Abstract:

Patent foramen ovale (PFO) is present in roughly one quarter of adults and is over-represented among younger patients with cryptogenic ischemic stroke. The past decade has produced compelling evidence from randomized trials showing that PFO closure is superior to medical therapy in preventing recurrent ischemic stroke in appropriately selected patients. Despite this, anticoagulation continues to be used when closure is not feasible, declined, contraindicated, or considered after recurrent events. The observation that some patients experience “breakthrough” stroke or transient ischemic attack (TIA) despite therapeutic anticoagulation raises a critical question: why does medical therapy fail in PFO-related stroke, and why does closure appear superior? This narrative review synthesizes the latest evidence on the pathophysiology of PFO-associated stroke, with attention to mechanisms that remain incompletely addressed by anticoagulation. It analyzes randomized trial data comparing antiplatelet therapy, anticoagulation, and transcatheter closure. It examines the role of high-risk PFO anatomical characteristics, the Risk of Paradoxical Embolism (RoPE) score, and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification in understanding medical therapy failure. Additionally, the review explores whether PFO “type” predicts anticoagulation failure and highlights future research directions needed to further optimize therapy. The conclusion is clear: in the selected patients with high-risk features closure offers superior stroke prevention beyond what anticoagulation can achieve.

Abstract:

Cerebrospinal fluid (CSF) oligoclonal band (OCB) analysis is central to the diagnostic evaluation of neuroinflammatory diseases of the central nervous system (CNS), yet its reliance on lumbar puncture limits utility in screening and longitudinal monitoring. Serum metabolomics provides a minimally invasive approach to capture peripheral correlates of intrathecal immune activity. This study extends our previous two-group comparison by incorporating all five classical OCB patterns to delineate serum metabolic gradients associated with varying degrees of intrathecal immunoglobulin synthesis. A total of 92 adults undergoing diagnostic evaluation for suspected CNS inflammatory disorders were stratified by OCB Type (1–5). Serum samples were analysed using targeted ¹H-NMR spectroscopy on a Bruker Avance Neo 600 MHz platform and processed with Bruker’s IVDr pipeline. Statistical analyses included Kruskal–Wallis testing with FDR correction, PCA, PLS-DA with VIP scoring, and ROC-AUC modelling. Six metabolites exhibited significant or near-significant differences, led by Leucine (p = 0.0047, q = 0.073) and 2-Oxoglutaric acid (p = 0.0022, q = 0.069). PLS-DA identified five key discriminators with VIP > 1.5: Leucine, 2-Oxoglutaric acid, Histidine, Valine, and Glycine. A combined logistic model (Leucine + Histidine + Citric acid) achieved an AUC of 0.83 for distinguishing OCB Type 1 from Type 2. This first targeted serum ¹H-NMR metabolomic evaluation across all OCB patterns reveals a graded biochemical trajectory reflective of intrathecal immune activation. Amino-acid and TCA-cycle intermediates emerge as promising minimally invasive candidates for neuroinflammatory stratification and precision evaluation beyond traditional MS paradigms.

Abstract: Major depressive disorder was, until recently, framed as a single entity arising from a linear stress–monoamine–hypothalamic–pituitary–adrenal (HPA) axis cascade, modeled by forced swim and learned helplessness tests and evaluated by brief Hamilton Depression Rating Scale (HAM-D)/Montgomery–Åsberg Depression Rating Scale (MADRS) symptom trials. This “unitary cascade” view has been dismantled by imaging, immune–metabolic and sleep profiling, and plasticity markers, which reveal divergent circuit, inflammatory, and chronobiological patterns across anxious, pain-laden, and cognitively weighted depression, with non-response and relapse common. Translationally, face-valid rodent assays that equated immobility with despair have yielded limited bedside benefit, whereas cross-species bridges—electroencephalography (EEG) motifs, rapid eye movement (REM) architecture, effort-based reward tasks, and inflammatory/metabolic panels—are beginning to provide mechanistically grounded, clinically actionable readouts. In current practice, depression care is shifting toward systems psychiatry: inflammation-high and metabolic-high archetypes, anhedonia- and circadian-dominant subgroups, formal treatment-resistant depression (TRD) staging, connectivity-guided neuromodulation, esketamine, selected pharmacogenomic panels, and early digital phenotyping, as endpoints broaden to functioning and durability. A central gap is that heterogeneity is acknowledged but rarely built into trial design or implementation. This perspective advances a plasticity-centered systems psychiatry in which a testable prediction is that manipulating defined prefrontal–striatal and prefrontal–limbic circuits in sex-balanced, chronic-stress models will reproduce human network-defined biotypes and treatment response, and proposes hybrid effectiveness–implementation platforms that embed immune–metabolic and sleep panels, circuit-sensitive tasks, and digital monitoring under a shared, preregistered data standard.

