The journal retracts the article titled “The Impact of COVID-19 on Cognitive Development and Executive Functioning in Adolescents: A First Exploratory Investigation” [...]
Hearing impairment is among the most prevalent sensory disorders worldwide, affecting far more than just auditory thresholds [...].
Objective: Previous studies of deep brain stimulation-related (DBS) artifacts in magnetoencephalography (MEG) have largely focused on the sensor level. In contrast, far less is known about their effects at the source level, where neuroscientific interpretations are typically derived. This study aims to quantify how DBS artifacts distort source-level MEG imaging. Methods: The study used a phantom-based experimental setup to assess dipole-fitting accuracy while systematically varying the stimulation amplitude, DBS electrode configuration, and the distance between the dipole and the DBS electrode. Results: Dipole location, angle, and amplitude errors remained within modest ranges, with the largest location and angle errors occurring at 5 mA ring-electrode stimulation (6.19 mm and 8.31 deg, respectively) and the largest amplitude errors at 15 mA ring electrodes (13.05 nAm). Location and angle errors increased significantly as the dipole moved closer to the DBS electrode, while amplitude error showed no such relationship. Continuous head position indicator coil signal quality remained stable and reliable at DBS on condition, compared to DBS off. Conclusions: The stimulation itself does not significantly impair MEG dipole estimation, as fitting errors are similar with DBS on and off. The study introduces a quantitative framework to systematically assess DBS-related distortion via dipole-fitting error, which can also be extended to evaluate noise from other implanted or external devices.
Background/Objectives: Spirituality is increasingly recognised as a core dimension of holistic and palliative care. Neurodegenerative diseases such as dementia, amyotrophic lateral sclerosis and Parkinson’s disease involve prolonged trajectories of loss, uncertainty and relational change, which may heighten spiritual and existential needs for patients, particularly among those involved in caregiving, such as family caregivers and, to a lesser extent, healthcare professionals. However, evidence on how spirituality is understood, experienced and addressed within neurodegenerative palliative care remains fragmented and conceptually heterogeneous. This scoping review aimed to map the literature on caregivers’ spiritual needs and challenges. Methods: A scoping review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews (PRISMA ScR). Searches were conducted across PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), APA PsycINFO, and Scopus, with no date or geographical restrictions. Grey literature was searched through Google Scholar and relevant organisational and policy sources in the field of palliative care and spirituality. Reference list screening of included studies and relevant reviews was also conducted. Quantitative, qualitative, and mixed methods studies published in English or Italian were included. Results: Twenty-four studies published between 2007 and 2025 were included. Findings were organised into three interconnected domains: spiritual needs, spiritual processes and spiritual care. Spirituality emerged as a dynamic, relational and context-dependent dimension of caregiving, encompassing meaning, identity, connection and coping with vulnerability and loss. Spiritual needs and processes were widely described, while spiritual care was inconsistently recognised within healthcare systems. Conceptual ambiguity, under-representation of end-of-life dementia and cultural imbalances were evident. The evidence predominantly focused on family caregivers, with limited representation of healthcare professionals. Conclusions: This scoping review highlights a persistent gap between caregivers’ lived spiritual experiences and system-level responses in neurodegenerative palliative care in caregiving contexts globally. The findings support integrated, caregiver-inclusive and culturally responsive approaches to spiritual care.
Chronic subdural hematoma (CSDH) is traditionally described as a post-traumatic blood collection within the subdural space; however, both its anatomical localization and pathophysiology have been increasingly questioned. Ultrastructural and histopathological evidence demonstrates that no true subdural space exists under physiological conditions and that CSDH originates instead within the dural border cell (DBC) layer, a mechanically fragile and biologically active meningeal interface. Accordingly, chronic "subdural" hematoma may be more accurately interpreted as an intradural border cell lesion. Beyond anatomy, CSDH is a dynamic, self-sustaining disease driven by chronic inflammation, pathological angiogenesis, vascular immaturity, and localized hemostatic dysregulation. Hypoxia-induced HIF-1α/VEGF activation promotes fragile, hyperpermeable neovessels, while local hyperfibrinolysis and kallikrein-kinin activation prevent stable clot formation, driving recurrent microbleeding and plasma exudation. Consequently, hematoma persistence and recurrence represent a biological failure rather than a purely technical surgical shortcoming. This conceptual shift provides a coherent rationale for dural-targeted therapies, including middle meningeal artery embolization and pharmacological modulation of angiogenesis and fibrinolysis. Reframing CSDH as a chronic intradural and biologically active disorder has important implications for terminology, classification, and the development of mechanism-oriented, multidisciplinary management strategies.
