Search Results (146)

Background and Objectives: Facial nerve palsy (FNP) remains a clinically relevant complication after vestibular schwannoma (VS) resection. Recovery trajectories vary according to the severity of neural injury and early postoperative facial function. This study aimed to characterize the temporal pattern of facial nerve recovery during the first postoperative year and to explore factors associated with favorable long-term function. Materials and Methods: We retrospectively analyzed 51 adult patients who developed FNP after VS surgery between 2020 and 2023. Facial nerve function was assessed using the House–Brackmann (HB) grading system and the Sunnybrook Facial Grading System (SBFGS) at discharge and at 1, 3, 6, and 12 months postoperatively. Longitudinal changes were analyzed using non-parametric repeated-measures methods with effect-size estimation. Favorable 12-month facial nerve function was defined as HB grade I–II. Given the limited number of unfavorable outcomes, associations with 12-month recovery were explored using parsimonious Firth-penalized logistic regression models. Results: At discharge, 45.1% of patients had HB II, 29.4% HB III–IV, and 25.5% HB V–VI. Facial function improved significantly during follow-up. Median SBFGS total score increased from 58.0 at discharge to 99.0 at 12 months (Friedman χ² = 118.78, df = 4, p < 0.001; Kendall’s W = 0.58), while HB grade also improved significantly (χ² = 107.48, df = 4, p < 0.001; W = 0.53). At 12 months, 37/51 patients (72.5%) achieved HB I–II and none remained in the HB V–VI category. Synkinesis, defined as an SBFGS synkinesis subscore > 0, was observed in 10/51 patients (19.6%) at 6 months and 19/51 (37.3%) at 12 months. HB grade and SBFGS score at discharge were strongly inversely correlated (Spearman ρ = −0.943, p < 0.001) and were therefore evaluated in separate models. After adjustment for age and tumor size, each one-grade increase in discharge HB was associated with lower odds of favorable 12-month function (OR 0.30, 95% CI 0.11–0.58; p < 0.001), whereas each 10-point increase in discharge SBFGS was associated with higher odds of favorable function (OR 1.90, 95% CI 1.32–3.53; p < 0.001). Conclusions: Facial nerve function showed substantial longitudinal improvement during the first year after VS surgery. Early postoperative facial function was independently associated with 12-month outcome in exploratory penalized regression analyses. Recovery may continue over several months, supporting prolonged functional surveillance, while the independent contribution of rehabilitation and the effect of nerve grafting require evaluation in larger prospective cohorts. Full article

Background/Objectives: To characterize the clinical and imaging phenotypes of schwannomatosis (SWN) in children, adolescents, and young adults (AYAs). Methods: This single-center retrospective cohort study included patients (age ≤ 25 years) with suspected SWN with archived magnetic resonance imaging (MRI) at Johns Hopkins between 2020–2026. Clinical characteristics, genetic testing results, and tumor imaging (including anatomic distribution), and treatment approaches were reviewed. Descriptive statistics were performed. Results: In total, thirty-eight patients with suspected SWN were identified (median age 20 years, range 6–25; 32% female). NF2-related SWN was the most common diagnosis (31/38, 82%; de novo: 24/31 (77%) and familial: 7/31 (23%)), followed by LZTR1-SWN (n = 1) and SWN-NOS/NEC (n = 2). A total of four patients (asymptomatic LZTR1 carriers (n = 2) and possible SWN (n = 2)) did not fulfill diagnostic criteria based on craniospinal and whole-body MRI. Familial NF2-SWN demonstrated a trend toward earlier presentation (median 5 vs. 8 years; p = 0.12). Visual manifestations occurred at a younger age than hearing loss (median 8 vs. 16 years; p = 0.053). Imaging burden was high (median 23 MRI/patient (range: 1–60). Bilateral vestibular schwannomas were nearly universal (30/31, 97%). Familial disease demonstrated a trend toward increased cranial meningiomas (86% vs. 54%; p = 0.20), while peripheral schwannomas (43% vs. 67%; p = 0.38) and ependymomas (14% vs. 42%; p = 0.37) were less frequent compared with de novo disease. Operative and non-operative management was documented in 65% (20/31) each. Conclusions: NF2-related SWN is the predominant subtype in a pediatric and AYA patient population and was associated with substantial early tumor burden at a tertiary specialty NF center. Full article

