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Our objective was to assess the role of Intrathecal Baclofen Therapy (ITB) in the cortical reorganization in a patient affected by multiple sclerosis (MS) undergoing physical therapy. We reported a case of a woman affected by MS and severe spasticity, who performed an fMRI examination, before and after the ITB implantation. The subject showed controlateral motor cortex activation after motor task. After a month of ITB implantation, patient showed ipsilateral and controlateral motor cortex activation although with a broader extension. fMRI examination supported the hypothesis of a central influence in patients who undergo physiotherapy and therapy with ITB. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients' outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome. [ABSTRACT FROM AUTHOR]

Introduction: Audit and feedback (A&F) is a systematic intervention that can be used to improve the quality of health care. The EASY-NET Network Project proposes an innovative A&F model., Aim: This study aimed to describe the newly proposed A&F model. An analysis was conducted, examining the participants' attitudes and their individual and interpersonal mechanisms to understand how they influence the work context and vice versa., Methods: Two A&F models were compared, involving emergency and rehabilitation health workers, who were divided into two groups. The classic A&F model was compared with a new model, using a desk audit followed by interactive feedback. Communication training was provided to the audit team by psychologists before commencement of the project. The experimental group underwent psychological screening using two standardized tools (COPE-NVI and ProQoL) to evaluate personal and relational dynamics using the context-mechanism-outcome (CMO) paradigm., Results: The exchange of ideas among health professionals is more effective when using face-to-face feedback than written feedback. The COPE-NVI and ProQoL questionnaires highlighted the difficulties experienced by health care professionals in implementing effective coping strategies to deal with stressful events., Conclusions: Identifying signs of stress in health care workers is essential for improvement strategies to be implemented and for establishing new, optimal conditions. Remote feedback makes it possible to overcome logistical barriers and, in the future, this method can be used for inter-organizational collaboration., Spanish Abstract: http://links.lww.com/IJEBH/A203., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the University of Adelaide, JBI.)

Peripersonal space (PPS) is a construct referring to the portion of space immediately surrounding our bodies, where most of the interactions between the subject and the environment, including other individuals, take place. Decades of animal and human neuroscience research have revealed that the brain holds a separate representation of this region of space: this distinct spatial representation has evolved to ensure proper relevance to stimuli that are close to the body and prompt an appropriate behavioral response. The neural underpinnings of such construct have been thoroughly investigated by different generations of studies involving anatomical and electrophysiological investigations in animal models, and, recently, neuroimaging experiments in human subjects. Here, we provide a comprehensive anatomical overview of the anatomical circuitry underlying PPS representation in the human brain. Gathering evidence from multiple areas of research, we identified cortical and subcortical regions that are involved in specific aspects of PPS encoding.We show how these regions are part of segregated, yet integrated functional networks within the brain, which are in turn involved in higher-order integration of information. This wide-scale circuitry accounts for the relevance of PPS encoding in multiple brain functions, including not only motor planning and visuospatial attention but also emotional and social cognitive aspects. A complete characterization of these circuits may clarify the derangements of PPS representation observed in different neurological and neuropsychiatric diseases., (© 2024. The Author(s).)

- Hip fracture is the most common cause of hospitalization in frail geriatric subjects due to osteoporosis and recurrent falls. The clinical practice guidelines for rehabilitation after surgery in patients with hip fractures recommend to start treatment early. However, the outbreak of SARS-CoV-2 pandemic between December 2019 and January 2020 forced to lockdown. Thus, telerehabilitation seemed the best solution to remote assistance. In this scenario, the aim of our study is to assess the effects of telerehabilitation and to clarify and rearrange the knowledge about its usability and feasibility in patients after hip fracture in emergency conditions, such as the pandemic of SARS-CoV-2. Three databases were systematically searched from caption to December 2023, considering only articles published in peer-reviewed journals, with the use of three macro-areas: 'telerehabilitation', 'remote rehabilitation' and 'hip fracture'. In the present review, 26 articles were considered eligible and 10 were included. Heterogeneous results were found due to the different characteristics of the patients recruited in the studies, designs and type of the studies, and reporting/conducting of the research. Also, the typologies of telerehabilitation provided were various. In conclusion, this review demonstrated that telerehabilitation is safe, effective and well tolerated from patients and seems to be not inferior to the conventional physiotherapy. It also plays a positive role in psychological rehabilitation, in the prevention of complications and in the maintenance of achieved goals. However, further studies are needed to guide the clinical practice in providing the better posology and typology of telerehabilitation., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2024 Università di Salerno.)

