Brain Sciences最新文献

{"title":"Priming the Brain Before Chemotherapy: Chronic Stress and HPA-Axis Dysregulation in Cancer-Related Cognitive Impairment.","authors":"Lijo Andrews, Yasmin El Khaldi, Tracy George, Tala Abuhamdah, Nebojsa Nick Knezevic","doi":"10.3390/brainsci16101071","DOIUrl":"10.3390/brainsci16101071","url":null,"abstract":"<p><p>Cancer-related cognitive impairment (CRCI) is often attributed to chemotherapy, yet cognitive deficits are detectable in some patients before systemic treatment begins. This review examines a proposed two-hit framework in which cancer-related psychological and physiological stress contributes to pretreatment neural vulnerability, followed by superimposed chemotherapy-associated neurotoxicity. The review focuses on adults with non-central nervous system cancers. This narrative review synthesizes epidemiologic, neuroendocrine, neuroimaging, neuroimmune, autonomic, preclinical, and clinical evidence addressing chronic stress biology, pretreatment cognitive and brain changes, chemotherapy-related neurotoxicity, hypothalamic-pituitary-adrenal (HPA) axis interactions, and potential interventions. Pretreatment cognitive impairment has been reported in approximately one-quarter of patients, accompanied by elevated inflammatory cytokines, altered neurotrophic signaling, and changes in amygdala-hippocampal connectivity. The first hit may reflect interacting cancer- and host-related factors, including systemic inflammation, distress, sleep disruption, fatigue, pain, and HPA-axis/circadian dysregulation. The second hit occurs when chemotherapy inflicts superimposed neurotoxic injury, including white matter degradation, suppressed hippocampal neurogenesis, and blood-brain barrier disruption. The relationship may also be bidirectional: chemotherapy can perturb HPA-axis function, while glucocorticoid signaling may influence treatment response and antitumor immunity. Behavioral, autonomic, and circadian interventions are mechanistically promising, although neuroprotective efficacy remains uncertain. CRCI is likely multifactorial and may begin before chemotherapy. The two-hit framework integrates pretreatment stress-related vulnerability with treatment-associated neurotoxicity but remains hypothesis-generating rather than causally established. Prospective studies beginning at diagnosis and incorporating serial cognitive, psychological, endocrine, inflammatory, autonomic, and neuroimaging measures are needed to test this model and identify patients at greatest risk.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Inhalation of Sulphureous Water Mitigates Early Amyloid Pathology and Associated Microglial Changes in 5XFAD Mice.","authors":"Martina Bodria, Eleonora Daini, Stefano Pioli, Monica Piemontese, Eleonora Vandini, Alessandra Ottani, Michele Zoli, Daniela Giuliani, Antonietta Vilella","doi":"10.3390/brainsci16101069","DOIUrl":"10.3390/brainsci16101069","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter that exerts pleiotropic neuromodulatory, anti-inflammatory, cytoprotective, and trophic effects within the central nervous system. Objectuves: This study investigated whether chronic inhalation of naturally H₂S-rich sulphureous water, a non-invasive and clinically applicable intervention, exerts neuroprotective effects in 5XFAD mice, a transgenic model of severe AD pathology.</p><p><strong>Methods: </strong>Two-month-old male and female wild-type and 5XFAD mice underwent daily inhalation of saline or sulphureous water for eight weeks. Sulphureous water exposure was well tolerated and did not impair baseline learning or memory in either genotype. A detailed analysis of swim trajectories revealed selective enhancement of spatially accurate navigation strategies in sulphureous water-exposed 5XFAD female mice, with nearly a threefold increase in effective search behaviors, whereas male mice showed no treatment-specific effects. In addition, sulphureous water inhalation significantly reduced the number and area of 6E10⁺ and 11A1⁺ amyloid-β plaques in corticohippocampal regions and decreased cortical microglia number. Transcriptional profiling of cortical tissue revealed strong genotype-dependent upregulation of microglial, inflammatory, and stress-response genes. Sulphureous water exposure selectively modulated inflammatory and stress-response genes, including <i>Cd11b</i>, <i>Cst</i>, <i>Sod1</i>, <i>Tgfb1</i>, and <i>Hsp90a</i>, with distinct genotype-dependent interactions.