Histological evaluation of ischemic alterations in donors after cardiac death: A useful tool to predict post-transplant renal function.

Kidneys retrieved from donors after cardiac death (DCD) pose significant challenges from a clinical and technical point of view, undergoing a variable degree of ischemia-reperfusion injury. At present, the utilization of kidneys is assessed according to the Karpinski score, which does not take into account the ischemic insult and does not predict the functional recovery of the organ once transplanted. Therefore, the correlation between biopsy results and post-transplant graft function is still debated. In this study we examined kidney biopsies from DCD donors; we calculated the Karpinski score and subsequently identified and quantified the ischemic lesions in the glomerular, interstitial, and tubular compartments. These same lesions were quantified in kidney biopsies from donors after brain death (DBD) in a case-control analysis. The collected data were correlated with the clinical data of the donors and the post-transplant follow-up. Proximal tubule alterations are crucial in ischemia-reperfusion damage, showing precise histological alterations, which are more frequent in DCD than in DBD donors and are statistically correlated with functional recovery of the organ. Quantification of ischemic tubular lesions in biopsies of kidneys from DCD donors is a useful tool for predicting post-transplant renal function and a valid parameter for assessing the quality of the graft.

Donation after circulatory death and liver transplantation: a cohort study.

Donations after circulatory death (DCD) are still challenging in Italy because of prolonged ischemia time (tWIT) due to the law and logistical issues. This cohort study was primarily aimed at assessing the association between successful transplantation and DCD types in the North Italy Transplant program. Adjusted risk ratios (RR) and 95% confidence intervals (CIs) for type III versus type II DCD were estimated using a Poisson regression model with a robust error variance. All consecutive DCD between 2008 and 2020 were included. Among 142 DCD, 102 were eligible for liver donation, and 96 were proposed: 68/69 (99%) and 28/33 (85%) type III and II DCD, respectively. Sixty-nine livers were recovered, 51/68 (75%) from type III and 18/28 (64%) from type II DCD, respectively (RR: 1.18; 95% CI: 0.87-1.60). After ex-vivo perfusion, 50/68 (74%) and 14/28 (50%) livers from type III and type II DCD were transplanted (RR: 1.49; 95% CI: 1.01-2.19). The estimate decreased after further controlling for tWIT (RR: 1.11; 95% CI: 0.55-2.24). Five patients (7.8%) experienced a PNF, 3/50 and 2/14 from type III and type II DCD, respectively. Type III DCD livers were more likely to be transplanted than type II. Warm ischemia time might explain this difference.

Breaking the ice to improve motor outcomes in patients with chronic stroke: a retrospective clinical study on neuromodulation plus robotics.

BACKGROUND: Stroke is one of the main causes of impairment affecting daily activities and quality of life. There is a growing effort to potentiate the recovery of functional gait and to enable stroke patients to walk independently. AIM: To estimate the effects of dual-site transcranial direct current stimulation (dstDCS) on gait recovery in chronic stroke patients provided with robot-aided gait training (RAGT). METHODS: Thirty-seven patients were included in this retrospective clinical study. Nine patients were provided with dstDCS during the first 10 min of RAGT by using Lokomat®Pro (on-RAGT), 15 patients immediately after RAGT (post-RAGT), and 13 patients immediately before RAGT (pre-RAGT). RESULTS: Each group improved over time concerning disability burden and lower limb strength. on-RAGT and post-RAGT experienced better improvement in balance (p < 0.001) and, moderately, gait endurance (p = 0.04) as compared to pre-RAGT. Furthermore, all treatments decreased the facilitation of the unaffected hemisphere (p < 0.001) and the inhibition of the affected hemisphere (p < 0.001). The duration of such aftereffects was found to be greater for post-RAGT. DISCUSSION AND CONCLUSION: This is the first trial with dstDCS coupled with RAGT in chronic stroke patients with gait impairment. When timely coupled with RAGT, dstDCS may be considered an effective tool for the recovery of lower limb function in patients with first unilateral stroke in the chronic phase. Moreover, our data suggest the ductility of dstDCS concerning RAGT timing, thus making this intervention suitable in a neurorehabilitation setting and well adaptable to patients' needs.

