Improving motor performance in Parkinson's disease: a preliminary study on the promising use of the computer assisted virtual reality environment (CAREN).

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by various motor symptoms including balance and gait impairment. Several studies have shown that physiotherapy, cueing techniques, treadmill training, and cognitive movement strategies are useful in improving balance and gait in patients with PD. Devices employing virtual reality (VR) have been shown to be promising in neurorehabilitation as they can provide the patients with multisensory stimulation creating a realistic environment and improve the motivation and the adhesion of patients to the rehabilitation program. This preliminary study is aimed at testing the efficacy and feasibility of gait training based on the computer-assisted virtual reality environment (CAREN) in a sample of PD. METHODS: In this preliminary study, 22 outpatients affected by PD who attended the Behavioral and Robotic Neurorehab Laboratory of the IRCCS Neurolesi between August 2017 and October 2018 were enrolled. All PD patients underwent 20 conventional physiotherapy sessions followed by 3-month of rest. Then, the patients were provided with 20 sessions of CAREN training. Gait and balance performances were rated before, after each training protocol, and 3 months later. Gait analysis was also performed before and after CAREN training. RESULTS: All patients completed both of the rehabilitation trainings without any adverse event. All considered scales improved significantly at the end of both rehabilitation treatments. However, patients presented with a greater clinical improvement after the CAREN training, compared with conventional physiotherapy. In particular, patients walked faster and with more stability, with wider, longer steps. CONCLUSIONS: Even though further neurophysiological details are required to identify the patients who may benefit from CAREN training, our findings suggest that this innovative device is an effective and feasible tool to train balance and gait in patients with PD.

Effects of robotic neurorehabilitation through lokomat plus virtual reality on cognitive function in patients with traumatic brain injury: A retrospective case-control study.

Background: Traumatic brain injury (TBI) is a clinical condition characterized by damage due to a mechanical physical event, which has a devastating impact on both the patient and his/her family. The purpose of this study is to evaluate the effects of robotic neurorehabilitation using Lokomat with virtual reality (VR) on attention processes and executive functions in patients with TBI.Materials and Methods: This is a retrospective case-control study. Fifty-six TBI patients have been included in the analysis, using an electronic recovery data system. The enrolled patients were divided into two groups: the experimental group (LPG) underwent rehabilitation training with Lokomat Pro, equipped with a VR screen, whereas the control group (LNG) performed rehabilitation training using Lokomat Nanos, without VR. The two groups matched for age, sex, education, brain lesions, interval from TBI. The rehabilitation protocol consisted of a total of 40 training sessions.Results: LPG and LNG had a significant improvement in mood and in the perception of physical well-being. However, only the LPG had a significant improvement in global cognitive, executive and attention functions. Furthermore, LPG presented a significant enhancement of the quality of life, with regard to the perception of the mental and physical state.Conclusion: Our study supports the idea that Lokomat is a useful tool in the rehabilitation of patients with TBI; in particular, the integration of the VR device can implement the cognitive and behavioral functions of TBI patients, enhancing also their physical and mental 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.

Shaping neuroplasticity by using powered exoskeletons in patients with stroke: a randomized clinical trial.

BACKGROUND: The use of neurorobotic devices may improve gait recovery by entraining specific brain plasticity mechanisms, which may be a key issue for successful rehabilitation using such approach. We assessed whether the wearable exoskeleton, Ekso™, could get higher gait performance than conventional overground gait training (OGT) in patients with hemiparesis due to stroke in a chronic phase, and foster the recovery of specific brain plasticity mechanisms. METHODS: We enrolled forty patients in a prospective, pre-post, randomized clinical study. Twenty patients underwent Ekso™ gait training (EGT) (45-min/session, five times/week), in addition to overground gait therapy, whilst 20 patients practiced an OGT of the same duration. All individuals were evaluated about gait performance (10 m walking test), gait cycle, muscle activation pattern (by recording surface electromyography from lower limb muscles), frontoparietal effective connectivity (FPEC) by using EEG, cortico-spinal excitability (CSE), and sensory-motor integration (SMI) from both primary motor areas by using Transcranial Magnetic Stimulation paradigm before and after the gait training. RESULTS: A significant effect size was found in the EGT-induced improvement in the 10 m walking test (d = 0.9, p < 0.001), CSE in the affected side (d = 0.7, p = 0.001), SMI in the affected side (d = 0.5, p = 0.03), overall gait quality (d = 0.8, p = 0.001), hip and knee muscle activation (d = 0.8, p = 0.001), and FPEC (d = 0.8, p = 0.001). The strengthening of FPEC (r = 0.601, p < 0.001), the increase of SMI in the affected side (r = 0.554, p < 0.001), and the decrease of SMI in the unaffected side (r = - 0.540, p < 0.001) were the most important factors correlated with the clinical improvement. CONCLUSIONS: Ekso™ gait training seems promising in gait rehabilitation for post-stroke patients, besides OGT. Our study proposes a putative neurophysiological basis supporting Ekso™ after-effects. This knowledge may be useful to plan highly patient-tailored gait rehabilitation protocols. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03162263 .

