Introduction:Multiple sclerosis (MS) affects different cognitive domains, including social cognition. Immersive Virtual Reality (VR) may provide a novel rehabilitative approach to treat motor and cognitive symptoms of MS. This exploratory pilot study evaluated the effects of immersive VR rehabilitation on social cognition in MS patients and explored related cortical neurophysiological signatures. Methods:Seven MS patients underwent immersive VR rehabilitation with the CAREN system (3 sessions/week, approximately 45 min of active training per session, about 1 h including preparation, 8 weeks), while seven healthy controls (HC) did not undergo any intervention. Patients were evaluated at baseline (T0) and post-treatment (T1) with standardized measures of cognitive, emotional, and motor functioning. EEG data were acquired from all participants, and, after artifact removal, spectral parameterization decomposed signals into aperiodic (exponent, offset) and periodic oscillatory components (alpha and beta power). Power spectral density was analyzed using group comparisons and Pearson correlations with neuropsychological measures. Results:Compared with HC, MS patients showed reduced alpha-band power, mainly over frontal and parieto-occipital regions, whereas aperiodic parameters did not differ between groups. In patients, alpha and beta power correlated with the Positive Emotions Self-Efficacy Scale (alpha: r = 0.92, p = 0.003; beta: r = 0.83, p = 0.020). Alpha power is also correlated with RAO SRT-LTS (r = 0.85, p = 0.016), and beta with EQ-CE (r = 0.82, p = 0.023). Overall, alpha and beta power were correlated with emotional self-efficacy, balance, memory, and empathy, suggesting that oscillatory markers are potential indicators of clinical outcomes. Discussion:Rehabilitation via immersive VR has shown promising clinically significant effects in the cognitive, emotional, and motor domains, supported by convergent EEG spectral signatures. Future studies employing predictive modeling approaches will be required to assess their prognostic value.

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. The hallmark pathophysiological alteration consists of involuntary, action-induced adductor spasms of the laryngeal muscles during respiration, particularly during inspiration. LABD must be distinguished from inducible laryngeal obstruction (ILO), a broader, heterogeneous condition encompassing episodic, stimulus-triggered supraglottic or glottic closure, associated with asthma, reflux, or psychological triggers, that is generally not task-specific and lacks the neurological substrate characteristic of dystonia. In contrast, LABD is a persistent, effort-dependent, neurologically driven dystonia, demonstrable by paradoxical adductor spasms on fibreoptic laryngoscopy during normal inspiration and confirmed electromyographically by paradoxical thyroarytenoid muscle activation instead of the expected inspiratory relaxation. Traditional treatments, including respiratory retraining, speech therapy, biofeedback, psychotherapy, benzodiazepines, dopamine-blocking agents, and anticholinergic drugs, have proved largely ineffective. Tracheostomy may be required in cases of severe respiratory compromise. Botulinum toxin type A (BoNT/A) injections have been reported to successfully reduce inspiratory stridor in selected patients. Here, we present three cases of LABD displaying distinct phenotypes, in which typical features were associated with involvement of extra-laryngeal cranial districts, further expanding the known phenotypic spectrum of this condition.

BACKGROUND:Broad 6-month death-or-dependency outcomes after acute ischemic stroke can conceal opposing early benefit and harm pathways after antithrombotic treatment. We examined these pathways in the corrected public-use International Stroke Trial dataset. METHODS:We analyzed 19,285 randomized participants with assignable 6-month outcome classification; 150 with missing classification were excluded. The mediator was the first recorded selected event within 14 days or earlier death/discharge: early death, intracranial hemorrhage or hemorrhagic stroke, major extracranial bleeding, pulmonary embolism, recurrent stroke, or no selected event. Standardized risks, risk differences per 1000 patients, and risk ratios were estimated using robust Poisson regression and g-computation. Interventional direct and indirect effects were estimated with multinomial mediator and outcome models, marginalizing factorial co-allocation. RESULTS:Aspirin was associated with a small reduction in 6-month death or dependency (risk difference, -12.1 per 1000; risk ratio, 0.981). The interventional direct component was -9.8 per 1000 and the first-event-mediated component was -2.3 per 1000. Low-dose heparin had a near-null total effect (3.0 per 1000), with opposing direct (6.4) and indirect (-3.4) components. Higher-dose heparin also had a near-null composite effect (-1.9 per 1000), but mortality sensitivity analysis showed an unfavorable signal (15.6 per 1000). CONCLUSIONS:In this historical megatrial, small or near-null disability-inclusive effects were compatible with divergent early ischemic-prevention and bleeding-hazard pathways. Recorded first early events explained only part of the treatment-outcome contrasts. These estimates are methodological and interpretive, not contemporary prescribing guidance.