Abstract: Traumatic brain injury (TBI) often leads to long-lasting motor deficits, yet the cellular mechanisms underlying these impairments remain incompletely understood. Here we examined glial and neuronal responses following focal ablation injury of the hindlimb sensorimotor cortex in adult male rats, a model previously shown to induce persistent gait asymmetry and postural deficits. Immunohistochemical analysis of resting and activated microglia, astrocytes, and neurons was performed bilaterally in peri-lesional cortex at 3, 7, 14, 21, and 28 days post-injury. The injury produced an early, sharply lo-calized increase in activated microglia and macrophages in the injured hemisphere, followed by sustained microglial activation that gradually extended contralaterally. Astrocytic activation displayed a delayed but more prolonged profile, rising ipsilater-ally within the first week, peaking around two weeks, and becoming bilaterally ele-vated by four weeks. Neuronal density and morphology were preserved throughout, indicating that motor impairments arose without secondary neuronal loss. These find-ings demonstrate a structured and temporally distinct cascade of glial responses mir-roring the evolution of motor deficits. The results suggest that focal cortical injury ini-tiates sequential inflammatory and astrocytic processes without secondary neuronal loss, highlighting glial–neuronal interactions as key targets for improving motor re-covery after TBI.

Abstract: Background: Spasticity significantly impacts quality of life, function, and social participation in individuals with neurological conditions. Despite the widespread use of botulinum toxin, variability persists in patient information, access to specialized rehabilitation, and follow-up models. Methods: This two-phase Delphi-Dialogue Patients-Professionals study (DDPP), promoted by the Spanish Society of Physical Medicine and Rehabilitation (SERMEF), integrated perspectives from 77 patients and 141 rehabilitation professionals. In Phase 1, parallel surveys assessed satisfaction, perceived effectiveness of botulinum toxin, communication preferences, and rehabilitation follow-up. In Phase 2, a Real-Time Delphi process with 38 experts generated consensus recommendations for improving spasticity management. Results: Patients and professionals broadly agreed on the benefits of botulinum toxin, the importance of ongoing rehabilitation, and the value of hybrid (in-person/remote) follow-up, but relevant gaps emerged regarding access to Physical Medicine and Rehabilitation services, clarity and timing of information, and shared goal setting. The expert panel converted these misalignments into a prioritized set of ten recommendations, with the highest feasibility assigned to actions that standardize access pathways, optimize botulinum toxin use, reinforce structured education, and consolidate hybrid rehabilitation models. Conclusions: The DDPP methodology provides a reproducible framework for aligning patient and professional perspectives in spasticity care by transforming quantified divergence into consensus-based innovation priorities. Implementing the agreed recommendations—especially those that reinforce communication, structured education, and hybrid rehabilitation pathways around botulinum toxin treatment—may help spasticity services evolve toward a more accessible, personalized, and patient-centered model.