Self-Efficacy, Poststroke Depression, and Rehabilitation Outcomes: Is There a Correlation?

BACKGROUND: The sudden live changes of stroke survivors may lead to negative psychological and behavioral outcomes, including anxiety and depressive mood, which may compromise the rehabilitation process. Some personality features, such as self-efficacy, could play an important role in mediating the degree of post-stroke depression. Aim of this study is to investigate the possible correlation between specific psychological dimensions, such as poststroke depression and self-efficacy, and rehabilitation outcomes. MATERIALS AND METHODS: Thirty-eight patients, affected by stroke, completed a four-hour-daily training lasting up to 8 weeks, including traditional and robotic-assisted physiotherapy. Patients were assessed at admission (T0) and at the end (T1) of the motor training, by means of the Montgomery-Asberg Depression Scale, the General Self-Efficacy Scale, and the Functional Independent Measure. RESULTS: We observed a significant T0-T1 difference in MADRS scores in patients with a better functional recovery (t = 5.76; P < .0001) and higher self-efficacy (t = 4.74; P < .001), but no significant T0-T1 difference in individuals without functional recovery (t = 1.21; P = .239) and low self-efficacy (t = 1.72; P = .103). CONCLUSIONS: Our study shows that rehabilitation outcomes and self-efficacy may influence mood, but not vice versa. Thus, to potentiate self-efficacy in the rehabilitation setting may help clinicians in obtaining better functional outcomes, including depression reduction.

Is there a correlation between family functioning and functional recovery in patients with acquired brain injury? An exploratory study.

BACKGROUND: Acquired Brain injury (ABI) is a very critical event in a family, as it is a highly distressing and traumatic experience, imposing a very deep reorganization of the whole family. OBJECTIVE: This study aims to evaluate the possible correlation between the family aspects and the patients' functional outcomes after rehabilitation. METHODS: Fifteen patient-caregiver pairs were enrolled in the study. All the patients were assessed by using specific neuropsychological and functional scales, including the Family Adaptability and Cohesion Evaluation Scales, before and after treatment. RESULTS: The results reveal that when the caregiver is the son or the spouse (p = 0,71), the perception of the emotional and physical burden is stronger, while the scores related to the burden were lower in the presence of other kinds of relationship. The family functioning seems to be connected to the burden level for the caregivers. Furthermore, there is a significant correlation between the improvements observed in the patients during their rehabilitative training and the family dynamics. CONCLUSIONS: in our opinion, the family plays a key role in allowing a suitable compliance of the patient to the treatments, and supports the processes of adaptive reorganization.

The role of virtual reality in improving motor performance as revealed by EEG: a randomized clinical trial.

BACKGROUND: Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations. METHODS: Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention. RESULTS: As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and ß bands and larger fronto-central cortical activations in the affected hemisphere. CONCLUSIONS: The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance. TRIAL REGISTRATION: Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .

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.

Do patients with multiple sclerosis benefit from semi-immersive virtual reality? A randomized clinical trial on cognitive and motor outcomes.

Multiple sclerosis (MS) is a demyelinating disease of autoimmune originate. A large proportion of patient present with cognitive deficits that negatively affect their quality of life, thus, a proper cognitive rehabilitation is mandatory. The aim of this study is to evaluate the effect of semi-immersive virtual reality training (sVRT) on neuropsychological and motor recovery individuals suffering from MS. We enrolled 60 MS patients, randomized into either the control group (CG: 30) undergoing a conventional cognitive training, or the experimental group (EG: 30), which performed sVRT. Cognitive and motor outcomes were investigated through clinical and neuropsychological scales before (T0) and at the end (T1) of each different training. Only in the EG, we observed a significant improvement in cognitive parameters and motor scores. Our data demonstrate that VR cognitive training could potentiate MS patients' rehabilitation outcome, with positive results on both motor and cognitive performance.