Background/Objectives: Rehospitalization after traumatic spinal cord injury (SCI) is common, but binary or count summaries may obscure heterogeneity in timing, recurrence, frequency, and duration. We aimed to identify clinically interpretable rehospitalization burden profiles in the SCIMS 2021ARPublic dataset and examine descriptive associations with clinical correlates and participation outcomes. Methods: We analyzed Form I, Form II, and Record Status public-use files. Among 29,310 individuals with at least one non-lost follow-up interview, 28,745 with at least one non-missing rehospitalization indicator entered latent class analysis. Four prespecified indicators captured early, recurrent, frequent, and prolonged rehospitalization. Candidate two- through six-class models were compared using AIC, BIC, entropy, class size, posterior probabilities, and interpretability. Pairwise adjusted logistic models examined candidate clinical correlates in 10,407 participants with complete 2016+ follow-up data. Adjusted linear models examined CHART participation domains in 20,766-20,949 participants. Results: A four-profile solution was retained: low rehospitalization burden (59.8%), early/prolonged rehospitalization (18.9%), frequent/prolonged rehospitalization (7.7%), and high recurrent/frequent/prolonged burden (13.6%). UTI and pressure ulcer history showed the most consistent associations with burdened profiles. Severe pain and frequent sleep problems were associated with selected heavier-burden profiles, while depressive symptoms showed smaller and less precise associations. Sensitivity analyses supported structural stability while highlighting observation-time bias and classification uncertainty inherent to wave-based public-use data. Compared with the low-burden profile, burden profiles showed lower CHART scores, especially for mobility and occupation. Conclusions: Rehospitalization after traumatic SCI is heterogeneous. These utilization burden profiles summarize distinct observed patterns but require prospective validation before use in risk stratification or follow-up planning.

Background: Aquatic therapy is increasingly used in post-stroke rehabilitation, but its effects on balance and gait in the chronic phase remain variably reported. This systematic review aimed to evaluate the effects of aquatic therapy, alone or combined with land-based rehabilitation, on balance and gait in individuals with chronic stroke. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted between February and March 2026. Randomized controlled trials enrolling adults with chronic stroke and evaluating aquatic-containing interventions with quantitative balance and/or gait outcomes were included. Owing to clinical and methodological heterogeneity, the primary synthesis was narrative. An exploratory random-effects meta-analysis was additionally performed for post-intervention Berg Balance Scale (BBS) scores. Results: Thirteen randomized controlled trials involving 468 participants were included. Overall, aquatic therapy was associated with more consistent improvements in balance than in gait, while combined aquatic and land-based programs generally showed broader functional gains than land-based rehabilitation alone. In the exploratory meta-analysis, the primary pooled analysis of four studies favored aquatic-containing interventions for post-intervention BBS scores (MD = 3.69, 95% CI 2.69 to 4.69; p < 0.001), with no observed heterogeneity (I2 = 0%). Conclusions: Aquatic therapy may be a useful adjunctive rehabilitation strategy for improving balance in chronic stroke, whereas effects on gait appear more variable. These findings should be interpreted cautiously because the quantitative synthesis was exploratory and the overall evidence base remains heterogeneous and limited by small sample sizes and short follow-up.