Perceived well-being and mental health in haemophilia.

The investigation of mental health among persons with haemophilia is mostly focused on negative and disease-related indicators. Literature however shows that psychosocial resources and optimal daily functioning can co-exist with chronic disease. The Dual Continua Model operationalizes positive mental health as 'flourishing', a condition comprising emotional, psychological, and social well-being dimensions. In the present study physical and mental health were comparatively assessed through positive and negative indicators in adults with haemophilia and a control group. Participants included 84 Italian persons with severe haemophilia (Mage = 43.44; SDage = 13.04) and 164 adults without history of chronic illness (Mage = 40.98; SDage = 12.26), who completed the Short Form Health Survey, the Positive and Negative Affect Schedule, and the Mental Health Continuum Short Form. MANOVA and post-hoc t-tests provided evidence of worse general health, lower negative affect and higher psychological well-being among participants with haemophilia compared with the control group. Moreover, the percentage of flourishing individuals was higher among participants with haemophilia. Results support previous evidence suggesting that a chronic disease does not prevent mental well-being attainment. The identification of assets and strengths allowing people with haemophilia to flourish can be fruitfully used to design resource-centered interventions.

Can robotic gait rehabilitation plus Virtual Reality affect cognitive and behavioural outcomes in patients with chronic stroke? A randomized controlled trial involving three different protocols.

BACKGROUND: The rehabilitation of cognitive and behavioral abnormalities in individuals with stroke is essential for promoting patient's recovery and autonomy. The aim of our study is to evaluate the effects of robotic neurorehabilitation using Lokomat with and without VR on cognitive functioning and psychological well-being in stroke patients, as compared to traditional therapy. METHODS: Ninety stroke patients were included in this randomized controlled clinical trial. The patients were assigned to one of the three treatment groups, i.e. the Robotic Rehabilitation group undergoing robotic rehab with VR (RRG+VR), the Robotic Rehabilitation Group (RRG-VR) using robotics without VR, and the Conventional Rehabilitation group (CRG) submitted to conventional physiotherapy and cognitive treatment. RESULTS: The analysis showed that either the robotic training (with and without VR) or the conventional rehabilitation led to significant improvements in the global cognitive functioning, mood, and executive functions, as well as in activities of daily living. However, only in the RRG+VR we observed a significant improvement in cognitive flexibility and shifting skills, selective attention/visual research, and quality of life, with regard to the perception of the mental and physical state. CONCLUSION: Our study shows that robotic treatment, especially if associated with VR, may positively affect cognitive recovery and psychological well-being in patients with chronic stroke, thanks to the complex interation between movement and cognition.

Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A.

The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors.

Theta burst stimulation for the treatment of obsessive-compulsive disorder: a pilot study.

A non-negligible part of patients with obsessive-compulsive disorder (OCD) experiences inadequate response to pharmacological and cognitive therapies. Therefore, new approaches are required to overcome this problem. The present pilot study estimates the capacity of theta burst stimulation (TBS) in reducing OCD symptoms, also focusing on the neurophysiological basis of TBS aftereffects. Ten patients with OCD who were unsatisfactorily responsive to the pharmacological and neuropsychological treatment, participated to the present randomized crossover pilot study, in which they were subjected to a real or sham intermittent TBS (iTBS) paradigm over the left dorsolateral prefrontal cortex (L-DLPFC) as add-on treatment. They were randomly assigned to a real or sham iTBS in a 1:1 allocation ratio. Patients received the TBS treatment every morning, 5 days a week for 1 month, and were clinically and electrophysiologically evaluated (EEG phase synchronization and coherence) before, immediately after (T0), and one (T1), three (T3) and six (T6) months after the end of the TBS treatment. Then, each patient was subjected to the alternative treatment (that was not practiced before), and followed up to 6 months. We found that all the patients improved in OCD symptomatology up to T1, while four among them improved up to T3. These patients were those showing a more extensive reshape of frontal areas phase synchronization and frontoparietal coherence compared to the other participants. Our pilot study suggests that iTBS over L-DLPFC may represent a feasible approach to improve OCD symptoms. The efficacy of iTBS seems to depend on the extent of frontal and frontoparietal connectivity modulation.

