Search Results (232)

Background: Artificial intelligence in medicine has largely relied on supervised training of disease-specific models, limiting scalability in conditions where labeled data are scarce. Large language models (LLMs), which encode broad medical knowledge through large-scale pretraining, offer an alternative paradigm in which structured physiological measurements can be interpreted directly without task-specific model training. Objective: To evaluate whether smartphone-derived ocular motor biomarkers can be translated into clinically meaningful probabilistic assessments of Huntington’s disease (HD) using general-purpose LLMs operating as inference engines. Methods: In this prospective proof-of-concept study, 26 participants (13 with genetically confirmed HD and 13 age-matched controls) completed a standardized ocular motor assessment using a custom smartphone application. Quantitative eye-movement metrics were validated against expert neurologist ratings. Structured physiological features were then provided to four general-purpose LLMs without task-specific training or diagnostic labels, and the models generated an AI-Assigned HD Probability Score (HAIPS). Discriminative performance and associations with clinical severity measures were evaluated. Results: Smartphone-derived ocular motor metrics showed strong agreement with clinician assessments (Spearman ρ = 0.76–0.95; all p < 0.001), confirming preservation of clinically meaningful physiological signals. LLM-derived HAIPS distinguished HD from controls with high accuracy (AUC 0.879–0.944), with no significant differences across models. Discrimination was statistically equivalent to a supervised logistic regression model trained on the same features. HAIPS correlated strongly with established measures of disease severity, including cognitive (MoCA, ρ = −0.86), functional (TFC, ρ = −0.74), and motor impairment (UHDRS, ρ = 0.85) (all p ≤ 0.003). Conclusions: Structured ocular motor biomarkers acquired using a consumer smartphone can be translated into clinically meaningful probabilistic assessments of HD by general-purpose LLMs without disease-specific model training. These findings support a framework in which physiologically grounded digital biomarkers are coupled with general-purpose inference models, potentially enabling scalable assessment in rare neurological diseases where labeled data are limited. Full article

Background/Objectives: To investigate the prevalence and associated factors of postoperative radiculitis in patients treated with Anterior Lumbar Interbody Fusion (ALIF) in L4–L5 or L5–S1 utilizing lumbopelvic sagittal parameters and ideal alignment values calculated with GAP score components. Methods: A retrospective review using Natural Language Processing (NLP) for automated data extraction from clinical notes was conducted. 61 adult patients were included in the analysis. Postoperative radiculitis was defined as the new onset of unilateral or bilateral pain in the L4–S1 radicular territory with preserved motor function. Clinical parameters (Oswestry Disability Index), radiographic parameters (lumbopelvic sagittal alignment using GAP score components), and surgical factors (cage size and disc height modification) were evaluated and subsequently entered into a multivariable logistic regression analysis. Results: Postoperative radiculitis occurred in 29.5% of patients, with symptoms primarily manifesting within the first six weeks following surgery and lasting up to six months. Patients in the Pain group showed notable differences in pre- and postoperative GAP score parameters, specifically higher values for relative lumbar lordosis (RLL) and relative pelvic version (RPV). Furthermore, multivariable logistic regression identified postoperative RLL and the anterior disc height (ADH) ratio to be independently associated with the development of radiculitis. Conclusions: Excessive disc space enlargement during ALIF is associated with a higher likelihood of postoperative radiculitis, particularly in patients with pre-existing near-ideal lumbar alignment. To mitigate this iatrogenic complication in this group, the degree of correction must be individualized. This tailored approach should incorporate parameters from the GAP score and a careful assessment of the relationship between the anterior disc height and the vertebral body. Full article