Background: Parkinson's Disease (PD) is a multisystem neurodegenerative disorder associated with cognitive and emotional disturbances, including visuospatial deficits and alexithymia, which may substantially affect quality of life (QoL). The metabolic underpinnings of non-motor and emotional features within deep basal ganglia nuclei remain poorly understood. This exploratory proof-of-concept study aimed to examine 1H-MRS-derived metabolite ratios in the substantia nigra (SN) and globus pallidus (GP) and to explore their preliminary associations with visuospatial-attentional abilities and alexithymia. Methods: Fifteen individuals with PD and 15 healthy controls (HCs) underwent Proton Magnetic Resonance Spectroscopy (1H-MRS) targeting the SN and GP bilaterally. Metabolite ratios were quantified with LCModel and analyzed as left, right, and hemisphere-averaged measures. PD participants completed a multidisciplinary assessment including motor severity, cognition, visuospatial abilities, mood and alexithymia. Multiple testing was controlled using false discovery rate (FDR). Given the between-group imbalance in age and education, exploratory covariate-adjusted sensitivity analyses were also performed. Results: PD participants were older, less educated, and showed lower global cognition than HCs, including significantly reduced MoCA scores (20.9 ± 6.6 vs. 28.7 ± 1.8; FDR-corrected p < 0.001). In uncorrected analyses, between-group metabolite comparisons showed lower myo-inositol (Ins) in the SN (p = 0.04) and higher glutamatergic signal in the right GP in PD relative to HCs (p = 0.03); however, these differences were not robust after adjustment for age, education and multiple testing. Within the PD group, an uncorrected right-left asymmetry was observed for pallidal Ins. Exploratory correlations suggested uncorrected associations between SN metabolites and alexithymia dimensions related to emotional awareness and verbalization, whereas GP metabolites were more frequently associated with selected visuospatial, attentional, language-related, and broader cognitive measures. None of these associations survived FDR correction. Conclusions: This exploratory proof-of-concept study provides preliminary feasibility data and effect-size estimates for future 1H-MRS investigations of basal ganglia metabolites in PD. Given the small sample size, lack of cognitive matching, age and education imbalance, and absence of correction-surviving associations, the findings should not be interpreted as evidence of PD-specific neurometabolic markers. Larger, prospectively matched, and adequately powered studies are needed.

Background: Post-stroke pain (PSP), particularly shoulder pain, is frequent and often underdiagnosed, limiting rehabilitation adherence and functional recovery. Current pharmacological and physical treatments offer only partial relief. Robotic-assisted therapy (RAT), such as the gravity-supporting Armeo® Spring exoskeleton, delivers intensive, task-specific training with visual 2D feedback that may also alleviate PSP while enhancing motor outcomes. This study investigates whether RAT performed with the Armeo® Spring reduces upper-limb PSP in chronic stroke patients versus conventional therapy and evaluates its effects on motor function and functional independence. Methods: In this retrospective parallel group study, 32 chronic post-stroke patients (8 females and 24 males with a mean age of 57 ± 11.74) were allocated to two groups: 16 received upper-limb RAT with the Armeo® Spring, a gravity-supporting exoskeleton, (RAT group) and 16 underwent conventional rehabilitation (CR). The RAT group completed one-hour sessions 6 days/week for 8 weeks, performing 2D/3D gamified tasks targeting shoulder, elbow and forearm movements. The CR group received an equivalent amount of standard therapy, including passive/active-assisted mobilization, Bobath-based neuromuscular facilitation and reaching exercises. Results: Both the Armeo® Spring and conventional therapy groups showed significant reductions in post-stroke pain (RAT p < 0.001 and conventional rehabilitation p = 0.004) and improvements in upper-limb motor function and functional independence (both p ≤ 0.002). Spasticity in the impaired limb decreased modestly in the RAT group (p = 0.031), with no significant between-group differences in pain or spasticity change (p = 0.437; p > 0.05, respectively). Conclusions: Gravity-support exoskeleton training reduced upper-limb spasticity, and no statistically significant between-group differences were observed compared with conventional physiotherapy for pain, mobility, and functional independence. Although clinical outcomes improved, health-related quality-of-life domains showed heterogeneous trajectories, underscoring the complexity of perceived health changes during chronic stroke rehabilitation. Larger randomized controlled trials incorporating neurophysiological and kinematic endpoints and longer follow-up are warranted to confirm effectiveness, particularly in chronic stroke and durability.

Art therapy has emerged as a complementary approach to Parkinson's Disease (PD), as it engages motor, cognitive, and emotional functions. However, individual responses to art therapy are highly variable and predictors of therapeutic efficacy are largely unknown. We hypothesized that the response heterogeneity may be related to individual patterns of brain activity and connectivity. Here, we combine functional connectomics, brain fingerprinting, and machine learning to identify such patterns and predict art therapy outcomes in PD. We mapped functional connectomes from high-resolution functional MRI of 23 patients with PD collected before a six-week art therapy protocol. We also assessed individual connectome fingerprints, examined their spatial specificity, and conducted meta-analytic functional decoding to link network topography with functional domains. Leveraging these network fingerprints, we computed topological measures and developed predictive models to identify patients most likely to benefit from art therapy, reaching an accuracy of 0.83 and a ROC-AUC of 0.80. Our results demonstrate that brain fingerprint-informed network measures can capture interindividual variability of therapy response, offering a data-driven, personalized approach to treatment. This study provides the first evidence that functional connectome fingerprints can guide personalized treatments in PD.