This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

Audit and Feedback (A&F) is a systematic process involving the collection of data, which are subsequently compared with the established reference standards and then subsequently disseminated to healthcare providers through feedback meetings. This allows continuous improvement to be ensured in the quality of care processes. Often, the parameters taken into account concern only the patient and the treatment processes, neglecting other variables. Quality of life in the workplace and coping skills are determining variables for the clinical performance of all healthcare professionals. For this reason, in this study, these variables were investigated and differences were highlighted in two different role categories and context: cardiovascular emergency and neurological rehabilitation. A psychological screening was carried out by sending the computerized Coping Orientation to Problems Experienced-Nuova Versione Italiana (COPE-NVI) and Professional Quality of Life Scale-5 (ProQoL) questionnaires to all healthcare workers involved. Ninety-five healthcare providers (mean ± SD age: 47 ± 10.4 years; 37.9% male) answered the questionnaire and were assigned into two groups (G1 and G2) based on the ward in which they worked. These were further divided into two subgroups (R1 and R2) based on their role. The obtained results show that avoidance strategies are used more by health professionals working in rehabilitation (G2) wards than in intensive-care units (G1). Moreover, in G1 nurses, physical therapists and speech therapists (R2) obtained higher scores in terms of turning to religion (TR) and compassion satisfaction (CS), while physicians and psychologists (R1) obtained higher scores on the burnout scale (BO). The TR score for R2 was found to be higher, even in G2. The response trend of the two groups in the different departments was analyzed and commented on.

Stroke is the leading global cause of permanent disability and the second leading cause of dementia within the first year of the event. Systematic quality improvement interventions such as Audit & Feedback (A&F) can monitor and improve the performance of post-stroke care in conjunction with the use of quality indicators (QIs). The scientific literature shows limited studies on quality improvement and QIs design for poststroke rehabilitation. In Italy, the National Outcomes Evaluation Programme (PNE) annually provides several QIs concerning the acute wards. On the contrary, indicators for quality assessment of post-acute stroke rehabilitation are not available nationwide. In recent years, the Italian Ministry of Health has funded a national network project, the aim of which is to provide and evaluate the effectiveness of A&F strategies in healthcare improvement. Part of this project is the development of a set of IQs for ischemic stroke rehabilitation used to conduct an A&F. In this study, we describe the design and development process of these QIs from administrative databases and report the results of the pilot test conducted on a small sample of Sicilian rehabilitation facilities, comparing them from 2019 to 2021. Feedback from the participating centers was mainly positive, and the quality indicators were found to be comprehensible and appreciated. However, the study highlighted the need for better adherence to indicators measuring processes of rehabilitation care. The set of quality indicators presented in this study, relevant to inpatient settings, could be considered a starting point on which to base quality improvement initiatives both nationally and internationally.

Audit and Feedback (A&F) is considered one of the most significant tools for implementing continuous Quality Improvement (QI) in the healthcare field. The audit process is a structured inspection of professional practice against known standards or targets. The results of this inspection are subsequently feedback from professionals in order to implement an improvement process. The Italian Ministry of Health has recently funded the network project EASY-NET, with the main objective of evaluating the effectiveness of A&F strategies to improve healthcare practice and equity in various clinical and organizational settings in seven Italian regions. The Sicily region is represented within the EASY-NET project by the IRCCS Centro Neurolesi Bonino-Pulejo of Messina as the Work Package 7 (WP7). One of the objectives of the WP7 is to assess mechanisms and tools to enhance the effectiveness of A&F strategies. The purpose of this study is to investigate the influence that training interventions can have on improving knowledge of A&F strategies among healthcare professionals. The study employed a quasi-experimental design with a pretest-posttest evaluation strategy. The participants' initial knowledge of A&F strategies was evaluated through a baseline survey. Subsequently, the participants attended an online training workshop led by A&F experts, and a follow-up survey consisting of the same set of questions was conducted at the end of the process. Results showed statistically significant positive changes in the level of knowledge of A&F among participants following the training intervention. Furthermore, dividing the participants into two subgroups based on their professional background revealed significant differences in the level of knowledge of A&F methodologies between the observed categories of healthcare professionals. In conclusion, the study revealed that training interventions can be facilitators to implementing effective A&F programs.