This paper presents the design and implementation of a field-programmable gate array (FPGA)-based System-on-Programmable-Chip (SoPC) architecture for sensorless speed control of permanent magnet synchronous motor (PMSM) drives. To enable real-time execution of the computationally intensive estimation stage, a parallelized Unscented Kalman Filter (UKF) is proposed for the joint estimation of rotor speed, position, and load torque. Unlike traditional sequential processor-based UKF implementations, the proposed parallel architecture simplifies the iterative process and significantly reduces computational latency and hardware resource utilization while preserving high estimation fidelity. This transformation reduces the number of sequential dependency stages within one estimation cycle and enables simultaneous execution of matrix operations using dedicated FPGA resources, thereby decreasing effective iteration latency. The complete control system comprises current regulators, a coordinate transformation module, a proportional–integral (PI) speed controller, and auxiliary functional blocks—all fully integrated within a single SoPC. The UKF estimator and control components are described using a hardware description language (HDL), enabling efficient hardware-level parallelism and real-time execution. The proposed system is validated through co-simulation and experimental verification on a Xilinx ZCU102 platform driving an inverter-fed PMSM. The results confirm correct real-time operation of the proposed architecture and demonstrate its feasibility for FPGA-based sensorless motor drive implementation. A detailed quantitative comparison with a fully sequential FPGA-based UKF implementation is identified as future work to further substantiate the reported latency reduction. Full article

Background: PPP1CB-related Noonan syndrome-like disorder with loose anagen hair type 2 (NSLH2; OMIM #617506) is a rare RASopathy caused by pathogenic variants in PPP1CB, encoding the catalytic beta subunit of protein phosphatase 1 (PP1C). Since its first description in 2016, only a limited number of patients have been reported, leaving the full phenotypic spectrum and genotype–phenotype correlations largely undefined. Objectives: To systematically review the clinical, molecular, and functional characteristics of NSLH2, we define its phenotypic spectrum, explore genotype–phenotype correlations, and summarize current evidence on therapeutic management. Methods: A systematic literature search was conducted across PubMed/MEDLINE, Embase, Web of Science, and Google Scholar, supplemented by searches of Orphanet, OMIM, and ClinVar, from 2016 to 2026. Studies reporting patients with pathogenic or likely pathogenic variants in PPP1CB were included. Individual patient-level data were extracted and analyzed descriptively. Additionally, we report a novel patient identified at our institution. Results: Thirty patients from 14 publications were included, harboring nine distinct PPP1CB variants. The most frequently identified variant was p.Pro49Arg (n = 17, 56.7%), followed by p.Met182Lys (n = 4, 13.3%) and p.Glu183Ala (n = 3, 10.0%). The majority of variants arose de novo (n = 26, 86.7%). Ectodermal anomalies, predominantly slow-growing and structurally abnormal hair consistent with loose anagen hair, were present in 79.3% of patients. Congenital heart defects were identified in 75.9%, with pulmonary stenosis and atrial septal defect representing the most common lesions. Short stature was documented in 69.2% of cases, and neurodevelopmental delay—encompassing motor and language delay—affected the majority of patients (72.4–84.6%). Brain structural anomalies were detected in 35.7%. Facial dysmorphic features were universal. Macrocephaly was present in 58.6% of cases, intellectual disability was reported in 26.9%, and epilepsy in 6.7%. Three familial cases with inherited p.Met182Lys transmission from an affected mother to three children are described, representing the largest reported familial cluster. Conclusions: NSLH2 is a clinically recognizable RASopathy with a consistent core phenotype comprising loose anagen hair, congenital heart defects, short stature, macrocephaly, and neurodevelopmental delay. The p.Pro49Arg variant accounts for the majority of reported cases and appears associated with a broad phenotypic expression. Larger cohorts and functional studies are needed to fully delineate genotype–phenotype correlations and guide therapeutic strategies. Full article

Introduction: Navigated transcranial magnetic stimulation (nTMS) is an advanced, noninvasive method for stimulation-based functional brain mapping. Its main clinical value in neurosurgery lies in preoperative identification of eloquent cortical areas and the integration of functional information into neuronavigation-based surgical planning. State of the Art: This narrative review with a structured literature search summarizes the historical and technical foundations of TMS/nTMS, but primarily focuses on neurosurgical applications, including motor and language mapping, comparison with functional MRI and direct cortical stimulation, safety considerations, and practical limitations. Broader neurological and therapeutic applications are discussed as contextual extensions rather than as a comprehensive disease-specific review. Clinical Implications: Current evidence is strongest for preoperative motor mapping in patients with tumors located in or near the motor–eloquent cortex. Language mapping, neurological diagnostics, and therapeutic repetitive TMS (rTMS) applications remain more heterogeneous and require careful interpretation according to the level of evidence, protocol standardization, and patient selection. Future Directions: Further multicenter studies, standardized mapping protocols, integration with advanced imaging and tractography, and health-system implementation strategies are needed to define the optimal role of nTMS in personalized neurosurgical and neurological care. Full article