Background: Pelvic floor dysfunction (PFD) is frequent in neurological disorders, but it is often approached as a secondary urological or gynecological problem rather than a functional rehabilitation target. Neurological disease can disturb cortical, pontine, spinal, sacral, autonomic, somatic, and sensory pathways that regulate bladder storage, voiding, bowel evacuation, sexual function, and pelvic pain modulation. Methods: This narrative review synthesized biomedical evidence identified through PubMed searches from database inception to 2 May 2026. Search concepts included neurogenic lower urinary tract dysfunction, urinary and bowel dysfunction, sexual dysfunction, pelvic pain, pelvic floor rehabilitation, biofeedback, electrical stimulation, neuromodulation, telerehabilitation, robotics, and major neurological disorders. The review was oriented according to the Scale for the Assessment of Narrative Review Articles (SANRA) and was not designed as a systematic review or meta-analysis. Results: Evidence from multiple sclerosis, stroke, Parkinson’s disease, Alzheimer’s disease and related dementias, spinal cord injury, and fibromyalgia or nociplastic pain syndromes supports a phenotype-based framework in which pelvic floor muscle training, bladder and bowel training, biofeedback, neuromuscular electrical stimulation, posterior tibial nerve stimulation, sacral neuromodulation, telerehabilitation, robotics, and multidisciplinary care are considered complementary rather than interchangeable strategies. Conclusions: PFD in neurological disorders may be more appropriately conceptualized as a multidimensional neurorehabilitation target. Effective care depends on disease-informed phenotyping, individualized rehabilitation goals, attention to cognition and adherence, and standardized outcome measurement. Future studies should test phenotype-specific pathways that integrate bladder, bowel, sexual, pain, participation, safety, and caregiver outcomes.

BACKGROUND:Cognitive impairment is a common non-motor symptom in Multiple Sclerosis (MS), negatively affecting autonomy and Quality of Life (QoL). Innovative rehabilitation strategies, such as semi-immersive virtual reality (VR) and computerized cognitive training (CCT), may offer advantages over traditional cognitive rehabilitation (TCR), particularly in terms of engagement, specificity, adaptability, and ecological validity. This study aimed to compare the efficacy of semi-immersive VR, CCT using the ERICA platform, and TCR on cognitive outcomes and depressive/anxiety symptoms in individuals with MS. METHODS:Eighty-seven patients with MS and mild to moderate cognitive impairment were randomly assigned to three groups: VR-based training, CCT, or TCR. Each group underwent 24 individual sessions delivered regularly three times per week over 8 weeks. Neuropsychological assessments were conducted at baseline (T0) and post-intervention (T1), evaluating information processing speed (SDMT), memory (SRT, SPART), executive functions (WLG), emotional status (BDI, HRS-A), and QoL (MSQOL-54). RESULTS:All groups showed significant improvements in most cognitive and depressive (BDI)/anxiety symptoms (HRS-A) after the intervention. However, the VR group demonstrated significantly greater gains in executive functions, working memory, and QoL (MSQOL-54 Physical and Mental Composite scores) compared to both the CCT and TCR groups (p < 0.001). While the CCT group showed selective improvements in mood and working memory, its overall efficacy did not significantly differ from that of TCR. CONCLUSIONS:Semi-immersive VR represents an effective and engaging approach to cognitive rehabilitation in MS, likely due to its capacity to deliver multisensory, adaptive, and ecologically valid stimulation. Nonetheless, a tailored hybrid model integrating VR with conventional and computer-based strategies may further optimize outcomes and support functional independence in individuals with MS.