Toward Improving Poststroke Aphasia: A Pilot Study on the Growing Use of Telerehabilitation for the Continuity of Care.

BACKGROUND: Aphasia is a quite common and very disabling symptom following stroke, negatively affecting patient's quality of life. Aim of the study is to evaluate the effectiveness of a rehabilitation training for aphasia that employ a touch-screen tablet using a virtual reality rehabilitation system (VRRS-Tablet). MATERIAL AND METHODS: Thirty patients with aphasia due to ischemic or hemorrhagic stroke were randomized into either the control or the experimental group and assessed by means of a specific neuropsychological evaluation. The study lasted 6 months and included 2 phases. During the former, the experimental group underwent an experimental linguistic treatment performed using the VRRS-Tablet, while the control group was trained with a traditional linguistic treatment. In the latter, the control groups were delivered to territorial services, while the experimental group was provided with the VRRS-Tablet. RESULTS: The experimental group improves in all the investigated areas, except for writing, while the control group only improves in comprehension, depression, and quality of life. CONCLUSIONS: Our study has demonstrated the effectiveness of a home-based telerehabilitation program specific for poststroke aphasia. The use of telerehabilitation by means of VRRS-Tablet could be one of the best solutions to treat aphasic patients after their discharge, promoting continuity of care by monitoring functional outcomes, maintaining preserved abilities, reducing depression, and improving linguistic functions, besides the psychological well-being.

Bridging the Gap Towards Awareness Detection in Disorders of Consciousness: An Experimental Study on the Mirror Neuron System.

Advanced functional neuroimaging approaches dealing with motor imagery have disclosed covert cognitive processes in patients with disorders of consciousness (DoC). However, motor impairment and cognitive-motor dissociation can bias such approaches. Fourteen patients with post-traumatic DoC and ten healthy controls (HC) were provided with three motor tasks related to mirror neuron system (MNS) activation (movement observation, movement execution, and passive motor imagery of a movement) while recording electroencephalographic (EEG) metrics [EEG power and Granger Casualty Index (GCI)] to detect residual signs of conscious awareness. The most relevant finding was that all HCs, all patients with Minimally Conscious State and one with Unresponsive Wakefulness Syndrome demonstrated an event-related synchronization in the gamma range over left frontal regions, with high GCI values, in the passive motor imagery condition. These data significantly correlated with the level of behavioral responsiveness measured by the Coma Recovery Scale-Revised. Thus, our findings may indicate that motor tasks related to MNS can activate frontoparietal networks, although leading to different conscious processes. Hence, MNS assessment can be usefully employed to differentiate among patients with DoC.

Audiomotor Integration in Minimally Conscious State: Proof of Concept!

Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment.

Enhancing the Quality of Life of Patients with Multiple Sclerosis: Promising Results on the Role of Cognitive Tele-Rehabilitation Plus Virtual Reality.