Understanding how well a clinician or health care team is performing provides an essential foundation for improvement. If done well, Audit and Feedback (A&F) provides data in non-judgemental, motivating insights and leads to changes in clinical processes that benefit patients. This article will explore obstacles to optimizing the potential positive effects of A&F to improve patient care and outcomes by examining three interrelated steps in the process: the audit; the feedback; and the action. The audit requires data that will be perceived as both valid and actionable. Acquiring and using such data properly often requires partnerships. Feedback recipients need to know how to turn data into action. The A&F, therefore, should include components that direct the recipient toward feasible next steps to undertake the change that will lead to improvement. The proposed actions may be individual (learning new diagnostic or therapeutic strategies, trying a more patient-centered approach, etc.) or organizational (more proactive approaches often including the involvement of additional team members). The ability to turn feedback into action will depend on the culture of the recipient-group, and its level of experience with these change processes. Feedback facilitation or coaching may be useful for some groups or certain kinds of desired changes in practice. Inadequate leadership and support for health professionals, as they try to respond to A&F, is also often a barrier. Finally, with the final focus on the challenges of the individual Work Packages (WP) within the Easy-Net network program, the article focuses on what were the facilitating and hindering factors, the obstacles encountered, and the resistance to change overcome, useful considerations in support of the increasingly widespread implementation of A&F activities in our Healthcare System in the future.

This article proposes a focus on Audit & Feedback (A&F)'s sustainability. If on one side, it is essential to ask how to bring A&F interventions out of research programs into clinical practices and contexts of care. On the other, it is fundamental to ensure that the experiences gained within care contexts can inform research, helping to define the research objectives and questions whose development can support paths of change. The reflection starts from two research programs on A&F carried out in the United Kingdom, respectively, at the regional level (Aspire) in the field of primary care and at the national level (Affinitie and Enact) in the field of the transfusion system. Aspire raised awareness of the importance of establishing a primary care implementation laboratory, which randomizes practices to different types of feedback to evaluate the effectiveness, also to improve patient care. The national Affinitie and Enact programs served to 'inform' recommendations to improve the conditions for sustainable collaboration between A&F researchers and audit programs. They represent an example to understand how to incorporate research results within a national clinical audit program. Finally, starting from the complex experience of the Easy-Net research program, the reflection moves on to how it was possible to make A&F interventions sustainable in Italy beyond research projects, in clinical-care contexts in which the resources provisions make continuous and structured interventions difficult and impractical. The Easy-Net program envisages different clinical care settings, study designs, interventions, and recipients, which require different actions to adapt research results to the specific realities to which A&F's interventions are addressed.

Introduction: A clinical audit is a tool that allows the evaluation of and improvement in the quality of stroke care processes. Fast, high-quality care and preventive interventions can reduce the negative impact of stroke., Objective: This review was conducted on studies investigating the effectiveness of clinical audits to improve the quality of stroke rehabilitation and stroke prevention., Method: We reviewed clinical trials involving stroke patients. Our search was performed on PubMed databases, Web of Science, and Cochrane library databases. Of the 2543 initial studies, 10 studies met the inclusion criteria., Results: Studies showed that an audit brought an improvement in rehabilitation processes when it included a team of experts, an active training phase with facilitators, and short-term feedback. In contrast, studies looking at an audit in stroke prevention showed contradictory results., Conclusions: A clinical audit highlights any deviations from clinical best practices in order to identify the causes of inefficient procedures so that changes can be implemented to improve the care system. In the rehabilitation phase, the audit is effective for improving the quality of care processes.

Telemedicine is a process of delivering health care using information and communication technologies. Audit and feedback (A&F) constitute a systematic intervention that is aimed at collecting data, which are subsequently compared with reference standards and then returned to health care operators through feedback meetings. The aim of this review is to analyse different audit procedures on and by mean of telemedicine services and to identify a practice that is more effective than the others. Systematic searches were performed in three databases evaluating studies focusing on clinical audits performed on and by means of telemedicine systems. Twenty-five studies were included in the review. Most of them focused on telecounselling services with an audit and a maximum duration of one year. Recipients of the audit were telemedicine systems and service users (general practitioners, referring doctors, and patients). Data resulting from the audit were inherent to the telemedicine service. The overall data collected concerned the number of teleconsultations, service activity, reasons for referral, response times, follow-up, reasons why treatment was not completed, technical issues, and other information specific to each telemedicine service. Only two of the considered studies dealt with organizational aspects, and of these, only one analysed communicative aspects. The complexity and heterogeneity of the treatments and services provided meant that no index of uniformity could be identified. Certainly, some audits were performed in an overlapping manner in the different studies, and these show that although attention is often paid to workers' opinions, needs, and issues, little interest was shown in communicative/organizational and team dynamics. Given the importance and influence that communication has in teamwork and care settings, an audit protocol that takes into account intra- and extra-team communication processes could be essential to improving the well-being of operators and the quality of the service provided., Competing Interests: The authors declare no conflicts of interest to disclose.