Peri-Personal Space Tracing by Hand-Blink Reflex Modulation in Patients with Chronic Disorders of Consciousness.

The assessment of awareness in patients with chronic Disorders of Consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. The level of awareness impairment may depend on the degree of deterioration of the large-scale cortical-thalamo-cortical networks induced by brain injury. Electrophysiological approaches may shed light on awareness presence in patients with DoC by estimating cortical functions related to the cortical-thalamo-cortical networks including, for example, the cortico-subcortical processes generating motor responses to the perturbation of the peri-personal space (PPS). We measured the amplitude, latency, and duration of the hand-blink reflex (HBR) responses by recording electromyography (EMG) signals from both the orbicularis oculi muscles while electrically stimulating the median nerve at the wrist. Such a BR is thought to be mediated by a neural circuit at the brainstem level. Despite its defensive-response nature, HBR can be modulated by the distance between the stimulated hand and the face. This suggests a functional top-down control of HBR as reflected by HBR features changes (latency, amplitude, and magnitude). We therefore estimated HBR responses in a sample of patients with DoC (8 MCS and 12 UWS, compared to 15 healthy controls -HC) while performing a motor task targeting the PPS. This consisted of passive movements in which the hand of the subject was positioned at different distances from the participant's face. We aimed at demonstrating a residual top-down modulation of HBR properties, which could be useful to differentiate patients with DoC and, potentially, demonstrate awareness preservation. We found a decrease in latency, and an increase in duration and magnitude of HBR responses, which were all inversely related to the hand-to-face distance in HC and patients with MCS, but not in individuals with UWS. Our data suggest that only patients with MCS have preserved, residual, top-down modulation of the processes related to the PPS from higher-order cortical areas to sensory-motor integration network. Although the sample size was relatively small, being thus our data preliminary, HBR assessment seems a rapid, easy, and first-level tool to differentiate patients with MCS from those with UWS. We may also hypothesize that such a HBR modulation suggests awareness preservation.

Improving neuropsychiatric symptoms following stroke using virtual reality: A case report.

RATIONALE: Post-stroke cognitive impairment occurs frequently in patients with stroke, with a 20% to 80% prevalence. Anxiety is common after stroke, and is associated with a poorer quality of life. The use of standard relaxation techniques in treating anxiety in patients undergoing post-stroke rehabilitation have shown some positive effects, whereas virtual reality seems to have a role in the treatment of anxiety disorders, especially when associated to neurological damage. PATIENTS CONCERNS: A 50-year-old woman, smokers, affected by hypertension and right ischemic stroke in the chronic phase (i.e., after 12 months by cerebrovascular event), came to our observation for a severe anxiety state and a mild cognitive deficit, mainly involving attention and visuo-executive processes, besides a mild left hemiparesis. DIAGNOSIS: Anxiety in a patient with ischemic stroke. INTERVENTIONS: Standard relaxation techniques alone in a common clinical setting or the same psychological approach in an immersive virtual environment (i.e., Computer Assisted Rehabilitation Environment - CAREN). OUTCOMES: The patient's cognitive and psychological profile, with regard to attention processes, mood, anxiety, and coping strategies, were evaluated before and after the 2 different trainings. A significant improvement in the functional and behavioral outcomes were observed only at the end of the combined approach. LESSONS: The immersive virtual reality environment CAREN might be useful to improve cognitive and psychological status, with regard to anxiety symptoms, in post-stroke individuals.

Overground exoskeletons may boost neuroplasticity in myotonic dystrophy type 1 rehabilitation: A case report.

