Does repetitive transcranial magnetic stimulation have a beneficial effect on improving unilateral spatial neglect caused by stroke? A meta-analysis.

This review aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS) in improving post-stroke unilateral spatial neglect (USN) using a meta-analysis. Further, we aimed to identify any association between rTMS parameters, patient demographics, and treatment effect sizes using subgroup analyses and meta-regression. A literature search was conducted through four databases from inception to March 6, 2024, to retrieve all relevant controlled trials investigating the effects of rTMS on symptoms of USN in post-stroke patients. Overall, rTMS significantly improved post-stroke USN, as measured by the line bisection test (Hedges' g = - 1.301, p < 0.0001), the cancelation test (Hedge's g = - 1.512, p < 0.0001), and the Catherine Bergego Scale (Hedges'g = - 0.770, p < 0.0001), compared to sham stimulation. Subgroup analysis found that generally larger effect sizes following excitatory rTMS across several outcome measures, indicating that excitatory rTMS on the ipsilesional hemisphere may be more effective than inhibitory rTMS on the contralesional hemisphere in ameliorating neglect symptoms. Meta-regression analysis of the line bisection test showed a significant difference in the chronicity of stroke patients, suggesting that rTMS may be more effective for USN in patients at the acute stage (within 3 months since stroke) than in those at the post-acute stage (p = 0.035). In conclusion, rTMS appears to be effective in promoting recovery from post-stroke USN. Excitatory protocols and early intervention may enhance recovery outcomes for neglect behaviors in post-stroke survivors.

[Rehabilitation for Unilateral Spatial Neglect].

Unilateral spatial neglect (USN) is a symptom of unilateral brain damage resulting in failure to report sensory phenomena in the contra-lesional space. It is associated with motor impairment as well as sensory deficits. Recent research suggests that USN, may be caused by a disruption in the interhemispheric balance of the visual attention network. Based on this hypothesis, non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), is utilized in the rehabilitation of USN patients. Presently, inhibitory stimulation by continuous theta burst stimulation (cTBS) on contra-lesional parietal cortex are believed to be the most promising method. Conversely, compensation by attentional network of the non-lesioned hemisphere plays an important role in the recovery of USN. Recent imaging studies revealed that functional and structural connectivity of attentional networks within a lesioned hemisphere and between lesioned and non-lesioned hemispheres affects spontaneous recovery and effectiveness of rehabilitation approach such as prism adaptation therapy. These findings are useful in elucidating the pathophysiology of USN and predicting functional outcome. Furthermore, we hope that understanding the pathophysiology will enable the development of new rehabilitation strategies and appropriate treatment selection.

Assessment and treatment of visuospatial neglect using active learning with Gaussian processes regression.

Visuospatial neglect is a disorder characterised by impaired awareness for visual stimuli located in regions of space and frames of reference. It is often associated with stroke. Patients can struggle with all aspects of daily living and community participation. Assessment methods are limited and show several shortcomings, considering they are mainly performed on paper and do not implement the complexity of daily life. Similarly, treatment options are sparse and often show only small improvements. We present an artificial intelligence solution designed to accurately assess a patient's visuospatial neglect in a three-dimensional setting. We implement an active learning method based on Gaussian process regression to reduce the effort it takes a patient to undergo an assessment. Furthermore, we describe how this model can be utilised in patient oriented treatment and how this opens the way to gamification, tele-rehabilitation and personalised healthcare, providing a promising avenue for improving patient engagement and rehabilitation outcomes. To validate our assessment module, we conducted clinical trials involving patients in a real-world setting. We compared the results obtained using our AI-based assessment with the widely used conventional visuospatial neglect tests currently employed in clinical practice. The validation process serves to establish the accuracy and reliability of our model, confirming its potential as a valuable tool for diagnosing and monitoring visuospatial neglect. Our VR application proves to be more sensitive, while intra-rater reliability remains high.