BACKGROUND:Substance use disorders (SUDs) are a major global health burden, and third-wave therapies that target transdiagnostic processes such as psychological flexibility and mindfulness have emerged as promising options. This systematic review synthesized evidence on third-wave interventions for adults with diagnostic and statistical manual of mental disorder (DSM)-defined SUDs. METHODS:A comprehensive search of seven databases (2014-2025) identified randomized and non-randomized studies of acceptance and commitment therapy (ACT), related mindfulness-based programs, and dialectical behavioral therapy skills training. Two reviewers screened records, extracted data, assessed risk of bias with Risk of Bias 2 (RoB 2) and risk of bias in non-randomized studies of interventions (ROBINS-I), and synthesized findings using SWiM-consistent narrative methods. The review was prospectively registered in PROSPERO (CRD420251028610). RESULTS:Forty-seven studies (35 randomized, 12 non-randomized) met inclusion criteria. Across modalities, third-wave interventions yielded small-to-moderate benefits on abstinence, craving, and substance use outcomes compared with control conditions, with larger and more consistent gains in psychological flexibility, emotion regulation, and mindfulness. Effect sizes varied and most trials showed some concerns or serious risk of bias, resulting in generally low-to-moderate certainty of evidence. CONCLUSIONS:Third-wave interventions may serve as adjunctive or alternative SUD treatments by engaging targeted mechanisms, enhancing psychological functioning, and producing modest but clinically relevant substance-use benefits. More rigorous, adequately powered mechanism-focused trials are needed to clarify comparative efficacy and guide process-based personalization and implementation in routine addiction services.

BackgroundFreezing of Gait (FoG) is a debilitating motor symptom affecting nearly half of individuals with Parkinson's disease (PD), increasing fall risk and reducing independence. Despite pharmacological and neuromodulation therapies, residual symptoms often persist, underscoring the need for complementary rehabilitation strategies.ObjectiveTo evaluate the effects of body weight-supported treadmill training using differential air pressure on gait and mobility in PD patients.MethodsForty patients with idiopathic PD were randomly assigned to an experimental group (EG, n = 20), who received gait training with a lower-body positive pressure treadmill, or to a control group (CG, n = 20), who underwent conventional physiotherapy. Both groups trained twice weekly for 4 months. Outcomes were assessed at baseline (T0) and post-intervention (T1), and classified as primary (gait speed, step length, balance, postural stability) or secondary (quality of life, fear of falling, anxiety).ResultsCompared to controls, the EG showed significant improvements in gait speed, step length, balance, and postural stability (all p < 0.01). Secondary outcomes also improved, with reductions in fear of falling (p < 0.01) and better quality of life scores (p < 0.01).ConclusionsThis pilot trial suggests that body weight-supported treadmill training through differential air pressure may improve gait performance and postural control, while also enhancing quality of life in PD patients with mobility impairments and FoG. These preliminary findings support its potential role as a complementary rehabilitation strategy, warranting confirmation in larger trials.

Background: Rapid Eye Movement (REM) sleep behavior disorder (RBD) is a parasomnia resulting from degeneration of pontine and medullary circuits responsible for muscle atonia during REM sleep, leading to dream-enactment behaviors and vocalizations. It is strongly linked to α-synucleinopathies, particularly Parkinson’s disease. Current biomarkers such as neurophysiological measures and imaging support diagnosis and monitoring, but remain invasive or costly. Aim: This study aims to evaluate vocal and speech alterations as exploratory, non-validated candidate biomarkers of REM sleep behavior disorder. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, IEEE Digital Library Web of Science, Embase and the Cochrane Library were systematically searched for studies published from database inception to November 2025, as preregistered on the Open Science Framework. Studies were selected through a multi-step screening process and underwent qualitative quality assessment. Results: Twelve studies met inclusion criteria. Individuals with RBD exhibited abnormal nocturnal vocalizations and early lexical, syntactic, and narrative disruptions despite preserved perceptual speech. Quantitative analyses identified consistent deficits in prosody, phonation stability, timing, and articulation, with significant group differences and diagnostic accuracy up to 96% sensitivity. Multilingual cohorts demonstrated progression over time, while digital phenotyping detected emerging Parkinsonian signs with AUC > 0.70. Conclusions: Speech and vocal abnormalities in iRBD reflect early neurodegenerative changes and show promising but still exploratory diagnostic and prognostic potential. Integrating vocal markers with established biomarkers may enhance early detection; however, further research is required to validate a reliable and reproducible vocal signature of prodromal synucleinopathies.