Background and Objectives: Cortical plasticity assessment using navigated transcranial magnetic stimulation (nTMS) represents a promising non-invasive strategy for predicting reorganisation of cortical circuits in neuro-oncological patients. This study examined how glioma grade influences cognitive network reorganisation by multiparametric analysis. Materials and Methods: We conducted a prospective monocentric study at the Neurosurgical Department in Florence and a comparative analysis of motor (M), language (Ln), calculation (C), and visuo-spatial functions (VS) between patients with low-grade gliomas (LGGs) and high-grade gliomas (HGGs) undergoing pre- and postoperative nTMS mapping (at 5 ± 2, 30 ± 10, and 90 ± 10 days of follow-up). Results: Between January2024 and September 2025, we enrolled 69 patients, and the total number of nTMS mapping procedures was 70: one relapse, (M:F = 345:365), level of scholarship 8–15 years, 21 LGGs, 30 HGGs, 19 non-glial lesions (excluded), left lesions n = 37, right lesions n = 31, bilateral n = 2, bi-hemispheric nTMS = 80%. Considering LGGs and HGGs, the major motor function displacement was obtained in the right hemisphere (Rh; predominantly for HGGs 64 mm vs. LGGs 39 mm), with more restrained displacement in the left hemisphere (Lh; LGGs 20 mm vs. HGGs 21 mm). For Ln, displacement was higher for HGGs (57 mm vs. LGGs 31 mm). However, surprisingly for HGGs in the Lh, the displacement was more significant (60 mm), whereas for LGGs it was major in the Rh (~80 mm). For C, displacement for HGGs was 72 mm Lh vs. 48.11 mm Rh, and for LGGs 50 mm Lh vs. 41 mm Rh. Insufficient data were obtained for the network. Qualitative analyses further characterised this reorganisation: motor f. demonstrated reshaping around the primary motor cortex; linguistic f. displaced from temporo-parietal areas to the inferior frontal gyrus; calculation and VS functions reorganised within frontoparietal circuits. The correlation between cognitive results and BPI revealed that higher BPI values were associated with prolonged recovery periods. Nevertheless, functional recovery was achieved in up to 90% of patients across all assessed functions. Conclusions: We propose non-invasively measuring cortical plasticity across different cognitive domains with a quantitative–qualitative framework for assessing functional reorganisation with a multimodal assessment in glioma patients. Full article

Background/Objectives: Maternal valaciclovir therapy is increasingly used to reduce fetal viral replication in cases of primary cytomegalovirus (CMV) infection during pregnancy. However, data on its impact on early neurodevelopmental outcomes remain limited. This study aimed to evaluate the association between prenatal valaciclovir exposure and early neurodevelopment in infants with confirmed congenital CMV infection (cCMV). Methods: In this retrospective monocentric cohort study, 30 infants with PCR-confirmed cCMV infection were assessed at 4–8 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants were stratified according to prenatal exposure to maternal valaciclovir. Univariate analyses and multivariable linear regression models were performed to evaluate the association between prenatal antiviral exposure and cognitive outcome, adjusting for brain MRI findings and selected clinical variables. Results: Fifteen infants (50%) were exposed to prenatal valaciclovir. Exposed infants demonstrated higher cognitive composite scores compared with unexposed infants (median 105 [IQR 100–110] vs. 90 [85–110]; p = 0.030). In multivariable analysis, prenatal valaciclovir exposure remained significantly associated with higher cognitive scores (β = 11.89, 95% CI 2.86–20.92; p = 0.012), while neonatal MRI abnormalities were not independently associated with outcome. No significant differences were observed in language or motor domains. The final model explained 30% of the variance in cognitive scores (R² = 0.30). Conclusions: Prenatal valaciclovir exposure was associated with higher cognitive composite scores after adjustment for selected covariates. Although causality cannot be inferred, these findings suggest a potential association with early neurodevelopmental outcomes and support the inclusion of functional neurodevelopmental endpoints in future prospective studies. These results should be considered exploratory and hypothesis-generating Full article