Optokinetic stimulation effects in the management of unilateral spatial neglect in patients with chronic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Unilateral spatial neglect (USN) is a stroke complication of stroke. Optokinetic stimulation (OKS) is one of the treatments, but its effects on motor symptoms, such as poverty or alterations in movements on the affected side, are not clear yet. The aim of this study will be to evaluate the OKS effects on the perceptual and postural complications of patients with USN. METHODS AND ANALYSIS: Randomised double-blinded clinical trial, with an intervention group that will undergo OKS and a control placebo group. The research will take place at the Faculty of Nursing and Physiotherapy, University of Salamanca, 102 patients older than 18 years with diagnosed USN will participate. The intervention group will receive 2 weekly OKS session for 10 weeks. Virtual reality glasses will be used for the application of a video. The video will project OKS at a preset speed and will request the participant's attention throughout the session. The control group will receive a placebo treatment, through a virtual reality video. The measurement variables will be posturography, Fluff test, line bisection, Fullerton Advance Balance Scale and Diller's cancellation test. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee University of Salamanca on February 2020 (registration number: 584). All patients in the study will be informed about the objective of the study and will give their written informed consent to participate in the study. The anonymised database will be available from the publication of the results for 10 years in the repository of the University of Salamanca GREDOS (https://gredos.usal.es/). The trial results will be shared with the scientific community at international conferences and by publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04663646.

Recent advances in treatment of spatial neglect: networks and neuropsychology.

INTRODUCTION: Spatial neglect remains an underdiagnosed and undertreated consequence of stroke that imposes significant disability. A growing appreciation of brain networks involved in spatial cognition is helping us to develop a mechanistic understanding of different therapies under development. AREAS COVERED: This review focuses on neuromodulation of brain networks for the treatment of spatial neglect after stroke, using evidence-based approaches including 1) Cognitive strategies that are more likely to impact frontal lobe executive function networks; 2) Visuomotor adaptation, which may depend on the integrity of parietal and parieto- and subcortical-frontal connections and the presence of a particular subtype of neglect labeled Aiming neglect; 3) Non-invasive brain stimulation that may modulate relative levels of activity of the two hemispheres and depend on corpus callosum connectivity; and 4) Pharmacological modulation that may exert its effect primarily via right-lateralized networks more closely involved in arousal. EXPERT OPINION: Despite promising results from individual studies, significant methodological heterogeneity between trials weakened conclusions drawn from meta-analyses. Improved classification of spatial neglect subtypes will benefit research and clinical care. Understanding the brain network mechanisms of different treatments and different types of spatial neglect will make possible a precision medicine treatment approach.

Unilateral Spatial Neglect Recovery Poststroke.

Unilateral spatial neglect (USN) is a common and disabling cognitive consequence of stroke wherein individuals demonstrate decreased response to contralesional information. Here, we provide an updated narrative review of studies that shed light on the neural mechanisms and predictors of recovery of USN. Additionally, we report a rapid review of randomized controlled trials focusing on USN intervention, both nonpharmacological and pharmacological, published in the last 5 years. Randomized controlled trials are reviewed within the context of systematic reviews and meta-analyses of USN interventions published within the same time frame. The quality of randomized controlled trials of treatment is higher compared to quality reported in previous reviews and meta-analyses. However, remaining weaknesses in participant demographic reporting, as well as small, heterogenous samples, render generalizability and cross-study interpretation a challenge. Nevertheless, evidence regarding neural mechanisms underlying USN recovery and regarding the effectiveness of targeted USN interventions is accumulating and strengthening, setting the foundation for future investigations into patient-specific factors that may influence treatment response. We identify gaps and provide suggestions for future USN intervention research.

Visuomotor misalignment induced through immersive virtual reality to improve spatial neglect: a case-series study.

