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Background/Objectives: Dementia leads to cognitive decline, affecting memory, reasoning, and daily activities, often requiring full-time care. Multisensory stimulation (MSS), combined with cognitive tasks, can slow this decline, improving mood, communication, and overall quality of life. This systematic review aims to explore methods that utilize MSS in the rehabilitation of patients with dementia. Its clinical value is rooted in its ability to offer a deep comprehension of how MSS can be successfully incorporated into rehabilitation treatments. Methods: Studies were identified from an online search of PubMed, EBSCOhost, Cochrane Library, Web of Science, Embase, and Scopus databases with a search time frame from 2014 to 2024. This review has been registered on Open OSF (n) 3KUQX. Results: Pilot studies investigating MSS interventions, encompassing Cognitive Stimulation Therapy (CST), Sonas therapy, and combined physical–cognitive exercise programs, have yielded mixed findings in individuals with dementia. CST has demonstrated significant improvements in general cognitive function, particularly in language skills, offering a promising approach for cognitive enhancement. Sonas therapy, while showing positive trends in some studies, does not consistently achieve statistically significant outcomes across all cognitive domains. Conversely, combined exercise programs have shown efficacy in improving dual-task performance, suggesting benefits for motor–cognitive integration. MSS delivered within specialized environments like Snoezelen rooms consistently produces positive effects on mood, reducing agitation and promoting relaxation. Conclusions: This review emphasizes how MSS can enhance cognitive, emotional, and behavioral results for individuals with dementia. It is essential for future research to standardize protocols, incorporate advanced technologies such as virtual reality, and rectify diversity gaps. Collaboration between different fields will improve the effectiveness and usefulness of MSS in caring for individuals with dementia.

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that requires comprehensive and personalized rehabilitation. This retrospective study focused primarily on the usability and patient acceptability of the innovative pathway. In addition, the secondary objective was to evaluate the effectiveness of a personalized and multidisciplinary rehabilitation pathway on cognitive function, especially executive functions. Methods: We conducted a retrospective study on 80 patients with PD (Hoehn and Yahr scores 1–3). Patients were divided into an experimental group (EG), which received the innovative pathway, and a control group (CG), which received traditional therapy. The rehabilitation program included three phases: initial outpatient assessment, a two-month inpatient program, and a telerehabilitation phase in a day hospital (DH) or home environment. Interventions combined traditional therapies with treatments based on robotic and virtual reality. Cognitive assessments (Mini Mental State Examination—MMSE—and frontal assessment battery—FAB), mood (Hamilton Rating Scale—Depression—HRS-D), anxiety (HRS-Anxiety—HRS-A), and goals achievement (GAS) were the primary outcome measures. Results: At baseline, there were no significant differences between the groups in terms of age, gender, education, or test scores. After rehabilitation, EG showed significant improvements in all measures (p < 0.001), particularly in cognitive tests and goal achievement. CG improved in GAS (p < 0.001) and mood (HRS-D, p = 0.0012), but less than EG. No significant changes were observed in the MMSE of CG (p = 0.23) or FAB (p = 0.003). Conclusions: This study highlights the high usability and acceptability of VR and robotics in PD rehabilitation, contributing to improved adherence and patient engagement. The experimental group showed greater cognitive benefits, particularly in executive functions. These results are in line with the existing literature on personalized technology-based rehabilitation strategies for PD.

Background and Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method that modulates cortical excitability and shows promising results for treating disorders of consciousness (DoCs). Robotic verticalization training (RVT) has been shown to enhance motor and cognitive recovery. This study evaluates the effects of an innovative approach combining RVT with tDCS in individuals with DoCs. Methods: Twenty-four subjects with DoCs, particularly those with chronic minimally conscious state (MCS) due to vascular or traumatic brain injury, participated in a quasi-randomized study at the Neurorehabilitation Unit, IRCCS Neurolesi (Messina, Italy). Participants were divided into either a control group (CG) receiving RVT alone or an experimental group (EG) receiving combined tDCS and RVT. Both groups underwent treatments five times weekly for four weeks, with tDCS/sham sessions over the dorsolateral prefrontal cortex (DLPFC) lasting 20 min before Erigo training sessions, which lasted 45 min. Results: The findings indicate that combining tDCS with Erigo® Pro RTT could lead to greater improvements in cognitive functioning and P300 latency compared to the CG. Conclusions: These results suggest that the integrated approach of tDCS with RVT could offer significant benefits for patients with MCS, highlighting its potential to enhance cognitive recovery, such as reducing P300 latency.

Introduction: Apraxia is a neurological disorder that is common after a stroke and impairs the planning and execution of movements. In the rehabilitation field, virtual reality (VR) presents new opportunities and offers advantages to both rehabilitation teams and individuals with neurological conditions. Indeed, VR can stimulate and improve cognitive reserve and abilities, including executive function, and enhance the patient’s emotional status. Aim: The objective of this research is to determine the effectiveness of VR in improving praxis skills and behavioural functioning in individuals with severe stroke. Methods: A total of 20 stroke patients were enrolled from February 2022 to March 2023 and divided by the order of their recruitment into two groups: the experimental group (EG: n = 10) received training to improve their praxis skills using VR whereas the control one (CG: n = 10) received the same amount of standard training. All patients underwent an evaluation using a psychometric battery that consisted of the Hamilton Rating Scale for Depression (HRS-D), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Spinnler and Tognoni test, and De Renzi and Faglioni test. Valuations were performed before rehabilitation (T0) and after its completion (T1). Results: Both groups demonstrated significant improvements post-intervention. The EG showed a greater enhancement in their MMSE scores (p = 0.002), and reductions in both ideomotor and constructive apraxia (p = 0.002 for both), compared to the CG. The VR-based training also resulted in significant improvements in their depression symptoms (HRSD scores improved, p = 0.012 in EG vs. p = 0.021 in CG). Conclusions: This pilot study suggests that VR could help reduce cognitive, constructive apraxia and ideomotor apraxia symptoms caused by stroke injury.

