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.

Surface electromyography (EMG) can drive assistive training systems in neurorehabilitation. This systematic review and meta-analysis evaluated whether EMG-driven device-assisted rehabilitation improves upper-limb (UL) and lower-limb (LL) outcomes versus conventional therapy (CT). The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in PROSPERO (CRD420251029642). We searched databases for randomized controlled trials in adults with neurological disorders; three reviewers screened records, extracted data, and assessed risk of bias using the Revised Cochrane risk-of-bias tool (RoB 2). Seven trials (n = 160) were included, all in post-stroke populations (UL: 3; LL: 4). UL trials showed mixed findings, and pooled effects were imprecise and not statistically significant for activities of daily living (ADL) (standardized mean difference, SMD −0.55; p = 0.09; I2 = 0%). LL pooled estimates showed no significant differences in motor function (Fugl-Meyer Assessment, lower extremity, FMA-LE) (mean difference, MD −1.69; p = 0.40), walking independence (Functional Ambulation Categories, FAC) (MD −0.24; p = 0.61), balance (SMD 0.12; p = 0.61), mobility (Timed Up and Go, TUG) (MD −3.24; p = 0.71), or endurance (SMD −0.19; p = 0.43). Current evidence does not demonstrate clinical superiority over CT. EMG-driven systems may be used as an adjunct, but larger trials with standardized protocols, implementation outcomes, and neurological pathologies beyond stroke are needed.

To provide a practical framework for neuropsychological assessment in adult epilepsy, specifying what each measure evaluates and how results can support clinical decisions regarding epileptic patients. This work is a clinically oriented narrative review and expert proposal for non-surgical adult epilepsy care in Italian settings. Test selection was guided by domains repeatedly emphasized in epilepsy neuropsychology, by their practical relevance to routine clinical decision-making, by compatibility with major international recommendations, and by the availability of Italian adaptations or normative data. For each test, we describe the primary construct assessed and the specific epilepsy-related clinical question it may help address. Structured cognitive exams can be sensitive to lateralization and localization, medication-related cognitive effects, and comorbid mood and anxiety symptoms. When integrated with electroencephalography and structural imaging, these profiles support clinical interpretation and guide counseling. Serial assessment can also inform medical management, rehabilitation planning, and quality-of-life interventions. The expanded framework clarifies which patients should be referred for assessment, why epilepsy must be conceptualized as a heterogeneous group of syndromes and network disorders, where neuropsychological data may support but not replace differential diagnosis, and how current ILAE recommendations contextualize the proposed battery. Neuropsychological assessment is a core component of comprehensive epilepsy care, but its clinical value is greatest when the battery is tailored to the referral question, syndrome, disease stage, treatment context, and patient priorities. The proposed battery should be read as a structured, adaptable framework for routine adult non-surgical practice, rather than as a rigid battery to be applied uniformly across patients.

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.

Neurorehabilitation has entered a phase of rapid conceptual expansion [...]

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.

Background/Objectives: Sexual health is frequently under-addressed after stroke, despite its relevance to intimacy, identity, relationships, and rehabilitation. This convergent mixed-methods study integrated sex-specific screening with descriptive narrative material to examine sexual functioning and patient-reported concerns in clinical rehabilitation. Methods: Twenty-six adults were assessed: ten with the Female Sexual Function Index (FSFI), sixteen with an International Index of Erectile Function six-item field (IIEF-6), and ten with analyzable semi-structured interview responses. The sex-specific measures were analyzed separately. Continuous variables were summarized by median and interquartile range; nonparametric correlations and group comparisons underwent Benjamini-Hochberg false discovery rate correction. Quantitative and qualitative findings were integrated in a participant-level joint display. This integration yielded case-level meta-inferences rather than inferential mixed-methods testing in this sample. Results: Nine of ten FSFI profiles and nine of sixteen IIEF-6 profiles met the respective exploratory threshold for possible dysfunction. No association or group comparison remained statistically significant after correction. Six of eighteen threshold-positive profiles had analyzable interviews, twelve represented narrative silence, and four interviewed participants were threshold-negative. Narratives documented fear, embarrassment, reduced desire or sexual frequency, relational or communication change, support needs, clinical sequelae, and positive or neutral adaptation. Screening and narratives showed convergence, complementarity, and divergence: low scores did not establish personal distress, whereas concerns could occur above a threshold. Conclusions: Responsive sexual rehabilitation should combine confidential, permission-based, patient-led screening and narrative inquiry with individualized information, optional support, appropriate referral, and reassessment according to readiness. These preliminary, hypothesis-generating findings do not validate an intervention or support confirmatory inference.

