Despite its potential clinical impact, the association of personal neglect (PN) with motor, activities of daily living (ADL), and participation outcomes after stroke is not well-understood. This first-ever systematic review on the topic therefore evaluates this association, taking into account suggested subtypes of PN, including body representation neglect, somatosensory neglect, motor neglect, and premotor neglect. A systematic literature search was conducted on February 17, 2023 in PubMed, Web of Science, Scopus, PubPsych, and PsycArticles databases. The study adheres to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and its protocol was registered on PROSPERO (CRD42020187460). Eleven observational studies were included, gathering 1,400 individuals after stroke (429 showed PN). Results show that individuals with body representation neglect after stroke have significantly decreased movement control and motor strength, lower functional mobility, and ADL independency compared with those without body representation neglect after stroke. Individuals with motor neglect after stroke showed worse motor function and spasticity than to those without motor neglect after stroke. Nonspecified PN (i.e., PN evaluated with an outcome measure that does not allow subcategorization) was related to worse lateropulsion with pushing, longer length of stay and greater odds of being discharged to somewhere other than home. No study evaluated somatosensory and premotor neglect. This review highlights the limited research in this area and emphasizes the need for a more comprehensive PN assessment. However, currently available assessment tools show limited ability to accurately diagnose PN subtypes and future research should prioritize the development of comprehensive diagnostic test batteries.

Although subjective sensory hypersensitivity is prevalent after stroke, it is rarely recognized by health care providers, and its neural mechanisms are largely unknown. To investigate the neuroanatomy of poststroke subjective sensory hypersensitivity as well as the sensory modalities in which subjective sensory hypersensitivity can occur by conducting both a systematic literature review and a multiple case study of patients with subjective sensory hypersensitivity. For the systematic review, we searched three databases (Web of Science, PubMed, and Scopus) for empirical articles discussing the neuroanatomy of poststroke subjective sensory hypersensitivity in humans. We assessed the methodological quality of the included studies using the case reports critical appraisal tool and summarized the results using a qualitative synthesis. For the multiple case study, we administered a patient-friendly sensory sensitivity questionnaire to three individuals with a subacute right-hemispheric stroke and a matched control group and delineated brain lesions on a clinical brain scan. Our systematic literature search resulted in four studies (describing eight stroke patients), all of which linked poststroke subjective sensory hypersensitivity to insular lesions. The results of our multiple case study indicated that all three stroke patients reported an atypically high sensitivity to different sensory modalities. These patients' lesions overlapped with the right anterior insula, the claustrum, and the Rolandic operculum. Both our systematic literature review and our multiple case study provide preliminary evidence for a role of the insula in poststroke subjective sensory hypersensitivity and suggest that poststroke subjective sensory hypersensitivity can occur in different sensory modalities.

Although most research on spatial neglect (SN) has focused on spatial perception deficits with regard to the lateral (left-right) axis, deficits of spatial perception with regard to the vertical (up-down) axis, such as disturbances in the perception of verticality (e.g., judgement of vertical orientations), have also been suggested. We aimed to systematically analyse reported associations between SN and characteristics of verticality perception while considering the time post-stroke. PubMed, Web of Science, Scopus, PubPsych and PsycArticles databases were searched on May 24, 2022 for articles written in English that evaluated the association between SN and verticality perception (i.e., the subjective visual vertical [SVV], subjective postural vertical [SPV] and subjective haptic vertical [SHV]) in adults after stroke. Left and right SN were considered and had to be assessed using standardized methods. Data were manually extracted, and risk of bias was assessed with the Newcastle-Ottawa Scale. The tilt of the line/chair relative to the gravitational vector and its direction, together with uncertainty (i.e., variability across measurements), were evaluated. Thirteen studies were included (431 participants after stroke); at least 191 participants exhibited SN. Mainly the first 3 to 6 months post-stroke were evaluated. SN was associated with SVV misperception, which resulted in larger SVV tilts (mostly in the contralesional direction) and uncertainty in participants with than without SN. SVV tilt magnitudes ranged from a mean/median of -8.9° to -2.3° in SN participants and from -1.6° to 0.6° in non-SN participants, the latter falling within normative ranges. For SPV and SHV measurements, the magnitude of tilt and the uncertainty were insufficiently assessed or results were inconclusive. SN was associated with larger SVV tilts and uncertainty, which suggests that SVV misperception is a key feature of SN. This observation highlights the importance of regular SVV assessment in people with SN in clinical practice. CRD42019127616.

This commentary is on the original articles by Huang et al. and Hov et al. on pages 640–663 of this issue.