Spinal Cord Injury (SCI) is a condition where the spinal cord is damaged and experiences partial or complete loss of motor and/or sensory function, which is typically less than normal. After SCI, patients may exhibit more severe psychiatric symptoms and experience cognitive impairments, including reduced speed and attention processing capacity, as well as difficulties with executive function and episodic memory retention. Among the behavioral and psychiatric symptoms, depression, anxiety, substance use disorder, and posttraumatic stress disorder are the most common. This review aims to investigate the cognitive, behavioral, or psychiatric symptoms of the patient with SCI and their influence on the rehabilitation process. Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases. Studies published between 2013-2023 were selected. This review has been registered on OSF (n) 3KB2U. We have found that patients with SCI are at high risk of cognitive impairment and experience a wide range of difficulties, including tasks based on processing speed and executive function. This clinical population may experience adjustment disorders with depression and anxiety, as well as other psychiatric symptoms such as fatigue, stress, and suicidal ideation. This review has demonstrated that SCI patients may experience psychiatric symptoms and cognitive impairments that affect their functioning. At the same time, these patients may be more prone to various adjustment and mood disorders. Moreover, these two aspects may interact with each other, causing a range of symptoms, increasing the risk of hospitalization, and delaying the rehabilitation process.

Vascular dementia, the second most common type of dementia, currently lacks a definitive cure. In the pursuit of therapies aimed at slowing its progression and alleviating symptoms, transcranial direct current stimulation (tDCS) emerges as a promising approach, characterized by its non-invasive nature and the ability to promote brain plasticity. In this study, the primary objective was to investigate the effects of a two-week cycle of tDCS on the dorsolateral prefrontal cortex (DLPFC) and neurophysiological functioning in thirty patients diagnosed with vascular dementia. Each participant was assigned to one of two groups: the experimental group, which received anodal tDCS to stimulate DPCFL, and the control group, which received sham tDCS. Neurophysiological functions were assessed before and after tDCS using P300 event-related potentials (ERPs), while neuropsychological function was evaluated through a Mini-Mental State Examination (MMSE). The results showed a reduction in P300 latency, indicating a faster cognitive process; an increase in P300 amplitude, suggesting a stronger neural response to cognitive stimuli; and a significant improvement in MMSE scores compared to the control group, indicating an overall enhancement in cognitive functions. These findings suggest that tDCS could represent a promising therapeutic option for improving both neurophysiological and cognitive aspects in patients with vascular dementia.

Background: In recent years, new technologies have been applied in cerebral palsy. Among these, immersive virtual reality is one with promising motor and cognitive effects along with the reduced costs of its application. The level of immersion of the subject in the illusional world gives the feeling of being a real part of the virtual environment. This study aims to investigate the safety and the efficacy of immersive virtual reality in children affected by cerebral palsy. Methods: PubMed, Embase, Cochrane Database of Systematic Reviews, RehabData, and Web of Science were screened up to February 2023 to identify eligible clinical studies. Results: Out of 788, we included 15 studies involving CP patients. There was high heterogeneity in the outcomes considered, and the results showed non-inferiority to conventional therapy and initial additional benefits in comparison with conventional rehabilitation. Conclusions: Immersive virtual reality emerges as a pivotal technological tool in rehabilitation, seamlessly integrating with conventional therapy within CP rehabilitation programs. Indeed, it not only enhances motivation but significantly increases children’s functional capacity and abilities.

Introduction: Parkinson’s disease (PD) is one the most common neurodegenerative movement disorder, leading to motor and non-motor symptoms, including deficits in executive functions (EF), memory, visuospatial abilities, and psychomotor speed. Current treatments are primarily symptomatic, involving pharmacological, surgical strategies. Neurologic Music Therapy (NMT) has gained recognition for its effectiveness in neurorehabilitation of PD patients and improving motor and cognitive domains, such as EF. This study combines NMT with the virtual reality (VR) platform Computer-Assisted Rehabilitation Environment (CAREN), offering customizable environments for rhythmic cue practice to provide an innovative approach to Parkinson’s rehabilitation. Methods: In our single-blind quasi-randomized controlled trial, forty patients were assigned to either an experimental group (EG = 20) or a control group (CG = 20). Both groups underwent two months of training with CAREN scenarios (three times a week for 24 sessions). The experimental group additionally received NMT applied to the selected scenarios. Participants were evaluated by a neuropsychologist at baseline and immediately after training. Results: Intra-group analysis showed significant improvements in the EG for MOCA (p = 0.007), FAB (p = 0.008), Stroop Error (p = 0.003), Stroop Time (p

The purpose of this study was to investigate the effects of a “human immersion model” (HIM) in improving psychological well-being in caregivers of patients with acquired brain injury (ABI) during the Omicron wave in Italy. Fifteen subjects affected by ABI, who attended our intensive neurorehabilitation unit from January to March 2022 and their caregivers were submitted to the HIM. This novel approach consisted of “real” long-lasting meetings between the patients and their careers in a hospital setting (1–72 h meeting per week for 8 weeks). Each ABI caregiver was assessed through the administration of a short psychometric battery before starting the first immersion session with their family member and at the end of the HIM. We found significant changes in the caregivers’ scores analyzed for anxiety, as per SAS (p < 0.0007, d = 1.02), burden and stress (ZBI-22; p < 0.001, d = 0.65), and emotive intelligence (TEIQue-SF; p < 0.0007, d = 0.82). Our data suggest that the HIM may be useful to promote ABI caregivers’ psycho-emotional well-being in the context of critical periods such as the COVID-19 pandemic.