Objectives: The facial nerve (FN) possesses one of the most intricate anatomical courses in the head and neck, traversing the brainstem, temporal bone, and parotid gland before terminating within the muscles of facial expression. Owing to its complex anatomy, marked anatomical variability, and frequent distortion by adjacent pathology, preservation of FN integrity remains a fundamental challenge in skull base, otologic, and head and neck surgery. This review aims to provide a comprehensive synthesis of the contemporary literature regarding the clinical anatomy of the FN and to examine how anatomical variation, pathology-induced distortion, surgical strategy, and emerging technologies influence nerve preservation and functional outcomes. Methods: A comprehensive narrative review of the literature was conducted using PubMed, Scopus, and Google Scholar. Publications from 1983 through 2026 were searched using combinations of keywords, including “facial nerve,” “facial nerve anatomy,” “anatomical variation,” “vestibular schwannoma,” “hemifacial spasm,” “parotid surgery,” “facial nerve injury,” “facial nerve reconstruction,” “facial reanimation,” “diffusion tensor imaging,” “intraoperative neurophysiological monitoring,” and “artificial intelligence.” Peer-reviewed anatomical, radiological, clinical, and review articles published in English were included, while conference abstracts and studies lacking direct anatomical or surgical relevance were excluded. Particular emphasis was placed on surgically relevant anatomical variations, pathology-related anatomical distortion, advanced imaging modalities, intraoperative neurophysiological monitoring, reconstructive techniques, and predictors of postoperative facial nerve function. Results: Facial nerve preservation was found to depend on the interplay between individual anatomical variability, disease-related anatomical distortion, and operative strategy. In vestibular schwannoma surgery, nerve displacement, capsular adhesion, and cystic tumor degeneration were consistently associated with increased surgical complexity and less favorable postoperative facial function. In hemifacial spasm, successful microvascular decompression relied on precise identification of neurovascular conflict at the root exit zone. Within the parotid gland, substantial variability in branching architecture and surgical landmarks contributed to an increased risk of iatrogenic injury. Advanced imaging techniques, particularly diffusion tensor imaging tractography, improved preoperative prediction of FN location, while intraoperative neurophysiological monitoring enabled real-time assessment of neural integrity and functional preservation. Emerging artificial intelligence-based predictive models demonstrated potential to enhance patient-specific surgical planning and prognostication. Conclusions: Contemporary facial nerve surgery has evolved toward an individualized, anatomy-driven, and function-preserving paradigm supported by advanced imaging, intraoperative monitoring, and reconstructive strategies. Detailed understanding of both normal FN anatomy and pathology-induced anatomical distortion remains essential for optimizing surgical decision-making, maximizing nerve preservation, and improving long-term functional outcomes. Future developments integrating multimodal imaging, predictive analytics, and artificial intelligence may further refine patient-specific management and enhance postoperative facial function. Full article

Background: Brain tumor magnetic resonance imaging (MRI) reporting and tumor segmentation for treatment planning are time-consuming and variable. This retrospective fixed-sequence paired workflow study evaluates whether AI assistance is associated with changes in efficiency, consistency, and reproducibility. Methods: Thirty MRI cases (10 vestibular schwannomas, 10 meningiomas, 10 brain metastases) were assessed. Two neuroradiologists completed diagnostic reporting with and without AI assistance, and two physicians completed tumor delineation with and without AI-generated preliminary contours after a 3-week washout. Results: Reporting time decreased from 42.94 to 27.90 min for Reader A and from 101.04 to 80.47 min for Reader B, corresponding to median paired case-level reductions of 40.39% and 11.51%, respectively; only Reader A reached statistical significance. Sensitivity remained 97.73% and 100.00%, while precision was numerically higher after AI assistance (89.58% to 97.73% and 83.02% to 91.67%). Report-similarity metrics increased across ROUGE-L, BERTScore F1, and Sentence-BERT cosine similarity (all p < 0.001). Contouring time decreased from 54.63 to 4.93 min for Reader 1 and from 184.44 to 44.19 min for Reader 2, with median paired reductions of 100.00% and 87.11%. Dice coefficients were numerically higher after AI assistance (0.81 to 0.87 and 0.83 to 0.87). Conclusions: AI assistance was associated with shorter task-completion times, higher report-similarity metrics, and numerically higher contour-overlap measures. Prospective validation should determine whether these workflow efficiency gains translate into broader clinical benefit. Full article