Abstract: Many molecules (mainly growth factors and/or cytokines) are produced by human central nervous system (CNS) cells and may positively or negatively influence oligodendrogenesis, proliferation, and the migration of oligodendrocyte precursor cells (OPCs). Multiple sclerosis (MS) leads to the destruction of CNS myelin sheaths and myelin-producing oligodendrocytes (ODCs). This review considers the few published studies of platelet-derived growth factor (PDGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ciliary-neurotrophic factor (CNTF) in cerebrospinal fluid and/or post-mortem CNS samples which, like previously reviewed studies of epidermal growth factor (EGF), have shown deranged levels in MS, and also considers the abnormal levels of Nuclear Factor kappa-light-chain-enhancer of activated B cells and some microRNAs in MS CNS. The derangements of all of these molecules in MS CNS surely hinder ODC differentiation, proliferation, and migration, and ultimately they contribute to remyelination failure. Despite the differences between MS and experimental autoimmune encephalomyelitis (EAE), it is also worth noting that the individual administration of PDGF, BDNF, CTNF, and EGF prevents the onset and/or “cures” EAE in mice, and so, together with findings concerning other aspects of MS, the results of the reviewed studies seem to support the idea that MS demyelination is a consequence of oligodendrocytopathy followed by an autoimmunity reaction.

Abstract: Hydrocephalus remains a complex neurosurgical pathology requiring permanent cerebrospinal fluid (CSF) shunting. This work explores the characteristics of polymer resins, intended to isolate and stabilize the micromagnets of the pressure and flow adjustment mechanism. The polymeric disc containing the micromagnets play a critical role in the functional stability and safety of programmable valves with magnetic mechanism: any failure of the coating can lead to corrosion phenomena and ion diffusion in the LCS. It has a diameter of 5.5 mm and on it are positioned 10 magnets with a diameter of 2 mm. However, corrosion phenomena and electrochemical interactions between the magnets and LCS represent a potential risk of ion release (Co, Sm, Nd, B, Pt and Fe) and toxicity in LCS. The study focuses on the nature of coating resins, by several techniques. Electrochemical measurements using rotating electrode technology, and by impedance (EIE), through Nielsen-Tuccillo tests and release kinetic tests on encapsulated magnets. Three resins were evaluated: Stycast 1266, Stycast 1267 and Loctite Medical Device Adhesives. The encapsulated magnets are of CoSmCo and CoNd Fe B nature. All tests reveal an ion exchange permeability between electrolyte NaCl 9 g/l is the coated magnets after three days of immersion. All three resins shift the sweeping polarisation curves into the domain of 10-7 – 10-12 A/cm2 Degradations by corrosion phenomena on the surfaces of magnets were found in the case of Stycast 1266 by the Nielsen-Tuccillo test after 30 days of immersion. The extraction kinetic tests were carried out for 30, 60 and 90 days. The series Stycast 1267 releases cobalt mainly in the first 60 days, then we note un niveau qui est établi à environ 0,8 µg /l. The Loctite series a level of about 0.15 µg/l is observed for 60 days, then cobalt release increases to 1.2 µg/l after 90 days. The Stycast 1267 series releases Nyodymium up to a concentration that could reach 0.6 µg.l-1. The release of Nyodymium from the Loctite series is at the detection limit < 0.2 6 g/l after 90 days. Future generations of valves, integrating electronic sensors and wireless telemetry, will have to take these constraints into account to ensure long-term reliability and biocompatibility in their functional environment.

Abstract: Alzheimer’s disease (AD) is considered one of the leading cause of death in the United States, and there is no effective cure for it. Understanding the neuropathological mechanisms underlying AD is essential for identifying early, reliable biomarkers and developing effective therapies. In this paper, we report on a comprehensive multimodal study of AD pathology using the 5xFAD mouse model. We employed light-scattering techniques, Partial Wave Spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect nanoscale structural alterations in brain tissues, nuclear components, and mitochondria. To support the light-scattering experiments, behavior, and histopathological studies were conducted. These analyses revealed significant increases in structural heterogeneity and mass density fluctuations in the brains of 5xFAD mice compared with Non-transgenic controls. Behavioral assessment demonstrated memory impairment in 5xFAD mice, reflected by a reduced recognition index. Histopathological analysis further revealed increased amyloid beta plaques and microglia activation in the hippocampus and cortex of 5xFAD mice compared with Non-transgenic controls. An increase in structural disorder within brain tissues can be attributed to higher mass density fluctuations, likely arising from macromolecular rearrangement driven by amyloid beta aggregation and neuroinflammatory responses as the disease progresses. Our findings suggest that PWS and IPR-derived metrics provide sensitive biophysical indicators of early cellular and subcellular disruption, offering potential as quantitative biomarkers for the detection and progression of AD.

