Cortical Thickness of Brain Areas Beyond Stroke Lesions and Sensory-Motor Recovery: A Systematic Review

Background: The clinical outcome of patients suffering from stroke is dependent on multiple factors. The features of the lesion itself play an important role but clinical recovery is remarkably influenced by the plasticity mechanisms triggered by the stroke and occurring at a distance from the lesion. The latter translate into functional and structural changes of which cortical thickness might be easy to quantify one of the main players. However, studies on the changes of cortical thickness in brain areas beyond stroke lesion and their relationship to sensory-motor recovery are sparse. Objectives: To evaluate the effects of cerebral stroke on cortical thickness (CT) beyond the stroke lesion and its association with sensory-motor recovery. Materials and Methods: Five electronic databases (PubMed, Embase, Web of Science, Scopus and the Cochrane Library) were searched. Methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale for non-randomized controlled trials and the Risk of Bias Cochrane tool for randomized controlled trials. Results: The search strategy retrieved 821 records, 12 studies were included and risk of bias assessed. In most of the included studies, cortical thinning was seen at the ipsilesional motor area (M1). Cortical thinning can occur beyond the stroke lesion, typically in regions anatomically connected because of anterograde degeneration. Nonetheless, studies also reported cortical thickening of regions of the unaffected hemisphere, likely related to compensatory plasticity. Some studies revealed a significant correlation between changes in cortical thickness of M1 or somatosensory (S1) cortical areas and motor function recovery. Discussion and Conclusions: Following a stroke, changes in cortical thickness occur both in regions directly connected to the stroke lesion and in contralateral hemisphere areas as well as in the cerebellum. The underlying mechanisms leading to these changes in cortical thickness are still to be fully understood and further research in the field is needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020200539; PROSPERO 2020, identifier: CRD42020200539

The use of respiratory muscle training in patients with pulmonary dysfunction, internal diseases or central nervous system disorders: a systematic review with meta-analysis

Objective: The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life. Methods: The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase. Results: From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments). Conclusion: Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1

Use of virtual reality-based training in different fields of rehabilitation: A systematic review and meta-analysis

Objectives: To analyse the effectiveness of virtual reality-based interventions within several fields of rehabilitation, and to investigate whether the outcomes of virtual realitybased interventions, in terms of upper or lower limb function, gait and balance, differ with respect to the virtual reality system used. Methods: A search of PubMed database resulted in an initial total of 481 records. Of these, 27 articles were included in the study. A final total of 20 articles, with neurological, orthoapedic, geriatric or paediatric patients, published between 2012 and 2019, were included in the study. Two independent reviewers selected potentially relevant articles based on the inclusion criteria for fulltext reading. They extracted data, and evaluated the methodological quality of each study. Results: Seventeen studies were included in the metaanalysis. Eight studies analysed upper limb function, with no significant evidence that specialized VR is superior to conventional treatment. Regarding Fugl-Meyer scale results, the effect of specialized virtual reality therapy was found to be significantly better than conventional treatment. No significant differences between specialized VR and conventional treatment were observed in effects on hand dexterity and gait. There was a significant difference in effects on balance in favour of specialized virtual reality as compared to conventional treatment. Gaming virtual reality was significantly better than conventional treatment for upper limb function, but not for hand dexterity, gait and balance. Conclusion: Use of specialized virtual reality and gaming virtual reality can be advantageous for treatment of the upper extremity, but not for hand dexterity and gait in all pathologies considered. Specialized virtual reality can improve balance in neurological patients

White matter tract disconnection in Gerstmann's syndrome: Insights from a single case study

It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr

Efficacy of non-immersive virtual reality-based telerehabilitation on postural stability in Parkinson's disease: a multicenter randomized controlled trial

BACKGROUND: The implementation of regular prolonged, and effective rehabilitation in people with Parkinson's disease is essential for ensuring a good quality of life. However, the continuity of rehabilitation care may find barriers related to economic, geographic, and social issues. In these scenarios, telerehabilitation could be a possible solution to guarantee the continuity of care. AIM: To investigate the efficacy of non-immersive virtual reality-based telerehabilitation on postural stability in people with Parkinson's disease, compared to at-home self-administered structured conventional motor activities. DESIGN: Multicenter randomized controlled trial. SETTING: Five rehabilitation hospitals of the Italian Neuroscience and Rehabilitation Network. POPULATION: Individuals diagnosed with Parkinson's disease. METHODS: Ninety-seven participants were randomized into two groups: 49 in the telerehabilitation group (non-immersive virtual reality-based telerehabilitation) and 48 in the control group (at-home self-administered structured conventional motor activities). Both treatments lasted 30 sessions (3-5 days/week for, 6-10 weeks). Static and dynamic balance, gait, and functional motor outcomes were registered before and after the treatments. RESULTS: All participants improved the outcomes at the end of the treatments. The primary outcome (mini-Balance Evaluation Systems Test) registered a greater significant improvement in the telerehabilitation group than in the control group. The gait and endurance significantly improved in the telerehabilitation group only, with significant within-group and between-group differences. CONCLUSIONS: Our results showed that non-immersive virtual reality-based telerehabilitation is feasible, improves static and dynamic balance, and is a reasonably valuable alternative for reducing postural instability in people with Parkinson's disease. CLINICAL REHABILITATION IMPACT: Non-immersive virtual reality-based telerehabilitation is an effective and well-tolerated modality of rehabilitation which may help to improve access and scale up rehabilitation services as suggested by the World Health Organization's Rehabilitation 2030 agenda