One evidence-based treatment for spatial neglect is prism adaptation (PA) treatment. PA after-effects, i.e., the implicit shifts in the arm reaching position toward the neglected side of space after prism removal, are considered fundamental to PA treatment effects. In the present study, the arm reaching position was shifted through a visuomotor misalignment procedure using immersive virtual reality (VR). To examine whether this procedure might have a beneficial impact on spatial neglect, we conducted a multi-baseline experiment in three individuals with chronic left-sided neglect post stroke. Improved spatial neglect was observed in all participants immediately after 5 sessions with two rounds in each. Two participants demonstrated lasting or continuous improvement two weeks later. Participants' pattern of brain lesions did not appear to clearly explain performance differences. The findings suggest that VR-induced visuomotor misalignment may improve spatial neglect immediately after a multi-session treatment course. The optimal number of sessions will be determined by future studies with a larger sample size, which may also elucidate the number of sessions sufficient for sustained improvement in most patients. Further investigations will identify the neural mechanisms underlying VR-induced visuomotor misalignment, which may or may not be identical to PA after-effects.

How effective and safe are non-drug treatments for spatial neglect following non-progressive brain injury? A Cochrane Review summary with commentary.

BACKGROUND: Around 30% of stroke survivors experience spatial neglect. Spatial neglect hinders rehabilitation outcomes and increases the risk of injury. Non-pharmacological interventions are available, yet their efficacy is unknown. OBJECTIVE: To evaluate the effectiveness of non-pharmacological interventions for spatial neglect (inattention) following stroke and other non-progressive brain injuries. METHODS: A summary of the Cochrane Review by Longley et al. 2020, with comments from a rehabilitation perspective. RESULTS: A total of 43 studies were included in meta-analysis and the quality of evidence was very low for all analyses. The benefits or risks associated with each intervention for spatial neglect including visual treatment, prism adaptation training, body awareness, mental function, movement treatment, non-invasive brain stimulation, electrical stimulation, and acupuncture remain unclear. CONCLUSIONS: Evidence in support or against the treatments is sparse and more rigorous studies are needed to evaluate their efficacy. Clinicians should continue to follow current guidelines when available to meet patients' rehabilitation goals.

Non-invasive Brain Stimulation Can Reduce Unilateral Spatial Neglect after Stroke: ELETRON Trial.

OBJECTIVE: Rehabilitation top-down techniques based on brain stimulation present variable outcomes in unilateral spatial neglect (USN) after stroke. This study aimed to examine the effects of physical therapy after anodal and cathodal transcranial direct current stimulation (A-tDCS and C-tDCS, respectively) to improve visuospatial and functional impairments in individuals with USN after stroke. METHODS: This double-blinded, pilot randomized clinical trial enrolled patients with USN after ischemic stroke. Randomization was stratified according to the Behavior Inattention Test-Conventional (BIT-C) and Catherine Bergego Scale (CBS). Outpatient physical therapy was conducted for 7.5 weeks after 20 minutes of tDCS. The primary outcome was the USN degree evaluated by the BIT-C. Secondary outcomes were the difference in CBS score, stroke severity (National Institutes of Health Stroke Scale [NIHSS]), disability (modified Rankin Scale), autonomy (Barthel Index, Functional Independence Measure), and quality of life (EuroQol Group 5-Dimension Self-Report Questionnaire). Outcomes were analyzed using an analysis of covariance model corrected by age, baseline NIHSS, and baseline BIT-C. Pairwise post hoc comparisons were performed using Bonferroni correction. RESULTS: In the primary outcomes, A-tDCS led to greater improvement in BIT-C after intervention (mean difference [MD] = 18.4, 95% confidence interval [CI] = 3.9-32.8, p = 0.008) compared to sham. However, no significant differences were observed between A-tDCS and C-tDCS (MD = 13.9, 95% CI = -0.3 to 28.1, p = 0.057), or C-tDCS and sham (MD = 4.5, 95% CI = -9.7 to 18.8, p = 0.99). There were no significant differences between groups in terms of secondary outcomes. INTERPRETATION: A-tDCS associated with physical therapy can decrease the severity of USN after stroke. However, these preliminary findings must be confirmed by collecting additional evidence in a larger phase 3 trial. ANN NEUROL 2022;92:400-410.