Abstract: Background/Objectives: Post-traumatic epilepsy (PTE) is a frequent complication of Traumatic Brain Injury (TBI), often contributing to exacerbate functional and neurological impairment. Since PTE is difficult to treat with traditional anticonvulsive therapies, there is a strong need for alternative strategies that optimize rehabilitation outcomes. This case study highlights the possible beneficial effects of the combined use of neurofeedback (NFB) and motor therapy in improving motor and cognitive functioning. Methods: The patient, hospitalised for TBI and who developed PTE, underwent baseline quantitative EEG (qEEG), neuromotor, functional and neuropsychological assessment before starting a three-week rehabilitation program (five days a week) integrating 30 sensorimotor (SMR) NFB training sessions, each lasting 35 minutes, with daily one-hour motor therapy. qEEG and clinical assessments were repeated post-intervention and after 6 months to evaluate treatment outcomes and their durability. Results: qEEG revealed significant post-intervention reductions in Delta and Theta power, indicating reduced cortical slowing and enhanced neural activation. Relative power analysis showed decreased Theta activity and normalization in Alpha, suggesting overall cortical activity stabilization. Significant improvement was observed in Beta and High-beta activity. The Theta/Beta ratio showed significant reductions, consistent with enhanced attentional regulation. Cognitive outcomes demonstrated reliable improvements in global cognition, memory, and visuospatial abilities, with most gains maintained or improved at follow-up, accompanied by marked reductions in depressive and anxiety symptoms. Motor and functional assessments indicated relevant gains in motor performance, coordination, and independence. Conclusions: Findings indicate that integrating NFB with motor therapy can foster sustained neuroplasticity and enhance recovery in PTE, considering the lack of available successful treatment options.

Abstract:

Background/objectives: Food craving is frequent with high palatable foods containing high levels of sugars and/or fat. Food cues can strongly induce food craving, and heightened food cue reactivity is associated with eating disorders and obesity. Sweet taste signalling is suggested to be an important regulator for appetite and food intake, with sensory-metabolic mismatch potentially relevant for food craving experience. This study investigated the interaction between taste and food cues on food craving in healthy people with and without ingestion of a sugary drink. Methods: Randomised crossover design with 47 healthy individuals performed two experimental trials. Fasted individuals were exposed to food cues with measurement of food craving pre- and post- exposure via a newly validated method using handgrip force as a response modality. This was followed either by ingestion (ingestion trial) or mouth rinse (mouth rinse trial) of a sugary drink and reassessment of food cue craving responses. Continuous interstitial glucose monitoring was performed using a glucose sensor inserted into the upper arm and a blood sample for leptin levels was taken. Results: Strong food craving response to food cues was bound to the fasted state, while ingestion of sugary drink blunted food cue reactivity and reduced craving levels. Mouth rinse induced a stable increase in food craving which showed maximum after food cues. Interstitial glucose levels over the after-trial periods (area under curve, AUC) were significantly higher for the rinse trial day than for the ingestion trial day suggesting higher carbohydrate/sugar intake after the rinse trial, while craving levels were associated with AUC in the rinse trial. Conclusions: Outcomes indicate that taste/flavour in connection with food cues may generate an error signal experienced as food cravings, whereas receipt of sugars, with concomitant physiological responses, reduce the signal and diminish food craving. Results highlight the importance of sensory-metabolic mismatch for food craving experience.