The link between neurodevelopment in infants exposed to maternal gestational diabetes mellitus (GDM) and fetal DNA methylation remains unexplored. We conducted this hypothesis-generating study to investigate the association between fetal DNA methylation and neurodevelopmental outcomes in children of mothers with GDM. We carried out a prospective, observational pilot cohort study comparing infants exposed to maternal GDM with an unexposed control group. Umbilical cord blood DNA methylation was assessed using targeted methylome sequencing covering 3.34 million CpG sites. Infant neurodevelopment was evaluated at age two years using the Bayley-III Scales. Bioinformatics processing identified differentially methylated regions (DMRs), followed by multiple enrichment analyses of DMR-associated genes and partial correlation analyses. Multi-dimensional enrichment analysis of the 1053 identified DMR-associated genes revealed a significant convergence of pathways related to neurogenesis, synaptic components, and axonal guidance. Infants born to mothers with GDM exhibited lower scores in cognitive, language, and motor domains, which were associated with identifiable DNA methylation signatures at birth. Significant correlations were observed in genes essential for brain scaffolding and synaptic circuitry, most notably WNT4, the PCDHG alpha/beta clusters, and PALM. Additionally, methylation patterns in FOXF2 and CHFR suggest a potential impact on blood–brain barrier integrity, while associations with FSTL3 and H6PD highlight a systemic metabolic ‘cross-talk’ influencing neurodevelopment. Although these pilot findings are hypothesis-generating and require further functional validation, this study provides pioneering evidence that neurodevelopmental alterations in the offspring of mothers with GDM are potentially associated with intrauterine epigenetic modifications detectable at birth. Full article

Background and Objectives: Fragmented anatomical, imaging, and surgical accounts of the gracilis muscle hinder reproducible reporting and operative planning. We aimed to integrate prior systems into an Integrated Gracilis Framework (IGF)—an integrative synthesis, not a new classification—that harmonizes terminology, defines imaging correlates/pitfalls, and links morphology to surgical decisions. Methods: Integrative narrative review (January 1900–October 2025) of PubMed/MEDLINE, Scopus, and Web of Science covering vascularization (pedicles, perforators), innervation (motor points/segments), imaging (ultrasound, MRI, MR neurography, CTA/MRA), and clinical applications (facial reanimation, elbow flexion, perineal and breast reconstruction). Two reviewers screened/extracted with consensus adjudication. Searches were restricted to English or records with reliable English-language summaries. Results: IGF consolidates morphological variants, motor-point/segmental innervation, and pedicle/perforator patterns with imaging correlates and common pitfalls. It provides a crosswalk mapping historical systems to IGF and a proposed preoperative workflow (anatomy → imaging → harvest → neurotization) for structured planning and reporting (proposed framework; not prospectively validated). We summarize considerations for free/functional gracilis in facial reanimation and elbow-flexion, and for pedicled/free myocutaneous or perforator flaps in perineal and breast reconstruction. Conclusions: IGF offers a standardized language and decision scaffold to improve study comparability and transparency in operative reporting; as a nonvalidated synthesis, it requires systematic validation through cadaver–imaging correlation and prospective surgical cohorts. Full article

Neurological injuries and disorders affecting hand motor control can severely impair the ability to perform activities of daily living and substantially reduce quality of life. Technologies such as virtual reality (VR) are increasingly used to address fundamental challenges in therapy, including motivation and engagement; further, programmable features of digital interfaces offer additional opportunities to personalize and optimize motor training. In this proof-of-concept study, we developed and evaluated a novel VR-based training framework to support improved dexterity and hand function using physiological (sensory-driven) and cognitive (memory) cues designed to promote greater task-relevant neural engagement. The proposed approach leverages the integration of augmented sensory feedback (ASF) with memory-anchored cues for motor learning of target hand gestures. Using a within-subjects design, thirteen neurotypical adults completed four training conditions: (1) control (baseline gesture-matching in VR), (2) visual ASF (enhanced visualization and feedback of gesture accuracy), (3) memory-anchored cues (associating gestures with semantically meaningful entities, loosely analogous to American Sign Language), and (4) hybrid multimodal (visual ASF + memory-anchored cues). Training with the hybrid condition produced the fastest skill acquisition (9.3 trials to reach an 80% accuracy threshold) and the steepest initial learning slope (1.86 ± 0.12%/trial), with all conditions differing significantly in initial slope (all p < 0.002). Post-training assessment showed that the hybrid condition achieved the highest gesture accuracy (95.2%), greatest normalized post-training accuracy gain (14.3% above baseline), fastest execution time to target gesture (1.14 s), and lowest variability in gestural kinematics (SD = 3.9%). Both ASF and memory-anchored cue conditions each also independently outperformed the control condition on gesture accuracy (both p ≤ 0.002), with omnibus ANOVAs indicating significant condition effects across metrics. Together, these findings suggest that pairing ASF cues with memory-based cognitive scaffolding can yield additive benefits for motor skill acquisition and stability. Pending validation in clinical populations, such approaches may inform the design of VR-based motor training frameworks for rehabilitation. Full article

