction that may provide more individualized risk assessment than conventional approaches. METHODS:We systematically searched PubMed and Embase for studies developing or validating ML models for predicting DCI after SAH. Qualitative assessment of study quality was performed with QUADAS-2 tool. The performance metrics were synthesized and compared among algorithm families and dataset types (training, test & validation). RESULTS:Among these 29 studies, 10,000 patients and more than 100 ML models were analyzed. The best discriminative performance was obtained by ensemble methods (Random Forest, XGBoost) with median AUCs of 0.80-0.85, and logistic regression was still the most common and interpretable model. Deep learning models performed variable and had greater overfitting. Sensitivity and specificity varied across models and cohorts, with ensemble models balancing both metrics best. External validation was, however, scarce. CONCLUSIONS:ML models and particularly ensemble approaches promise to improve DCI prediction after SAH. External validation, model calibration and prospective clinical integration warrant future work.

Background:Familial cerebral cavernous malformations (fCCMs) are a rare genetic autosomal dominant cerebrovascular disease characterized by multiple cerebral and spinal angiomas. The condition is caused by mutations in KRIT1 (CCM1), CCM2 (malcavernin), or PDCD10 (CCM3) and may lead to intracerebral hemorrhage (ICH) or non-hemorrhagic focal neurological deficits (FNDs), potentially leading to severe disability and even death. To date, little is known about disease progression, and tools to identify patients at higher risk are lacking. Methods:Pediatric and adult fCCM patients, whether symptomatic or asymptomatic, will be enrolled and followed annually over a 2-year period. Participants will undergo clinical assessments, blood sampling, and 3 T brain MRI scans at baseline, 12 months, and 24 months. The primary outcome is the new occurrence of symptomatic ICH or FNDs attributable to CCMs over 24 months. Patient characteristics will be assessed for the primary and secondary endpoints and illustrated using Kaplan-Meier curves and Cox proportional hazard regressions. This trial is registered with ClinicalTrials.gov, NCT06983132 and is currently recruiting participants. Discussion/conclusion:Despite increasing efforts in basic and clinical research and an improved understanding of the pathogenic mechanisms underlying fCCM, tools to predict disease progression, identify at-risk individuals, and pinpoint effective therapeutic targets are still lacking. This study aims to create the largest Italian cohort of fCCM patients, who will be monitored closely over time to collect data that may help identify risk factors and disease trajectories. The collection of standardized information on clinical and radiological evolution, along with results from circulating biomarkers, will help address the complexities of the disease and may suggest potential reliable markers of disease progression. Clinical trial registration:ClinicalTrials.gov, identifier NCT06983132.

The resection of cerebral arteriovenous malformations (AVMs) involving eloquent motor regions remains one of the most challenging tasks in neurosurgery due to the risk of irreversible motor deficits. Historically, such lesions have often been managed conservatively or with radiosurgery, particularly when located near primary motor cortex or corticospinal tracts. However, the advent of intraoperative neurophysiological monitoring (IONM) allows for real-time feedback on motor pathway function, potentially enabling safer resections in areas previously considered inoperable. This study investigates the effectiveness of IONM in reducing motor morbidity during AVM surgery. We prospectively enrolled 48 patients who underwent AVM resection between 2018 and 2025 at a single center. All surgeries incorporated a standardized IONM protocol, including continuous somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), and dynamic cortical and subcortical mapping. Patients were stratified into high and low motor-risk groups based on AVM topography. Clinical, imaging, and angioarchitectural data were analyzed. Primary outcomes were new postoperative motor deficits; secondary outcomes included modified Rankin Scale (mRS) scores and residual nidus presence. Statistical analysis included univariate and multivariate regression. Of the 48 patients (mean age 45.2), 42% presented with hemorrhage and 50% had left-hemisphere AVMs. Spetzler-Martin grades ranged from I to IV. Three patients (6.25%) had residual AVM postoperatively, two of which were intentional due to IONM alerts. None developed new deficits. One residual spontaneously thrombosed during follow-up. Multivariate analysis showed preoperative mRS, not motor eloquence, was the main predictor of outcome in ruptured AVMs. No significant difference in postoperative motor function or mRS was found between high- and low-risk groups. IONM enables safe, function-preserving AVM resection in motor eloquent areas. It supports intraoperative decision-making, reducing morbidity and expanding surgical indications guiding a “maximal safe resection” strategy focused on functional preservation rather than angiographic radicality alone.

Spinal arteriovenous fistulas, especially dural types (SdAVFs), are often misdiagnosed as inflammatory myelopathies, leading to inadvertent corticosteroid therapy. This study systematically evaluated the clinical consequences of steroid pretreatment in SdAVF and its underlying pathophysiological mechanisms. A PRISMA-compliant systematic review and pooled analysis were conducted across PubMed, Scopus, and Embase on October 10th, 2025. Quantitative data on patients receiving corticosteroids before SdAVF diagnosis were extracted, including demographic, clinical, radiologic, and outcome measures. Comparative and paired analyses (χ², Kruskal-Wallis and Wilcoxon tests) assessed associations between steroid exposure, fistula location, and modified Aminoff–Logue Scale (mALS) outcomes. Seventy-one studies, including 161 patients from case series and 86 from pooled case reports, were included. Across the pooled cohort of case reports, 81.4

Cerebral vasospasm remains a leading cause of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH). Despite advances in critical care, current monitoring strategies are reactive and non-personalized. Machine learning (ML) has emerged as a promising tool to anticipate vasospasm risk. A systematic review and meta-analysis were performed following PRISMA 2020 guidelines. PubMed and Embase databases were searched for studies applying ML algorithms to predict clinical or radiological vasospasm. Data were pooled using bivariate and proportional meta-analyses and their quality was assessed with the PROBAST tool. Twelve studies (2011–2025) encompassing 25 ML models were included. Deep learning achieved the highest sensitivity (mean: 97.6