Visual working memory (VWM) declines with age and has been explained by multiple mechanisms, including reduced precision, capacity limitations, binding deficits, and altered attentional control. However, these accounts are typically framed within a unitary processing architecture and do not fully capture the distributed nature of visual cognition. This review advances a coordination-based framework in which age-related differences in VWM are understood as partly reflecting reduced efficiency in integrating and regulating representations across the two cerebral hemispheres. Behavioural, electrophysiological, and neurophysiological evidence is synthesised to characterise the role of inter-hemispheric communication in VWM. Age-related changes in corpus callosum structure and function are then considered in relation to these coordination processes. Deficits in precision, capacity, binding, and attention are proposed to reflect different behavioural expressions of a common limitation in coordinating distributed representations, providing a unifying account of multiple behavioural signatures, particularly under conditions that place high demands on inter-hemispheric coordination. The framework offers a mechanistic explanation of the task-dependent nature of ageing effects and generates testable predictions for future research, highlighting the role of network-level coordination mechanisms in cognitive ageing.
Objective: Hemispherotomy is an effective treatment for select forms of drug-resistant hemispheric epilepsy, including perinatal stroke, Rasmussen's encephalitis, and Sturge-Weber syndrome. Post-traumatic epilepsy (PTE) has been reported to occur in ~10% of children following traumatic brain injury (TBI). TBI has not been extensively evaluated as an indication for hemispherotomy, as its effects are rarely unilateral. Here, we report the results from five pediatric cases of hemispherotomy for drug-resistant hemispheric PTE. Methods: A retrospective review was performed of all pediatric patients with drug-resistant PTE secondary to TBI who underwent hemispherotomy between 2018 and 2022 at the Children's Hospital of Philadelphia (n = 5). All patients initially underwent craniectomy and subsequent cranioplasty due to TBI; criteria for hemispherotomy were met in the following years, leading to a recommendation for hemispherotomy at the epilepsy surgery conference. Clinical characteristics, seizure and functional outcomes, and postoperative complications were reviewed. Seizure outcomes were classified according to the Engel criteria. Results: Five children (median age: 8.3 years, range: 5.0-10.3 years) with drug-resistant PTE underwent lateral trans-sylvian hemispherotomy. TBI etiology included non-accidental trauma (n = 3) and motor vehicle accidents (n = 2). All patients exhibited Engel Class Ia seizure outcomes (median follow-up: 15 months, range: 5-39 months), with a reduction in anti-seizure medications from a median of five preoperatively to one postoperatively. No patient experienced re-operation. Neuropsychological outcomes were patient-specific, with most exhibiting a mix of gains and challenges after surgery. Conclusion: We demonstrate the use of hemispherotomy to treat drug-resistant, hemispheric PTE in five children, with excellent reduction in seizure frequency and mixed or improved neuropsychological outcomes.