Insomnia is the most prevalent sleep disorder worldwide, affecting up to 30% of the population, and is frequently accompanied by cognitive complaints and measurable cognitive impairments. Chronic insomnia is characterized by persistent hyperarousal across physiological, cognitive, and neurobiological domains, which may compromise multiple cognitive systems. This review synthesizes current evidence on the impact of insomnia on major cognitive domains, including attention, language, memory and learning, executive functions, perceptual–motor skills, and social cognition. We critically evaluate methodological factors contributing to heterogeneous findings across studies, such as variability in diagnostic criteria, insomnia phenotypes, cognitive assessments, and sample characteristics. Additionally, we summarize emerging evidence on neuroanatomical and molecular correlates of insomnia-related cognitive impairment, including alterations in hippocampal and prefrontal brain structures, amyloid-β accumulation, dysregulation of brain-derived neurotrophic factor, neurotransmitter imbalance, neuroinflammation, and disrupted signaling pathways. Insights from preclinical studies show mechanistic links between sleep loss, synaptic dysfunction, oxidative stress, and memory decline. Despite substantial advances, the precise pathophysiological mechanisms underlying cognitive dysfunction in insomnia remain incompletely understood, suggesting that cognitive impairment arises from the convergence of multiple biological processes rather than a single causal pathway. A deeper mechanistic understanding is essential for developing targeted interventions for preventing cognitive decline in individuals with insomnia. Full article

This study investigates the relationship between language, motor, and social–relational development in early childhood and the development of executive functions in a sample of 110 preschoolers (M = 57 months, SD = 9.8; 47.3% male, 52.7% female). Through the administration of the Preschool Observation of Development and Self-Regulation questionnaire to parents, information about motor, language, and socio-relational skills at 6–36 months and 37–72 months was collected for each participant. Executive functions were investigated by the administration of a neuropsychological battery. The scores obtained on these tests were summarized through confirmatory factor analysis in the two dimensions: working memory–cognitive flexibility and inhibitory control. Multiple regressions were performed to determine whether the development of certain motor, language or social–relational skills had an impact on the development of working memory, flexibility and inhibitory control observed at preschool. The results show that prior language skills, especially grammatical skills, are predictive factors for the development of working memory and cognitive flexibility at preschool. Additionally, some gross-motor skills at 6–36 months are significant predictors for the development of inhibitory control. These skills are therefore clinically important to prevent possible executive impairment in preschool children and to intercept early at-risk children. Full article

Background: Navigated repetitive TMS (nrTMS) is widely used for non-invasive mapping of cortical functions. Methodological improvement might be achieved by optimizing coil positioning based on electric-field modeling and augmented reality (AR)-guided neuronavigation to enhance spatial targeting accuracy and stimulation-induced language errors. Therefore, we compared electric-field-optimized, AR-guided nrTMS with conventional nrTMS using manually planned coil positioning. Methods: Twenty-eight healthy subjects underwent two MRI-guided left hemispheric nrTMS language mapping sessions. Each session used 10 Hz stimulation at a 100% resting motor threshold applied for 1.5 s per region of interest (ROI) during a synchronized object naming task. ROIs were defined according to the Corina cortical parcellation system. Manually defined and electric-field-optimized coil placements obtained using SimNIBS (v4.1.0) were applied; the optimized session was assisted by AR goggles. The primary outcome was the quantitative and categorical differences in cortical regions mapped as language-eloquent. Resting-state fMRI was acquired to provide a reference for comparing nrTMS-derived language maps. Outcomes: Electric-field-optimized nrTMS did not result in an increase in positively mapped ROIs. A different distribution of language errors was observed between sessions. Manual mapping roughly followed the extracted resting-state language and motor networks, whereas electric-field-optimized mapping might correspond less. Optimized coil positions were not always practically feasible. AR guidance improved target location accuracy. Conclusions: While AR was a useful addition to the TMS experiment, electric-field optimization did not translate into significant behavioral differences. However, altered distribution of language errors can give insight into underlying neurophysiological processes of rTMS. Full article