</p><p><strong>Results: </strong>Overall, chronic inhalation of naturally H₂S-rich sulphureous water during the prodromal phase of AD-like pathology mitigated early amyloid burden, reduced cortical microgliosis, and improved qualitative aspects of spatial navigation, particularly in female mice.</p><p><strong>Conclusions: </strong>These findings warrant further translational investigation of sulphureous water inhalation as a potential preventive or disease-modifying strategy for AD in humans.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topographic Organization of Median Nerve Muscular Branches Reveals Frequent Shared Motor Pathways in the Human Forearm.","authors":"Alexandre Merí-Vived, Pedro Víctor López Plaza, Antoni Morral, Manuel Llusà-Pérez, Marcel García-Cuesta, Aroa Casado Rodríguez","doi":"10.3390/brainsci16101068","DOIUrl":"10.3390/brainsci16101068","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Classical descriptions of median nerve motor anatomy often emphasize muscle-specific destinations, although a single muscular branch may divide to supply several muscles. This can obscure the hierarchical relationship between branch origin and downstream ramification. We therefore quantified the two-dimensional topography of muscular branches arising directly from the median nerve and analyzed each branch origin as a single spatial event linked to its subsequent muscular destinations. <b>Methods</b>: Sixteen fresh, non-frozen right upper limbs from 16 independent adult body donors (8 male and 8 female; mean age, 82.2 ± 9.6 years) underwent standardized dissection. Cartesian coordinates were assigned only to the origin of each first-order muscular branch from the median nerve. Branches were ordered proximodistally and linked to downstream subbranch count and target muscles. Coordinates were normalized to bistyloid distance (RPX) and forearm length (RPY). Donor-clustered bootstrap confidence intervals and mixed-effects models with donor-specific random intercepts summarized spatial variation across branch rank, with the longitudinal association interpreted descriptively because rank was defined proximodistally. <b>Results</b>: Seventy muscular branches generated 274 recorded downstream subbranches and 146 unique branch-muscle associations. Limbs contained a median of 4 muscular branches (range, 2-6), and 32/70 branches (45.7%) supplied two or more target muscles; this proportion includes the anterior interosseous nerve when its origin met the study's branch-centered definition. The first branch participated in pronator teres innervation in all 16 limbs and was exclusive to that muscle in 11 (68.8%); all five sixth-ranked branches observed in this sample supplied flexor digitorum superficialis. As expected from the ranking definition, increasing branch order was descriptively associated with a more distal origin (β = 0.084; 95% CI, 0.063-0.104) and was associated with a higher normalized transverse coordinate (β = 0.077; 95% CI, 0.050-0.103; <i>p</i> < 0.001). Branch order explained substantially more longitudinal than transverse variance (marginal R², 0.444 vs. 0.183). <b>Conclusions</b>: Proximodistally ranked median nerve branch origins were associated with frequent and variable downstream multi-muscle pathways. The rank-longitudinal coordinate association does not independently establish anatomical reproducibility. Treating the muscular-branch origin as the coordinate-level unit preserves the anatomical hierarchy, prevents pseudoreplication of shared coordinates, and provides an anatomical framework with potential relevance to peripheral nerve surgery; clinical benefits remain untested.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Numerical Cognition in Neurodegenerative Disorders: A Systematic Review of Patterns of Preservation and Impairment.","authors":"Joël Macoir","doi":"10.3390/brainsci16101067","DOIUrl":"10.3390/brainsci16101067","url":null,"abstract":"<p><strong>Background/objectives: </strong>Numerical cognition comprises multiple processes supporting the representation, comprehension, production, and manipulation of numerical information. Although numerical impairments have been described in neurodegenerative diseases, findings remain fragmented across disorders and numerical domains. This systematic review aimed to characterize patterns of preserved and impaired core numerical abilities across neurodegenerative disorders and to examine their implications for cognitive models and clinical assessment.