BACKGROUND/OBJECTIVES:Lysophosphatidic acid (LPA) is a bioactive lipid mediator implicated in neuropathic pain (NP). Depressive symptoms frequently accompany NP and adversely affect outcomes, yet objective biomarkers remain limited. This study aimed to identify cerebrospinal fluid (CSF) LPA molecular species associated with depressive symptoms in patients with NP. METHODS:CSF samples were obtained from 48 patients, and LPA species, including positional isomers (sn-1 and sn-2), were quantified using liquid chromatography-tandem mass spectrometry. Depressive symptoms were assessed using the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Statistical analyses were performed to evaluate associations among depressive symptoms, clinical variables, and LPA species. RESULTS:CSF LPA18:0 was significantly associated with HADS-D scores (r = 0.380, p = 0.010), with the strongest association observed for the sn-1 isoform (r = 0.385, p = 0.009). In multivariable analysis, LPA18:0 sn-1 remained independently associated with depressive symptoms, alongside pain intensity and pain catastrophizing (R2 = 0.386). Structural equation modeling supported an association between LPA18:0 sn-1 and depressive symptoms independent of pain-related factors. CONCLUSIONS:These findings suggest that CSF LPA18:0 sn-1 may be associated with a biological dimension of depressive distress and may represent a candidate biomarker of depressive distress in NP. However, these findings should be interpreted cautiously, as the analyses were exploratory, and further validation in independent and longitudinal cohorts is warranted.
BACKGROUND:Acute carbon monoxide (CO) poisoning can cause delayed neuropsychiatric sequelae (DNS) after a latent period, yet its pathophysiology remains poorly understood because of the lack of reproducible experimental models. METHODS:We established a rat model of DNS using acute CO poisoning (6500 ppm for 25 min). Behavioral assessments evaluated cognition, locomotion, sensorimotor function, exploratory behavior, and reward responsiveness. Histopathological analyses assessed brain injury, and regional monoamine concentrations were quantified using high-performance liquid chromatography. RESULTS:CO-exposed rats developed delayed and progressive behavioral abnormalities, including impaired spatial working memory, reduced locomotor activity, sensorimotor dysfunction, and diminished exploratory behavior. At 4 weeks, CO-exposed rats showed reduced Y-maze alternation (49.3% vs. 72.2%, p < 0.0001), complete loss of tape-removal success (0% vs. 100%, p < 0.001), reduced digging behavior (10.1 ± 6.9 vs. 27.4 ± 3.9, p < 0.01), and decreased locomotor activity (330.5 ± 172.1 vs. 730.5 ± 139.5 cm, p < 0.01). In contrast, olfactory discrimination, sucrose preference, and grip strength were preserved. Histopathology demonstrated persistent neuronal and inflammatory alterations. Dopamine concentrations were significantly reduced in the cortex and basal ganglia, whereas thalamic serotonin levels were increased following CO poisoning. CONCLUSION:Acute CO poisoning induces a reproducible DNS characterized by progressive behavioral impairment, persistent histopathological abnormalities, and regional monoaminergic dysregulation. These findings support the concept that DNS is an evolving neuropathological process and identify dopaminergic pathways as potential therapeutic targets.
Traumatic injury is one of the most common causes of disorders of consciousness (DoC) worldwide, but the management and prognosis of DoC remain enigmatic. The uncertainty surrounding the natural course of DoC, the tendency of consciousness to wax and wane, and a lack of effective treatments outside of avoiding additional insults renders trauma-associated DoC complex for both providers and patient surrogates to navigate. This review explores the acute clinical course of DoC after traumatic injury chronologically and aims to compile recommendations based on the current best practices for diagnosis, management, and prognostication when caring for these patients during their acute hospitalization. Updates from trauma and Traumatic Brain Injury (TBI) resources, such as the American College of Surgeons, as well as new recommendations in the field of DoC are summarized. Serial clinical assessment with a standardized neurobehavioral battery such as the CRSR-FAST remains the mainstay of clinical care and research for DoC. Accurate diagnosis, multifaceted management, and humility surrounding prognostic discussions are all critical to caring for patients with DoC after trauma. Most of the care for trauma patients with a DoC remains supportive and aimed at avoiding secondary insults while allowing time for the patient’s recovery. In the same way that clinical care focuses on a cycle of diagnosis, treatment, and prognosis with each providing insight for the next, ongoing and future DoC research will compound on itself and hopefully lead to more advances in the future.