Background/Objectives: For patients with profound deafness resulting from auditory nerve pathology, as in Neurofibromatosis type 2, auditory brainstem implantation (ABI) can restore meaningful acoustic input. The literature reporting real-world results for ABI users is limited, especially regarding patients with bilateral implants. Here, we provide an updated report on the audiologic outcomes among all ABI patients treated at a tertiary institution, including high-performing bilateral ABI users. Methods: In this updated and expanded retrospective case series, audiologic outcomes were reviewed in sixteen consecutive patients who underwent ABI placement by a single neurosurgeon-neurotologist team at our center since 2018. Implantation in four of these patients was on their second side after having undergone first side implantation prior to receiving care at our hospital. Main outcome measures were sound awareness (sound-field threshold testing) and speech understanding (pattern perception, spondee, open-set speech testing). Results: Sound awareness was achieved in 100% of patients (16/16) using an average of 12 electrodes (range 7–20). Persistent non-auditory sensations were reported by 12.5% (2/16). Postoperative speech differentiation (with or without lip-reading) was experienced in 87.5% (14/16). Two second-sided ABI recipients experienced exceptional outcomes as high-performing outliers: one achieved 57% audio only and 86% audio + visual hearing in noise test (HINT) sentence scores; the second bilateral user scored 92% with auditory-only input. Conclusions: ABI represents a viable option for patients who are at risk of developing bilateral profound deafness resulting from auditory nerve disruption. Second sided device implantation is safe and has the potential to significantly improve auditory outcomes. Full article

Background/Objectives: Hyperventilation-induced nystagmus (HVIN) has been described as a sensitive clinical sign in vestibular schwannoma (VS), potentially reflecting a reversible conduction block in partially demyelinated vestibular nerve fibers. However, its relationship with tumor size and instrumental vestibular deficits remains controversial. This study aimed to investigate the association between HVIN, tumor size, clinical presentation, and vestibular function assessed by the video Head Impulse Test (vHIT) and functional Head Impulse Test (fHIT). Methods: Eighty consecutive patients with unilateral VS were retrospectively evaluated. All underwent bedside vestibular examination, the vHIT, the fHIT, and the Hyperventilation Test (HVT). Tumors were classified according to the modified Koos–Sanna grading system. Associations between HVIN (presence and direction), demographic and clinical variables, vestibular deficits, and tumor size were analyzed using binary logistic regression, Fisher’s exact test, Welch’s independent samples t-test, and the Mann–Whitney U test. Results: HVIN was observed in 73% of patients. Among the patients with HVIN, ipsilesional horizontal nystagmus occurred in 57% of cases, 41% of the subjects showed contralesional nystagmus and one patient had downbeat nystagmus. vHIT abnormalities were identified in 54% of patients, while 30% of these also demonstrated fHIT deficits. No patient presented isolated fHIT abnormality. HVIN was detected even in patients with intracanalicular or small tumors and in some asymptomatic individuals. No statistically significant correlations were found between tumor size and HVIN presence, HVIN direction, or vestibular deficits in the vHIT/fHIT (all p > 0.05). Conclusions: HVIN is frequently observed in patients with VS, including those with small or asymptomatic lesions. However, neither its presence nor direction correlates with tumor size or objective vestibular deficit. The Hyperventilation Test should not be considered a prognostic tool but may serve as a simple and valuable adjunctive bedside examination in the early diagnostic suspicion of vestibular schwannoma. Full article