RATIONALE: Myotonic dystrophy type 1 (DM1) is a slowly progressive multisystem neuromuscular disease characterized by myotonia and muscle weakness and wasting of distal and axial muscles. People with DM1, due to the disease progression, are often concerned about their ability to carry out and participate in the activities of daily living. Rehabilitation approaches in DM1, including moderate-to-intense strength training, have shown not univocal efficacy to face such difficulties. Aim of this case-study was to demonstrate the effects of a combined approach by using conventional plus robotic training in rare neuromuscular diseases, such as DM1. PATIENT CONCERNS: A 46-year-old woman came to our observation complaining of difficulty in opening fist after strong voluntary muscle contraction for about 20 years. Over the years, she referred swallowing difficulties for solid foods, balance impairment complicated by tendency to stumble and falls, fatigability, hand muscle weakness with difficulty to open bottles and lifting weights, and daytime sleepiness DIAGNOSIS:: Paraparesis in DM1. INTERVENTIONS: The patient underwent 2 different trainings. The first period of treatment was carried out by using conventional physiotherapy, 6 times a week (twice a day) for 4 weeks. Then, she underwent a two-month specific task-oriented robotic rehabilitation training for the gait impairment using an overground exoskeleton, namely Ekso-GT, combined to the conventional therapy. OUTCOMES: The patient, after the EKSO training, gained a significant improvement in walking, balance and lower limbs muscle strength, as per 10-meter walking test and Left Lower Limb Motricity Index. Neurophysiological data (electroencephalography and surface electromyography) were also collected to more objectively assess the functional outcomes. LESSONS: Rehabilitation approaches in DM1, including moderate-to-intense strength training, have shown not univocal efficacy. Emerging and advancing robotic technologies can enhance clinical therapeutic outcomes by allowing therapists to activate and/or modulate neural networks to maximize motor and functional recovery.

Use of virtual reality in improving poststroke neglect: Promising neuropsychological and neurophysiological findings from a case study.

After experiencing a stroke in the right hemisphere, almost 50% of patients show unilateral spatial neglect (USN). Virtual Reality technologies offer impressive opportunities for both the rehabilitation and assessment of different cognitive deficits, including USN. A 57-year-old woman, affected by subarachnoid hemorrhage presented a severe left hemiparesis with severe cognitive and behavioral alterations, including temporal and spatial disorientation, reduction of attention and memory process, slowing ideation, USN, and depression of mood. She underwent two different rehabilitation trainings, including standard cognitive training (SCT) in addition to semi-immersive virtual training with her shadow (S-IVT_s) and SCT in addition to a Semi- immersive virtual training, without her shadow (S-IVT). The patient was assessed before and after each of the two different trainings, by using a specific psychometric battery and the event related potential, P300. Only at the end of the use of the S-IVT, we observed a significant improvement in the motor and cognitive function, with regard to USN. SCT in addition to S-IVT with Bts-Nirvana System may be a promising approach in improving attention process, spatial cognition, and mood in patients with post stroke USN, as also demonstrated by the electrophysiological parameters.

A novel use of virtual reality in the treatment of cognitive and motor deficit in spinal cord injury: A case report.

RATIONALE: Aim of this study is to evaluate the cognitive and motor outcomes after a combined rehabilitative training using a standard cognitive approach and virtual reality (VR), in a patient with spinal cord injury (SCI). PATIENT'S CONCERNS: A 60-year-old right-handed man, affected by incomplete cervical SCI, came to our observation for a moderate tetraparesis, mainly involving the left side, after about 6-months from the acute event. The neurological examination showed imbalance with upper limb incoordination, besides the paresis mainly involving the left side. At a neuropsychological evaluation, he presented important impairment in cognitive and behavioural status, with temporal and spatial disorientation, a reduction of attention and memory process, deficit of executive function and a severe depression of mood, which was not detected during the previous recovery. DIAGNOSIS: Motor and cognitive deficits in SCI. INTERVENTIONS: The patient was 1st submitted to standard cognitive training and traditional physiotherapy, and then to a combined therapeutic approach, in which virtual reality training was provided by means of the virtual reality rehabilitation system (VRRS, Khymeia, Italy). OUTCOMES: After the combined therapeutic approach with the VRRS training, we observed a significant improvement in different cognitive domains, a notable reduction of anxiety and depressive symptoms, as well as motor performance, and balance improvement. LESSONS: Virtual reality can be considered a promising tool for the rehabilitation of different neurological disorders, including patients with both motor and cognitive deficits following SCI.

Reducing the rate of misdiagnosis in patients with chronic disorders of consciousness: Is there a place for audiovisual stimulation?