BackgroundIn neurorehabilitation, the use of innovative technologies offers many opportunities to monitor and improve the health status of patients with severe acquired brain injury (SABI). Telerehabilitation allows for continuity of service through the entire rehabilitation cycle, including assessment, intervention, consultation, and education, affording early reintegration and positively enhancing the quality of life (QoL). ObjectiveThe main purpose of this multicenter randomized controlled trial was to test the effectiveness of advanced training provided using a nonimmersive virtual reality rehabilitation system (ie, the VRRS HomeKit device) in improving functional outcomes in patients with SABI. MethodsIn total, 40 patients with SABI and their 40 caregivers visiting 2 Italian rehabilitation centers were enrolled in the study protocol and randomized into 2 groups. Of the 40 patients, 20 (50%) underwent the experimental training using the VRRS HomeKit (teleneuro-VRRS group), whereas the other 20 (50%) were administered usual territorial rehabilitative treatments (UTRTs; control group). To investigate motor and neuropsychological functioning, patients with SABI were evaluated before (T0) and at the end of (T1) each training session by a multispecialist team through a complete clinical and psychometric battery: the Barthel Index (BI), the Tinetti Scale (TS), the Modified Ashworth Scale (MAS), the Montreal Cognitive Assessment (MoCa), the Frontal Assessment Battery (FAB), the Beck Depression Inventory II (BDI-II), the Short Form Health Survey 36 (SF-36), and the Psychological General Well-Being Index (PGWBI). In addition, the Caregiver Burden Inventory (CBI) was administered to each caregiver to investigate the emotional burden status. ResultsThe teleneuro-VRRS group achieved a statistically significant improvement in both general and motor outcomes, as well as psychological well-being and QoL, compared to the control group. In particular, the BI (P

Introduction: Severe acquired brain injury (SABI) is a leading cause of death and disability, and it is defined as a brain injury that occurs after birth due to traumatic or non-traumatic causes. Reality orientation therapy (ROT) uses repeated time–place–person orientation and meaningful stimuli to develop a better understanding of the environment and has great potential as an effective strategy to improve cognitive and behavioral functioning. Objective: This study aims to investigate the feasibility and potential effects of virtual reality orientation therapy (VR-rot) on optimizing cognitive and behavioral functioning and depressive symptoms post-SABI. Method: Forty patients with SABI were enrolled from October 2022 to December 2023 and divided into two groups: the experimental group (EG, n = 20) received VR_rot, while the control group (CG, n = 20) received standard ROT (S_rot). All patients were evaluated with a psychometric battery, including the Mini-Mental State Examination (MMSE) and the Hamilton Rating Scale for Depression (HRS-D), administered before (T0) and after the end (T1) of rehabilitation. Results: Within-group comparisons indicated a statistically significant change in MMSE scores from T0 to T1 in the EG and CG, with the EG showing a greater improvement than the CG. Regarding HRS-D scores, the EG showed a statistically significant change. VR-ROT could be a valuable tool for improving cognitive–behavioral functioning in SABI patients. Conclusions: The VRRS can help reduce depressive symptoms and improve the reality orientation deficit caused by traumatic brain injury and stroke on brain tissue. This study highlights the benefits of virtual reality.

In disorders of consciousness, verticalization is considered an effective type of treatment to improve motor and cognitive recovery. Our purpose is to investigate neurophysiological effects of robotic verticalization training (RVT) in patients with minimally conscious state (MCS). Thirty subjects affected by MCS due to traumatic or vascular brain injury, attending the intensive Neurorehabilitation Unit of the IRCCS Neurolesi (Messina, Italy), were included in this retrospective study. They were equally divided into two groups: the control group (CG) received traditional verticalization with a static bed and the experimental group (EG) received advanced robotic verticalization using the Erigo device. Each patient was evaluated using both clinical scales, including Levels of Cognitive Functioning (LCF) and Functional Independence Measure (FIM), and quantitative EEG pre (T0) and post each treatment (T1). The treatment lasted for eight consecutive weeks, and sessions were held three times a week, in addition to standard neurorehabilitation. In addition to a notable improvement in clinical parameters, such as functional (FIM) (p < 0.01) and cognitive (LCF) (p < 0.01) outcomes, our findings showed a significant modification in alpha and beta bands post-intervention, underscoring the promising effect of the Erigo device to influence neural plasticity and indicating a noteworthy difference between pre-post intervention. This was not observed in the CG. The observed changes in alpha and beta bands underscore the potential of the Erigo device to induce neural plasticity. The device’s custom features and programming, tailored to individual patient needs, may contribute to its unique impact on brain responses.

Background and Objectives: Traumatic Brain Injury (TBI) is a condition in which an external force, usually a violent blow to the head, causes functional impairment in the brain. Neuromodulation techniques are thought to restore altered function in the brain, resulting in improved function and reduced symptoms. Brain stimulation can alter the firing of neurons, boost synaptic strength, alter neurotransmitters and excitotoxicity, and modify the connections in their neural networks. All these are potential effects on brain activity. Accordingly, this is a promising therapy for TBI. These techniques are flexible because they can target different brain areas and vary in frequency and amplitude. This review aims to investigate the recent literature about neuromodulation techniques used in the rehabilitation of TBI patients. Materials and Methods: The identification of studies was made possible by conducting online searches on PubMed, Web of Science, Cochrane, Embase, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF (JEP3S). Results: We have found that neuromodulation techniques can improve the rehabilitation process for TBI patients in several ways. Transcranial Magnetic Stimulation (TMS) can improve cognitive functions such as recall ability, neural substrates, and overall improved performance on neuropsychological tests. Repetitive TMS has the potential to increase neural connections in many TBI patients but not in all patients, such as those with chronic diffuse axonal damage.Conclusions: This review has demonstrated that neuromodulation techniques are promising instruments in the rehabilitation field, including those affected by TBI. The efficacy of neuromodulation can have a significant impact on their lives and improve functional outcomes for TBI patients.