Background/Objectives: Vestibular evoked myogenic potentials (VEMPs) and the video head impulse test (vHIT) enable receptor-specific assessment of otolithic organs and semicircular canals. Their increasing use has revealed selective or apparently isolated vestibular abnormalities, although the clinical significance of these findings remains uncertain. This mini-review examines selective otolithic and semicircular canal dysfunction, with emphasis on diagnostic interpretation, methodological limitations, and future research needs. Methods: A structured narrative review of PubMed/MEDLINE and Scopus was conducted, focusing on studies reporting isolated, selective, or disproportionate vestibular abnormalities assessed by VEMPs and/or vHIT. Relevant original studies, case series, case reports, reviews, and diagnostic or consensus papers were considered. Results: Selective otolithic dysfunction may involve the utricle, saccule, or both and is often associated with imbalance, tilting, swaying, spatial disorientation, nausea, or postural instability. Selective semicircular canal dysfunction may involve one or more canals and may present with vertigo, dizziness, nystagmus, or gait instability. Similar VEMP and vHIT patterns occur across vestibular neuritis, Ménière’s disease, vestibular migraine, benign paroxysmal positional vertigo, bilateral vestibulopathy, superior semicircular canal dehiscence, vestibular schwannoma, central vestibular disorders, systemic diseases, and idiopathic presentations. Conclusions: Selective vestibular abnormalities should be interpreted as context-dependent laboratory findings rather than discrete disease entities. Their value depends on reproducibility, anatomical plausibility, clinical concordance, complementary testing, and longitudinal follow-up. Full article

Vestibular schwannomas (VSs) are benign tumors of the vestibulocochlear nerve that often cause significant neurological and functional impairment, affecting patients’ overall quality of life (QoL). While clinical assessments have traditionally focused on hearing preservation and tumor control, patients often emphasize other critical symptoms such as dizziness, pain, cognitive difficulties and satisfaction with care. Therefore, patient-centered care that addresses the full range of patient experiences is essential. Despite its importance, patient-centered care in VS remains underexplored. This study will address this gap by psychometrically validating the German version of the Vestibular Schwannoma Quality of Life (VSQOL) Index, a newly developed QoL tool that includes key patient-centered domains. The primary objective is to validate the reliability and validity of the German VSQOL Index. The secondary aim is to assess VS patients’ experience of patient-centered care and its impact on their well-being. This multicenter, cross-sectional study will involve German-speaking VS patients from several clinical centers in Germany and Switzerland as well as an online cohort. Psychometric testing of the German VSQOL will include reliability assessments (e.g., Cronbach’s alpha, test–retest reliability), confirmatory factor analysis and convergent validity. In parallel, the study will assess patient-centered experiences of care using the EPAT questionnaire. Ethical approval has been obtained and all participants will be asked to provide written informed consent. The results will be shared through scientific publications and conferences, as well as with patient groups, in order to support improvements in clinical care. Full article

Background: Vestibular schwannoma (VS) stereotactic radiosurgery (SRS) requires high target conformality and rapid dose falloff to spare adjacent organs at risk (OARs), particularly the brainstem. HyperArc (HA) is an automated noncoplanar volumetric-modulated arc therapy (VMAT) approach designed to standardize and streamline cranial SRS planning and delivery. We compared CyberKnife (CK) with HA for single-fraction VS SRS and evaluated the impact of multileaf collimator (MLC) leaf width. Methods: Fifteen VS cases previously treated with single-fraction CK SRS (12.5 Gy) were retrospectively replanned using HA. HA plans used four preconfigured noncoplanar partial arcs and were created with either a standard 5.0 mm MLC (HA-SMLC) or a 2.5 mm high-definition MLC (HA-HDMLC). HA plans were normalized to match the prescription dose target coverage of the corresponding CK plan for each of the patients. Endpoints included planning target volume (PTV) dosimetric statistics (Dmean, Dmin, Dmax, D98%), Paddick conformity index (PCI), Paddick gradient index (GI), ICRU Report 83 homogeneity index (HI), brain V12Gy, and brainstem Dmax. Because plans were generated for the same patients, paired comparisons were performed using two-sided Wilcoxon signed-rank tests (p < 0.05). Results: Both HA techniques achieved a higher near-minimum target dose than CK, with significantly higher PTV D98% (CK 12.35 ± 0.52 Gy; HA-SMLC 12.54 ± 0.28 Gy; HA-HDMLC 12.57 ± 0.35 Gy; p < 0.05). HA reduced target hotspots, with lower PTV Dmax than CK (CK 15.25 ± 0.32 Gy; HA-SMLC 14.70 ± 0.39 Gy; HA-HDMLC 14.73 ± 0.32 Gy; p < 0.05), and improved homogeneity and dose falloff as reflected by HI and GI (p < 0.05). CK achieved the highest conformity by PCI (p < 0.05), while HA-HDMLC improved PCI compared with HA-SMLC (p < 0.05). Brain V12Gy and brainstem Dmax were low and did not differ significantly among techniques. Conclusions: HA provides dosimetric performance comparable to CK for single-fraction VS SRS, with improved near-minimum PTV dose, reduced hotspots, and steeper dose gradients. Although CK showed the highest PCI overall, conformity improved with HA when a high-definition MLC was used. Overall, these findings support HA, particularly HA-HDMLC, as an efficient and clinically practical option for VS SRS treatment planning. Full article

