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The Economy of action hypothesis postulates that bodily states rescale the perception of the individual's environment's spatial layout. The estimation of distances and slopes in navigation space (i.e. the space reachable by locomotion) is influenced by sensations relating to body condition and the metabolic cost of the actions. The results of the studies investigating the impact of pain on distance estimation remain inconclusive. 28 women suffering from chronic pain and fibromyalgia (FM), and 24 healthy women (HC) were assessed for musculoskeletal, neuropathic, and visceral pain by means of the Widespread Pain Index, the Symptom Severity Scale and an ad-hoc devised questionnaire for pain (the Verona Pain Questionnaire). In a VR-mediated task, they observed a 3D scenario and estimated the distance of a flag positioned at different distances (1, 2, 3, 4 or 5 m) on virtual ramps with either a 4% or 24% inclination in two different conditions: sitting and standing. Overestimation of distances in the steeper ramp condition was expected, if participants executed the task by internally simulating the movement. The results showed a dissociation between the effects of musculoskeletal and visceral-neuropathic pain on distance estimations. While, according to the Economy of Action hypothesis, the HCs estimated the distances as being farther away when the ramp was more inclined (i.e. with a 24% inclination), there was no effect related to the different ramp inclinations in the FM group. Furthermore, visceral and neuropathic pain were found to affect the performance of the FM group. These results suggest that chronic and widespread pain conditions, that typically characterize fibromyalgia, can affect space representations. In line with the Economy of Action hypothesis, bodily based estimation of distances is compromised in these patients., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The authors report there are no competing interests to be declared.

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Advances in resuscitation techniques have resulted in more patients surviving cardio-circulatory arrest (CA) and consequently developing hypoxic/anoxic brain damage. The aim of this study is to evaluate the role of PET/CT (Positron Emission Tomography/Computerized Tomography scan) with F-18 FDG (F-18 fluorodeoxyglucose) during the early rehabilitative hospitalization phase in determining the V/C (Vermis/Cerebellar) ratio as a prognostic index to predict patient outcome, as defined by clinical evaluation scales., Methods: This is a single-center retrospective study of 37 consecutive adult patients admitted to the neurorehabilitation center between January 2011 and June 2019. Functional status was measured by the following clinical scales: FIM (Functional Indipendence Measure), LCFS (Levels of Cognitive Functioning Scale), GOS (Glasgow Outcome Scale) and CRS-R (Coma Recovery Scale-Revised). PET/CT with F-18 FDG as a functional imaging technique was used to calculate the V/C ratio as a ratio between the metabolism of the vermis and of the Cerebellar Hemisphere., Results: A statistically significant correlation was observed between the V/C ratio and the delta values (difference between discharge and admission value) for each clinical evaluation scale (Delta FIM: P=0.0014; Delta LCFS P=0.0003). A statistically significant difference was observed between the V/C ratio of patients with LCFS ≥4 that showed an improved outcome (defined as an improvement of at least two points in LCFS), and that of patients with LCFS <4 that did not improve (P=0.0011). A V/C ratio cut-off of 1.5 corresponded with a positive predictive power of 80% and a negative predictive power of 82%; a value <1.5 predicted a better outcome., Conclusions: Clinical evaluation scales when associated with F-18 FDG PET/CT measurement of metabolism, provide a more reliable prognosis. This allows for more focused rehabilitation treatment and better management of family members' expectation.

Spasticity is a clinical condition secondary to central nervous system damage, which impairs patients' mobility and quality of life. Stereotactic radiosurgery (SRS) to the spinal roots responsible of the spasms might represent a non-invasive therapy. The present are the preliminary results of the first clinical use of this novel technique., Competing Interests: Conflicts of interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The disabling effects of traumatic brain injuries (TBI) present a significant healthcare concern to developed countries. In order to achieve a reliable prognosis, validated assessment scales are used to monitor the cognitive outcome, like the Level of Cognitive Functioning Scale, or the overall functional outcome, namely the Functional Independence Measure and Glasgow Outcome Scale. The aim of our study was to evaluate the role of Level of Cognitive Functioning Scale (LCF) as an outcome prognostic index in patients with TBI., Materials and Methods: Fifty-four patients with TBI with a mean age of 44.9 years (SD 20.915) were enrolled in this retrospective study. Patients were evaluated at admission and at discharge using the Glasgow Outcome Scale, Functional Independence Measure, and Level of Cognitive Functioning Scale. The Glasgow Outcome Scale was also implemented at 6 months after discharge (OUTCOME.GOS), whereas the LCF was used twice a week throughout hospitalization. For our purpose, we named LCF at admission LCFa, whereas permanence in the same LCF value (number of days), LCFaL., Results: Δ.GOS, Δ.FIM (Δ = difference between value at discharge and at admission), and OUTCOME.GOS were significantly affected by age, length of stay, LCFa, and LCFaL., Conclusion: The LCF can give a valuable indication to the prognosis of patients with TBI besides monitoring changes in cognitive function. This allows for individual rehabilitation plan, and long-term management strategies could be developed more quickly upon patient's discharge. Consequently, valuable healthcare and social care resources could be assigned correctly.