BACKGROUND: The patients with chronic Disorders of Consciousness (DoC) mostly present with extremely challenging differential diagnosis. The advanced analysis of electroencephalographic (EEG) signals induced by brain stimulation paradigms may provide an appropriate approach to differentiate patients with DoC, besides the clinical assessment. OBJECTIVE: This study was performed with an objective of identifying residual brain network perturbations following an innovative, non-invasive audiovisual stimulation protocol, which could be related to behavioral responsiveness in patients with DoC. METHODS: The study comprised of ten healthy controls (HC), seven patients with Minimally Conscious State (MCS), and nine patients with Unresponsive Wakefulness Syndrome (UWS). Both synchronous as well as asynchronous transorbital and transauricolar alternating current were employed as stimuli and their effects were measured in terms of functional and effective connectivity. RESULTS: A more noticeable deterioration of long range connectivity patterns were found in patients with UWS than in those with MCS, with an exception of two patients with UWS, who showed connectivity values similar to those of MCS patients. CONCLUSION: The audiovisual stimulation paradigm used in the present study may be employed as a supportive bedside tool for improving the differential diagnosis in patients with DoC.

Breakthroughs in the spasticity management: Are non-pharmacological treatments the future?

The present paper aims at providing an objective narrative review of the existing non-pharmacological treatments for spasticity. Whereas pharmacologic and conventional physiotherapy approaches result well effective in managing spasticity due to stroke, multiple sclerosis, traumatic brain injury, cerebral palsy and incomplete spinal cord injury, the real usefulness of the non-pharmacological ones is still debated. We performed a narrative literature review of the contribution of non-pharmacological treatments to spasticity management, focusing on the role of non-invasive neurostimulation protocols (NINM). Spasticity therapeutic options available to the physicians include various pharmacological and non-pharmacological approaches (including NINM and vibration therapy), aimed at achieving functional goals for patients and their caregivers. A successful treatment of spasticity depends on a clear comprehension of the underlying pathophysiology, the natural history, and the impact on patient's performances. Even though further studies aimed at validating non-pharmacological treatments for spasticity should be fostered, there is growing evidence supporting the usefulness of non-pharmacologic approaches in significantly helping conventional treatments (physiotherapy and drugs) to reduce spasticity and improving patient's quality of life. Hence, non-pharmacological treatments should be considered as a crucial part of an effective management of spasticity.

Unravelling motor networks in patients with chronic disorders of consciousness: A promising minimally invasive approach.

Behavioral responsiveness and awareness levels correlate with the degree of functional connectivity within cortical-thalamocortical networks, whose breakdown accounts for chronic disorders of consciousness (DOC). Our study was aimed at assessing the role of the primary motor area (M1) and premotor-M1 circuitry dysfunction in motor output deterioration in minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients. As a control group, we included a healthy subject (HC) sample in the study. We evaluated the effects of different types of transcranial magnetic stimuli over M1 by recording post-stimulus time histogram (PSTH), which includes a series of peaks of unit firing activity that match with D and I-waves, characterizing the descending corticospinal volleys evoked by transcranial magnetic stimuli. As compared to HC, DOC patients showed a dysfunction of intra-M1 and premotor-M1 circuits, which correlated with the Coma Recovery Scale-Revised scorings. Nonetheless, one UWS patient showed a partially preserved premotor-M1 circuitry, paralleled by a severe intra-M1 circuitry dysfunction. Our data suggest that motor unresponsiveness in some DOC patients may be due to a pure motor output failure, as in the functional locked-in syndrome (fLIS), rather than to a premotor-motor connectivity impairment, which instead characterizes MCS and UWS.

Do you see me? The role of visual fixation in chronic disorders of consciousness differential diagnosis.

Visual fixation (VF) of a target is a possible, although atypical, feature of the Unresponsive Wakefulness Syndrome (UWS). Whether VF may indicate residual awareness in these patients is debatable, since it may simply subtend a series of reflex processes. Objective tools should therefore be used to identify aware VF, which depends on the integrity of visuomotor networks encompassing frontal-parietal-occipital areas. The aim of our study was to detect residual visuomotor network functionality potentially sustaining aware VF. To this end, we evaluated the visuomotor integration (VMI) and visual P300 patterns in a chronic Disorder of Consciousness (DOC) sample and a control group of healthy individuals (HC), using an associative stimulation protocol combining transcranial magnetic stimulation (TMS) with visual stimulation through transorbital alternating current stimulation. The Minimally Conscious State (MCS) patients showed preserved patterns of VMI and P300, whereas nearly all the UWS patients showed no significant VMI. Notably, the electrophysiological findings were correlated with the visual domain of the Coma Recovery Scale-Revised. Nonetheless, two fixating UWS individuals had a VMI similar to MCS patients. Our data suggest that some UWS patients showing VF could be aware, but unable to manifest it clearly, probably because of a severe motor output impairment, which is a condition compatible with the Functional Locked-In Syndrome.