Background: Gamma Knife radiosurgery (GKS) delivers highly conformal intracranial irradiation, yet clinical decision-making still relies predominantly on physical dose metrics that do not account for fractionation, dose rate, treatment time, or DNA repair. Classical radiobiological models—including the linear–quadratic (LQ) formula and the Jones–Hopewell single-session repair model—do not extend naturally to 3- and 5-fraction GKS. Meanwhile, growing evidence suggests that biologically effective dose (BED) may better capture radiosurgical response in selected pathologies. A unified, biologically grounded, multi-fraction GKS framework has been lacking. Methods: We developed AI-BED-Fx, the first multi-fraction extension of the Jones–Hopewell radiobiological model capable of computing fraction-resolved BED for 1-, 3-, and 5-fraction GKS. The framework incorporates α/β ratio, dual-component repair kinetics, isocentre geometry, beam-on–time structure, and lesion-specific biological parameters. Four synthetic pathology-specific cohorts—arteriovenous malformation (AVM), meningioma (MEN), vestibular schwannoma (VS), and brain metastasis (BM)—were generated using distinct radiobiological signatures. Machine-learning models were trained to quantify the predictive value of physical dose versus BED for local control or obliteration. Additional experiments included Bayesian estimation of α/β and a neural-network surrogate for fast BED prediction. An exploratory comparison with a 60-lesion clinical brain–metastasis dataset was performed to assess whether key trends observed in the synthetic BM cohort were consistent with real radiosurgical outcomes. Results: AI-BED-Fx produced realistic pathology-specific BED distributions (AVM 60–210 Gy_2.47; MEN 41–85 Gy_3.5; VS 46–68 Gy₃; BM 37–75 Gy₁₀) and biologically coherent dose–response relationships. Predictive modeling demonstrated strong pathology dependence. In AVM, the three models achieved AUCs of 0.921 (Model A), 0.922 (Model B), and 0.924 (Model C), with corresponding Brier scores of 0.054, 0.051, and 0.051, with BED-based models performing best. In meningioma, BED was the dominant predictor, with AUCs of 0.642 (Model A), 0.660 (Model B), and 0.661 (Model C) and Brier scores of 0.181, 0.177, and 0.179, respectively. In vestibular schwannoma, the narrow BED range resulted in minimal BED contribution, with AUCs of 0.812, 0.827, and 0.830 and Brier scores of 0.165, 0.160, and 0.162, with physical dose and tumor volume determining performance. In brain metastases, outcomes were driven primarily by volume and physical dose, with AUCs of 0.614, 0.630, and 0.629 and Brier scores of 0.254, 0.250, and 0.253, showing negligible improvement from BED. AI-BED-Fx also accurately recovered the true α/β from synthetic outcomes (posterior mean 2.54 vs. true 2.47), and a neural-network surrogate reproduced full radiobiological BED calculations with near-perfect fidelity (R² = 0.9991). Conclusions: AI-BED-Fx provides the first unified, biologically explicit framework for modeling single- and multi-fraction Gamma Knife radiosurgery. The findings show that the predictive usefulness of BED is pathology-specific rather than universal, and that radiobiological dose provides additional predictive value only when repair kinetics and dose–response biology support it. By integrating mechanistic radiobiology with machine learning, AI-BED-Fx establishes the conceptual and computational foundations for biologically adaptive, AI-guided radiosurgery, and cross-pathology comparison of treatment response. This work uses large radiobiologically grounded synthetic cohorts for methodological validation; limited real-patient data are included only for exploratory consistency checks, and full clinical validation is planned. Full article