(1) Background: Patients with multiple sclerosis often face obstacles accessing traditional rehabilitation programs, primarily due to mobility limitations. Tele-rehabilitation (TR) is seen as a promising solution to overcome these barriers, though its precise influence on patients' quality of life (QoL) has not been thoroughly investigated. Thus, the aim of the present study was to assess the feasibility of a cognitive TR in a sample of Italian patients with MS. (2) Methods: Thirty-six patients diagnosed with MS, attending the Robotic and Behavioral Neurorehabilitation Unit of the IRCCS "Bonino-Pulejo" Neurolesi Center in Messina, Italy, between October 2019 and March 2020 were enrolled in the study. All patients were randomly assigned, using block randomization with a block size of 2 × 2, to two groups: the control group (CG), composed of 16 patients who received traditional cognitive training, and the experimental group (EG), composed of 20 patients who underwent TR training with a VRRS (virtual reality rehabilitation system). Each patient underwent an assessment before (T0) and immediately after (T1) the rehabilitation treatment, using the Quality of Life-54 Multiple Sclerosis (MSQoL-54). (3) Results: Only in the EG, we observed a statistically significant improvement in the QoL related to mental well-being following the paired T-test (MSQoL p-value < 0.001). Notably, no significant differences were found in the CG (MSQoL p-value of 0.67). (4) Conclusions: Our data suggest that TR training combined with VR has the potential to improve the well-being of individuals with MS.

Healthcare worker burnout during the first COVID-19 lockdown in Italy: experiences from an intensive neurological rehabilitation unit.

OBJECTIVE: The study aim was to investigate the prevalence of behavioral symptoms and burnout in healthcare workers in an intensive neurological rehabilitation unit in Messina, Italy, during the first COVID-19 lockdown in Italy. METHODS: Forty-seven healthcare workers (including neurologists, physiatrists, nurses and rehabilitation therapists) were enrolled in this cross-sectional study from February 2020 to June 2020. Participants were administered the following psychometric tests to investigate burnout and related symptoms: the Maslach Burnout Inventory, which measures emotional exhaustion, depersonalization and reduced personal accomplishment; the Zung Self-Rating Depression Scale (SDS); the Pre-Sleep Arousal Scale (PSAS); the Dyadic Adjustment Scale; and the Buss-Perry Aggression Questionnaire (BPAQ). RESULTS: We found several correlations between test scores and burnout subdimensions. Emotional exhaustion was correlated with SDS (r = 0.67), PSAS-Cognitive (r = 0.67) and PSAS-Somatic (r = 0.70) scores, and moderately correlated with all BPAQ dimensions (r = 0.42). Depersonalization was moderately correlated with SDS (r = 0.54), PSAS-Cognitive (r = 0.53) and PSAS-Somatic (r = 0.50) scores. CONCLUSION: During the first COVID-19 lockdown in Italy, healthcare workers were more exposed to physical and mental exhaustion and burnout. Research evaluating organizational and system-level interventions to promote psychological well-being at work for healthcare workers are needed.

Relationship between advanced oxidation protein products, advanced glycation end products, and S-nitrosylated proteins with biological risk and MDR-1 polymorphisms in patients affected by B-chronic lymphocytic leukemia.

The aim of our study was to analyze the serum levels of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs), and protein nitrosylation in patients with B-chronic lymphocytic leukemia (B-CLL). AOPPs, AGEs, and S-nitrosylated were increased in B-CLL patients. The mutation of IgVH gene, CD 38, and Zap 70 expression were not associated with increased oxidative stress. The mutant 2677GT genotype was found to be associated with higher AGEs levels with respect to wild-type genotype, while as far the C3435T MDR1 polymorphism is concerned, subjects presenting wild-type genotype showed higher values of AOPPs with respect to heterozygous genotype. Our results suggest that B-CLL is associated with oxidative stress.

Increase of novel biomarkers for oxidative stress in patients with plasma cell disorders and in multiple myeloma patients with bone lesions.

OBJECTIVES: Protein oxidation plays a key role in the pathogenesis of oncological diseases. In this study, we analyzed the oxidative stress in untreated multiple myeloma (MM) patients and in patients affected by monoclonal gammopathy of uncertain significance (MGUS). METHODS: We evaluated serum levels of advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and protein nitrosylation in patients with monoclonal gammopathy and in control subjects. RESULTS: Serum levels of AOPPs and S-nitrosylated proteins were significantly increased in MM patients in comparison to controls and to MGUS subjects. Moreover, in MM patients the levels of AOPPs, AGEs and S-nitrosylated proteins were significantly higher in patients with bone lesions compared with those without lytic bone lesions. CONCLUSIONS: MM is closely associated with oxidative stress and further investigation might provide an insight to understand a putative causal link between oxidative stress and MM disease onset and progression or MM complications.