Post-traumatic Olfactory Dysfunction (PTOD) consists of a complete or partial loss of olfactory function that may occur after a traumatic brain injury (TBI). PTOD may be linked to some neuropsychiatric features, such as social, cognitive and executive dysfunction, as well as behavioral symptoms, especially when TBI involves the orbito-frontal cortex. The diagnosis of PTOD is based on medical history and clinical data and it is supported by psychometric tests (i.e., subjective tools) as well as electrophysiological and neuroimaging measures (i.e., objective methods). The assessment methods allow monitoring the changes in olfactory function over time and help to establish the right therapeutic and rehabilitative approach. In this context, the use of the olfactory training (OT), which is a non-pharmacological and non-invasive treatment option, could promote olfactory function through top-down (central) and bottom-up (peripheral) processes. To better manage patients with TBI, PTOD should be detected early and properly treated using the various therapeutic rehabilitative possibilities, both conventional and advanced, also taking into consideration the emerging neuromodulation approach.

Objective The study aim was to investigate the prevalence of behavioral symptoms and burnout in healthcare workers in an intensive neurological rehabilitation unit in Messina, Italy, during the first COVID-19 lockdown in Italy. Methods Forty-seven healthcare workers (including neurologists, physiatrists, nurses and rehabilitation therapists) were enrolled in this cross-sectional study from February 2020 to June 2020. Participants were administered the following psychometric tests to investigate burnout and related symptoms: the Maslach Burnout Inventory, which measures emotional exhaustion, depersonalization and reduced personal accomplishment; the Zung Self-Rating Depression Scale (SDS); the Pre-Sleep Arousal Scale (PSAS); the Dyadic Adjustment Scale; and the Buss–Perry Aggression Questionnaire (BPAQ). Results We found several correlations between test scores and burnout subdimensions. Emotional exhaustion was correlated with SDS (r = 0.67), PSAS-Cognitive (r = 0.67) and PSAS-Somatic (r = 0.70) scores, and moderately correlated with all BPAQ dimensions (r = 0.42). Depersonalization was moderately correlated with SDS (r = 0.54), PSAS-Cognitive (r = 0.53) and PSAS-Somatic (r = 0.50) scores. Conclusion During the first COVID-19 lockdown in Italy, healthcare workers were more exposed to physical and mental exhaustion and burnout. Research evaluating organizational and system-level interventions to promote psychological well-being at work for healthcare workers are needed.

Cognitive Rehabilitation (CR) is a therapeutic approach designed to improve cognitive functioning after a brain injury, including stroke. Two major categories of techniques, namely traditional and advanced (including virtual reality—VR), are widely used in CR for patients with various neurological disorders. More objective outcome measures are needed to better investigate cognitive recovery after a stroke. In the last ten years, the application of electroencephalography (EEG) as a non-invasive and portable neuroimaging method has been explored to extract the hallmarks of neuroplasticity induced by VR rehabilitation approaches, particularly within the chronic stroke population. The aim of this study is to investigate the neurophysiological effects of CR conducted in a virtual environment using the VRRS device. Thirty patients with moderate-to-severe ischemic stroke in the chronic phase (at least 6 months after the event), with a mean age of 58.13 (±8.33) for the experimental group and 57.33 (±11.06) for the control group, were enrolled. They were divided into two groups: an experimental group and a control group, receiving neurocognitive stimulation using VR and the same amount of conventional neurorehabilitation, respectively. To study neuroplasticity changes after the training, we focused on the power band spectra of theta, alpha, and beta EEG rhythms in both groups. We observed that when VR technology was employed to amplify the effects of treatments on cognitive recovery, significant EEG-related neural improvements were detected in the primary motor circuit in terms of power spectral density and time-frequency domains. Indeed, EEG analysis suggested that VR resulted in a significant increase in both the alpha band power in the occipital areas and the beta band power in the frontal areas, while no significant variations were observed in the theta band power. Our data suggest the potential effectiveness of a VR-based rehabilitation approach in promoting neuroplastic changes even in the chronic phase of ischemic stroke.

In the last ten years, technological innovations have led to the development of new, advanced sensory stimulation (SS) tools, such as PC-based rehabilitative programs or virtual reality training. These are meant to stimulate residual cognitive abilities and, at the same time, assess cognition and awareness, also in patients with a minimally conscious state (MCS). Our purpose was to evaluate the clinical and neurophysiological effects of multi-sensory and emotional stimulation provided by Neurowave in patients with MCS, as compared to a conventional SS treatment. The psychological status of their caregivers was also monitored. In this retrospective study, we have included forty-two MCS patients and their caregivers. Each MCS subject was included in either the control group (CG), receiving a conventional SS, or the experimental group (EG), who was submitted to the experimental training with the Neurowave. They were assessed before (T0) and after the training (T1) through a specific clinical battery, including both motor and cognitive outcomes. Moreover, in the EG, we also monitored the brain electrophysiological activity (EEG and P300). In both study groups (EG and CG), the psychological caregiver’s aspects, including anxiety levels, were measured using the Zung Self-Rating Anxiety Scale (SAS). The intra-group analysis (T0-T1) of the EG showed statistical significances in all patients’ outcome measures, while in the CG, we found statistical significances in consciousness and awareness outcomes. The inter-group analysis between the EG and the CG showed no statistical differences, except for global communication skills. In conclusion, the multi-sensory stimulation approach through Neurowave was found to be an innovative rehabilitation treatment, also allowing the registration of brain activity during treatment.