There is no approved drug therapy for schwannomas associated with NF2-related schwannomatosis (NF2-SWN). Neither life-saving surgical resection or radiation are curative and can compound the debilitating neurological effects of the schwannomas. We previously identified fimepinostat, a dual histone deacetylase (HDAC)/phosphoinositide-3 kinase (PI3K) inhibitor, as a promising drug candidate with pro-apoptotic effects on NF2-related schwannomas. This preclinical study used the pharmaceutical formulation of fimepinostat to confirm its efficacy in schwannomas and identify pro-apoptotic signaling pathways. Fimepinostat was tested in human schwannoma model cells, patient-derived primary vestibular and non-vestibular schwannoma cells, and in a sciatic nerve allograft model. The signaling pathways leading to caspase-3-dependent apoptosis were elucidated using immune assays, flow cytometry, imaging, proteome, and acetylome analysis. Acute exposure to fimepinostat led to p21-dependent cell cycle inhibition, upregulation of tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL R2), and downregulation of tumor necrosis factor receptor 1 (TNFR1), Yes-associated protein (YAP), and inhibitors of apoptosis. Moreover, fimepinostat downregulated cytokine and chemokine secretion increased by merlin loss in schwannoma cells. Fimepinostat is a promising new drug intervention for NF2-SWN patients with the potential to promote tumor regression. Full article

Background: Vestibular schwannomas (VSs) are benign tumors that can cause significant morbidity, particularly in neurofibromatosis 2 (NF2) patients, in whom conventional treatments have important limitations. Merlin is a tumor suppressor protein encoded by the Neurofibromin 2 (NF2) gene, and the loss of its function leads to the activation of multiple signaling pathways, providing a rationale for targeted pharmacological therapies. Agents such as bevacizumab and other receptor tyrosine kinase inhibitors (TKIs) have shown variable efficacy but remain limited by toxicity and inconsistent responses. This review aims to evaluate the efficacy and safety of targeted therapies for VSs. Methods: This study was conducted according to PRISMA 2020 guidelines, using a PICO-based search of PubMed, EMBASE, and Scopus to identify studies on pharmacological therapies for VSs published between 2000 and 2025. Eligible human studies included clinical trials and observational studies reporting efficacy, safety, neuroimaging and audiological outcomes. Results: In total, 23 studies were analyzed, predominantly involving NF2-associated VSs. Treatment with bevacizumab was the most frequently investigated medical therapy and yielded the most consistent tumor control along with occasional hearing improvement, albeit with frequent but mostly manageable adverse events. Other targeted agents, including everolimus and TKIs, demonstrated limited or variable efficacy with acceptable toxicity profiles. Conclusions: VSs, particularly in NF2 patients, can cause significant morbidity and are often poorly managed by surgery or radiotherapy. Consequently, targeted medical therapies, especially anti-angiogenic agents, have emerged as valuable alternatives. Bevacizumab shows the most consistent benefits in tumor control, hearing stabilization, and quality of life, despite heterogeneous responses and notable toxicity. Evidence suggests that treatment discontinuation may lead to rapid tumor rebound, highlighting the need for long-term or maintenance strategies and careful monitoring. Future studies are needed to evaluate medical therapy integration with conventional treatments. Full article

Background/Objectives: Hypofractionated stereotactic radiosurgery (hfSRS) is increasingly used for benign intracranial tumors that are large or located near critical neural structures to reduce treatment-related toxicity. However, the optimal interval between fractions remains poorly defined, particularly for slowly proliferating benign tumors. This study evaluated clinical outcomes and longitudinal volumetric response patterns following Gamma Knife hfSRS delivered at fixed two-week intervals, with particular attention to the biological relevance of fraction timing. Methods: We retrospectively analyzed 126 patients with benign intracranial tumors, including meningioma, non-functioning pituitary neuroendocrine tumor (PitNET), vestibular schwannoma, and craniopharyngioma, treated between 2016 and 2022. Treatment was delivered in 2–5 fractions at fixed two-week intervals using Gamma Knife radiosurgery. Radiological outcomes included tumor control rate and longitudinal volumetric changes, while clinical outcomes included visual, auditory, and endocrine function. Propensity score matching was performed in PitNET and vestibular schwannoma cohorts to compare hfSRS with single-fraction stereotactic radiosurgery while minimizing baseline imbalances. Results: The overall tumor control rate was 98.4%. Across the entire cohort, tumors demonstrated a median volume reduction of −0.64% per month. In the propensity score–matched PitNET cohort, tumor control was comparable between treatment groups, whereas hfSRS was associated with earlier and greater volumetric reduction over time compared with single-fraction treatment. In the matched vestibular schwannoma cohort, long-term tumor control was similar between groups; however, transient tumor enlargement occurred more frequently after hfSRS without adversely affecting long-term tumor control or functional hearing outcomes. Conclusions: Hypofractionated stereotactic radiosurgery delivered at fixed two-week intervals achieved excellent tumor control with acceptable toxicity in selected benign intracranial tumors. These findings support the clinical feasibility of a fixed two-week inter-fraction interval and suggest that fraction timing may represent a biologically relevant treatment parameter influencing early volumetric response patterns without compromising long-term outcomes. Full article

