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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.

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.

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.

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.

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 (1H-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 1H-MRS. Forty healthy controls (HC) underwent 1H-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 1H-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 1H-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.

The contribution of structural connectivity to functional connectivity dynamics is still far from being fully 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.

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.

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.

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.

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.

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 reliability 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 stereotacting targeting.

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 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.

The parosmia is a distorted olfactory sensation in the presence of an odor that can affect the quality of life of most of the patients who experience it. Qualitative olfactory dysfunction, such as parosmia, may be clinical condition secondary to neurological diseases. The incidence of parosmia is underestimated as well as its association with neurological diseases, due to poor self-reporting of patients and lack of objective methods for its measure. In this paper, we show selected clinical cases of parosmia associated with neurological disorders, such as traumatic brain injury, mesial temporal sclerosis and multiple sclerosis.This clinical cases have show how the correct diagnosis of parosmia can represent the tip of the iceberg of important underlying neurological disorders and be a good prognostic indicator of their progression or recovery.

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.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has posed a serious threat to global health. As no specific therapeutics are yet available to control disease evolution, more in-depth understanding of the pathogenic mechanisms induced by SARS-CoV-2 will help to characterize new targets for the management of COVID-19. The present study identified a specific set of biological pathways altered in primary human lung epithelium upon SARS-CoV-2 infection, and a comparison with SARS-CoV from the 2003 pandemic was studied. The transcriptomic profiles were also exploited as possible novel therapeutic targets, and anti-signature perturbation analysis predicted potential drugs to control disease progression. Among them, Mitogen-activated protein kinase kinase (MEK), serine-threonine kinase (AKT), mammalian target of rapamycin (mTOR) and I kappa B Kinase (IKK) inhibitors emerged as candidate drugs. Finally, sex-specific differences that may underlie the higher COVID-19 mortality in men are proposed.

Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive and negative symptoms, including cognitive dysfunction, decline in motivation, delusion and hallucinations. Antipsychotic agents are currently the standard of care treatment for SCZ. However, only about one-third of SCZ patients respond to antipsychotic medications. In the current study, we have performed a meta-analysis of publicly available whole-genome expression datasets on Brodmann area 46 of the brain dorsolateral prefrontal cortex in order to prioritize potential pathways underlying SCZ pathology. Moreover, we have evaluated whether the differentially expressed genes in SCZ belong to specific subsets of cell types. Finally, a cross-tissue comparison at both the gene and functional level was performed by analyzing the transcriptomic pattern of peripheral blood mononuclear cells of SCZ patients. Our study identified a robust disease-specific set of dysfunctional biological pathways characterizing SCZ patients that could in the future be exploited as potential therapeutic targets.

The gold standard of treatment in Parkinson’s disease (PD) is levodopa/carbidopa whose long-term use induces motor and non-motor fluctuations and dyskinesias. Continuous infusion of intrajejunal levodopa/carbidopa intestinal gel (Duodopa®) reduces motor and non-motor symptoms and dyskinesias, and improves the quality of life of patients. The aim of this open observational prospective study was to evaluate the impact of Duodopa® on conditions of PD patients and caregivers, and their quality of life. We enrolled 12 patients with advanced PD and their caregivers. The PD patients were assessed at baseline, 3 and 6 months after Duodopa® treatment initiation using Unified Parkinson’s Disease Rating Scale-Part III and IV (UPDRS-III and IV), Unified Dyskinesia Rating Scale (UdysRS), Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A) and Parkinson’s Disease Quality of Life Questionnaire (PDQ-39). The caregivers were assessed, at the same time as the patients, using BDI-II, HAM-A, Caregiver Burden Inventory (CBI) and SF-36 Health Status Questionnaire. Six months after Duodopa® therapy, the scores of UPDRS-III and IV, UdysRS, BDI-II, HAM-A and PDQ-39 were significantly decreased (p

Anosmia is a possible complication of Traumatic Brain Injury (TBI). Psychometric and electrophysiological methods of olfaction measure and Magnetic Resonance Imaging (MRI) are the tools to evaluate the post-traumatic olfactory loss. Diffusion Tensor Imaging (DTI) provides useful data for a better understanding of etiopathogenesis TBI-related anosmia, in particular the loss of neural connections and their eventual recovery over time.This study describes a case of TBI-related anosmia. The olfactory function was evaluated by Sniffin' Sticks Test (SST), Olfactory Event-Related Potentials (OERPs), MRI and DTI at baseline (T0) and after one year (T1).At baseline, SST highlighted a functional anosmia. The OERPs showed the presence of a small N1-P2 complex. MRI confirmed the presence of a scarring involved in the right orbitofrontal cortex (OFC). DTI detected a reduction in the average length and the number of neuronal fibre pathways of right OFC. At T1, a recovery of olfactory function was confirmed by SST and OERPs.While MRI images are unchanged from T0, DTI showed an increase in average length and number of fibre tracts in the right OFC. DTI could be a valid tool to display a post-traumatic loss of neural connections and to better understand TBI-recovery mechanisms.