Glioblastoma (GBM) is an aggressive brain tumor characterized by an immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance and disease progression. Background: Tumor-associated macrophages (TAMs), comprising both resident microglia and bone marrow-derived macrophages, play a central role in supporting tumor growth, angiogenesis, and immune evasion. Most TAMs adopt an M2-like immunosuppressive phenotype, making them a promising target for immunomodulatory strategies in GBM. Method: According to PRISMA guidelines, we conducted a systematic literature review and recruited eligible studies focused on therapeutic approaches targeting TAMs in GBM, emphasizing mechanisms of action, efficacy, and challenges. Data extraction focused on therapeutic classes, outcomes, and TAM-related biomarkers. Results: We identified 30 studies meeting the inclusion criteria. These therapies are categorized into three main strategies: inhibition of TAM recruitment, enhancement of TAM-mediated phagocytosis, and reprogramming of TAMs. Combination strategies, including TAM-targeting with checkpoint inhibitors, nanoparticles, and oncolytic viruses, show synergistic effects in preclinical models. Conclusions: Targeting TAMs represents a multifaceted strategy for GBM treatment. Current evidence underscores the need for combination approaches integrating TAM modulation with existing standard-of-care therapies. Clinical translation remains limited due to challenges such as TAM heterogeneity, plasticity, immunosuppressive therapies, and restricted drug delivery across the blood-brain barrier. Future directions should highlight personalized treatments based on detailed TME profiling. Combining TAM-targeted therapies with agents modulating metabolic or immune pathways, and leveraging advanced delivery systems and spatial transcriptomics may improve efficacy.

BACKGROUND:Klippel-Trénaunay syndrome (KTS) and Parkes Weber syndrome (PWS) are rare vascular disorders that share clinical features such as limb overgrowth and capillary malformations. However, they differ in the vascular flow dynamics. KTS is a low-flow malformation, while PWS is characterized by high-flow arteriovenous shunts. METHODS:A systematic review of the literature was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on case reports and series describing patients with confirmed KTS or PWS and documented cerebrovascular or spinal vascular findings. Studies were analyzed for type and location of central nervous system lesions, and genetic data were reviewed where available. RESULTS:Forty studies comprising 76 patients met inclusion criteria. In KTS (61 patients), cerebrovascular anomalies were mostly venous in nature, including developmental venous anomalies, venous malformations, and cavernomas, with no spinal arteriovenous malformations reported. In contrast, PWS (n = 15) was exclusively associated with high-flow spinal arteriovenous malformations or fistulas, primarily affecting the thoracolumbar region. No cerebral lesions were identified in PWS. PIK3CA mutations were observed in KTS cases, while Ras GTPase-activating protein 1 mutations were more common in PWS. CONCLUSIONS:Cerebrovascular findings might offer valuable diagnostic insight into distinguishing KTS from PWS. These vascular recurrent findings, coupled with genetic testing, can enhance diagnostic precision and guide appropriate management strategies for these complex vascular syndromes.

BACKGROUND:Spontaneous intracranial hypotension (SIH) is characterized by CSF leakage leading to orthostatic headaches and neurological deficits. In some cases, it can be extremely severe to cause nausea, vomiting, and vertigo. Despite conservative treatment, epidural blood patch remains the optimal approach for empiric resolution of symptoms. However, the medical community lacks consensus regarding the best approach to use: targeted epidural blood patch (TEBP) versus nontargeted epidural blood patch (NTEBP). METHODS:A systematic review and metanalysis was conducted on multiple databases with a two-step selection process in order to exclude studies with insufficient data, irrelevance, and lack of comparative analysis between the two procedures. From the included studies, we comparatively analyzed overall good outcomes, success at first attempts, and relapse rates between the groups of study. RESULTS:We included seven studies matching our inclusion criteria. No significant difference was noted between the TEBP and NTEBP groups concerning the improved overall outcome and success at first attempt. Similarly, comparable statistical significance was noted concerning the relapse rates. CONCLUSION:TEBP and NTEBP are both effective treatments for SIH. However, given the lack of statistical difference between the interventions, along with considerations such as the patient risk profiles, physician expertise, and avoidance of invasive imaging procedures, the analysis suggests that NTEBP may be considered a viable initial approach, regardless of the identification of the leak.

Idiopathic normal-pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait disturbance, cognitive decline, and urinary incontinence. Cerebrospinal fluid (CSF) diversion is the gold standard treatment. Despite ventriculo-peritoneal shunt (VPS) is more commonly used, lumbo-peritoneal shunt (LPS) offers a minimally invasive alternative, raising questions about their relative efficacy and safety. A systematic review was conducted on multiple databases with a two-step selection process in order to exclude studies with insufficient data, irrelevance, and lacking of comparative analysis between the two procedures. From the included studies we comparatively analyzed preoperative clinical-radiological characteristics, surgical details and clinical-radiological outcome. We included 6 studies matching out inclusion criteria. Both VPS and LPS improved functional and cognitive performance. VPS provided faster symptoms relief, but has been related with higher risks of infection, whereas LPS showed a safer profile but required more frequent revisions due to mechanical issues. VPS and LPS are both effective treatments for iNPH. The choice of intervention should be tailored on the individual patient risk profiles, resource availability, and surgical expertise. Future research should focus on standardizing assessment scores, solve controversies, and evaluate long-term outcomes.