</p><p><strong>Methods: </strong>PubMed, Web of Science, and PsycINFO were systematically searched for original empirical studies in English or French examining core numerical cognition in adults with neurodegenerative disorders or mild cognitive impairment. Reference lists were additionally screened. Methodological quality was appraised using design-specific Joanna Briggs Institute critical appraisal tools. Forty-seven studies published between 1989 and 2026 met the eligibility criteria. Findings were synthesized qualitatively because of substantial heterogeneity in study designs, clinical populations, and numerical measures.</p><p><strong>Results: </strong>Numerical profiles varied considerably across disorders, individuals, and disease stages, but several broad patterns emerged. Basic number comprehension and magnitude processing were often relatively preserved, whereas greater vulnerability was observed for processes requiring transformation, retrieval, or manipulation of numerical information. Arithmetic fact knowledge showed variable preservation, including dissociations between stored knowledge and its retrieval. Calculation procedures and complex calculation were among the most consistently affected abilities. Evidence was strongest for Alzheimer's disease and semantic variant primary progressive aphasia and remained limited for several other neurodegenerative disorders.</p><p><strong>Conclusions: </strong>Numerical cognition is differentially affected across neurodegenerative diseases, supporting its multicomponent organization. These findings suggest the potential value of multidomain assessment rather than reliance on isolated calculation tasks. However, methodological heterogeneity, variation in methodological strength across studies, and the limited evidence available for several disorders reduce confidence in the generalizability of these patterns and currently preclude defining reliable disease-specific numerical signatures.</p><p><strong>Registration: </strong>OSF, 10.17605/OSF.IO/DU2Y9.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Factors in Brain-Computer Interfaces: Boundaries, Key Issues, and Methodological Approaches.","authors":"Liu Yan, Tianwen Li, Lei Zhao, Anmin Gong, Hao Fang, Wuheng Zuo, Yunfa Fu","doi":"10.3390/brainsci16101066","DOIUrl":"10.3390/brainsci16101066","url":null,"abstract":"<p><p>The large-scale, real-world deployment of brain-computer interface (BCI) is confronted with human factors bottlenecks, including reliability and usability. While modern human factors engineering has encompassed domains such as cognitive ergonomics, workload, adaptive automation, and human-in-the-loop systems, its theories and methodologies have historically placed their main emphasis on overt behavior and peripheral physiological measures, rather than on central neural activity as a primary control input. For the emerging interaction paradigm that takes central nervous activity as direct input and emphasizes long-term brain-computer co-adaptation, there remains a shortage of targeted conceptual and methodological frameworks. As a conceptual review, this paper discusses the necessity and disciplinary foundations for developing Human Factors Engineering for BCIs as an emerging interdisciplinary research direction. First, grounded in the defining features of BCI interaction-such as the implicit nature of input and brain-computer co-adaptation-it delineates the research boundaries and summarizes the core research objects as user neurocognitive characteristics, brain-computer collaborative adaptation mechanisms, multimodal feedback regulation, and contextual adaptation patterns. Second, it identifies three core scientific questions: individual differences and dynamic adaptation, human factors optimization and fault tolerance, and contextual generalizability principles, with ethics, privacy, and user rights and interests as an overarching dimension. Furthermore, it constructs a methodological system consisting of multimodal measurement and modeling, closed-loop validation, and multidimensional evaluation, and examines the supporting role of artificial intelligence approaches within this framework. Centered on the collaborative adaptation across neural, cognitive, and system levels, Human Factors Engineering for BCIs represents a deepening of the human-centered design philosophy. It provides theoretical reference for user-friendly BCI design and extends the research boundaries of human factors engineering.