Background/Objectives: In this three-stage study, we aimed to adapt an Auditory-Visual Stroop test (AV-Stroop test) for tinnitus subjects, evaluate the correlation between performance in the conventional Stroop test (C-Stroop test) and the AV-Stroop test; assess the effect of cognitive screening test performance on the AV-Stroop test’s results; and apply the AV-Stroop test in participants with tinnitus and controls. Methods: At the First Stage, the AV-Stroop test was adapted using white noise (WN), pure tone (PT), and narrow band (NB) sound stimuli. At the Second Stage, results of the AV-Stroop test, the C-Stroop test, and the Montreal Cognitive Assessment (MOCA) were compared (n = 45). At the Third Stage, the AV-Stroop test was applied to participants with and without tinnitus (n = 70). The tinnitus group was assessed with an additional test track (stimuli matched to tinnitus spectral characteristics, Tinnitus Pitch). Results: We adapted 34 training and evaluation tracks for the AV-Stroop test. AV-Stroop test’s results were correlated with C-Stroop test’s total task time (WN, p-value = 0.002; NB and PT, p-value < 0.001 comparing C-Stroop word reading task; and WN, NB, and PT, p-value < 0.001 for C-Stroop color naming task), and number of errors (NB, p-value < 0.001 comparing C-Stroop word reading task, and p-value = 0.012 for C-Stroop color naming task). Participants’ MOCA scores were not associated with AV-Stroop test performance. Participants with tinnitus required more time and made more errors in the AV-Stroop test. Additionally, the tinnitus group made more errors in the Tinnitus Pitch track. Conclusions: The AV-Stroop test proved to be an accessible, easy-to-administer tool for evaluating attentional and inhibitory control in participants with tinnitus. The stimulus with spectral characteristics similar to tinnitus perception was more effective in assessing top-down executive control in participants with the symptom.
Background/Objectives: Minor physical anomalies (MPAs) are subtle morphological markers of disrupted neuroectodermal development occurring during early gestation. Their increased prevalence has been reported in several neurodevelopmental and psychiatric conditions, including schizophrenia. However, data on MPAs in pediatric psychosis remain limited. This exploratory descriptive study aimed to characterize the occurrence of MPAs and congenital malformations in children presenting with early-onset psychotic symptoms and to illustrate the clinical heterogeneity through two representative cases. Methods: All participants underwent a comprehensive head-to-toe examination by a trained child and adolescent psychiatrist to identify MPAs. Key anatomical regions, including the face, hair vortex, palate, and extremities, were systematically photographed. Results were corroborated by MRI brain screening and consulted with a clinical geneticist. Anomalies were classified using the standardized Elements of Morphology terminology. Results: Among the 19 study participants, seven (37%) were diagnosed with very early-onset schizophrenia (VEOS). Identified minor physical anomalies included epicanthus (n = 5), café au lait spots (n = 2), and discoloured spots (n = 1). Furthermore, major congenital malformations were detected, specifically Arnold-Chiari malformation type I (n = 1), incomplete hippocampal inversion (n = 1), and a temporal cortex malformation (n = 1). Conclusions: MPAs and selected neuroanatomical anomalies were observed in a subset of children with early-onset psychotic symptoms. While the small sample size and absence of a control group limit interpretability, these exploratory findings suggest that systematic physical examination may provide supportive clinical information in the assessment of pediatric psychosis. Larger, controlled studies are needed to clarify whether specific MPAs may serve as early markers of neurodevelopmental vulnerability.
The question "what is an emotion" is as old as the study of the mind and brain. Scientists from Western, English-speaking, Industrialized, Rich, and Democratic (WEIRD) nations tend to adopt certain definitions, but these definitions do not map onto the lived experiences of all people around the world. My approach to the question "what is an emotion?" is thus to accept that emotions are folk concepts that do not "cut nature at its joints." Instead, I draw from models of predictive brain function to ask, "how does the brain make mental states in general, and experiences that we call "emotions" in particular?" I discuss recent models of predictive processing and how it is thought that the brain gives rise to feelings of valence and, arousal, and how, in some cultures, categorical emotional predictions (e.g., "anger") might have evolved as a particularly useful class of predictions for navigating humans' social worlds.