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: 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.

Gait dysfunction is a common and disabling consequence of stroke, frequently associated with impaired lower-limb torque generation and reduced balance. Robot-assisted gait training (RAGT) has emerged as a promising intervention; however, its phase-specific biomechanical effects remain incompletely characterized. This pilot mechanistic study investigated the effects of Walkbot-assisted gait training on phase-specific lower-limb torque and clinical outcomes in individuals with unilateral hemiplegia. Fifteen patients with hemiplegia underwent Walkbot-assisted gait training. Joint torque values were normalized to body mass (Nm/kg). Phase-specific torque was analyzed during the swing and stance phases for the affected and unaffected limbs. Pre-post differences were evaluated using the Wilcoxon signed-rank test. Functional balance and motor impairment were assessed using the Berg Balance Scale (BBS) and the Fugl-Meyer Assessment-Lower Extremity (FMA-LE). Significant torque increases were observed in both gait phases. Median swing-phase torque increased from 0.261 to 0.361 Nm/kg in the affected limb and from 0.254 to 0.334 Nm/kg in the unaffected limb (p ≤ 0.017). Stance-phase torque increased from 0.197 to 0.454 Nm/kg in the affected limb and from 0.158 to 0.471 Nm/kg in the unaffected limb. Clinical outcomes improved significantly, with median BBS scores increasing from 22.0 to 34.0 and FMA-LE scores from 14.0 to 24.0 (p = 0.001). Walkbot-assisted gait training was associated with significant phase-specific torque gains, accompanied by improvements in balance and lower-limb motor recovery.

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/Objectives : Severe acquired brain injury (sABI) disrupts early rehabilitation because arousal fluctuates, trunk control is fragile, and agitation limits therapy tolerance; land-based practice is frequently constrained by fall risk and staffing. We aim to reframe aquatic therapy as a programmable multisensory environment to stabilize arousal and support axial alignment before conventional impairment targets are feasible. Here, programmable denotes the deliberate titration and reporting of water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support as intervention inputs. Methods : This perspective integrates principles from neurobehavioral assessment, motor control, and immersion physiology to propose the Arousal-Alignment-Action loop as a falsifiable model and to define manipulable aquatic inputs (water depth, turbulence or perturbation, temperature, body orientation, and flotation and manual support) as dosing parameters. We outline a pragmatic testing ladder (within-session micro-experiments, feasibility studies, and embedded evaluations) and a minimal outcomes and confounder set to support cumulative evidence. Results : The framework links state regulation to alignment and goal-directed behavior, specifies predictions that can fail, and highlights boundary conditions (sedation, autonomic instability, pain, recent surgery or wounds, and cervical or cardiopulmonary constraints). A minimal outcome package spanning arousal/responsiveness, trunk control, behavioral dysregulation, participation/tolerance, and basic physiology is proposed, with optional objective adjuncts for mechanism-oriented studies. Conclusions : Treating water as a measurable and titratable medium, rather than a generic modality, may reduce early intensity bottlenecks and improve implementability and comparability of aquatic neurorehabilitation research in medically stable sABI; however, the model is intended as hypothesis-generating until supported by stronger direct clinical evidence.

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.