Objective:The aim of this study was to assess differences in brain activation in a large sample of Vegetative State (VS) and Minimally Conscious State (MCS) patients, using functional magnetic resonance imaging (fMRI).Methods:We studied 50 patients four to seven months after brain injury. By using international clinical criteria and validated behavioural scales such as the Glasgow Coma Scale and the Clinical Unawareness Assessment Scale, the patients were grouped intoVS(n=23) and MCS (n=27). All patients underwent to fMRI examination. After 6 months, the patients were reassessed using Glasgow Outcome Scale and Revised Coma Recovery Scale.Results:fMRI showed significant (pConclusion:Brain activity could help in discerning whether the status of wakefulness inVSis also accompanied by partial awareness, as occurs in MCS. This may have very important prognostic implications.

The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million people. The spectrum of clinical manifestations observed during COVID-19 infection varies from asymptomatic to critical life-threatening clinical conditions. Emerging evidence shows that COVID-19 affects far more organs than just the respiratory system, including the heart, kidneys, blood vessels, liver, as well as the central nervous system (CNS) and the peripheral nervous system (PNS). It is also becoming clear that the neurological and psychological disturbances that occur during the acute phase of the infection may persist well beyond the recovery. The aim of this review is to propel further this emerging and relevant field of research related to the pathophysiology of neurological manifestation of COVID-19 infection (Neuro-COVID). We will summarize the PNS and CNS symptoms experienced by people with COVID-19 both during infection and in the recovery phase. Diagnostic and pharmacological findings in this field of study are strongly warranted to address the neurological and psychological symptoms of COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel s coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID­19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID­19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID­19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID­19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D­dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS­CoV­2 infection may represent a secondary anti­phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID­19 infection. Diagnostic and therapeutic implications of this are also discussed.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression signatures of brain cortex of ASD patients, by using two publicly available RNA-seq studies, in order to discover new ASD-related genes. Results: We detected 1567 differentially expressed genes (DEGs) by meta-analysis, where 1194 were upregulated and 373 were downregulated genes. Several ASD-related genes previously reported were also identified. Our meta-analysis identified 235 new DEGs that were not detected using the individual RNA-seq studies used. Some of those genes, including seven DEGs (PAK1, DNAH17, DOCK8, DAPP1, PCDHAC2, and ERBIN, SLC7A7), have been confirmed in previous reports to be associated with ASD. Gene Ontology (GO) and pathways analysis showed several molecular pathways enriched by the DEGs, namely, osteoclast differentiation, TNF signaling pathway, complement and coagulation cascade. Topological analysis of protein&ndash, protein interaction of the ASD brain cortex revealed proteomics hub gene signatures: MYC, TP53, HDAC1, CDK2, BAG3, CDKN1A, GABARAPL1, EZH2, VIM, and TRAF1. We also identified the transcriptional factors (TFs) regulating DEGs, namely, FOXC1, GATA2, YY1, FOXL1, USF2, NFIC, NFKB1, E2F1, TFAP2A, HINFP. Conclusion: Novel core genes and molecular signatures involved with ASD were identified by our meta-analysis.

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.

Impulsivity is a frequent non-motor symptom in Parkinson disease (PD). It comprises psycho-behavioral alterations that negatively impact quality of life. Dopaminergic treatments underpin many impulsive controls disorders however, side effects, such as increased impulsivity, are described also after neurosurgical procedure of deep brain stimulation (DBS). We investigated the effect of deep brain stimulation on psycho-behavioral alterations and quality of life (QoL) in PD patients, analyzing, also, the role of dopaminergic therapies. Twenty idiopathic PD patients with and 20 idiopathic PD patients without DBS were included in the study. All patient underwent to neuropsychological assessment for a screening of executive functions, impulsivity, anxiety and depressive symptoms and QoL. Differences were found between DBS and no DBS groups and in term of dopaminergic therapies. The comparison between 2 groups showed a greater motor and attentional impulsivity in DBS patients. Moreover, this impulsivity worse QoL and interpersonal relationships. The combination of Levodopa and dopamine agonists exerted a great impact on impulsivity behavior. The emergence of postoperative impulsivity seems to be a neurostimulator phenomenon related to the computational role of the subthalamic nucleus in modulation of behavior.

The aim of this study was to assess metabolic changes in the motor cortex in de novo Parkinson's disease (PD) patients before and after therapy with ropinirole. Twenty de novo drug-naive PD patients and 15 healthy controls underwent conventional magnetic resonance imaging and proton magnetic resonance spectroscopy imaging ((1)H-MRSI). The resonance intensities of N-acetylaspartate (NAA) and choline (Cho) were normalized for the resonance intensities of creatine (Cr). At baseline, lower NAA/Cr and NAA/Cho ratios and higher Cho/Cr ratios were found in the motor cortex of PD patients compared with controls (p

The gold standard of treatment in Parkinson's disease (PD) is levodopa/carbidopa whose long-term use induces motor and non-motor fluctuations and dyskinesias. Continuous infusion of intrajejunal levodopa/carbidopa intestinal gel (Duodopa