BACKGROUND:Cognitive decline involves a progressive loss of higher mental functions and may lead to impairment of independence in daily activities. Depressive symptoms represent a potential factor that can worsen functional decline. OBJECTIVE:To evaluate the impact of depressive symptoms on basic and instrumental autonomy in patients with cognitive decline. METHODS:A retrospective analysis was conducted on the medical records of 148 patients attending the Neuropsychology Clinic of the IRCCS Centro Neurolesi Bonino Pulejo. Patients were divided into two groups with and without depressive symptoms according to the Geriatric Depression Scale. The Milan Overall Dementia Assessment (MODA), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL) were administered. Between-group comparisons were performed using the Mann-Whitney U test and permutation-based regression analysis, controlling for age, sex, and MODA. Correlations were assessed using Spearman's rho coefficient. RESULTS:Patients with depressive symptoms showed lower ADL and IADL scores compared with those without depressive symptoms. These differences remained significant after adjustment for demographic and cognitive variables. The severity of depressive symptoms were strongly associated with reduced functional autonomy. CONCLUSIONS:The findings highlight the importance of early diagnosis and targeted interventions for depressive symptoms to improve patient management in everyday life. Clinical trial registration: www.clinicaltrials.gov identifier is NCT07287410.

Background/Objectives: Digital technologies are increasingly explored as complementary tools in speech and language therapy for children with neurodevelopmental disorders. However, evidence on virtual reality-based interventions for children with developmental language disorder (DLD) remains limited. This study aimed to evaluate the effects of a Virtual Reality Rehabilitation System (VRRS)-based language intervention combined with standard speech therapy in preschool children with DLD. Secondary objectives included assessing the feasibility, usability, and safety of the VRRS-integrated intervention. Methods: A randomized controlled pilot study was conducted in preschool children diagnosed with DLD. Participants were allocated to an experimental group receiving VRRS-based language intervention integrated with conventional therapy or to a control group receiving standard speech therapy alone. Both groups attended two 60 min sessions per week for six months. Clinical language outcomes were assessed at baseline (T0) and post-intervention (T1). Feasibility was evaluated through adherence and retention rates, usability through a therapist-completed questionnaire, and safety through monitoring of adverse events during sessions. Results: All participants in the experimental group completed the intervention (100% retention). No adverse events were observed. Therapists reported good usability of the VRRS system, highlighting ease of exercise customization, intuitive monitoring of progress, and good integration into routine therapy. Conclusions: VRRS-based activities integrated into conventional speech therapy appear feasible, safe, and well accepted in preschool children with DLD. Further controlled studies with larger samples are needed to confirm these findings. Trial Registration: ClinicalTrials.gov (NCT07438639).

Abstract Parkinson’s disease (PD) is characterized by widespread neurodegeneration across neuromodulatory systems, profoundly affecting cortico–basal ganglia–thalamic loops. The resulting cortical alterations can be detected with electroencephalography (EEG). Emerging evidence shows that non-oscillatory, aperiodic EEG activity provides meaningful information that complements the oscillatory, periodic features traditionally examined. Nonetheless, available information on periodic alpha and beta power as well as aperiodic features in PD patients during the OFF-medication state are inconclusive. Moreover, replicability of spectral EEG findings across different EEG systems has received little attention. Herein, we aimed at characterizing aperiodic and periodic EEG signatures in PD during OFF-medication resting-state and examining their relationships with age, disease duration, and levodopa-induced dyskinesias. Resting-state EEG was recorded from forty patients with PD OFF-medication and twenty-six age-and sex-matched healthy controls, and a subset of patients and controls returned for a second visit using a different EEG amplifier. Power spectra were parametrized to extract aperiodic parameters (exponent and offset, i.e. the slope and the intercept of the broadband signal, respectively) and power in the alpha and beta frequency bands, adjusted for the aperiodic component. Bayesian statistical tests were used to assess between-group differences and associations with clinical (MDS-UPRDS-III, LEDD, disease duration) and demographic (age) variables. We found that aperiodic offset and alpha power were higher in patients than controls across all channels (BF 10 =80.74; BF 10 =26.81) and when restricting analysis to pericentral channels (BF 10 =70.75; BF 10 =16.90). These differences were equally expressed in patients with and without a positive history of levodopa-induced dyskinesias and replicated at follow-up using a different EEG recording system. In patients, aperiodic offset and exponent, but not periodic alpha or beta power, scaled positively with age and disease duration (BF 10 =2.16–9.76). The successful replication of increased aperiodic offset and periodic alpha power highlights their potential as robust neurophysiological markers of PD, while aperiodic parameters may track disease duration.