Traumatic brain injury is damage to the brain occurring after birth, often resulting in the deterioration of cognitive, behavioural, and emotional functions. Neuropsychological evaluation can assist clinicians to better assess the patient’s clinical condition, reach differential diagnoses, and develop interventional strategies. However, considering the multiple rating scales available, it is not easy to establish which tool is most suitable for the different brain injury conditions. The aim of this review is to investigate and describe the most used neurocognitive assessment tools in patients with traumatic brain injury to provide clinicians with clear indications on their use in clinical practice. Indeed, during the acute phase, after the head trauma, alertness and wakefulness of the patients affected by a disorder of consciousness can be assessed using different scales, such as the Coma Recovery Scale-Revised. In both postacute and chronic phases after traumatic brain injury, general cognitive assessment tools (such as the Mini Mental State Examination) or more specific cognitive tests (e.g., Wisconsin Card Sorting Test and Trail Making Test) could be administered according to the patient’s functional status. In this way, clinicians may be aware of the patient’s neuropsychological and cognitive level, so they can guarantee a personalized and tailored rehabilitation approach in this frail patient population.

A spinal cord injury (SCI) is damage to any part of the spinal cord, caused by traumatic or non-traumatic events. Clinically, SCI is associated with partial or complete loss of motor, sensory, and autonomic functions below the site of injury. However, cognitive alterations in specific domains can also occur. The aim of this study was to evaluate the effects of semi-immersive virtual reality (VR) cognitive training (using the BTS Nirvana, Italy) in promoting global functional recovery in patients with SCI. Forty-two SCI patients were included in this retrospective case-control study, and the analysis was carried out using an electronic data retrieval system. The enrolled patients were divided into two groups with the same demographic and medical characteristics: the control group (CG: 21 patients) participated in traditional therapy, whereas the experimental group (EG: 21 patients) received training using semi-immersive VR. In both groups, there were patients with A- or B-grade impairments according to the American Spinal Injury Association (ASIA) scale. Both study groups underwent the same amount of cognitive training (but using a different type of training: conventional vs. innovative), consisting of three weekly sessions for eight weeks (24 sessions in total), each session lasting approximately sixty minutes, as well as the same amount of physiotherapy. The effect of the two treatments (EG/CG) was significantly different in global cognitive functioning (MOCA: p = 0.001), mood (BDI: p = 0.006), and overall quality of life (SF12 Total: p < 0.001), especially in physical perception (SF12-Physics: p = 0.004). Our results suggest that SCI patients could benefit from cognitive training using semi-immersive VR. Indeed, the integration of cognitive exercises that require movement and provide increased feedback could allow for better motor and cognitive recovery in people with SCI.

Background and Objectives: Normal human sexual functioning is a complex integration of an intact neuroanatomic substrate, vascular supply, a balanced hormonal profile, and a predominance of excitatory over inhibitory psychological mechanisms. However, sexual functioning in Parkinson’s disease (PD) is often overlooked in clinical practice, especially in female patients. Materials and Methods: In this cross-sectional study, we have investigated the frequency of sexual dysfunction and the possible correlation with psycho-endocrinological factors in a sample of women with idiopathic PD. Patients were assessed using a semi-structured sexual interview, in addition to psychometric tools, including the Hamilton Rating Scale for Anxiety and for Depression and the Coping Orientation to the Problems Experiences—New Italian Version. Specific blood tests, including testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen E2, prolactin (PRL), and vitamin D3 were also evaluated. Results: Our results reported a statistical difference in sexual intercourse frequency before and after the onset of PD (p < 0.001). The percentage of women who complained about reduced sexual desire increased after diagnosis (52.7%) compared to the period before the onset of the illness (36.8%). The endocrinological profile in females with PD revealed statistically significant differences regarding testosterone (p < 0.0006), estradiol (p < 0.00), vitamin D3 (p < 0.006), and calcium (0.002). Depression (44% characterized by perceived feelings of anger and frustration during sexual intercourse) and anxiety symptoms (29.5% reported feelings of fear and anxiety for not satisfying the partner) with abnormal coping strategies (48.14% experienced feelings of anger and intolerance) were also found to be statistically significant. This study showed a high frequency of sexual dysfunction in female patients with PD, which correlated with sexual hormone abnormalities, mood/anxiety, and coping strategies alterations. This supports the idea that there is a need to better investigate the sexual function of female patients with PD to provide them with an adequate therapeutic approach and potentially improve quality of life.