Abstract: Background/Objectives: Nilotinib (NTB) a tyrosine kinase inhibitor, helps CML patients with the Philadelphia chromosome. An increasingly rigorous dose regimen and a boxed warning limit the drug's use. NTB should be taken orally on an empty stomach two hours before and one hour after the dosage. A new reduced-dose nanoparticle formulation of NTB reduces the effect of food on PK and achieves equivalent bioavailability (BA) while fasting. The study investigated if nanostructured lipid carriers could make BCS class II medication NTB more soluble and easier to swallow. Methods: The formulation was optimized using the "Box-Behnken design (3-factor, 3-level)". Polydispersity index, Zeta potential, EE, and particle size were dependent variables, while total lipid concentration, surfactant concentration, and sonication time were independent. Investigation of the optimized formulation's in vivo pharmacokinetics, tissue absorption, and in vitro release. Results: In the optimized formulation, PDI, particle size, EE%, and ZP were 135.26±3.86 nm, 0.126±0.09, 89.62±1.26%, and -42.16±1.75mV, respectively. Transmission electron microscopy revealed circular particles. In vitro, NTB released 96.15% with pure NTB dispersion and 56.34% with NTB-NLCs after 24 hours. The data was acquired using a zero order. NTB was ad-ministered to acute myeloid, acute lymphoblastic, and acute T cell leukaemia at IC50 values of 251, 302, 398, 218, 248, and 225 µg/mL, respectively. NTB had IC50 values of 124, 118, 146, 125, 139, and 135 µg/mL against acute myeloid, acute lymphoblastic, and acute T cell leukaemia cell lines. Conclusions: The malignant leukaemia cell line's vitality decreased dose-dependently with NLCs and NTB. Our cytotoxicity experiments in various cell lines and Wistar rats enhanced oral bioavailability of NTB suggest that the optimized NTB-loaded NLCs.

Abstract:

Background/Objectives: physical activity alleviates symptoms and may slow Parkinson’s disease (PD) progression, yet many individuals with PD remain sedentary. Kinesiophobia, the fear of movement, may represent a significant but underexplored psychological barrier to physical activity in this population. Virtual reality (VR), already effective in phobias, may represent a promising approach to address this challenge. This review initially aimed to systematically examine Exposure-based interventions in VR (E-IVR) directly targeting kinesiophobia in PD. Methods: database searches using keywords such as “kinesiophobia,” “fear of movement,” and “virtual reality” combined with “Parkinson’s disease” yielded no eligible studies. Consequently, the scope was broadened to include populations with neurological or musculoskeletal conditions, and a narrative review format was adopted to synthesize the available evidence. Furthermore, relevant studies of interventions in VR applied in PD, although not specifically addressing kinesiophobia, are detailed to provide evidence of efficacy and feasibility of VR interventions in PD. Finally, directions are offered to support the creation of Exposure-based interventions in VR targeting kinesiophobia in individuals with PD. Results: meta-analyses in neurological and musculoskeletal populations demonstrate moderate to large reductions in kinesiophobia following VR interventions, although effects vary depending on assessment tools, degree of immersion, and exposure design. In PD, VR has been applied to rehabilitation, anxiety reduction, and quality of life enhancement. These interventions achieved high adherence (≥90%), were well tolerated, and reported no major adverse events. Conclusions: kinesiophobia is prevalent in PD and could contribute to physical inactivity. E-IVR appears feasible, safe, and innovative for addressing kinesiophobia in people living with PD.

Abstract: Background/Objectives: In amyotrophic lateral sclerosis (ALS) late or incorrect diagnosis significantly reduces the therapeutic window, while also increasing the risk of inappropriate interventions, with a negative impact on disease progression rate. We aim to identify and characterize the clinical profile of ALS patients followed in our center who underwent surgeries due to initial clinical presentation, and to review the literature. Methods: We conducted a prospective observational study of patients newly diagnosed with ALS at our center between 2021 and 2024. Patients were categorized into two groups: those who underwent surgical intervention (Surgery Group, n=17) and those who did not (non-Surgery Group, n=284). Variables analyzed included demographic characteristics, onset region, diagnostic delay, baseline disease progression rate (ΔFS), the first specialist consulted, upper motor neuron (UMN)/lower motor neuron (LMN) predominance, and presence of fasciculations at onset. English medical literature was reviewed. Results: Of 301 ALS patients, 17 (5.6%) underwent surgery due to initial symptoms. These patients had a significantly longer diagnostic delay (median 14.95 vs. 8.99 months, p=0.010) and all had spinal-onset ALS (p=0.014). No significant differences were found in sex (p=0.354), progression rate (p=0.453), UMN/LMN predominance (p=0.708), or fasciculations at onset (p=0.129). Conclusions: Surgical interventions in ALS, particularly in spinal-onset cases, remains a clinical concern. Surgeries may delay diagnosis and bypass early neurological assessment. We advocate for increased ALS awareness among non-neurologists and emphasize the necessity of neurological evaluation prior to elective spinal surgery in patients exhibiting progressive motor symptoms.