Imatinib mesylate therapy induces reduction in neutrophil gelatinase-associated lipocalin serum levels and increase in leptin concentrations in chronic myeloid leukemia patients in molecular remission.

The aim of the present study was to determine serum levels of neutrophil gelatinase-associated lipocalin (NGAL) and leptin in patients with chronic myeloid leukemia (CML) at diagnosis and after imatinib therapy when patients achieved a complete molecular remission. The study was conducted on 22 patients with CML in the chronic phase and 10 healthy subjects. The median serum NGAL levels in CML patients at diagnosis were significantly higher compared to age-matched controls. After imatinib therapy, all patients achieved complete molecular remission and NGAL levels decreased and were found significantly lower with respect to the baseline. No significant correlations were found between NGAL levels and other disease parameters. Before imatinib therapy, the median blood leptin levels were not significantly different from those of controls. After therapy with imatinib, all patients in molecular remission presented an increase in leptin levels. Future research is eagerly awaited as it may demonstrate the real role of NGAL and leptin in the onset and progression of CML.

Immunomodulatory drugs in multiple myeloma: from molecular mechanisms of action to clinical practice.

Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as "immunomodulatory drugs" (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.

Successful management with intravenous immunoglobulins in alemtuzumab-induced acute inflammatory demyelinating neuropathy: clinical report of three patients.

Several neurological complications have been associated with the use of monoclonal antibodies (mAbs), and demyelinating disorders have been estimated to affect the 0.02-0.20% of treated patients. Alemtuzumab is a humanized chimeric mAbthat targets the CD52 antigen, it is currently approved for relapsed/refractory and high-risk untreated chronic lymphocytic leukemia (CLL). The major complication of alemtuzumab therapy is the increased risk of opportunistic infections secondary to the profound immunosuppression. Autoimmune diseases as Graves disease, immune thrombocytopenic purpura and Good pasture syndrome, have been reported to be associated to the treatment. In the present report, we present three CLL patients developing acute inflammatory demyelinating neuropathy during treatment with alemtuzumab. Despite the severity of the complication, all the patients showed an univocal good clinical response after treatment with intravenous immunoglobulin (IVIG). As alemtuzumab represents, nowadays, a key therapeutic option for CLL, clinicians should be aware of this rare and disabling toxicity.

Etching and Doping of Pores in Polyethylene Terephthalate Analyzed by Ion Transmission Spectroscopy and Nuclear Depth Profiling.

This work is devoted to the study of controlled preparation and filling of pores in polyethylene terephthalate (PET) membranes. A standard wet chemical etching with different protocols (isothermal and isochronous etching for different times and temperatures and etching from one or both sides of the films) was used to prepare the micrometric pores. The pores were filled with either a LiCl solution or boron deposited by magnetron sputtering. Subsequent control of the pore shape and dopant filling was performed using the nuclear methods of ion transmission spectroscopy (ITS) and neutron depth profiling (NDP). It turned out that wet chemical etching, monitored and quantified by ITS, was shown to enable the preparation of the desired simple pore geometry. Furthermore, the effect of dopant filling on the pore shape could be well observed and analyzed by ITS and, for relevant light elements, by NDP, which can determine their depth (and spatial) distribution. In addition, both non-destructive methods were proven to be suitable and effective tools for studying the preparation and filling of pores in thin films. Thus, they can be considered promising for research into nanostructure technologies of thin porous membranes.

Demonstration of an intense lithium beam for forward-directed pulsed neutron generation.