Background and Aim: Low back pain (LBP) represents an important public health issue, with approximately 20% of acute cases progressing to chronic low back pain (CLBP). In addition to pain, patients with CLBP also suffer from reduced cognitive performance, depressive symptoms and catastrophic thoughts. Central sensitization (CS) is considered a key point in pain persistence. This study examines CS and its impact on cognitive, emotional, and behavioral functioning in patients with CLBP. Methods: In this cross-sectional study, 67 patients with CLBP were classified using the Central Sensitization Inventory (CSI) into groups with (WCS, n = 32) and without central sensitization (WoCS, n = 35). Cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA), emotional functioning using the Center for Epidemiologic Studies Depression Scale (CES-D), and behavioral functioning using the Pain Catastrophizing Scale (PCS), including helplessness, rumination, and magnification domains. Normality was assessed using the Shapiro-Wilk test. Between-group comparisons were performed using Mann-Whitney U, chi-square, or Welch's t-tests. Multivariable linear regression analyses adjusted for age and gender were conducted. Results: Compared with the WoCS group, patients with central sensitization were older (median 58 vs. 50 years, p = 0.001) and more frequently female (71.9% vs. 40.0%, p = 0.018). The WCS group showed higher PCS total scores (31.8 ± 14.2 vs. 16.0 ± 11.9), higher helplessness (14.3 ± 6.1 vs. 6.9 ± 5.5), rumination (12.7 ± 6.2 vs. 7.0 ± 4.8), and magnification scores (4.8 ± 2.4 vs. 2.1 ± 2.1), higher CES-D scores (26.3 ± 10.4 vs. 11.7 ± 7.2), and lower MoCA scores (23.6 ± 3.0 vs. 26.1 ± 2.1) (all p < 0.001). All associations remained significant after adjustment for age and gender. Conclusions: Central sensitization in CLBP is independently associated with greater pain catastrophizing across all domains, increased depressive symptoms, and reduced cognitive performance, supporting its role as a multidimensional clinical phenotype.

Background:PLP1-related disorders, including the Pelizaeus-Merzbacher disease spectrum and X-linked spastic paraplegia type 2, are rare hypomyelinating conditions characterized by progressive gait impairment, lower limb spasticity, and motor disability. Evidence supporting rehabilitation strategies in these disorders remains limited, particularly for technology-assisted interventions. Case presentation:We report the case of a 29-year-old man with progressive PLP1-related spastic paraparesis, prominent gait impairment, recurrent falls, lower limb spasticity, and preserved independence in activities of daily living. Genetic testing identified a hemizygous PLP1 variant, classified as likely pathogenic. The patient underwent a 20-session outpatient rehabilitation program organized into two sequential blocks: 10 sessions of anti-gravity treadmill training (Alter-G), followed by 10 sessions combining Alter-G and EXOPULSE Mollii Suit stimulation. Methods and outcomes:Clinical, gait analysis, and posturographic outcomes were collected at baseline (T0), after the first block (T1), and after completion of the full intervention (T2). Across the intervention period, balance, lower limb strength, and spasticity showed overall improvement, whereas timed mobility and endurance displayed an initial worsening at T1 followed by partial recovery at T2. Instrumental gait analysis revealed marked step-length reduction after the first block, with substantial recovery by T2, alongside side-specific changes in gait quality indices. Static posturography showed progressive normalization of foot load distribution under eyes-open conditions, while residual asymmetry persisted with eyes closed. Fatigue scores, assessed during the second block only, improved over time. Conclusion:This case suggests that sequential technology-assisted rehabilitation combining body weight-supported treadmill training and wearable electrical stimulation is feasible in PLP1-related spastic paraparesis and may be associated with improvements in selected domains, including balance, strength, spasticity, and selected gait parameters. Given the single-case design, multimodal treatment structure, and potential confounding factors, these findings should be considered exploratory and hypothesis-generating.