Telerehabilitation for Neurological Motor Impairment: A Systematic Review and Meta-Analysis on Quality of Life, Satisfaction, and Acceptance in Stroke, Multiple Sclerosis, and Parkinson’s Disease

Telerehabilitation (TR) seems to be a viable and feasible solution to face the rehabilitative challenges posed by neurological impairments and to improve patients’ quality of life (QoL). This review aims to synthesize and analyze the evidence on the impact of physiotherapy intervention through TR on QoL in patients with stroke, Parkinson’s disease (PD), and multiple sclerosis (MS), together with an evaluation of their satisfaction and technology acceptance levels. Through a systematic search of the literature and a screening process, treatment effects were assessed with meta-analyses using the standardized mean difference, setting the confidence interval at 95%. We included 28 studies in the review, which were analyzed for methodological quality, whereas 16 studies were included in the meta-analyses. The results suggest a significant improvement in QoL in patients who underwent TR. We were unable to perform analyses for satisfaction and technology acceptance outcomes due to insufficient data. Overall, motor TR has a positive impact on the QoL of patients with neurological diseases, especially in stroke patients; although caution is needed in the interpretation of the results due to the high heterogeneity found. For PD and MS, TR seems to yield comparable results to in-person treatment

Clinical Predictors for Upper Limb Recovery after Stroke Rehabilitation: Retrospective Cohort Study

After stroke, recovery of upper limb (UL) motor function is enhanced by a high dose of rehabilitation and is supposed to be supported by attentive functions. However, their mutual influence during rehabilitation is not well known yet. The aim of this retrospective observational cohort study was to investigate the association between rehabilitation dose and motor and cognitive functions, during UL motor recovery. Inpatients with first unilateral stroke, without time restrictions from onset, and undergoing at least 15 h of rehabilitation were enrolled. Data on dose and modalities of rehabilitation received, together with motor and cognitive outcomes before and after therapy, were collected. Fugl-Meyer values for the Upper Extremity were the primary outcome measure. Logistic regression models were used to detect any associations between UL motor improvement and motor and cognitive-linguistic features at acceptance, regarding dose of rehabilitation received. Thirty-five patients were enrolled and received 80.57 +/- 30.1 h of rehabilitation on average. Manual dexterity, level of independence and UL motor function improved after rehabilitation, with no influence of attentive functions on motor recovery. The total amount of rehabilitation delivered was the strongest factor (p = 0.031) influencing the recovery of UL motor function after stroke, whereas cognitive-linguistic characteristics were not found to influence UL motor gains

Language and gesture neural correlates: A meta-analysis of functional magnetic resonance imaging studies

BackgroundHumans often use co-speech gestures to promote effective communication. Attention has been paid to the cortical areas engaged in the processing of co-speech gestures.AimsTo investigate the neural network underpinned in the processing of co-speech gestures and to observe whether there is a relationship between areas involved in language and gesture processing.Methods & ProceduresWe planned to include studies with neurotypical and/or stroke participants who underwent a bimodal task (i.e., processing of co-speech gestures with relative speech) and a unimodal task (i.e., speech or gesture alone) during a functional magnetic resonance imaging (fMRI) session. After a database search, abstract and full-text screening were conducted. Qualitative and quantitative data were extracted, and a meta-analysis was performed with the software GingerALE 3.0.2, performing contrast analyses of uni- and bimodal tasks.Main ContributionThe database search produced 1024 records. After the screening process, 27 studies were included in the review. Data from 15 studies were quantitatively analysed through meta-analysis. Meta-analysis found three clusters with a significant activation of the left middle frontal gyrus and inferior frontal gyrus, and bilateral middle occipital gyrus and inferior temporal gyrus.ConclusionsThere is a close link at the neural level for the semantic processing of auditory and visual information during communication. These findings encourage the integration of the use of co-speech gestures during aphasia treatment as a strategy to foster the possibility to communicate effectively for people with aphasia

Cell-specific vulnerability to metabolic failure: the crucial role of parvalbumin expressing neurons in creatine transporter deficiency

Mutations in the solute carrier family 6-member 8 (Slc6a8) gene, encoding the protein responsible for cellular creatine (Cr) uptake, cause Creatine Transporter Deficiency (CTD), an X-linked neurometabolic disorder presenting with intellectual disability, autistic-like features, and epilepsy. The pathological determinants of CTD are still poorly understood, hindering the development of therapies. In this study, we generated an extensive transcriptomic profile of CTD showing that Cr deficiency causes perturbations of gene expression in excitatory neurons, inhibitory cells, and oligodendrocytes which result in remodeling of circuit excitability and synaptic wiring. We also identified specific alterations of parvalbumin-expressing (PV+) interneurons, exhibiting a reduction in cellular and synaptic density, and a hypofunctional electrophysiological phenotype. Mice lacking Slc6a8 only in PV+ interneurons recapitulated numerous CTD features, including cognitive deterioration, impaired cortical processing and hyperexcitability of brain circuits, demonstrating that Cr deficit in PV+ interneurons is sufficient to determine the neurological phenotype of CTD. Moreover, a pharmacological treatment targeted to restore the efficiency of PV+ synapses significantly improved cortical activity in Slc6a8 knock-out animals. Altogether, these data demonstrate that Slc6a8 is critical for the normal function of PV+ interneurons and that impairment of these cells is central in the disease pathogenesis, suggesting a novel therapeutic venue for CTD