Background/Objectives: To study the hypothesis that cognitive functions and learning skills are impaired in child/adolescent childhood cancer survivors (CCS). Secondary outcomes included psychosocial parameters and quality of life. Methods: This case–control study was conducted over four years (2017–2021) at the largest pediatric Aghia Sophia Children’s Hospital, in Greece. Eligible participants were children and adolescents in Greece. For CCS, ≥1 year should have elapsed from completion of cancer treatment. Assessments of neurocognitive function, learning and psychosocial skills and health-related quality of life (HRQoL) were performed with validated instruments (WISC-III, LAMDA software, Achenbach CBCL/6-18 and YSR, KIDSCREEN-52, respectively). Results: In total, 219 participants (47.49% males, mean age ± SD 11.72 ± 2.32 years), 70 CCS and 149 controls (matched for age, sex, family income), were included. Cases were CCS of acute lymphoblastic leukemia (n = 25)/brain tumors (n = 19)/lymphoma (n = 17)/nephroblastoma (n = 5)/Ewing sarcoma (n = 3)/rhabdomyosarcoma (n = 1). CCS had worse scores in full-scale Intelligence Quotient (FSIQ) (p = 0.004), verbal IQ (VIQ) (p = 0.005) and all its subscales, performance IQ (PIQ) (p = 0.021), and almost all learning parameters than controls. Attention, working memory, writing/visual–motor coordination, processing accuracy/speed, language acquisition/expression, all psychosocial scales, and HRQoL domains of mood and emotions, were negatively affected in CCS. Female CCS demonstrated lower FSIQ (p = 0.019) and VIQ (p = 0.014) than control females, whereas male CCS retained their total IQ unaffected. Among CCS, those with non-central nervous system (CNS) tumors, higher parental educational level or higher family income had significantly higher IQ than those with CNS tumors, lower parental educational level or lower family income, respectively. Conclusions: CCS in Greece carry a significant burden of cognitive and psychological morbidity. Cognitive/educational and psychosocial support to CCS is imperative. Full article

Background/Objectives: Performing presurgical functional magnetic resonance imaging (fMRI) mapping in young patients is considered a challenge for clinicians, as fMRI maps are the sole source of information about the functional organization of cognitive functions/areas, especially when an awake craniotomy is not possible, as is often the case for pediatric populations. The literature on the fMRI tasks used in pediatric populations with brain injuries shows a certain heterogeneity in the approaches (task-based or resting states) and tasks, with a preference for motor/language mapping: tasks assessing extra-language functions are lacking. Methods: We have designed fMRI tasks focused on language and extra-language functions, which can be easily be applied when clinicians need to perform presurgical mapping. We present a retrospective case series of 17 patients. Results: Seventeen young patients (13.4 ± 2.8 years; range 7–16) were included in the study, for whom fMRI was performed. All underwent successful fMRI mapping by completing fMRI tasks selected based on their lesion site. The number of tasks performed by each patient significantly correlated with their age (r(17) = 0.561, p = 0.019). The patients tolerated the assessment and had good motion control: their movement parameters were minimal (range of rotation of −0.015–0.01 degrees; range of translation of −0.8–0.2 mm). The most administered fMRI tasks were tongue motor localizer (60%) and object naming (70%), with some patients performing extra-language function mapping involving visuo-spatial processing, selective attention, memory, and inhibition. Conclusions: This is an exploratory study given the sample size. fMRI measurements were considered feasible, as patients were able to complete the tasks under clinically realistic conditions. We discuss the clinical implication/usefulness of administering tasks for a personalized functional assessment of the young patient before surgery. Full article