Effect of acupuncture on unilateral spatial neglect after stroke: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effects of acupuncture in patients with unilateral spatial neglect (USN) after stroke. DATA SOURCES: Relevant English- and Chinese- language studies published until 12th February 2022, were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journals Database (VIP), SinoMed, PubMed, Cochrane Library, Embase, Web of Science and OVID. REVIEW METHODS: Randomized controlled trials (RCTs) assessing the effects of acupuncture in patients with USN after stroke were included. Two researchers independently identified eligible studies and extracted the data. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. RESULTS: Twelve studies (731 participants) were included. The meta-analysis found that compared with the control group, acupuncture increased MMSE, BI, MBI, and FMA scores and reduced the USN scores (all P < 0.05). These results indicated that acupuncture improved cognitive function, activities of daily living (ADLs), and motor function and relieved the degree of USN in patients with USN after stroke. CONCLUSION: Acupuncture could promote the rehabilitation of cognitive function, ADLs, and motor function and relieve the symptoms of USN in patients with USN after stroke. It may be a good complementary treatment to rehabilitation therapy for USN.

Perceptual Disorders After Stroke: A Scoping Review of Interventions.

Perceptual disorders relating to hearing, smell, somatosensation, taste, touch, and vision commonly impair stroke survivors' ability to interpret sensory information, impacting on their ability to interact with the world. We aimed to identify and summarize the existing evidence for perceptual disorder interventions poststroke and identify evidence gaps. We searched 13 electronic databases including MEDLINE and Embase and Grey literature and performed citation tracking. Two authors independently applied a priori-defined selection criteria; studies involving stroke survivors with perceptual impairments and interventions addressing those impairments were included. We extracted data on study design, population, perceptual disorders, interventions, and outcomes. Data were tabulated and synthesized narratively. Stroke survivors, carers, and clinicians were involved in agreeing definitions and organizing and interpreting data. From 91 869 records, 80 studies were identified (888 adults and 5 children); participant numbers were small (median, 3.5; range, 1-80), with a broad range of stroke types and time points. Primarily focused on vision (34/80, 42.5%) and somatosensation (28/80; 35.0%), included studies were often case reports (36/80; 45.0%) or randomized controlled trials (22/80; 27.5%). Rehabilitation approaches (78/93; 83.9%), primarily aimed to restore function, and were delivered by clinicians (30/78; 38.5%) or technology (28/78; 35.9%; including robotic interventions for somatosensory disorders). Pharmacological (6/93; 6.5%) and noninvasive brain stimulation (7/93; 7.5%) approaches were also evident. Intervention delivery was poorly reported, but most were delivered in hospital settings (56/93; 60.2%). Study outcomes failed to assess the transfer of training to daily life. Interventions for stroke-related perceptual disorders are underresearched, particularly for pediatric populations. Evidence gaps include interventions for disorders of hearing, taste, touch, and smell perception. Future studies must involve key stakeholders and report this fully. Optimization of intervention design, evaluation, and reporting is required, to support the development of effective, acceptable, and implementable interventions. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019160270.

Prism adaptation effects in complex regional pain syndrome: A therapo-physiological single case experimental design exploratory report.

Complex Regional Pain Syndrome (CRPS) is an invalidating chronic condition that can occur after an acute peripheral lesion. Prism adaptation therapy is regarded as a promising tool to improve chronic pain in this syndrome but the mechanisms which lead to pain amelioration remain unknown. In this exploratory report we performed a retrospective analysis of longitudinal data collected from a single, atypical patient, who showed hyper-attention toward her affected (left) hand. Repeated assessments of pain and spatial neglect made during the course of the prism adaptation treatment revealed differential contributions of the two hands to adaptation-induced pain reduction. Treatment response appeared to be associated with a relative modification of the spatial behaviour of the two hands. This case study provides a new example of pain relief following prismatic deviation away from the pathological side.