Communication constitutes an essential aspect of teamwork. This is especially true for audit teams, where communication takes place not only within the work group but also with the audit recipients. For this reason, given the poor evidence in the literature, communication training was carried out on an audit team. Training was divided into 10 meetings of two hours each, with the meetings taking place over 2 months. Questionnaires were administered to identify the characteristics and styles of communication, to assess the sense of perceived self-efficacy in general and at work, and to evaluate the knowledge inherent in the communication. This battery was administered before and after the training to evaluate its effectiveness and its effects on self-efficacy, communication style, and knowledge. Furthermore, a communication audit was performed on the feedback provided by the team, to highlight satisfaction, strengths, and any critical issues that emerged during the feedback phase. The results obtained suggest that training has an effect not only on individual knowledge but also on personological aspects. Communication among colleagues and general self-efficacy appear to be improved by the process. Self-efficacy also specifically improves in the work environment, with subjects feeling more able to manage relationships and collaborations with colleagues and supervisors. Moreover, the audit team members were satisfied with the training received, perceiving an improvement in their own communication skills during the feedback phases.

Teriflunomide is a drug with immunosuppressive and selective immunomodulatory action, characterized by anti-inflammatory and antiproliferative properties. Several clinical studies have demonstrated the efficacy and safety of this drug in Multiple Sclerosis, estimating a significant improvement in cognitive performance.The aim of our study is to evaluate the effects of teriflunomide by analysing the correlation between brain atrophy and the general cognitive profile and evaluating long-term changes. The effect of teriflunomide was studied in 30 patients with multiple sclerosis and 30 control subjects. Patients underwent a full cognitive profile assessment using the Brief Repeatable Battery of Neuropsychological Tests and a neuroimaging examination with a 3.0 T working scanner.Our results suggested that treatment with teriflunomide could potentially not only slow down the accumulation of microstructural tissue damage in Grey Matter and With Matter, but also better preserve the cognitive profile, particularly by highlighting the benefits in the memory domain. Thanks to drug therapy, brain volume in our patients has remained constant, leading to improvements in memory, indicating teriflunomide as a neuroprotective potential and further strengthening the evidence of a link between loss of brain volume and cognitive impairment.

The human subthalamic area is a region of high anatomical complexity, tightly packed with tiny fiber bundles. Some of them, including the pallidothalamic, cerebello-thalamic, and mammillothalamic tracts, are relevant targets in functional neurosurgery for various brain diseases. Diffusion-weighted imaging-based tractography has been suggested as a useful tool to map white matter pathways in the human brain in vivo and non-invasively, though the reconstruction of these specific fiber bundles is challenging due to their small dimensions and complex anatomy. To the best of our knowledge, a population-based, in vivo probabilistic atlas of subthalamic white matter tracts is still missing. In the present work, we devised an optimized tractography protocol for reproducible reconstruction of the tracts of subthalamic area in a large data sample from the Human Connectome Project repository. First, we leveraged the super-resolution properties and high anatomical detail provided by short tracks track-density imaging (stTDI) to identify the white matter bundles of the subthalamic area on a group-level template. Tracts identification on the stTDI template was also aided by visualization of histological sections of human specimens. Then, we employed this anatomical information to drive tractography at the subject-level, optimizing tracking parameters to maximize between-subject and within-subject similarities as well as anatomical accuracy. Finally, we gathered subject level tracts reconstructed with optimized tractography into a large-scale, normative population atlas. We suggest that this atlas could be useful in both clinical anatomy and functional neurosurgery settings, to improve our understanding of the complex morphology of this important brain region., (© 2022. The Author(s).)

The contribution of structural connectivity to functional connectivity dynamics is still far from being elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance., Competing Interests: Declaration of interest The authors have nothing to declare., (Copyright © 2022. Published by Elsevier Inc.)

Adopting audit and feedback (A&F) strategies could be a suitable healthcare intervention to fulfill the challenge of monitoring and improving clinical guidelines in evidence-based medicine. Indeed, A&F is used to encourage professionals to better adhere to standard guidelines to improve healthcare performance. Briefly, an audit is an inspection of professional practice in comparison to professional standards or targets whose results are subsequently communicated to professionals in a structured manner. Although A&F strategies have been adopted in several time-dependent settings, such as for acute myocardial infarction (AMI) and stroke, interest of audits in rehabilitation care is also emerging. Recently, the Italian Ministry of Health has funded a national network project called EASY-NET, whose main objective is to evaluate the effectiveness of A&F strategies to improve healthcare practice and equity in various clinical and organizational settings in seven Italian regions. Last but not the least of these regions is the Sicily, represented within the project by the IRCCS Centro Neurolesi Bonino-Pulejo of Messina as the work package 7 (WP7). The EASY-NET WP7 is focused on the effectiveness of A&F strategies in both AMI and ischemic stroke setting, from acute to rehabilitation process of care. In this study, we described the study protocol, including the study design and methodology, providing a detailed description of the new model of A&F based on telemedicine, and discussing the possible challenges of this project., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ciurleo, De Cola, Agabiti, Di Martino, Bramanti and Corallo.)