Background/Objectives: This study introduces Lightweight ScaleDense-Transformer (LST-Net), a design-driven framework for whole-lifespan brain age prediction, aiming to improve prediction accuracy while maintaining structural and biological plausibility. Methods: LST-Net utilizes a ScaleDense-Transformer architecture specifically engineered to mirror the dual-nature of brain aging: ScaleDense modules capture fine-grained local anatomical changes, while Transformers model global, network-level reorganizations. The framework was developed and evaluated using a modeling cohort of 22,271 subjects from 17 heterogeneous data sources, covering a 96-year lifespan. Additionally, an auxiliary quantum module (VQC) was incorporated within the latent bottleneck to facilitate nonlinear latent representation transformation and improve representation expressiveness. Performance was primarily assessed using Mean Absolute Error (MAE). Results: LST-Net achieved a competitive MAE of 2.71 years in brain age prediction, demonstrating stability across a wide lifespan (0-96 years) and varying data sources. Longitudinal assessments and test-retest analysis further confirmed the model's high reproducibility, yielding an Intraclass Correlation Coefficient (ICC) of 0.994. Conclusions: The current findings establish LST-Net as a scalable tool for brain health monitoring and large-scale screenings.
Background/Objectives: Alzheimer's disease (AD) remains a significant global health challenge, characterised by a persistent resistance to traditional pharmacological interventions. While non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) show therapeutic promise, their limited depth of penetration restricts their efficacy in targeting deep-brain AD pathology. Transcranial focused ultrasound stimulation (tFUS) has emerged as a novel, non-invasive neuromodulatory tool capable of precise deep-brain targeting. This scoping review aims to systematically map the current evidence base regarding the neuromodulatory application of tFUS in AD. Methods: Following PRISMA-ScR guidelines, a scoping search was conducted across four major databases (Ovid MEDLINE, Embase, Web of Science, and CENTRAL). Studies were included if they investigated focused ultrasound stimulation (FUS) as a neuromodulatory intervention for AD, excluding applications involving blood-brain-barrier disruption via microbubbles. Two independent reviewers performed screening and data extraction, with inter-rater reliability assessed via Cohen's kappa. Results: Our analysis indicates that tFUS represents a safe and potent multi-modal intervention for AD that addresses both pathological protein aggregation and electrophysiological network failure. Its ability to modulate neuroplasticity and metabolic recovery suggests a promising therapeutic trajectory. Conclusions: Future research should prioritise the standardisation of acoustic protocols and the pursuit of longitudinal clinical cohorts to establish the long-term efficacy of this non-invasive technology.
Background/Objectives: A current debate addresses where syntactic Merge primarily resides: the left-hemisphere posterior inferior frontal gyrus (IFG) or the temporo-parietal cortex. For proponents of the former, the temporo-parietal cortex supports more effortful processing; for the latter, the IFG supports integration and conflict resolution. We examine aperiodic activity in processing wh-filler-gap dependencies in French for evidence from network dynamics addressing engagement in syntax across L1 and L2. Methods: We extracted aperiodic activity 1/f components (considering offsets as a reflection of neuronal spiking and exponents as a reflection of excitatory-inhibitory balance) out of power spectrum density at 0.5-40 Hz across occipital and bilateral frontal and temporo-parietal regions of interest (ROIs) in reading. Results: Greater exponents arose in temporo-parietal than frontal ROIs in L1 and L2, with strong spiking and regulation suggested by greater offsets and exponents in the occipital ROI in L2-unlike L1-and with potential modulation by L1-L2 representation overlaps. These patterns suggest distributed cell assemblies for L1 and L2 processing. Increased regulation in temporo-parietal ROIs across L1 and L2 cell assemblies might suggest a structural function across temporo-parietal cortices in syntactic processing. Conclusions: Aperiodic activity reflecting connectivity in L1 and L2 processing supports distinct L1 and L2 cell assemblies, with L2 patterns suggesting potential overlap between L1 and L2 circuit modules. Greater exponents in bilateral temporo-parietal ROIs across L1 and L2 indicate increased regulation, supporting the engagement of lateralized temporo-parietal cortices in computations. These effects are discussed by considering advances in syntactic theory and the biology of language readiness.
