Paolo Ferroli

Background: Postoperative epileptic seizures are a recognized complication after superficial temporal artery–middle cerebral artery (STA–MCA) bypass for Moyamoya angiopathy (MMA), but their determinants remain incompletely understood. We aimed to identify clinical, radiological, and perioperative factors associated with early postoperative seizures following adult STA–MCA bypass. Methods: We retrospectively analyzed 75 hemispheric revascularization procedures performed in adult MMA patients between 2005 and 2023, with each operated hemisphere treated as an independent analytical unit. The primary outcome was the occurrence of at least one in-hospital postoperative seizure; the primary exposure was cerebral hyperperfusion syndrome. Univariate and multivariable Firth penalized-likelihood logistic regression was used to account for the small sample size and rare outcome. Results: Postoperative seizures occurred in 14 of 75 procedures (18.7%). Hyperperfusion was identified in 6 procedures (8.0%) and showed the strongest univariate association with seizures (OR 10.20), followed by diabetes mellitus (OR 6.05). Right-hemispheric procedures showed a protective effect in the univariate analysis (OR 0.24). In separate multivariate adjusted models, hyperperfusion (OR 10.28) and diabetes mellitus (OR 5.70) remained associated with postoperative seizures (OR 10.28 and OR 5.70, respectively). Pre-existing epilepsy, antiepileptic treatment, and preoperative EEG abnormalities were not associated with seizure risk. Conclusions: Early postoperative seizures after direct STA–MCA bypass in adult MMA were most consistently associated with postoperative cerebral hyperperfusion in our cohort, while pre-existing epilepsy and preoperative EEG abnormalities showed no statistically significant associations. Early recognition of hyperperfusion may support risk-stratified postoperative surveillance and individualized management.

Background: Flow diverters (FDs) are widely used to treat intracranial aneurysms. Although effective, FD-related thrombosis or progressive stenosis may lead to acute or delayed cerebral hypoperfusion with significant neurological morbidity. Management options are limited when medical or endovascular rescue strategies fail. This study aims to evaluate the role of extracranial–intracranial bypass (EC-IC bypass) as a rescue strategy across the spectrum of FD-related cerebral hypoperfusion. Methods: We retrospectively reviewed all patients who underwent EC-IC bypass for FD-related cerebral hypoperfusion over a 10-year period in our institution. Both acute and chronic presentations were included. Clinical status was assessed using the modified Rankin Scale (mRS). Imaging evaluation included digital subtraction angiography (DSA), computed tomography angiography (CTA), magnetic resonance angiography (MRA) and quantitative magnetic resonance imaging for bypass flow assessment. Surgical technique, antiplatelet therapy, timing of intervention and clinical outcomes were analysed. Results: Five patients with FD-related cerebral hypoperfusion who underwent superficial temporal artery–middle cerebral artery bypass (STA-MCA bypass) were identified. Two distinct patterns emerged. Three patients developed early hypoperfusion within the first month of FD placement, presenting with acute neurological deficits and treated by emergent or urgent bypass under dual antiplatelet therapy. Two patients developed late hypoperfusion years after the procedure, presenting with progressive haemodynamic symptoms and treated by elective flow-augmentation bypass under aspirin monotherapy. At discharge, only one patient had an mRS ≥ 3. At one-year follow-up, a favourable outcome (mRS ≤ 2) was observed in all patients with available data. Follow-up data were missing for one patient. Conclusions: EC-IC bypass represents a feasible rescue strategy for FD-related cerebral hypoperfusion when medical or endovascular treatments fail. In our experience, though limited, STA-MCA bypass can provide sufficient cerebral reperfusion, even in urgent settings and under dual antiplatelet therapy, leading to favourable neurological outcomes.