Patients with Alzheimer’s disease (AD) exhibit early alterations in the Default Mode Network (DMN), a key brain network involved in episodic memory where the precuneus plays a central role. Precision-targeted, non-invasive brain stimulation represents a promising strategy to improve cognitive function in individuals with dementia. The DMN can be modulated through personalized non-invasive electromagnetic stimulation, a therapeutic approach that enhances neural plasticity and stabilizes network connectivity. This trial implements an innovative therapeutic protocol based on precision delivery of personalized electromagnetic stimulation targeting the precuneus, the main hub of the DMN. This phase 2 multicenter, randomized, double-blind, sham-controlled, three-arm trial evaluates the safety and efficacy of combined repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) targeting the precuneus in AD patients. rTMS will be applied using the intermittent theta burst stimulation (iTBS) protocol, while tACS will be delivered at gamma frequency (70 Hz). Personalization of iTBS-tACS treatment is established using neuronavigated TMS with electroencephalography (TMS-EEG). The 24-week intervention starts with a 2-week intensive course of daily combined treatment over the precuneus (5 sessions per week), followed by a 22-week maintenance phase with weekly stimulation. The primary outcome measure is the change in the integrated Alzheimer Disease Rating Scale (iADRS) between baseline and week 24. Secondary outcomes include score changes in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale, Clinical Dementia Rating Scale–Sum of Boxes (CDR-SoB), the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog13), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Frontal Assessment Battery (FAB), the Face-Name Association Task (FNAT), the Neuropsychiatric Inventory (NPI), and the Apathy Motivation Index (AMI). Exploratory outcomes will include changes in cortical activity and connectivity (assessed through TMS-EEG, MRI), in blood based biomarkers of neurodegeneration, synaptic activity and neural inflammation, and sensorimotor functions in virtual environments. Evaluation at week 12 and a follow-up assessment at week 32 will be conducted to assess short-term and follow-up treatment effects, respectively. This trial aims to provide evidence that personalized combined electrical and magnetic stimulation of the DMN may slow functional and cognitive decline in AD patients, contributing to the development of personalized interventions for AD treatment. ClinicalTrials.gov, NCT07075770, registered 10 July 2025.

Background:Robotic-assisted therapy (RAT) has emerged as an effective approach to upper limb neurorehabilitation. Among available systems, the Armeo®Spring enables task-oriented, customizable training supported by virtual reality (VR), fostering motivation and neuroplasticity. This retrospective observational study aimed to evaluate longitudinal changes in performance across different VR exercises using Armeo®Spring session data from patients with diverse neurological conditions and to identify tasks exhibiting significant improvement within particular diagnoses, thereby supporting personalized robotic rehabilitation. Methods:The dataset included adults (≥18) with common neurological disorders who completed ≥20 Armeo®Spring sessions using frequent integrated VR exercises. Performance across the first 20 sessions was analyzed using linear mixed-effects models with fixed effects for session, disease, age, sex, difficulty, and mechanical support, and random patient intercepts and slopes. False discovery rate (FDR) correction was applied to identify disease- and task-specific improvement trajectories. Results:After sequential filtering, the final cohort included 71 patients (30 with ischemic stroke, 15 with hemorrhagic stroke, 15 with multiple sclerosis, and 11 with Parkinson's disease) who underwent rehabilitation using five different VR exercises: Balloons, Roll the Ball, Fly High-Elbow, The Goalkeeper, and Pirate Adventure. A significant improvement in Roll the Ball scores was detected for MS (slope = +9.41 points/session, FDR = 0.0015), IS (+9.18 points/session, FDR = 0.0001), and HS (+7.28 points/session, FDR = 0.023). In Fly High (Elbow), MS patients demonstrated a significant improvement (+6.84 points/session, FDR <0.001) as for IS patients (+5.00 points/session, FDR <0.001). Task difficulty was consistently correlated with lower scores across all games (FDR <0.05), whereas age and sex were not significant predictors in the adjusted models. Conclusion:Disease-specific recovery profiles suggest that proximal, multi-joint VR exercises, such as Roll the Ball and Fly High (Elbow), may be particularly effective for patients with multiple sclerosis and ischemic stroke, whereas other exercises show smaller or non-significant improvements. These findings support tailoring VR-based rehabilitation to the patient's neurological condition, enabling targeted, condition-specific exercise selection and progression, which may enhance the effectiveness and efficiency of upper-limb recovery.