Background/Objectives: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle. In preliminary studies, macrophage infiltration has been suggested to influence disease progression. However, the infiltration of other immune cells in VS remains largely unexplored. The aim of this study was to comprehensively characterize the immune cells in sporadic VS. Methods: Cryosections of five tumor samples from VS patients with different tumor volumes were examined. The abundance of fourteen immune-cell markers, one vascular marker, and two tumor markers were detected using multi-epitope ligand cartography (MELC). This enabled the spatial distribution and colocalization of immune- and tumor cell markers to be examined. Furthermore, using qPCR and bulk RNAseq, the mRNA levels of the immune-cell markers were examined in 204 VS samples of different tumor sizes. Results: VSs with greater tumor volumes showed an increased number of immune cells, more precisely T-helper cells (T_H cells), cytotoxic T cells (T_c cells), CD68⁺, and CD163⁺ macrophages, as well as CD279⁺ (PD-1) and CTLA4⁺ cells (p < 0.05). In addition, an increased number of CD274⁺ (PD-L1) tumor cells were detected in VSs with higher tumor volume (p < 0.05). Conclusions: These results indicate that an increased diversity of immune-cell subtypes influences VS tumor size. Thus, novel diagnostic and therapeutic options could be developed by targeting the tumor-associated immune-cell populations in VSs. Full article

Background: The vestibular schwannoma (VS) is the most common cerebellopontine angle tumor in adults, exhibiting a highly variable natural history, from stability to rapid growth. Accurate, the non-invasive prediction of tumor behavior is essential to guide personalized management and avoid overtreatment or delayed intervention. Objective: To systematically review and synthesize the evidence on MRI-based biomarkers for predicting VS growth and treatment responses. Methods: We conducted a PRISMA-compliant search of PubMed, EMBASE, and Cochrane databases for studies published between 1 January 2000 and 1 January 2025, addressing MRI predictors of VS growth. Cohort studies evaluating texture features, signal intensity ratios, perfusion parameters, and apparent diffusion coefficient (ADC) metrics were included. Study quality was assessed using the NOS (Newcastle–Ottawa Scale) score, GRADE (Grading of Recommendations, Assessment, Development and Evaluation), and ROBIS (Risk of Bias in Systematic reviews) tool. Data on diagnostic performance, including the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and p value, were extracted and descriptively analyzed. Results: Ten cohort studies (five retrospective, five prospective, total n = 525 patients) met the inclusion criteria. Texture analysis metrics, such as kurtosis and gray-level co-occurrence matrix (GLCM) features, yielded AUCs of 0.65–0.99 for predicting volumetric or linear growth thresholds. Signal intensity ratios on gadolinium-enhanced T1-weighted images for tumor/temporalis muscle achieved a 100% sensitivity and 93.75% specificity. Perfusion MRI parameters (K^trans, v_e, ASL, and DSC derived blood-flow metrics) differentiated growing from stable tumors with AUCs up to 0.85. ADC changes post-gamma knife surgery predicted a favorable response, though the baseline ADC had limited value for natural growth prediction. The heterogeneity in growth definitions, MRI protocols, and retrospective designs remains a key limitation. Conclusions: MRI-based biomarkers may provide exploratory signals associated with VS growth and treatment responses. However, substantial heterogeneity in growth definitions and MRI protocols, small single-center cohorts, and the absence of external validation currently limit clinical implementation. Full article