As an alternative to research nuclear reactors, a compact accelerator-driven neutron generator that uses a lithium beam driver could be a promising candidate since it produces almost no undesired radiation. However, providing an intense lithium-ion beam has been difficult, and it has been thought that the practical application of such a device would be impossible. The most critical problem of insufficient ion fluxes has been solved by applying a direct plasma injection scheme. In this scheme, a pulsed high-density plasma from a metallic lithium foil generated by laser ablation is efficiently injected and accelerated by a radio-frequency quadrupole linear accelerator (RFQ linac). We have obtained a peak beam current of 35 mA accelerated to 1.43 MeV, which is two orders of magnitude higher than a conventional injector and accelerator system can deliver.

Toward improving functional recovery in spinal cord injury using robotics: a pilot study focusing on ankle rehabilitation.

BACKGROUND: Conventional physical therapy interventions are strongly recommended to improve ambulation potential and upright mobility in persons with incomplete spinal cord injury (iSCI). Ankle rehabilitation plays a significant role, as it aims to stem drop foot consequences. RESEARCH QUESTION: This pilot study aimed to assess the neurophysiological underpinnings of robot-aided ankle rehabilitation (using a platform robot) compared to conventional physiotherapy and its efficacy in improving gait performance and balance in persons with iSCI. METHODS: Ten individuals with subacute/chronic iSCI (six males and four females, 39 ± 13 years, time since injury 8 ± 4 months, ASIA impairment scale grade C-D) were provided with one-month intensive training for robot-aided ankle rehabilitation (24 sessions, 1 h daily, six times a week). Clinical (10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), and Timed Up and Go test (TUG)), and electrophysiological aftereffects (surface-EMG from tibialis anterior and medial gastrocnemius muscles to estimate muscle activation patterns; and corticomuscular coherence-CMC-to assess functional synchronization between sensorimotor cortex and muscles, i.e. the functional integrity of corticospinal output) were assessed at baseline (PRE) and after the trial completion (POST). The experimental group (EG) data were compared with those coming from a retrospective control group (CG; n = 10) matched for clinical-demographic characteristics, who previously underwent conventional ankle rehabilitation. RESULTS: the EG achieved a greater improvement in balance and gait as compared to the CG (TUG EG from 70 ± 18 to 45 ± 15 s, p = 0.002; CG from 68 ± 21 to 48 ± 18 s, p = 0.01; group-comparison p = 0.001; 10MWT EG from 0.43 ± 0.11 to 0.51 ± 0.09 m/s, p = 0.006; CG from 0.4 ± 0.13 to 0.45 ± 0.12, p = 0.01; group-comparison p = 0.006; 6 MWT EG from 231 ± 13 to 274 ± 15 m, p < 0.001; CG from 236 ± 13 to 262 ± 15 m, p = 0.003; group-comparison p = 0.01). Furthermore, the EG showed a retraining of muscle activation (an increase within proper movements, with a reduction of co-contractions) and CMC (beta frequency increase within proper movements, i.e. in a framework of preserved motor coordination). The improvements in CMC, gait, balance, and muscle activation were not correlated with each other. CONCLUSIONS: Robot-aided ankle rehabilitation improved gait performance by selectively ameliorating CMC, muscle activation patterns, and, lastly, gait balance and speed. Despite CMC, gait, balance, and muscle activation were not correlated, this pilot study suggests that robot-aided ankle rehabilitation may favor a better communication between above-SCI and below-SCI structures. This communication improvement may depend on a more synchronized corticospinal output (as per CMC increase) and a better responsiveness of below-SCI motorneurons to corticospinal output (as per specific and ankle movement focused muscle activation increases at the surface EMG), thus favoring greater recruitment of spinal motor units and, ultimately, improving muscle activation pattern and strength. SIGNIFICANCE: Adopting robot-aided ankle rehabilitation protocols for persons with iSCI in the subacute/chronic phase may allow achieving a clinically significant improvement in gait performance.