Stroke is the second cause of disability and death worldwide, highly impacting patient's quality of life. Several changes in brain architecture and function led by stroke can be disclosed by neurophysiological techniques. Specifically, electroencephalogram (EEG) can disclose brain oscillatory rhythms, which can be considered as a possible outcome measure for stroke recovery, and potentially shaped by neuromodulation techniques. We performed a review of randomized controlled trials on the role of brain oscillations in patients with post-stroke searching the following databases: Pubmed, Scopus, and the Web of Science, from 2012 to 2022. Thirteen studies involving 346 patients in total were included. Patients in the control groups received various treatments (sham or different stimulation modalities) in different post-stroke phases. This review describes the state of the art in the existing randomized controlled trials evaluating post-stroke motor function recovery after conventional rehabilitation treatment associated with neuromodulation techniques. Moreover, the role of brain pattern rhythms to modulate cortical excitability has been analyzed. To date, neuromodulation approaches could be considered a valid tool to improve stroke rehabilitation outcomes, despite more high-quality, and homogeneous randomized clinical trials are needed to determine to which extent motor functional impairment after stroke can be improved by neuromodulation approaches and which one could provide better functional outcomes. However, the high reproducibility of brain oscillatory rhythms could be considered a promising predictive outcome measure applicable to evaluate patients with stroke recovery after rehabilitation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leonardi, Ciurleo, Cucinotta, Fonti, Borzelli, Costa, Tisano, Portaro and Alito.)

The subthalamic nucleus (STN) is commonly used as a surgical target for deep brain stimulation in movement disorders such as Parkinson's Disease. Tractography-derived connectivity-based parcellation (CBP) has been recently proposed as a suitable tool for non-invasive in vivo identification and pre-operative targeting of specific functional territories within the human STN. However, a well-established, accurate and reproducible protocol for STN parcellation is still lacking. The present work aims at testing the effects of different tractography-based approaches for the reconstruction of STN functional territories. We reconstructed functional territories of the STN on the high-quality dataset of 100 unrelated healthy subjects and on the test-retest dataset of the Human Connectome Project (HCP) repository. Connectivity-based parcellation was performed with a hypothesis-driven approach according to cortico-subthalamic connectivity, after dividing cortical areas into three groups: associative, limbic and sensorimotor. Four parcellation pipelines were compared, combining different signal modeling techniques (single-fiber vs multi-fiber) and different parcellation approaches (winner takes all parcellation vs fiber density thresholding). We tested these procedures on STN regions of interest obtained from three different, commonly employed, subcortical atlases. We evaluated the pipelines both in terms of between-subject similarity, assessed on the cohort of 100 unrelated healthy subjects, and of within-subject similarity, using a second cohort of 44 subjects with available test-retest data. We found that each parcellation provides converging results in terms of location of the identified parcels, but with significative variations in size and shape. All pipelines obtained very high within-subject similarity, with tensor-based approaches outperforming multi-fiber pipelines. On the other hand, higher between-subject similarity was found with multi-fiber signal modeling techniques combined with fiber density thresholding. We suggest that a fine-tuning of tractography-based parcellation may lead to higher reproducibility and aid the development of an optimized surgical targeting protocol., Competing Interests: Declaration of Competing Interest The authors have nothing to declare, (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Parkinson's Disease (PD) is the most common neurodegenerative movement disorder whose treatment is symptomatic. No suitable methods for assessing the effects of dopaminergic drugs on disease progression in clinical trials have yet been provided. The aim of this longitudinal study is to evaluate the influence of rasagiline and selegiline on neurometabolic profile in de novo PD patients by using Proton Magnetic Resonance Spectroscopy ( 1 H-MRS). We enrolled de novo PD patients who were divided into two groups of 20 patients each, according to the dopaminergic treatment prescribed at the baseline visit (rasagiline or selegiline). At the baseline visit and after 12 months, all patients underwent neurological evaluation as well as 1 H-MRS. Forty healthy controls (HC) underwent 1 H-MRS at baseline and after 12 months. PD patients, compared to HC, showed significantly lower concentrations of NAA in the motor cortex, while the Cho levels showed a decreasing trend. After 12 months of therapy, the 1 H-MRS study revealed that rasagiline and selegiline in a similar way were able to restore the NAA levels to values similar to those of HC. In addition, this neurometabolic change showed a correlation with UPDRS-III scores. This is the first longitudinal study that provides preliminary evidence that 1 H-MRS may be a suitable method to evaluate objectively the influence of MAO-B inhibitors on the neurometabolic profile of PD patients. These results could open a new scenario on the hypothesis of a drug-induced slowing effect of PD progression.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the newly discovered coronavirus, SARS-CoV-2. Increased severity of COVID-19 has been observed in patients with diabetes mellitus (DM). This study aimed to identify common transcriptional signatures, regulators and pathways between COVID-19 and DM. We have integrated human whole-genome transcriptomic datasets from COVID-19 and DM, followed by functional assessment with gene ontology (GO) and pathway analyses. In peripheral blood mononuclear cells (PBMCs), among the upregulated differentially expressed genes (DEGs), 32 were found to be commonly modulated in COVID-19 and type 2 diabetes (T2D), while 10 DEGs were commonly downregulated. As regards type 1 diabetes (T1D), 21 DEGs were commonly upregulated, and 29 DEGs were commonly downregulated in COVID-19 and T1D. Moreover, 35 DEGs were commonly upregulated in SARS-CoV-2 infected pancreas organoids and T2D islets, while 14 were commonly downregulated. Several GO terms were found in common between COVID-19 and DM. Prediction of the putative transcription factors involved in the upregulation of genes in COVID-19 and DM identified RELA to be implicated in both PBMCs and pancreas. Here, for the first time, we have characterized the biological processes and pathways commonly dysregulated in COVID-19 and DM, which could be in the next future used for the design of personalized treatment of COVID-19 patients suffering from DM as comorbidity., (© The Author(s) 2021. Published by Oxford University Press.)