We report a case of astrocytoma IDH-mutant grade 2, which progressed to an IDH-mutant sarcomatous neoplasia after multiple treatments, including radiotherapy. The last recurrence histologically exhibited sarcomatous morphology, characterized by spindle cells, necrosis, and brisk mitotic activity. The neoplastic cells were negative for GFAP and OLIG2, positive for IDH1p.R132H and P53, with loss of ATRX expression and focal loss of H3 K27me3. Focal immunoreactivity for smooth muscle actin, desmin, and YAP1 was also observed. DNA methylation profiling yielded subthreshold scores suggestive of oligosarcoma, IDH-mutant, using the Heidelberg classifier and undifferentiated sarcoma using the sarcoma classifier. The Bethesda classifier did not provide a confident match. Nevertheless, UMAP analysis showed proximity of the recurrent tumor to the oligosarcoma methylation cluster. Overall, the sarcomatous recurrent neoplasia retained immunophenotypic and molecular features of astrocytomas IDH-mutant, while exhibiting an epigenetic divergent profile. This case expands the spectrum of sarcomatous progression in IDH-mutant diffuse gliomas and raises the possibility that astrocytomas, similar to oligodendrogliomas, may rarely undergo sarcomatous transformation. Additional cases and integrated molecular studies will be required to determine whether such tumors represent a distinct biological subgroup.

Background: Brain metastases are the most common intracranial tumors in adults and are traditionally considered well-demarcated lesions amenable to complete surgical resection. Nonetheless, increasing histopathological evidence demonstrates that metastatic cells may infiltrate beyond the contrast-enhancing margin into surrounding brain parenchyma, challenging the reliability of conventional imaging for defining true tumor boundaries. Confocal laser endomicroscopy (CLE) using Sodium Fluorescein (SF) has emerged as a novel intraoperative imaging modality capable of providing real-time, high-resolution optical biopsies, potentially improving margin assessment during metastasis surgery. Methods: A systematic literature search was performed according to PRISMA guidelines across PubMed, Embase, Scopus, Cochrane Library, and Google Scholar up to 3 March 2026. Studies evaluating intraoperative CLE with SF in adult patients with brain metastases were included. Data regarding study design, patient population, CLE system, imaging characteristics, and diagnostic performance were extracted. Risk of bias was assessed using the QUADAS-2 tool. Results: Ten studies met the inclusion criteria for qualitative synthesis, comprising over 650 patients; however, most studies included heterogeneous intracranial tumor populations, with only a subset specifically involving brain metastases. CLE enabled real-time visualization of tumor microarchitecture and demonstrated high sensitivity for tumor detection, frequently exceeding 90% in prospective studies. Specificity varied across studies, reflecting challenges in distinguishing tumor infiltration from reactive tissue at the tumor–brain interface. The MetInfilt trial highlighted that infiltrative growth patterns are common in brain metastases and can be visualized intraoperatively using CLE. Additional studies demonstrated that fluorescein-based CLE allows differentiation of tumor zones and may facilitate targeted margin assessment; however, evidence demonstrating improvement in clinically meaningful outcomes such as extent of resection, local recurrence, progression-free survival, or overall survival remains limited. Conclusions: Confocal laser endomicroscopy using SF represents a promising intraoperative adjunct for assessing tumor margins in brain metastasis surgery. By enabling real-time microscopic visualization of the metastasis–brain interface, CLE may support a more biologically informed surgical strategy.

Background: The pathophysiological mechanisms of Moyamoya angiopathy (MA) are still largely unknown, although a dysfunctional vasculogenesis has been hypothesized to contribute to it. The association between this rare cerebrovascular condition and variants of Ring Finger Protein 213 (RNF213) strengthens the role of genetic factors in MA pathogenesis. Methods: To investigate the molecular mechanisms of MA, we carried out RNA interference (RNAi) targeting RNF213 in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). The combined effect of RNAi and/or hypoxia on expression of key angiogenic factors was analyzed through qRT-PCR and Western blot. Functional assays were performed to characterize the impact of RNAi on vasculogenesis. Gene-expression arrays were performed on vessel walls of MA patients and controls. Results: RNF213-RNAi impaired angiogenic capability in ECs, whereas the simultaneous silencing of RNF213 and its phosphatase PTP1B restored angiogenesis function in ECs but worsened it in VSMCs. Angiogenic factor expression appeared to be modulated in ECs by the combined effects of RNAi and/or hypoxia, and in pathological vessels of MA patients as compared with controls. Conclusions: Our findings contribute to associating the relevance of RNF213 in MA cellular models and highlight the importance of EC-VSMC crosstalk for vascular integrity. Additionally, the study could lay the foundations for improving experimental models of MA pathophysiology.