Abstract: Drug-resistant epilepsy (DRE) remains a major therapeutic challenge, as a considerable proportion of epilepsy patients fail to achieve seizure control with conventional anti-seizure medications or surgical therapy. Closed-loop systems have emerged as a promising alternative, offering patient-specific, on-demand neuromodulation. Despite notable advances in the academic domain, clinical translation has stagnated, and surgical resection remains the intervention with the highest probability of achieving seizure freedom. In this review, we delineate the principal limitations currently constraining progress in epilepsy neuromodulation and conceptualise these systems as instantiations of the read-write architecture characteristic of brain-computer interfaces. The read component entails the continuous acquisition and analysis of neurophysiological signals to predict or detect imminent seizures. In contrast, the write component involves the delivery of targeted interventions to disrupt epileptiform dynamics and prevent clinical seizure manifestation. We outline the closed-loop processing pipeline, survey the current state of the art, and discuss key methodological and translational challenges, particularly in algorithm validation and long-term reliability. Finally, we address patients’ and caregivers’ perspectives on the acceptance and practical integration of such technologies. This work synthesises current advances in the field and delineates the path toward fully autonomous clinically effective closed-loop neuromodulation as a viable treatment paradigm for DRE, aiming to improve patients’ quality of life.

Abstract:

The intracellular accumulation of amyloid beta 42 (iAβ42) has been proposed as an early pathological indicator of familial Alzheimer’s disease (FAD). DJ-1 is a multifunctional protein sensitive to oxidative stress (OS) that has been associated with neurodegeneration; however, its role in iAβ42 pathology is unclear. In this study, we examined whether oxidized (sulfonic) DJ-1 (Cys¹⁰⁶-SO₃) drives iAβ42 accumulation using postmortem brain samples and in vitro 3D (iPSC-derived cerebral organoids, COs) or 2D induced pluripotent stem cells (iPSC)-derived ChLNs (cholinergic-like neurons) models from a PSEN1 E280A patient and a healthy volunteer (as a control sample). Post-mortem analyses of the temporal and frontal cortices and hippocampus from FAD PSEN1 E280A patients revealed strong intracellular co-localization of sulfonic DJ-1 and iAβ42, which was absent in control samples. To validate these findings, we generated cerebral organoids (COs) from an iPSCs PSEN1 E280A FAD patient and a healthy donor. In these organoids, we observed the co-localization of oxidized DJ-1 and Aβ42 in the absence of extracellular fibrils or plaques, as confirmed by BTA-1 staining. To further support these observations, 2D iPSC PSEN1 E280A-derived ChLNs cultures showed that intracellular Aβ42 accumulates progressively in direct correlation with increasing DJ-1 oxidation, as demonstrated by immunofluorescence microscopy and Western blotting analysis. These results indicate that DJ-1 oxidation accompanies the earliest intracellular stages of Aβ42 pathology. Furthermore, complementary in silico molecular docking analysis revealed a higher affinity between Aβ42 and oxidized sulfonic DJ-1 (DJ-1 1Cys¹⁰⁶-SO₃) compared to sulfenic (DJ-1 Cys¹⁰⁶-SOH) or sulfinic acid (DJ-1 Cys¹⁰⁶-SO₂H) forms. Likewise, ELISA tests and seeding assays confirmed that oxidized DJ-1 binds to and decelerates Aβ42 aggregation kinetics. Together, our results identify DJ-1 oxidation as a critical molecular event in the accumulation of iAβ42 in FAD. These findings suggest that oxidized DJ-1 represents not only a potential early biomarker of intracellular pathology but also a pharmacological target. Preventing the oxidation of DJ-1 or its pathological aggregation could provide new biomarkers and therapeutic strategies for reducing the intracellular accumulation of Aβ42 and neurodegeneration in FAD.