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification. Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed. We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject variability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotactic targeting., (Copyright © 2021. Published by Elsevier Inc.)

The development of novel techniques for the in vivo, non-invasive visualization and identification of thalamic nuclei has represented a major challenge for human neuroimaging research in the last decades. Thalamic nuclei have important implications in various key aspects of brain physiology and many of them show selective alterations in various neurologic and psychiatric disorders. In addition, both surgical stimulation and ablation of specific thalamic nuclei have been proven to be useful for the treatment of different neuropsychiatric diseases. The present work aimed at describing a novel protocol for histologically guided delineation of thalamic nuclei based on short-tracks track-density imaging (stTDI), which is an advanced imaging technique exploiting high angular resolution diffusion tractography to obtain super-resolved white matter maps. We demonstrated that this approach can identify up to 13 distinct thalamic nuclei bilaterally with very high inter-subject (ICC: 0.996, 95% CI: 0.993-0.998) and inter-rater (ICC:0.981; 95% CI:0.963-0.989) reliability, and that both subject-based and group-level thalamic parcellation show a fair share of similarity to a recent standard-space histological thalamic atlas. Finally, we showed that stTDI-derived thalamic maps can be successfully employed to study structural and functional connectivity of the thalamus and may have potential implications both for basic and translational research, as well as for presurgical planning purposes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The striatum represents the major hub of the basal ganglia, receiving projections from the entire cerebral cortex and it is assumed to play a key role in a wide array of complex behavioral tasks. Despite being extensively investigated during the last decades, the topographical organization of the striatum is not well understood yet. Ongoing efforts in neuroscience are focused on analyzing striatal anatomy at different spatial scales, to understand how structure relates to function and how derangements of this organization are involved in various neuropsychiatric diseases. While being subdivided at the macroscale level into dorsal and ventral divisions, at a mesoscale level the striatum represents an anatomical continuum sharing the same cellular makeup. At the same time, it is now increasingly ascertained that different striatal compartments show subtle histochemical differences, and their neurons exhibit peculiar patterns of gene expression, supporting functional diversity across the whole basal ganglia circuitry. Such diversity is further supported by afferent connections which are heterogenous both anatomically, as they originate from distributed cortical areas and subcortical structures, and biochemically, as they involve a variety of neurotransmitters. Specifically, the cortico-striatal projection system is topographically organized delineating a functional organization which is maintained throughout the basal ganglia, subserving motor, cognitive and affective behavioral functions. While such functional heterogeneity has been firstly conceptualized as a tripartite organization, with sharply defined limbic, associative and sensorimotor territories within the striatum, it has been proposed that such territories are more likely to fade into one another, delineating a gradient-like organization along medio-lateral and ventro-dorsal axes. However, the molecular and cellular underpinnings of such organization are less understood, and their relations to behavior remains an open question, especially in humans. In this review we aimed at summarizing the available knowledge on striatal organization, especially focusing on how it links structure to function and its alterations in neuropsychiatric diseases. We examined studies conducted on different species, covering a wide array of different methodologies: from tract-tracing and immunohistochemistry to neuroimaging and transcriptomic experiments, aimed at bridging the gap between macroscopic and molecular levels.