AbstractIn many autoimmune diseases, FOXP3+regulatory T cells (Tregs) skew towards a pro-inflammatory and non-suppressive phenotype and are therefore unable to control the exaggerated autoimmune response. This may largely impact the success of autologous Treg therapy which is currently under investigation for treatment of autoimmune diseases, including multiple sclerosis (MS). Thus, there is a need to ensurein vivostability of Tregs before successful Treg therapy can be applied. Using a murine genetic fate-mapping model, we demonstrate that inflammatory exFOXP3 T cells accumulate in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE). In a humanin vitroBBB model, we discovered that interaction with inflamed blood-brain barrier (BBB)-endothelial cells induces loss of suppressive function in Tregs. Transcriptome analysis further revealed that Tregs which migrated across inflamed BBB-endothelial cellsin vitrohave a pro-inflammatory Th1/17 signature and upregulate the mTORC1 signaling pathway compared to non-migrated Tregs. These findings suggest that interaction with BBB-endothelial cells is sufficient to affect Treg function, and that transmigration triggers an additive pro-inflammatory phenotype switch, which was also seen in CNS-derived exFOXP3 T cells of EAE mice.In vitrotreatment of migrated human Tregs with the clinically-approved mTORC1 inhibitor rapamycin completely restored the loss of suppressive function. Finally, flow cytometric analysis indicated an enrichment of inflammatory, less suppressive CD49d+Tregs in the cerebrospinal fluid of MS patients, thereby underscoring the relevance of our findings for human disease. In sum, our findings provide firm evidence that the inflamed BBB affects human Treg stability, which can be restored using a mTORC1 inhibitor. These insights can help in significantly improving the efficacy of autologous Treg therapy of MS.

Patients with acquired brain injury frequently report experiencing sensory stimuli as abnormally under- (sensory hyposensitivity) or overwhelming (sensory hypersensitivity). Although they can negatively impact daily functioning, these symptoms are poorly understood. To provide an overview of the current evidence on atypical sensory sensitivity after acquired brain injury, we conducted a systematic literature review. The primary aim of the review was to investigate the behavioural and neural mechanisms that are associated with self-reported sensory sensitivity. Studies were included when they studied sensory sensitivity in acquired brain injury populations, and excluded when they were not written in English, consisted of non-empirical research, did not study human subjects, studied pain, related sensory sensitivity to peripheral injury or studied patients with a neurodegenerative disorder, meningitis, encephalitis or a brain tumour. The Web of Science, PubMed and Scopus databases were searched for appropriate studies. A qualitative synthesis of the results of the 81 studies that were included suggests that abnormal sensory thresholds and a reduced information processing speed are candidate behavioural mechanisms of atypical subjective sensory sensitivity after acquired brain injury. Furthermore, there was evidence for an association between subjective sensory sensitivity and structural grey or white matter abnormalities, and to functional abnormalities in sensory cortices. However, further research is needed to explore the causation of atypical sensory sensitivity. In addition, there is a need for the development of adequate diagnostic tools. This can significantly advance the quantity and quality of research on the prevalence, aetiology, prognosis and treatment of these symptoms.

IntroductionAlthough most stroke survivors show some spontaneous neurological recovery from motor impairments of the most-affected leg, the contribution of this leg to standing balance control remains often poor. Consequently, it is unclear how spontaneous processes of neurological recovery contributes to early improvements in standing balance.ObjectiveWe aim to investigate (1) the time course of recovery of quiet stance balance control in the first 12 weeks poststroke and (2) how clinically observed improvements of lower limb motor impairments longitudinally relate to this limb's relative contribution to balance control.Methods and AnalysisIn this prospective longitudinal study, a cohort of 60 adults will be recruited within the first 3 weeks after a first-ever hemispheric stroke and mild-to-severe motor impairments. Individual recovery trajectories will be investigated by means of repeated measurements scheduled at 3, 5, 8, and 12 weeks poststroke. The Fugl-Meyer Motor Assessment and Motricity Index of the lower limb serve as clinical measures of motor impairments at the hemiplegic side. As soon as subjects are able to stand independently, bilateral posturography during quietly standing will be measured. First, the obtained center-of-pressure (COP) trajectories at each foot will be used for synchronization and contribution measures that establish (a-)symmetries between lower limbs. Second, the COP underneath both feet combined will be used to estimate overall stability. Random coefficient analyses will be used to model time-dependent changes in these measures and, subsequently, a hybrid model will be used to investigate longitudinal associations with improved motor impairments.DiscussionThe current study aims to investigate how stroke survivors “re-learn” to maintain standing balance as an integral part of daily life activities. The knowledge gained through this study may contribute to recommending treatment strategies for early stroke rehabilitation targeting behavioral restitution of the most-affected leg or learning to compensate with the less-affected leg.