Integrating visual search, eye movement training and reversing prism exposure in the treatment of Balint-Holmes syndrome: a single case report.

OBJECTIVE: For the first time, we administered reversing prism exposure to treat optic ataxia in a single patient with Balint-Holmes Syndrome (BHS), who also underwent specific trainings for simultanagnosia and ocular apraxia. METHOD AND RESULTS: By an introduction and withdrawal experimental design, we observed that the active treatment periods improved patient's visuospatial defects and functional autonomy. CONCLUSIONS: We thus provided a proof of principle supporting the use of reversing prism exposure in optic ataxia within an integrated and personalized rehabilitative approach for BHS.

Current trends in the treatment of patients with post-stroke unilateral spatial neglect: a scoping review.

PURPOSE: The purpose of this scoping review was to explore the current treatment approaches for patients with post-stroke unilateral spatial neglect. METHODS: A three-step search strategy using the Johanna Briggs Institute (JBI) guidelines, was undertaken. PubMed, CINAHL, The Cochrane Central Register of Controlled Trial, SCOPUS, PROSPERO, JBI, Sport Discus, and Google Scholar databases were searched. Searches were limited to publications from January 1, 2008, to May 1, 2020. Critical appraisal was undertaken by two independent reviewers using a standardized critical appraisal instrument developed by JBI. Data were extracted using a study-specific charting table. RESULTS: A total of 3,648 articles were identified, 311 full-text articles were screened and 86 articles were critically appraised, with 83 articles included in the review. Intervention approaches for post-stroke unilateral spatial neglect symptom amelioration were identified and categorized as prism adaptation and visual scanning, mental practice and mirror therapy, electrical stimulation and robotics, combination therapy, pharmacological therapy, and other interventions. Both positive and negative results across identified interventions were identified without specific reference to the phase of recovery. CONCLUSION: This review provides insight into current interventions for post-stroke unilateral spatial neglect. A plethora of intervention studies have been explored to ameliorate neglect symptoms post-stroke.IMPLICATION FOR REHABILITATIONPrism adaptation (PA) and combination therapy are most commonly investigated intervention for unilateral spatial neglect (USN) and showed promise in ameliorating USN symptoms.No single treatment approach seems optimally superior in the rehabilitation of USN post-stroke.Evidence for the selection of treatment at a specific phase of recovery is not conclusive as both positive and negative outcome on neglect measure were observed across all treatment approaches without specific reference to the phase of recovery.Evidence for the long-term use of PA in USN rehabilitation appears to be modest.

Examination and treatment of unilateral spatial neglect using virtual reality in three-dimensional space.

Here, we developed a method that randomly generates balloons in the left-right, up-down, and near-far spaces on a monitor using a head-mounted display. In this study, we evaluated a lack of stimulus-driven attention case that was undetected by conventional assessments such as the Behavioral Inattention Test. We could identify mild neglect with our virtual reality method, as later confirmed using the Catherine Bergego scale. After repeated practice under a tilted background space condition, the patient demonstrated a reduction in the time needed to perceive the appearing balloons, suggesting a therapeutic effect.

Lateropulsion After Hemispheric Stroke: A Form of Spatial Neglect Involving Graviception.