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 ( Galectin-8 ) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.

Background and Objective: Disorders of consciousness include coma (cannot be aroused, eye remain closed), vegetative state-VS (can appear to be awake, but unable to purposefully interact) and minimally conscious state-MCS (minimal but definite awareness). The objective of this study is to assess the impact of the SARS-CoV-2 infection on the Disorder of Consciousness (DOC) Rehabilitation Unit., Methods: This is a retrospective, longitudinal, descriptive, observational, pilot study. We consecutively enrolled 18 patients (age range: 40-72 years, 9 females and 9 males), from three to five months after a brain injury. They were grouped into VS (n = 8) and MCS (n = 10). A confirmed case of COVID-19 was defined as a positive result on high-throughput sequencing or real-time reverse-transcription polymerase chain reaction analysis of throat swab specimens. We collected data of lung Computed Tomography (CT) and laboratory exams. DOC patients who were positive for SARS-CoV-2 were classified into severe and no severe infected group, according to the American Thoracic Society guidelines., Results: A total of 18 hospitalized patients with (16) and without confirmed (2) SARS-CoV-2 infection were included in the analysis. After one month, a follow-up clinical evaluation reported that one patient died, one patient was transferred from Covid Unit to Emergency Unit and 3 patients were resulted negative to double swab and they returned to Rehabilitative Unit. Significant differences were reported about hypertension, cardiac disease and respiratory problems between the patients with severe infection and patients without severe infection (P< 0.001). The laboratory findings, such as blood cell counts (P < 0.001), C-reactive protein, D-dimer, potassium and vitamin D levels, seemed to be considered as useful prognostic predictors., Conclusions: To our knowledge, this is the first longitudinal study on a sample of chronic DOC patients affected by SARS-CoV-2. This study may offer important new clinical information on COVID-19 for management of DOC patients. Our findings showed that for the subjects with severe infection due to COVID-19, rapid clinical deterioration or worsening could be associated with clinical and laboratory findings, which could contribute to high mortality rate. During the COVID-19 epidemic period, the clinicians should consider all the reported risk factors to avoid delayed diagnosis or misdiagnosis and to prevent the infection transmission in DOC Rehabilitation Unit., Competing Interests: The authors have declared that no competing interests exist.

On March 2019 the World Health Organization declared Coronavirus disease (COVID-19) pandemic. Several recent reports disclose that the outcome of the infection is related to age, sex and can be influenced by underlying clinical conditions. Parkinson's disease (PD) and other parkinsonisms are the most common chronic disease which can cause, directly or indirectly, the patient to be more exposed to other diseases, mostly respiratory system's ones. Our primary outcome is to evaluate if PD patients are more susceptible than non-PD to take COVID-19 infection. Second, to detect if the infection course is worse in PD-COVID+ patients versus non-PD. This is a retrospective observational study on a cohort of 18 patients (13 PD- 5 non-PD), hospitalized in a Rehabilitative Unit during the occurrence of SARS-CoV2 epidemic outbreak. All patients performed laboratory tests, lung Computed Tomography (CT) and have been tested for COVID-19 thorough pharyngeal swab. PD and non-PD groups were comparable for age, gender and Hoehn and Yahr stage. Seventy-seven (77)% of PD and 60% of non-PD resulted positive for COVID-19. PD-COVID+ and PD-COVID- did not differ for age, disease duration and L-dopa daily dose. PD COVID-19+ subjects were mainly asymptomatic (50%) while non-PD ones were all symptomatic, mostly with respiratory difficulties. PD doesn't seem to be a risk factor to take SARS-COV2 infection, even if our study is related to a limited sample size. Our results, together with those of other recent studies, highlight the need to evaluate the actual susceptibility of patients with Parkinson's disease to develop COVID-19 disease, and how the infection may influence the risk of clinical worsening and increase of mortality., Competing Interests: The authors have declared that no competing interests exist.

Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease caused by a lack of dystrophin, leading to membrane instability, cell damage, and inflammatory response. However, gene-editing alone is not enough to restore the healthy phenotype and additional treatments are required. In the present study, we have first conducted a meta-analysis of three microarray datasets, GSE38417, GSE3307, and GSE6011, to identify the differentially expressed genes (DEGs) between healthy donors and DMD patients. We have then integrated this analysis with the knowledge obtained from DisGeNET and DIAMOnD, a well-known algorithm for drug-gene association discoveries in the human interactome. The data obtained allowed us to identify novel possible target genes and were used to predict potential therapeutical options that could reverse the pathological condition.