Hand erosive osteoarthritis (HEOA) and Psoriatic Arthritis (PsA) with DIP involvement are common diseases affecting the hand. Both of them evolve with a progressive limitation in grip due to limited range of motion of the affected joints and stenosing tenosynovitis. Pharmacological options currently available (corticosteroids and clodronate or Idrossicloroquine) for the treatment of EHOA are mostly symptomatic and currently there are no effective drugs able to modify the course of the disease. In addition, data on drug effectiveness of PsA with DIP involvement are lacking. Conservative therapy should be considered in order to reduce pain and improve hand functionality. There are many studies debating a wide range of non-pharmacological intervention in the management of HEOA: joint protection program, range of motion and strengthening exercise, hand exercise with electromagnetic therapy, application of heat with paraffin wax or balneotherapy, occupational therapy and education. Concerning conservative treatment strategies to treat PsA, on the contrary, current evidence is still weak. Further research is needed to find the correct place of physical therapy to prevent stiffness and ankylosis due to the vicious circle of inflammation-pain-immobility-rigidity.

Aim : to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies.. Design: Multi-center cross-sectional observational study. Setting : 23 intensive neurorehabilitation units. Subjects : 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury. Main Measures : Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications. Results : patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology. Conclusion : overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

In a patient suffering from tactile agnosia a comparison was made (using the ABABAB paradigm) between three blocks of neuropsychological rehabilitation sessions involving off-line anodal transcranial direct current stimulation (anodal-tDCS) and three blocks of rehabilitation sessions without tDCS. During the blocks with anodal-tDCS, the stimulation was administered in counterbalanced order to two sites: i) the perilesional parietal area (specific stimulation) and ii) an occipital area far from the lesion (nonspecific stimulation).Rehabilitation associated with anodal-tDCS (in particular in the perilesional areas) is more efficacious than without stimulation.

Recent studies on recovery of consciousness of subjects in a vegetative state (VS) admitted to rehabilitation units have focused mainly on the identification of prognostic factors, whereas few studies have focused on outcome. The aim of this study was to compare demographic and clinical data and report functional outcome of patients in a VS due to severe acquired brain injury (ABI) of different aetiologies. The study was a retrospective multicentre cohort study and involved 492 patients in a VS due to traumatic (TBI) or non-traumatic (NTBI) severe ABI admitted to 29 Italian rehabilitation units. Demographic and clinical data recorded included age, gender, aetiology, Glasgow Coma Scale score; onset-to-admission interval; length of stay in the rehabilitation unit; the department from which they were referred; and the presence of percutaneous endoscopic gastrostomy or tracheostomy. Recovery of consciousness and disability were evaluated using a discharge Disability Rating Scale. At discharge, 53.11% patients had emerged from VS, with TBI subjects significantly more likely to recover consciousness than NTBI ones. Subjects with NTBI had a significantly worse prognosis than those with TBI, and within the NTBI group, subjects with a cerebrovascular aetiology had a better outcome than those with an anoxic aetiology. Among the patients who emerged from VS, 71.30% of TBI and 83.06% of NTBI subjects presented extremely severe disability. Only 37.93% of subjects affected by TBI and 17.44% of those affected by NTBI who presented extremely severe disability returned home after their rehabilitation stay. Even though almost a half of the patients emerged from VS, a large number of these subjects showed severe disability, often making it impossible for them to return home. This situation has a major impact on the healthcare system.

Objective: Rheumatoid arthritis (RA), one of the most frequent chronic inflammatory rheumatic disorders, is characterized by the presence of autoantibodies and joint infiltration by activated immune cells, leading to cartilage and bone destruction. IgA occurs predominantly as monomers (mIgA) in plasma and regulates many cell responses through interaction with the Fcα receptor type I (FcαRI). FcαRI targeting by anti-FcαRI Fab inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) configuration through SH2 domain-containing phosphatase 1 (SHP-1) recruitment. The aim of this study was to investigate the potential utility of mIgA for the treatment of arthritis by acting as an inducer of ITAMi signaling., Methods: The effect of plasma-derived human mIgA on inhibition of multiple heterologous receptors was evaluated on FcαRI+ cell transfectants, blood phagocytes from healthy individuals, and synovial cells from RA patients. FcαRI-transgenic mice and wild-type mice treated with mIgA were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The mice were assessed for development of arthritis using an arthritis score, and joint tissue samples were evaluated for the extent of leukocyte infiltration and expression of phosphatase., Results: Treatment with mIgA impaired cell activation in an FcαRI-FcRγ-dependent manner, involving ITAMi signaling. Human mIgA or anti-FcαRI Fab were strongly effective in either preventing or attenuating CAIA or CIA in FcαRI-transgenic mice. Administration of mIgA markedly inhibited the recruitment of leukocytes to the inflamed joints of mice, which was associated with induction of SHP-1 phosphorylation in joint tissue cells. Moreover, mIgA reversed the state of inflammation in the synovial fluid of RA patients by inducing an ITAMi configuration., Conclusion: These results demonstrate a therapeutic potential of human mIgA in experimental arthritis. The findings support future clinical exploration of mIgA for the treatment of RA., (© 2015, American College of Rheumatology.)