Abstract: BACKGROUND: Extramedullary spinal tumor represents a challenge for every spine surgeon. Today there are so many techniques for performing this surgery with safety and better outcomes for the patients. When we talk about spinal tumor resection surgery, most of the knowledge speaks about open surgery and in the last two decades, the MISS technique has gained importance because of the benefits and better outcomes obtained in terms of recovery of patients. Specifically in the case of UBE. There is so little written on this technique, and we think it will become the gold standard for spinal tumor resection surgery. METHODS: we use the UBE technique for resection of 11thoracolumbar extramedullary tumors. We retrospective review 11 cases from clinical files and endoscopy transporter videos and describe our surgical technique step by step for a better understanding of UBE surgery. We also analyze all the advantages of this type of surgery in terms of resection, surgery time, bleeding and hospital stay. We also review a case example in a videotape. RESULTS: In all cases, we achieve a clinical resolution, patient improvement in symptoms and functional and pain scales. In terms of lesion resection, we have similar results as other MISS techniques and open surgery with a low percentage of complications. CONCLUSIONS: The scope of UBE hasn’t been reached yet. We can say that in this case, series UBE is safe for spinal tumor resection with better outcomes than other MISS techniques, and we will be pushing the frontier in unilateral biportal endoscopy spine surgery.

Abstract: Background: Aging brains are shaped by a persistent dialogue between declining neurogenesis and rising neuroinflammation. Neural stem cells progressively lose regenerative capacity, while microglia and astrocytes shift toward maladaptive states that erode synaptic plasticity and cognition. This convergence defines inflammaging, a slow yet relentless process that undermines resilience. However, the field remains hampered by critical gaps: incomplete mapping of microglial heterogeneity, poorly understood epigenetic scars from inflammasome signaling, lack of longitudinal data, unclear niche-specific immune mechanisms, and uncertain cross-species relevance. This review addresses these pressing barriers, aiming to transform fragmented insights into actionable strategies. Summary: I chart how neurogenesis and neuroinflammation operate in continuous dialogue, identify five major knowledge gaps, and evaluate strategies to reprogram this interaction. Approaches include longitudinal imaging, niche-focused immunomodulation, glial subtype reprogramming, brain-penetrant inflammasome inhibitors, and CRISPR-based epigenetic editing. Each strategy is mapped against translational potential, short-term feasibility, and long-term vision, with emphasis on how mechanistic precision can guide clinical innovation. Conclusion: Here I highlight that neurogenic potential is not entirely lost with age but may be preserved or restored by tuning immune and epigenetic environments. This review proposes a roadmap for reshaping the aging brain’s fate, offering mechanistically grounded strategies to delay cognitive decline. Beyond neurology, the work underscores a broader principle: by integrating cellular plasticity with immune modulation, science edges closer to re-engineering resilience across the lifespan.