Trunk training after stroke is an effective method for improving trunk control, standing balance and mobility. The SWEAT2 study attempts to discover the underlying mechanisms leading to the observed mobility carry-over effects after trunk training. A secondary analysis investigating the effect of trunk training on muscle activation patterns, muscle synergies and motor unit recruitment of trunk and lower limbs muscles, aimed to provide new insights in gait recovery after stroke. Randomized controlled trial. Monocentric study performed in the RevArte Rehabilitation Hospital (Antwerp, Belgium). Forty-five adults diagnosed with first stroke within five months, of which 39 completed treatment and were included in the analysis. Participants received 16 hours of additional trunk training (N.=19) or cognitive training (N.=20) over the course of four weeks (1 hour, 4 times a week). They were assessed by an instrumented gait analysis with electromyography of trunk and lower limb muscles. Outcome measures were linear integrated normalized envelopes of the electromyography signal, the amount and composition of muscle synergies calculated by nonnegative matrix factorization and motor unit recruitment calculated, by mean center wavelet frequencies. Multivariate analysis with post-hoc analysis and statistical parametric mapping of the continuous curves were performed. No significant differences were found in muscle activation patterns and the amount of muscle synergies. In 42% of the subjects, trunk training resulted in an additional muscle synergy activating trunk muscles in isolation, as compared to 5% in the control group. Motor unit recruitment of the of trunk musculature showed decreased fast-twitch motor recruitment in the erector spinae muscle after trunk training: for the hemiplegic (t[37]=2.44, P=0.021) and non-hemiplegic erector spinae muscle (t[37]=2.36, P=0.024). Trunk training improves selective control and endurance of trunk musculature after sub-acute stroke. What is new to the actual clinical rehabilitation knowledge is that: trunk training does not alter muscle activation patterns or the amount of muscle synergies over time; a decrease in fast-twitch motor recruitment in the erector spinae muscle was found during walking after trunk training; trunk training seems to increase the fatigue-resistance of the back muscles and enables more isolated activation.

Integration of accurate vestibular, visual, and proprioceptive information is crucial in managing the centre of mass in relation to the base of support during gait. Therefore, bilateral loss of peripheral vestibular function can be highly debilitating when performing activities of daily life. To further investigate the influence of an impaired peripheral vestibular system on gait stability, spatiotemporal parameters, step-to-step variability, and mechanical stability parameters were examined in 20 patients with bilateral vestibulopathy and 20 matched healthy controls during preferred overground walking. Additionally, using a partial least squares analysis the relationship between spatiotemporal parameters of gait and the margins of stability was explored in both groups. Patients with bilateral vestibulopathy showed an increased cadence compared to healthy controls (121 ± 9 vs 115 ± 8 steps/min; p = 0.02; d = 0.77). In addition, although not significant (p = 0.07), a moderate effect size (d = 0.60) was found for step width variability (Coefficient of Variation (%); Bilateral vestibulopathy: 19 ± 11%; Healthy controls: 13 ± 5%). Results of the partial least squares analysis suggest that patients with peripheral vestibular failure implement a different balance control strategy. Instead of altering the step parameters, as is the case in healthy controls, they use the single and double support phases to control the state of the centre of mass to improve the mechanical stability.

Patients with bilateral vestibulopathy (BVP) present with unsteadiness during standing and walking, limiting their activities of daily life and, more importantly, resulting in an increased risk of falling. In BVP patients, falls are considered as one of the major complications, with patients having a 31-fold increased risk of falling compared to healthy subjects. Thus, highlighting objective measures that can easily and accurately assess the risk of falling in BVP patients is an important step in reducing the incidence of falls and the accompanying burdens. Therefore, this study investigated the interrelations between demographic characteristics, vestibular function, questionnaires on self-perceived handicap and balance confidence, clinical balance measures, gait variables, and fall status in 27 BVP patients. Based on the history of falls in the preceding 12 months, the patients were subdivided in a “faller” or “non-faller” group. Results on the different outcome measures were compared between the “faller” and “non-faller” subgroups using Pearson's chi-square test in the case of categorical data; for continuous data, Mann–Whitney U test was used. Performances on the clinical balance measures were comparable between fallers and non-fallers, indicating that, independent from fall status, the BVP patients present with an increased risk of falling. However, fallers tended to report a worse self-perceived handicap and confidence during performing activities of daily life. Spatiotemporal parameters of gait did not differ between fallers and non-fallers during walking at slow, preferred, or fast walking speed. These results may thus imply that, when aiming to distinguish fallers from non-fallers, the BVP patients' beliefs concerning their capabilities may be more important than the moderately or severely affected physical performance within a clinical setting. Outcome measures addressing the self-efficacy and fear of falling in BVP patients should therefore be incorporated in future research to investigate whether these are indeed able to distinguish fallers form non-fallers. Additionally, information regarding physical activity could provide valuable insights on the contextual information influencing behavior and falls in BVP.