BACKGROUND AND OBJECTIVES: Preventive treatment of unruptured intracranial aneurysms (UIAs) requires assessment of treatment risks vs expected benefit. Although established scores exist to estimate rupture and growth risk, currently, no externally validated tools exist to estimate the risks of microsurgical treatment of UIAs. Clinical prediction models based on machine learning enable generation of personalized risk estimates for each individual patient based on their specific patient and aneurysm characteristics. METHODS: Using data from 20 international centers from the prediction of adverse events after microsurgery for intracranial unruptured aneurysms study on patients treated microsurgically for UIAs, we developed and externally validated clinical prediction models for 3 outcomes measured at hospital discharge: poor neurological outcome (modified Rankin Score ≥3), new sensorimotor neurological deficits, and all-cause adverse events (Clavien-Dindo Grade ≥1). RESULTS: A total of 3705 patients were included. Data from 13 centers (2881, 78%) were used for model development. Fully trained models were evaluated on 824 patients (22%) from 7 additional centers. Average age was 56 ± 12 years, and 1049 (28%) were male. At discharge, poor neurological outcome was seen in 514 patients (14%). New sensorimotor deficits were observed in 534 patients (14%), and 894 patients (24%) experienced adverse events until discharge. At external validation, prediction of poor neurological outcome was achieved with good calibration and an area under the curve (AUC) = 0.70 (95% CI: 0.63-0.75). Similarly, new neurological deficits were predicted with good calibration and with an AUC = 0.69 (95% CI: 0.63-0.74). Prediction of all-cause adverse events only achieved an AUC = 0.59 (95% CI: 0.55-0.64) with fair calibration. The prediction model was integrated into a web application accessible at https://neurosurgery.shinyapps.io/PRAEMIUM/. CONCLUSION: The developed models for prediction of poor neurological outcome and new sensorimotor neurological deficits at discharge exhibit good calibration and fair discrimination based on a multinational external validation, indicating that the predicted probabilities correspond well to real-world risks and may thus be clinically useful in more objectively estimating the risk of microsurgical treatment.

BACKGROUND: Fusiform middle cerebral artery (MCA) bifurcation aneurysms can be challenging to treat, and high-flow bypass with proximal/distal parent vessel clipping may be an effective treatment option. Intraoperative ultrasound (ioUS)–contrast-enhanced ultrasound (CEUS) may offer real-time critical insights regarding the perisaccular/intrasaccular flow dynamic, to guide the intraoperative decision-making regarding different possibilities of trapping. OBSERVATIONS: A 65-year-old man with fibromuscular dysplasia, previously treated in 2012 for a right giant fusiform MCA prebifurcation aneurysm via superficial temporal artery–MCA bypass/clipping, presented with left upper limb paresthesia and confusion. Neuroradiological workup revealed a recurrence of the aneurysm distal to the previous clips, involving an M2 branch, with a dysplastic M1-M2 appearance and previous bypass failure. A high-flow external carotid (EC)–internal carotid (IC) bypass with aneurysm trapping was planned. Multiple ioUS scans showed a significant reduction in intra-aneurysmal flow after EC-IC bypass, progressing to flow cessation and initial thrombosis after distal clipping alone, eliminating the need for proximal dissection and reducing intraoperative morbidity. LESSONS: The ioUS-CEUS confirmation of the changes in aneurysm flow after the bypass and of the rapid intraoperative aneurysm thrombosis that could be observed after distal clipping underscores the pivotal role that ioUS may have in intraoperative decision-making in complex vascular cases. https://thejns.org/doi/10.3171/CASE25107

Moyamoya angiopathy (MMA) is a cerebrovascular disease determining chronic progressive steno-occlusion of the supraclinoid internal carotid arteries and their main branches. The pathogenesis of MMA remains largely unknown. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system characterized by the progressive accumulation of focal demyelinating lesions, whose pathophysiology has been theorized but still incompletely understood. Beyond misdiagnoses due to mimicking features among the two disorders, MS coexisting with MMA have been previously, rarely, reported. Herein, we present two other cases of patients with MMA with a concomitant, previously missed, diagnosis of MS and discuss their overlapping features as a hint for a potentially shared pathophysiology. The finding of typical angiographic features enables MMA diagnosis, yet it does not allow us to rule out other potentially concomitant disorders affecting the CNS. The association may be easily missed if the clinical/neuroradiological picture is not carefully assessed. Cerebral spinal fluid analysis and spine neuroimaging should be suggested in all MMA patients with atypical MRI lesions.