Background: Computer Aided Diagnosis (CAD) systems have been developing in the last years with the aim of helping the diagnosis and monitoring of several diseases. We present a novel CAD system based on a hybrid Watershed-Clustering algorithm for the detection of lesions in Multiple Sclerosis., Methods: Magnetic Resonance Imaging scans (FLAIR sequences without gadolinium) of 20 patients affected by Multiple Sclerosis with hyperintense lesions were studied. The CAD system consisted of the following automated processing steps: images recording, automated segmentation based on the Watershed algorithm, detection of lesions, extraction of both dynamic and morphological features, and classification of lesions by Cluster Analysis., Results: The investigation was performed on 316 suspect regions including 255 lesion and 61 non-lesion cases. The Receiver Operating Characteristic analysis revealed a highly significant difference between lesions and non-lesions; the diagnostic accuracy was 87% (95% CI: 0.83-0.90), with an appropriate cut-off of 192.8; the sensitivity was 77% and the specificity was 87%., Conclusions: In conclusion, we developed a CAD system by using a modified algorithm for automated image segmentation which may discriminate MS lesions from non-lesions. The proposed method generates a detection out-put that may be support the clinical evaluation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Anxiety and depression in Parkinson's disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi "Bonino-Pulejo" Ethical Committee (approval No. 6/2016) in June 2016., Competing Interests: None

Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive symptoms (i.e., psychosis) and negative symptoms (such as apathy, anhedonia, and poverty of speech). Epidemiological data show a high likelihood of early onset of type 2 diabetes mellitus (T2DM) in SCZ patients. However, the molecular processes that could explain the epidemiological association between SCZ and T2DM have not yet been characterized. Therefore, in the present study, we aimed to identify underlying common molecular pathogenetic processes and pathways between SCZ and T2DM. To this aim, we analyzed peripheral blood mononuclear cell (PBMC) transcriptomic data from SCZ and T2DM patients, and we detected 28 differentially expressed genes (DEGs) commonly modulated between SCZ and T2DM. Inflammatory-associated processes and membrane trafficking pathways as common biological processes were found to be in common between SCZ and T2DM. Analysis of the putative transcription factors involved in the regulation of the DEGs revealed that STAT1 (Signal Transducer and Activator of Transcription 1), RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian)), NFKB1 (Nuclear Factor Kappa B Subunit 1), and ERG (ETS-related gene) are involved in the expression of common DEGs in SCZ and T2DM. In conclusion, we provide core molecular signatures and pathways that are shared between SCZ and T2DM, which may contribute to the epidemiological association between them.

Cognitive decline refers to a deterioration of intellectual and learning abilities and related memory problems, and is often associated with behavioral alterations, which prevents sufferers from carrying out the most common daily activities, such as maintaining normal productive interpersonal relationships, communicating, and leading an autonomous life. Numerous studies have highlighted the association between cognitive decline and autoimmune disorders, including rheumatoid arthritis (RA). RA is a chronic, inflammatory, autoimmune disease that involves systems and organs other than the bones and joints, with varying severity among patients. Here, we review the studies investigating the link between cognitive decline and RA, focusing on the main molecular pathogenetic mechanisms involved. The emerging body of data suggests that clinical, psychological, and biological factors may contribute to the pathogenesis of cognitive decline in RA, including cardiovascular complications, chronic pain, depression, inflammatory factors, changes in hormone levels, drug side effects, and genetics. Further studies are warranted in order to fully clarify the basis underlying the association between cognitive decline and RA and to find new possible diagnostic strategies and therapeutic targets for RA patients.

Hypertensive crisis, defined as an increase in systolic blood pressure >179 mmHg or diastolic blood pressure >109 mmHg, typically causes end-organ damage; the brain is an elective and early target, among others. The strong relationship between arterial hypertension and cerebrovascular diseases is supported by extensive evidence, with hypertension being the main modifiable risk factor for both ischemic and hemorrhagic stroke, especially when it is uncontrolled or rapidly increasing. However, despite the large amount of data on the preventive strategies and therapeutic measures that can be adopted, the management of high BP in patients with acute cerebrovascular diseases presenting at the emergency department is still an area of debate. Overall, the outcome of stroke patients with high blood pressure values basically depends on the occurrence of hypertensive emergency or hypertensive urgency, the treatment regimen adopted, the drug dosages and their timing, and certain stroke features. In this narrative review, we provide a timely update on the current treatment, debated issues, and future directions related to hypertensive crisis in patients referred to the emergency department because of an acute cerebrovascular event. This will also focus greater attention on the management of certain stroke-related, time-dependent interventions, such as intravenous thrombolysis and mechanic thrombectomy.