Abstract: Background/ Objectives; After negative results of the SAMMPRIS-trial the indication for endovascular treatment of atherosclerotic intracranial artery stenosis (ICAS) was widely restricted. It was the aim of our study to report whether intracranial arterial percutaneous transluminal angioplasty and stenting (PTAS) as ultima ratio therapy is still effective and safe enough. Methods: Between February 2011 and June 2019, 63 consecutive patients with and without emergent large vessel occlusion (ELVO) who received PTAS for symptomatic ICAS in the anterior or vertebrobasilar circulation were in-cluded in our study. Results: 32 patients had ELVO. In the remaining 31 patients, a known ICAS was treated with PTAS either because of recurrent stroke despite aggressive medical therapy with dual antiplatelet inhibition (n=24) or due to progressive hemodynamic ischemia (n=7). Stenting was successful in all 63 cases. Successful reperfusion was achieved in 94% of ELVO patients. Complications with new neurologic deficits, including dissection, subarachnoid hemorrhage, in-tracerebral hemorrhage (PH2), and stent-thrombosis, were seen in 5 ELVO patients (16%). At discharge, neuro-logical status improved in 16 patients (50%) and deteriorated in 7 patients (22%). In-hospital mortality happened in 5 of 32 ELVO cases (16%), all of them had lesions in the vertebrobasilar circulation. Regarding non-ELVO cases, two patients (6%) developed new neurologic deficits due to perforator strokes. There was no in-hospital mortality in this group. Conclusion: Even in unfavorable situations with acute atherothrombotic occlusions or recurrent strokes under ag-gressive medical therapy of known ICAS, PTAS remains a treatment option with reasonable efficacy and tolerable complication rates.

Abstract: Background: The TCAT (Testamentary Capacity Assessment Tool) is a short instrument with good psychometric properties, specialized for the assessment of testamentary capacity (TC) in dementia. It assesses memory, perception of financial parameters and judgment. It evaluates cognitive functions, such as social cognition, not measured by other traditional tools, while collateral sources of information regarding financial parameters are not needed. The present study is a review including all the relevant studies both for TCAT’s use in clinical settings and its validation in different cultures. Methods: Pubmed database has been used. Results: At the present, there are no other specialized screening TC assessment instruments with measured psychometric properties in the scientific literature. The TCAT has been validated in healthy Italian population and is highlighted that it is useful as an adjuvant instrument for TC assessment in the elderly. It is clinically useful in acute ischemic stroke, while its strengths are emphasized in a systematic review of the existing TC assessment instruments. Conclusions: TCAT is a useful screening specialized tool, easily applicable in clinical practice both from experts and non-experts. More studies are recommended to be held in different cultures, both in healthy and cognitively impaired adults, for its standardized use in forensic and clinical settings.

Abstract: Development of new therapeutic approaches and strategies for common neuropsychiatric disorders, including Major Depressive Disorder, anxiety disorders, and Post-Traumatic Stress Disorder, represent a significant global health challenge. Recent research indicates that emotional dysregulation and persistent inflammation are closely linked and serve as key pathophysiological features of these conditions. Emotional dysregulation is mechanistically coupled to the activity of the locus coeruleus and norepinephrine (LC-NE; noradrenergic) system. Arising from chronic stress, persistently elevated activity of the noradrenergic system leads to hypervigilance, anxious states, and depressed mood. Concurrently, these disorders are marked by systemic inflammation as indicated by elevated pro-inflammatory cytokines, and central neuroinflammation indicated by microglial activation in brain regions and networks involved in mood regulation and emotional control. In turn, chronic inflammation increases sympathetic tone and LC-NE activity resulting in a vortex of psychoneuroimmunological dysfunction that worsens mental health. Transcutaneous auricular vagus nerve stimulation (taVNS) in a non-invasive neuromodulation method uniquely positioned to address both noradrenergic dysfunction and chronic inflammation in neuropsychiatric applications. Evidence spanning the past couple decades demonstrates taVNS works via two complementary mechanisms. An ascending pathway engages vagal afferents projecting to the LC-NE system in the brain stem, which has been shown to modulate cortical arousal, cognitive function, mood, and stress responses. Through descending circuits taVNS can modulate the cholinergic anti-inflammatory pathway to suppresses the production of pro-inflammatory cytokines like TNF-α and IL-6 mitigating poor health outcomes caused by inflammation. By enhancing both central brain function and peripheral immune responses, taVNS has shown significant potential for recalibrating perturbed affective-cognitive processing. The present article describes and discusses recent evidence suggesting that taVNS offers a promising network-based paradigm for restoring psychoneuroimmunological homeostasis in common neuropsychiatric conditions.