Executive dysfunction is among the most common and disabling facets of cognitive impairment following traumatic brain injury (TBI), and may include deficits in reasoning, planning, mental flexibility, some aspects of attention and orientation, awareness and behavior. Rehabilitation programs based on cognitive-behavioral approaches to retrain planning and problem-solving and other executive deficits may improve such cognitive dysfunction. The purpose of this study is to investigate the effects of non-immersive virtual reality-based training to improve executive abilities and to reduce anxiety and depression symptoms in patients with TBI. Twenty patients with moderate to severe TBI were enrolled at our Neurorehabilitation Unit and divided to receive either the standard cognitive training or the virtual reality (VR) based cognitive training using the virtual reality rehabilitation system (VRRS-Evo). Each group received the same amount of rehabilitative training, including ROT (Reality Orientation Therapy) and Executive Training (ET), but using a different approach, i.e., a paper and pencil and an advanced approach. All patients were evaluated with a specific psychometric battery before (T0) and after the end (T1) of each program. Comparing pre- and post- treatment scores, in the VR-CT group, we found statistically significant differences in all administered outcome measures for cognitive and executive functioning, i.e., MoCA (p < 0.005), FAB (p < 0.005), TMT-A (p < 0.005), TMT-B (p < 0.005), TMT-BA (p < 0.001), and mood, i.e., HRS-D (p < 0.008). In the Conventional cognitive training (C-CT) group, we found a significant improvement only in MoCA (p < 0.03), FAB (p < 0.02) and in TMT-BA (p < 0.01). Coping strategies also improved, with better results in the VR-CT group. Our results suggest that VR rehabilitation, using the VRRS system, may be a valuable and motivational approach to improve visuo-executive abilities and coping strategies as well as mood in chronic TBI patients.

Motor and cognitive rehabilitation in individuals with traumatic brain injury (TBI) is a growing field of clinical and research interest. In fact, novel rehabilitative approaches allow a very early verticalization and gait training through robotic devices and other innovative tools boosting neuroplasticity, thanks to the high-intensity, repetitive and task-oriented training. In the same way, cognitive rehabilitation is also evolving towards advanced interventions using virtual reality (VR), computer-based approaches, telerehabilitation and neuromodulation devices. This review aimed to systematically investigate the existing evidence concerning the role of innovative technologies in the motor and cognitive neurorehabilitation of TBI patients. We searched and reviewed the studies published in the Cochrane Library, PEDro, PubMed and Scopus between January 2012 and September 2022. After an accurate screening, only 29 papers were included in this review. This systematic review has demonstrated the beneficial role of innovative technologies when applied to cognitive rehabilitation in patients with TBI, while evidence of their effect on motor rehabilitation in this patient population is poor and still controversial.

Cerebral palsy (CP) is a non-progressive congenital neurological disorder that affects different physical and cognitive functions in children. In addition to standard rehabilitation, advanced robotic gait devices are novel tools that are becoming progressively more common as part of the treatment of CP. The aim of this study is to evaluate the effects of Lokomat training, in addition to conventional rehabilitation, on the motor function and quality of life of children with ataxic-spastic CP (ASCP). Ten children with ASCP who attended the Robotic Rehabilitation OutClinic of the IRCCS Centro Neurolesi “Bonino Pulejo”, from April to June 2019, were enrolled in this study. They received twenty-four robotic rehabilitation sessions, twice a week for three months, each session lasting about 45 min. They were also provided with conventional physical and occupational therapy. After the innovative training, we found significant changes in the children’s outcomes, i.e., in GMFM (p < 0.001), with significant improvements in sitting (p < 0.03) and walking (p < 0.03). Moreover, the quality of life of the young patients, evaluated by their parents, significantly improved (p < 0.005). The use of robotic systems could be considered to be an effective complementary treatment to improve gait, as well as quality of life, in children with CP.

Traumatic brain injury (TBI) is a sudden injury that causes damage to the brain. Rehabilitation therapies include specific training, such as attention process training (APT) programs using either standard or innovative approaches. The aim of this study is to evaluate the effects of a non-immersive virtual reality-based attention training to stimulate attention processes and mood in TBI patients. Thirty subjects with TBI were enrolled at the Neurorehabilitation Unit of the IRCCS Neurolesi Center and divided into either the Conventional Attention Process Training Group (C_APT: n = 15) or the Virtual-Based Attention Processes Training Group (VB_APT: n = 15), treated with the Virtual Reality Rehabilitation System (VRRS-Evo). All of the patients were evaluated with a specific psychometric battery before (T0) and after the end (T1) of each program. We found statistically significant differences between the two groups, in particular concerning global cognitive status (p < 0.02), attention processes (p < 0.03), depression symptoms (p < 0.04) and visual attention (p < 0.01). Experimental intragroup analysis showed great statistical significances in all psychometric tests, i.e., the Montreal Cognitive Assessment (p < 0.0006), Attention Matrices (p < 0.0007), the Hamilton Rating Scale-Depression (p < 0.004), the Trail Making Test-A (p < 0.0007), the Trail Making Test-B (p < 0.0007), and the Trail Making test-BA (p < 0.007). Our results suggest that non-immersive virtual reality may be a useful and effective approach for the attention processes recovery and mood of TBI patients, leading to better cognitive and behavioral outcomes.

Post-SSRI sexual dysfunction (PSSD) is a set of heterogeneous sexual problems, which may arise during the administration of selective serotonin reuptake inhibitors (SSRIs) and persist after their discontinuation. PSSD is a rare clinical entity, and it is commonly associated with non-sexual concerns, including emotional and cognitive problems and poor quality of life. To date, however, no effective treatment is available. The aim of this study was to retrospectively evaluate the potential efficacy of the different treatments used in clinical practice in improving male PSSD. Of the 30 patients referred to our neurobehavioral outpatient clinic from January 2020 to December 2021, 13 Caucasian male patients (mean age 29.53 ± 4.57 years), previously treated with SSRIs, were included in the study. Patients with major depressive disorder and/or psychotic symptoms were excluded a priori to avoid overlapping symptomatology, and potentially reduce the misdiagnosis rate. To treat PSSD, we decided to use drugs positively affecting the brain dopamine/serotonin ratio, such as bupropion and vortioxetine, as well as other compounds. This latter drug is known not to cause or reverse iatrogenic SD. Most patients, after treatment with vortioxetine and/or nutraceuticals, reported a significant improvement in all International Index of Erectile Function-(IIEF-5) domains (p < 0.05) from baseline (T0) to 12-month follow-up (T1). Moreover, the only patient treated with pelvic muscle vibration reached very positive results. Although our data come from a retrospective open-label study with a small sample size, drugs positively modulating the central nervous system serotonin/dopamine ratio, such as vortioxetine, could be used to potentially improve PSSD. Large-sample prospective cohort studies and randomized clinical trials are needed to investigate the real prevalence of this clinical entity and confirm such a promising approach to a potentially debilitating illness.