OBJECTIVE: To test the hypothesis that lateropulsion is an entity expressing an impaired body orientation with respect to gravity in relation to a biased graviception and spatial neglect. METHODS: Data from the DOBRAS cohort (ClinicalTrials.gov: NCT03203109) were collected 30 days after a first hemisphere stroke. Lateral body tilt, pushing, and resistance were assessed with the Scale for Contraversive Pushing. RESULTS: Among 220 individuals, 72% were upright and 28% showed lateropulsion (tilters [14%] less severe than pushers [14%]). The 3 signs had very high factor loadings (>0.90) on a same dimension, demonstrating that lateropulsion was effectively an entity comprising body tilt (cardinal sign), pushing, and resistance. The factorial analyses also showed that lateropulsion was inseparable from the visual vertical (VV), a criterion referring to vertical orientation (graviception). Contralesional VV biases were frequent (44%), with a magnitude related to lateropulsion severity: upright -0.6° (-2.9; 2.4), tilters -2.9° (-7; 0.8), and pushers -12.3° (-15.4; -8.5). Ipsilesional VV biases were less frequent and milder (p < 0.001). They did not deal with graviception, 84% being found in upright individuals. Multivariate, factorial, contingency, and prediction analyses congruently showed strong similarities between lateropulsion and spatial neglect, the latter encompassing the former. CONCLUSIONS: Lateropulsion (pusher syndrome) is a trinity constituted by body tilt, pushing, and resistance. It is a way to adjust the body orientation in the roll plane to a wrong reference of verticality. Referring to straight above, lateropulsion might correspond to a form of spatial neglect (referring to straight ahead), which would advocate for 3D maps in the human brain involving the internal model of verticality.

Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Left hemispatial neglect (LHN) is a neuropsychological syndrome often associated with right hemispheric stroke. Patients with LHN have difficulties in attending, responding, and consciously representing the right side of space. Various rehabilitation protocols have been proposed to reduce clinical symptoms related to LHN, using cognitive treatments, or on non-invasive brain stimulation. However, evidence of their benefit is still lacking; in particular, only a few studies focused on the efficacy of combining different approaches in the same patient. METHODS: In the present study, we present the SMART ATLAS trial (Stimolazione MAgnetica Ripetitiva Transcranica nell'ATtenzione LAteralizzata dopo Stroke), a multicenter, randomized, controlled trial with pre-test (baseline), post-test, and 12 weeks follow-up assessments based on a novel rehabilitation protocol based on the combination of brain stimulation and standard cognitive treatment. In particular, we will compare the efficacy of inhibitory repetitive-transcranial magnetic stimulation (r-TMS), applied over the left intact parietal cortex of LHN patients, followed by visual scanning treatment, in comparison with a placebo stimulation (SHAM control) followed by the same visual scanning treatment, on visuospatial symptoms and neurophysiological parameters of LHN in a population of stroke patients. DISCUSSION: Our trial results may provide scientific evidence of a new, relatively low-cost rehabilitation protocol for the treatment of LHN. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080999 . Registered on September 2019.

Impaired motor control after sport-related concussion could increase risk for musculoskeletal injury: Implications for clinical management and rehabilitation.

This review presents a conceptual framework and supporting evidence that links impaired motor control after sport-related concussion (SRC) to increased risk for musculoskeletal injury. Multiple studies have found that athletes who are post-SRC have higher risk for musculoskeletal injury compared to their counterparts. A small body of research suggests that impairments in motor control are associated with musculoskeletal injury risk. Motor control involves the perception and processing of sensory information and subsequent coordination of motor output within the central nervous system to perform a motor task. Motor control is inclusive of motor planning and motor learning. If sensory information is not accurately perceived or there is interference with sensory information processing and cognition, motor function will be altered, and an athlete may become vulnerable to injury during sport participation. Athletes with SRC show neuroanatomic and neurophysiological changes relevant to motor control even after meeting return to sport criteria, including a normal neurological examination, resolution of symptoms, and return to baseline function on traditional concussion testing. In conjunction, altered motor function is demonstrated after SRC in muscle activation and force production, movement patterns, balance/postural stability, and motor task performance, especially performance of a motor task paired with a cognitive task (i.e., dual-task condition). The clinical implications of this conceptual framework include a need to intentionally address motor control impairments after SRC to mitigate musculoskeletal injury risk and to monitor motor control as the athlete progresses through the return to sport continuum.