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalamic <i>Htr3a</i> Gene Expression in Hemi-Parkinsonian Rats Subjected to Persistent Pain.","authors":"José Luis Cortes-Altamirano, Alfonso Alfaro-Rodríguez, Samuel Reyes-Long, Francisco Ulises Ortiz-Moreno, Herlinda Bonilla-Jaime, Angelica González-Maciel, Beatriz Pérez-Guille, Rosa Eugenia Soriano-Rosales, Rafael Reynoso-Robles, David Calderon-Guzman, Hugo Juaréz-Olguín","doi":"10.3390/brainsci16101065","DOIUrl":"10.3390/brainsci16101065","url":null,"abstract":"<p><p><b>Background</b>: Pain is a frequent and debilitating non-motor symptom of Parkinson's disease; however, its central neurochemical mechanisms remain incompletely understood. Serotonin modulates nociceptive processing, and the 5-HT3A receptor has been implicated in excitatory signaling and central sensitization. However, thalamic <i>Htr3a</i> transcript regulation during persistent pain associated with dopaminergic injury remains unclear. <b>Objective</b>: To evaluate thalamic <i>Htr3a</i> mRNA expression in 6-OHDA hemi-Parkinsonian rats subjected to formalin-induced persistent pain. <b>Methods</b>: Male Wistar rats were assigned to six groups (n = 6/group): Saline, Formalin, SHAM + Saline, SHAM + Formalin, 6-OHDA + Saline, and 6-OHDA + Formalin. 6-OHDA lesions were validated via apomorphine-induced rotations (>7 turns/min). Nociceptive behavior (flinches) was recorded over 60 min post-formalin injection. Bilateral thalamic <i>Htr3a</i> mRNA expression was quantified by RT-qPCR using Rpl27 as a validated reference gene. <b>Results</b>: 6-OHDA + Formalin rats exhibited a significant increase in persistent-phase nociceptive behavior compared to controls (<i>p</i> < 0.05). <i>Htr3a</i> mRNA expression showed a significant bilateral reduction in 6-OHDA-lesioned rats compared to controls (<i>p</i> < 0.05), with the decrease being significantly more severe in the ipsilateral thalamus (<i>p</i> < 0.001). <b>Conclusions</b>: Unilateral 6-OHDA lesion is associated with a region-dependent reduction in thalamic <i>Htr3a</i> mRNA expression during persistent pain. These results demonstrate transcriptional adaptations of the thalamic serotonergic system in experimental parkinsonian persistent pain.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease.","authors":"Pavan Kumar","doi":"10.3390/brainsci16101064","DOIUrl":"10.3390/brainsci16101064","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive neurodegenerative disease in the elderly population [...].</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Language Perception and Processing.","authors":"Ratree Wayland","doi":"10.3390/brainsci16101063","DOIUrl":"10.3390/brainsci16101063","url":null,"abstract":"<p><p>When I proposed this Special Issue, I used the term language processing broadly to encompass not only the perception and processing of speech sounds but also the use of syntactic, semantic, and contextual information during language comprehension [...].</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Resting-State Neural Oscillations and Functional Connectivity in Persistent Postural-Perceptual Dizziness.","authors":"Feng Li, Chi Zhang, Weiwei Jiang, Bo Song, Yingxin Wang, Lu Tang, Shanshan Chen, Xiangyi Liu, Jingping Shi","doi":"10.3390/brainsci16101056","DOIUrl":"10.3390/brainsci16101056","url":null,"abstract":"<p><p><b>Background:</b> Persistent postural-perceptual dizziness (PPPD) is a chronic functional neuro-otologic disorder marked by persistent dizziness, unsteadiness, and visual dependence. Its electrophysiological mechanisms remain unclear. This study examined resting-state EEG spectral power and functional connectivity in PPPD and their associations with postural stability and clinical symptoms. <b>Methods:</b> Forty patients with PPPD and 40 age- and sex-matched healthy controls were studied with an eyes-closed resting-state EEG recording. Static postural stability was measured with the Pro-Kin system. Spectral power