Background: Music stimulation is considered a valuable form of intervention in disorders of consciousness (DoC); for instance, verticalization may improve motor and cognitive recovery. Our purpose is to investigate the effects of a novel rehabilitative approach combining robotic verticalization training (RVT) with personalized music stimulation in people with DoC. Methods: Sixteen subjects affected by minimally conscious state due to traumatic brain lesions who attended our Intensive Neuro-Rehabilitation Unit were enrolled in this randomized trial. They received either music robotic verticalization (MRV) using the Erigo device plus a personalized music playlist or only RVT without music stimuli. Each treatment was performed 2 times a week for 8 consecutive weeks in addition to standard neurorehabilitation. Results: We found significant improvements in all patients’ outcomes in the experimental group (who received MRV): Coma Recovery Scale-Revised (CRS-R) (p < 0.01), Level of Cognitive Functioning (LCF) (p < 0.02), Functional Independence Measure (FIM) (p < 0.03), Functional Communication Scale (FCS) (p < 0.007), Trunk Control Test (TCT) (p = 0.05). Significant differences between the two groups were also found in the main outcome measure CRS-R (p < 0.01) but not for TCT and FIM. Conclusions: Our study supports the safety and effectiveness of RVT with the Erigo device in chronic MCS, and the achievement of better outcomes when RVT is combined with music stimulation.

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID. Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID.

Current research suggests that the management of neurological diseases, both in adults and children, requires an ever increasing commitment of resources for the national healthcare system (NHS). In Italy, due to the aging of the population, increase in chronicity and morbidity of pathologies, and presence of islands and rural areas, health needs to be supported by innovative technologies. Telemedicine is a method of providing healthcare services at distance, remotely connecting health professionals and patients (or two professionals). In Italy, telemedicine is under development, and the NHS has not yet exploited and independently developed all the possibilities that telemedicine offers. Tele-rehabilitation consists in the use of information and communication technologies for the remote support of rehabilitation services. By allowing “home care,” it represents a valid support during the home rehabilitation process. This review is aimed at evaluating the role of telerehabilitation in Italy, with regard to the motor and cognitive rehabilitation programs applied to neurological pathologies, in both pediatric and adult patients. We screened the studies published between 2010 and 2019 on PubMed, Scopus, Cochrane, and Web of Sciences databases. Using the PICO model, the search combined the terms “telerehabilitation”; “neurological disorders”; “neurodegenerative disease,” “motor telerehabilitation”; “cognitive rehabilitation.” This review showed that telerehabilitation is a promising healthcare tool, as it guarantees continuity of care over time (after discharge) and in space (from hospital to patient's home), especially in patients with stroke. Furthermore, it allows to increase the frequency and intensity of rehabilitation programs, provide individualized rehabilitation treatment in comfortable and familiar environment for patient, monitor and evaluate patients' needs and progress, stimulate patient motivation and achieve better patient satisfaction, verify the results achieved by the patients, and potentially reduce the service costs. Unfortunately, almost all neurorehabilitation studies are characterized by small samples and wide variability of results, and would benefit from standardized procedures, aims and targets. Future telerehabilitation trials should include cost-effectiveness analysis associated with clinical outcomes to better assess the validity of this promising tool.

Background: The healthcare reforms have led to the development of new primary care systems. These models allowed responding to people's needs but with problems in maintaining the relational continuity between the patient and therapist. Materials and Methods: We performed a survey on 12 May 2018, in Messina (Sicily, Italy), during an informational event. Participants were invited to fill in a self-reported Italian questionnaire composed of 12 multiple-choice questions, specifically created by the authors. The tool included the assessment of the social status, the presence of chronic diseases, preference in health care, and evaluation of the services offered in the territory. Results: As for the territorial services, we observed that the general practitioner (GP) was the most appreciated healthcare provider, followed by the nurse. Conclusions: We believe that nurses can represent the most appropriate healthcare figure to potentiate GP's patient management in primary territorial care.

Abstract Background Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations. Methods Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention. Results As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and β bands and larger fronto-central cortical activations in the affected hemisphere. Conclusions The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance. Trial registration Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .

Traumatic brain injury (TBI) is the most common cause of long-term disability and death among young adults, and it represents an enormous socioeconomic and healthcare burden. Our purpose is to evaluate the effects of a virtual reality training with BTs-Nirvana (BTs-N) on the recovery of cognitive functions in TBI subjects, using the interactive semi-immersive program. One hundred patients with TBI were enrolled in this study and randomized into either the Traditional Cognitive Rehabilitation Group (TCRG: n=50) or the Virtual Reality Training Group (VRTG: n=50). The VRTG underwent a VRT with BTs-N, whereas the TCRG received a standard cognitive treatment. Each treatment session lasted 60 minutes and was repeated three times a week for 8 weeks. All of the patients were evaluated by a specific psychometric battery before (T0) and immediately (T1) after the end of the training. VRTG and TCRG had a significant improvement in cognitive functioning and in mood, but only VRTG presented with a significant increase in cognitive flexibility and shifting skills and in selective attention. In conclusion, our results suggest that VR may be a useful and effective approach for the rehabilitation of patients with TBI, leading to better cognitive and behavioral outcomes.