Rheumatoid arthritis-associated (RA-associated) inflammation is mediated through the interaction between RA IgG immune complexes and IgG Fc receptors on immune cells. Polymorphisms within the gene encoding the human IgG Fc receptor IIA (hFcγRIIA) are associated with an increased risk of developing RA. Within the hFcγRIIA intracytoplasmic domain, there are 2 conserved tyrosine residues arranged in a noncanonical immunoreceptor tyrosine-based activation motif (ITAM). Here, we reveal that inhibitory engagement of the hFcγRIIA ITAM either with anti-hFcγRII F(ab')2 fragments or intravenous hIgG (IVIg) ameliorates RA-associated inflammation, and this effect was characteristic of previously described inhibitory ITAM (ITAMi) signaling for hFcαRI and hFcγRIIIA, but only involves a single tyrosine. In hFcγRIIA-expressing mice, arthritis induction was inhibited following hFcγRIIA engagement. Moreover, hFcγRIIA ITAMi-signaling reduced ROS and inflammatory cytokine production through inhibition of guanine nucleotide exchange factor VAV-1 and IL-1 receptor-associated kinase 1 (IRAK-1), respectively. ITAMi signaling was mediated by tyrosine 304 (Y304) within the hFcγRIIA ITAM, which was required for recruitment of tyrosine kinase SYK and tyrosine phosphatase SHP-1. Anti-hFcγRII F(ab')2 treatment of inflammatory synovial cells from RA patients inhibited ROS production through induction of ITAMi signaling. These data suggest that shifting constitutive hFcγRIIA-mediated activation to ITAMi signaling could ameliorate RA-associated inflammation.

Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in mammals. The primary function of IgA is to maintain homeostasis at mucosal surfaces and play a role in immune protection. IgA functions mainly through interaction with multiple receptors including IgA Fc receptor I (FcαRI), transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcα/μR, FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating anti-inflammatory functions of IgA through two receptors, the FcαRI and DC-SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is able to mediate an inhibitory signal following the interaction with FcαRI. It results in partial phosphorylation of its FcRγ-ITAM and the recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition following the formation of intracellular clusters named inhibisomes. In contrast, cross-linking of FcαRI by multimeric ligands induces a full phosphorylation of the FcRγ-ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation. In addition, secretory IgA can mediate a potent anti-inflammatory function following the sugar-dependent interaction with SIGNR1 on dendritic cells which induces an immune tolerance via regulatory T cell expansion. Overall, the anti-inflammatory effect of serum and secretory IgA plays a crucial role in the physiology and in the prevention of tissue damage in multiple autoimmune and inflammatory diseases.

The human immunoglobulin A (IgA) plays a key role in immune protection. IgA is the second most prevalent antibody in the serum. IgA-deficient patients frequently develop autoimmune or inflammatory diseases. The IgA function is mainly mediated through its interaction with the myeloid IgA Fc receptor FcαRI (CD89). FcαRI, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing receptor, has a dual function in immunity. Monovalent targeting of FcαRI, by anti-FcαRI Fab or monomeric IgA, triggers potent inhibitory ITAM (ITAMi) signaling through the associated FcRγ chain. This results in a low-intensity signaling cascade promoting recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition of multiple types of activation signals. In contrast, cross-linking of FcαRI by multimeric ligand induces a high-intensity signaling pathway that leads to the recruitment of the tyrosine kinase Syk and to cell activation. Thus, FcαRI acts as a regulator, which mediates both anti- and pro-inflammatory functions of IgA depending on the type of interaction. This balance is of great importance to prevent tissue damage in immunopathology and to ensure the return of activated cells to a resting state. The role of the IgA-FcαRI interaction in the activation of different signaling pathways and its multifaceted role in immunity are discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Intravenous immunoglobulin (IVIg) has been used in the treatment of several autoimmune and inflammatory diseases. However, its mechanism of action remains incompletely understood. Here, we investigated the possibility that IVIg induces its anti-inflammatory effects through activating Fcγ receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM) in the FcRγ signaling adaptor. Recently, the concept of inhibitory ITAM (ITAMi) has emerged as a new means to negatively control the immune response. We found that interaction of FcRγ-associated mouse or human FcγRIII with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab')(2) reduced calcium responses, reactive oxygen species production, endocytosis, and phagocytosis, induced by heterologous activating receptors on monocyte/macrophages and FcγRIII(+) transfectants. Inhibition required the ITAMi configuration of the FcγRIII-associated FcRγ subunit and SHP-1 recruitment involving formation of intracellular "inhibisome" clusters containing FcγRIII, and the targeted heterologous activating receptor. IVIg as well as anti-FcγRIII treatments controlled the development of nonimmune mediated inflammation in vivo independently of FcγRIIB. These results demonstrate that circulating immunoglobulins (Ig)Gs are not functionally inert but act through continuous interaction with FcγRIII-inducing ITAMi signaling to maintain immune homeostasis. These data support a new mechanism of action for IVIg and demonstrate the therapeutic potential of FcγRIIIA targeting in inflammation.