Background/Objectives: Emotion processing has increasingly been conceptualized as a transdiagnostic mechanism underlying psychological adaptation and psychopathology. From an attachment perspective, individual differences in emotion perception may be rooted in internal working models shaped by early relationships. This systematic review synthesized the literature on the relationship between adult attachment representations and intrapersonal emotion perception (Impathy) and interpersonal emotion perception (Empathy). Methods: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted on 9 February 2026, in PsycINFO, PsycArticles, and PubMed. Studies were included if they investigated adolescents or adults, assessed attachment representations using narrative-based measures (Adult Attachment Interview (AAI) or Adult Attachment Projective Picture System (AAP)), and examined intrapersonal and/or interpersonal emotion perception. Findings were synthesized narratively, and a random-effects meta-analysis examined the association between attachment security and reflective functioning. Results: Thirty-eight studies, including 2736 participants, met the inclusion criteria. Across studies, attachment representations were systematically associated with intrapersonal and interpersonal emotion perception. The strongest evidence emerged for reflective functioning, the Impathy dimensions Perceiving and Understanding, and cognitive-empathic processes. Secure attachment representations were consistently associated with higher reflective functioning and more adaptive emotion perception, whereas insecure and especially unresolved attachment representations were linked to impairments in emotional self-awareness, alexithymia-related processes, differentiated emotional understanding, and cognitive-empathic processing. The meta-analysis showed a large positive association between secure attachment representations and reflective functioning (k = 8; r = 0.64, 95% CI [0.50, 0.74]). Conclusions: Attachment representations appear systematically associated with the perceptual foundations of emotion processing. Intrapersonal and interpersonal emotion perception may therefore represent attachment-sensitive processes relevant to psychological adaptation, psychopathology, caregiving, and therapeutic change.
Background: Intracranial hypertension is a critical complication of acute intracerebral hemorrhage (ICH), contributing to high early mortality and poor functional outcomes. Invasive intracranial pressure (ICP) monitoring remains the gold standard but carries procedural risks and is resource-intensive. This study evaluated the diagnostic and prognostic utility of optic nerve sheath diameter (ONSD) ultrasonography and transcranial Doppler (TCD)-derived pulsatility index (PI) as non-invasive ICP surrogates in patients with severe ICH. Methods: A prospective observational study was conducted in 42 patients with acute ICH who underwent concurrent invasive ICP monitoring and serial ONSD/PI measurements at 10 time points (T0-T9) between October 2021 and August 2024. Diagnostic performance was assessed using measurement-level receiver operating characteristic (ROC) curve analysis. Exploratory early mortality prediction was evaluated using random forest machine learning models incorporating ONSD, PI, age, and sex. Results: A total of 274 paired ONSD-PI-ICP measurements were obtained. Both ONSD and PI showed moderate positive correlations with invasive ICP (rho = 0.49 and 0.43, respectively; p < 0.001). ONSD demonstrated superior diagnostic accuracy for detecting ICP ≥ 20 mmHg (AUC = 0.83; optimal threshold: 5.88 mm; sensitivity: 81%; specificity: 82%) compared to PI (AUC = 0.75). In exploratory random forest analyses, the combined ONSD-PI model showed high apparent discrimination for elevated ICP detection (AUC = 0.98), while the model incorporating ONSD, PI, age, and sex showed promising but potentially optimistic discrimination for early mortality prediction (AUC = 0.95). These machine learning results should be interpreted cautiously because of the small sample size, repeated-measurement structure, measurement-level data partitioning, and limited number of early deaths. Conclusions: ONSD ultrasonography and TCD-derived PI showed promising performance as non-invasive ICP markers in severe acute ICH. However, because of the small sample size, repeated-measurement design, measurement-level analyses, and exploratory nature of the machine learning models, these findings require validation in larger external cohorts before routine clinical implementation.