was calculated for delta, theta, alpha, beta, and gamma bands. Functional connectivity was assessed using the weighted phase lag index. <b>Results:</b> Static posturography showed impaired postural stability in patients with PPPD compared with healthy controls. Spectral power analysis showed increased theta-band relative power over the frontal and left parieto-occipital regions. Connectivity analysis showed increased prefrontal-temporal and decreased temporal-occipital connectivity in the theta band, increased fronto-parieto-occipital and decreased parietal-temporal connectivity in the alpha band, and decreased cerebellar and temporal, central connectivity in the gamma band. <b>Conclusions:</b> PPPD was associated with frequency-specific alterations in resting-state cortical oscillations and functional connectivity involving cognitive-affective, visual, and sensorimotor networks. Resting-state EEG may help characterize network-level abnormalities in PPPD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gyroscopic Radiosurgery for Trigeminal Neuralgia: Results of a Retrospective Series of >50 Patients.","authors":"Luis Real Peña, Morena Sallabanda, Marta Quirós Martí, Kita Sallabanda","doi":"10.3390/brainsci16101061","DOIUrl":"10.3390/brainsci16101061","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic radiosurgery (SRS) is an established treatment option for medically refractory trigeminal neuralgia (TN). However, clinical evidence regarding dedicated gyroscopic radiosurgery systems remains limited. This study aimed to evaluate the efficacy, latency of response, safety, retreatment rate, and potential clinical and dosimetric predictors of outcome following ZAP-X gyroscopic radiosurgery for TN.</p><p><strong>Methods: </strong>A consecutive series of patients with pharmacologically refractory TN treated with ZAP-X gyroscopic radiosurgery between February 2023 and September 2025 was analyzed. Treatment consisted of a single isocenter targeting approximately 5 mm of the cisternal-retrogasserian trigeminal nerve, with a maximum dose of 90 Gy and a V70 Gy coverage objective ≥ 50%, using 4 or 5 mm collimators. Pain outcome was assessed using the Barrow Neurological Institute Pain Intensity Scale (BNI), and sensory toxicity was evaluated using the BNI Facial Numbness Scale. Clinical and treatment-related predictors of failure and retreatment were explored using binary logistic regression.</p><p><strong>Results: </strong>Following radiosurgery, 87.5% of patients achieved satisfactory pain control (BNI I-IIIb; 95% CI, 78.8-96.2%), with a significant overall improvement in BNI score compared with baseline (<i>p</i> < 0.001) at the 12 months of follow-up. Half of the patients experienced clinical improvement within the first 15 days. Treatment-related toxicity occurred in 8.9% of patients, while 26.8% required repeat radiosurgery during follow-up. The decision to perform retreatment is made when the patient has shown no improvement in the BNI score at 6 months after the initial treatment. Baseline BNI grade V was the only statistically significant predictor of treatment failure, conferring a more than ninefold higher odds of non-response compared with BNI grade IV (OR 9.33; 95% CI, 1.66-52.3; <i>p</i> = 0.011). Female sex showed a nonsignificant trend toward a lower risk of failure (OR 0.65; 95% CI, 0.13-3.24; <i>p</i> = 0.596). Neither multiple sclerosis-associated TN nor other etiological or dosimetric variables significantly predicted treatment failure. A greater number of beams showed a trend toward an increased probability of retreatment (OR 1.01; <i>p</i> = 0.091), although statistical significance was not reached.</p><p><strong>Conclusions: </strong>Gyroscopic radiosurgery with ZAP-X provides high rates of pain control, rapid clinical response, and a favorable safety profile in patients with refractory TN. Greater baseline pain severity appears to be associated with poorer treatment response. These findings support ZAP-X as an effective frameless radiosurgical alternative for TN, although larger prospective studies are required to identify robust clinical, dosimetric, and radiobiological predictors of long-term outcome.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"16 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149262593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}