The assessment of behavioral responsiveness in patients suffering from chronic disorders of consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. Even if a patient is unresponsive, he/she may be covertly aware in reason of a cognitive-motor dissociation, i.e., a preservation of cognitive functions despite a solely reflexive behavioral responsiveness. The approach of an external stimulus to the peripersonal space (PPS) modifies some biological measures (e.g., hand-blink reflex amplitude) to the purpose of defensive responses from threats. Such modulation depends on a top-down control of subcortical neural circuits, which can be explored through changes in cerebral blood flow velocity (CBFV), using functional transcranial Doppler (fTCD) and, thus, gaining useful, indirect information on brain connectivity. These data may be used for the DoC differential diagnosis. We evaluated the changes in CBFV by measuring the pulsatility index (PI) in 21 patients with DoC (10 patients with MCS and 11 with UWS) and 25 healthy controls (HC) during a passive movement and motor imagery (MI) task in which the hand of the subject approached and, then, moved away from the subject’s face. In the passive movement task, the PI increased progressively in the HCs when the hand was moved toward the face and, then, it decreased when the hand was removed from the face. The PI increased when the hand was moved toward the face in patients with DoC, but then, it remained high when the hand was removed from the face and up to 30 s after the end of the movement in the patients with MCS (both MCS+ and MCS−) and 1 min in those with UWS, thus differentiating between patients with MCS and UWS. In the MI task, all the HCs, three out of four patients with MCS+, and one out of six patients with MCS− showed an increase–decrease PI change, whereas the remaining patients with MCS and all the patients with UWS showed no PI changes. Even though there is the possibility that our findings will not be replicated in all patients with DoC, we propose fTCD as a rapid and very easy tool to differentiate between patients with MCS and UWS, by identifying residual top-down modulation processes from higher-order cortical areas to sensory-motor integration networks related to the PPS, when using passive movement tasks.

The last few years have been characterized by a growing interest of the medical and scientific world for the field of consciousness and its related disorders. Medically speaking, consciousness can be defined as the state of awareness of self and environment and the alertness to external stimulation, besides responsiveness to inner need. Transient loss of consciousness can be due to alterations in cerebral blood flow leading to fainting or syncope, migraine, metabolic dysfunctions, unexpected intracranial pressure increases, epileptic seizures, and sleep disorders. Chronic disorders of consciousness are a tragic success of high-technology treatment, in an attempt to maintain or reestablish brain function, which is to be considered as the main goal of therapeutics. Management of vegetative or a minimally conscious state individuals involves charily getting the right diagnosis with an evidence-based prognosis, also taking into account the medical, ethical, and legal key factors of the ideal treatment. This paper is aimed at exploring the wide spectrum of consciousness disorders and their clinical differential diagnosis, with particular regards to those with a negative impact on patient and their caregiver quality of life, including epilepsy, sleep disorders, and vegetative/minimally conscious state.

Background: Mild cognitive impairment (MCI) is characterized by cognition impairment that does not interfere with the usual activities of daily living. It is considered to be a transitional stage between normal aging and dementia. No treatment is available for MCI. Methods: This retrospective cohort study included 55 patients (29 males and 26 females, aged 56−75 years) with a diagnosis of amnestic MCI who attended the Center for Cognitive Disorder and Dementia of the IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy) between January and December of 2017. As we aimed to evaluate the effect of cocoa polyphenols on cognition, the study population was separated into two groups depending on the change in their Mini-Mental State Examination (MMSE) score at a one-year follow-up. Results: Compared to G2 (i.e., patients with a worsening in cognitive functions), the rate of polyphenol intake was significantly higher in patients without a worsening in cognition (i.e., G1) (χ2 = 13.79, df = 1, p-value < 0.001). By subdividing G1 patients based on whether they improved or were stable at follow-up, we found that 46.2% of those who had improved were treated with polyphenols. Conclusions: Dietary supplementation of cocoa flavonoids seems to reduce the progression of MCI to dementia. Further prospective studies with larger sample volumes are required to confirm these promising findings.

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPAR–γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamic–pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.

The dysregulation of renin-angiotensin-system (RAS) plays a pivotal role in hypertension and in the development of the related target organ damage (TOD). The main goal of treating hypertension is represented by the long-term reduction of cardiovascular (CV) risk. RAS inhibition either by angiotensin converting enzyme (ACE)-inhibitors or by type 1 Angiotensin II receptors blockers (ARBs), reduce the incidence of CV events in hypertensive patients. Actually, ACE-inhibitors and ARBs have been demonstrated to be effective to prevent, or delay TOD like left ventricular hypertrophy, chronic kidney disease, and atherosclerosis. The beneficial effects of RAS blockers on clinical outcome of hypertensive patients are due to the key role of angiotensin II in the pathogenesis of TOD. In particular, Angiotensin II through an inflammatory-mediated mechanism plays a role in the initiation, progression and vulnerability of atherosclerotic plaque. In addition, Angiotensin II can be considered the hormonal transductor of the pressure overload in cardiac myocytes, and through an autocrine-paracrine mechanism plays a role in the development of left ventricular hypertrophy. Angiotensin II by modulating the redox status and the immune system participates to the development of chronic kidney disease. The RAS blocker should be considered the first therapeutic option in patients with hypertension, even if ACE-inhibitors and ARBs have different impact on CV prevention. ARBs seem to have greater neuro-protective effects, while ACE-inhibitors have greater cardio-protective action.