Background/Objectives: Adverse events (AE) associated with neurosurgical interventions can cause neurological deficits and impaired functional outcomes. The Therapy-Disability-Neurology (TDN) grade classifies AE severity based on treatment requirements, disability, and neurological deficits, but has not been validated in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to validate the TDN grade in predicting functional outcomes and length of hospital stay (LOS) in aSAH patients, treated surgically and/or endovascularly. Methods: We conducted a single-center retrospective cohort study of a prospectively collected database of aSAH patients. Patients were recruited between 2009 and 2022. The TDN grade was retrospectively applied. Primary outcome variables were functional outcomes, assessed using the Glasgow Outcome Scale (GOS, selected for comparability with prior aSAH outcome literature), at discharge and last follow-up, and LOS. Results: We included 355 patients: mean age was 57.2 (12.9 SD) and 235 (66.1%) were female. The TDN grade showed a moderate positive correlation with length of hospital stay (rho = 0.4, p < 0.001). Negative correlations were observed with functional outcomes at discharge (GOS: rho = -0.56, p < 0.0001) and at last follow-up (GOS: rho = -0.58, p < 0.0001). The TDN grade demonstrated good discrimination for unfavorable outcome at last follow-up (AUC = 0.82) and good discrimination for employment status (AUC = 0.71). Patients with AEs stayed 7.63 days longer on average (p < 0.001). Conclusions: The TDN grade predicted hospital stay and functional outcomes in aSAH patients treated surgically and/or endovascularly, demonstrating good discrimination for unfavorable outcomes and employment status. These findings extend the grade's applicability to both treatment- and disease-related complications and support its potential utility as a standardized tool for prognostication and resource planning. Results should be interpreted in light of the single-center retrospective design and selection bias.
Background/Objective: Intracranial arteriovenous malformations (AVMs) are high-flow cerebrovascular lesions associated with a significant risk of intracranial hemorrhage, neurological morbidity, and mortality. Current management strategies, including microsurgical resection, endovascular embolization, stereotactic radiosurgery, and conservative observation, remain limited by procedural risk and uncertain long-term outcomes. Beta-blockers, particularly propranolol, have recently attracted interest as potential adjunctive therapies because of their vasoconstrictive, antiangiogenic, and vascular remodeling properties. This review evaluates the mechanistic rationale and current evidence regarding beta-blocker use in intracranial AVMs. Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar databases through January 2026 using combinations of the terms “arteriovenous malformation,” “AVM,” “beta-blocker,” “propranolol,” “angiogenesis,” “hemorrhage,” and “cerebral cavernous malformation.” Eligible studies included experimental investigations, translational studies, observational cohorts, case reports, clinical trials, systematic reviews, and meta-analyses evaluating beta-blocker use in intracranial AVMs or related vascular malformations. Studies unrelated to cerebrovascular lesions, duplicate reports, and non-English publications were excluded. Given the heterogeneity and limited volume of available AVM-specific literature, findings were synthesized narratively rather than through formal systematic review methodology. Discussion: Preclinical studies suggest that beta-blockers modulate molecular pathways implicated in AVM pathophysiology, including VEGF, HIF-1α, SDF1α/CXCR4, MMP-9, and Notch-associated signaling. These mechanisms may reduce abnormal angiogenesis, endothelial instability, and pathological vascular remodeling. Clinical evidence, however, remains limited to retrospective studies, perioperative reports, and indirect evidence from cerebral cavernous malformations. Observational studies have reported associations between beta-blocker exposure and certain favorable AVM characteristics, including lower rates of hemorrhagic presentation and less complex angioarchitecture. However, these findings are highly susceptible to confounding, reverse causation, and selection bias and should not be interpreted as evidence of disease modification. Conclusions: Beta-blockers cannot currently be recommended as definitive therapy for intracranial AVMs. Their established role remains perioperative hemodynamic control, while potential disease-modifying effects require validation through prospective studies and randomized clinical trials.
