Sham-controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double-blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS. METHODS: Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months' follow-up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non-traumatic). Interim analyses were planned to continue or stop the trial. RESULTS: The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post-injury, 18 women, 32 MCS, 39 non-traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months' follow-up revealed a significant improvement for patients in MCS and with traumatic aetiology. CONCLUSIONS: Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

BACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

Effectiveness of a combined transcranial direct current stimulation and virtual reality-based intervention on upper limb function in chronic individuals post-stroke with persistent severe hemiparesis: a randomized controlled trial.

BACKGROUND: Functional impairments derived from the non-use of severely affected upper limb after stroke have been proposed to be mitigated by action observation and imagination-based techniques, whose effectiveness is enhanced when combined with transcranial direct current stimulation (tDCS). Preliminary studies in mildly impaired individuals in the acute phase post-stroke show intensified effects when action is facilitated by tDCS and mediated by virtual reality (VR) but the effectiveness in cases of severe impairment and chronic stroke is unknown. This study investigated the effectiveness of a combined tDCS and VR-based intervention in the sensorimotor function of chronic individuals post-stroke with persistent severe hemiparesis compared to conventional physical therapy. METHODS: Twenty-nine participants were randomized into an experimental group, who received 30 minutes of the combined tDCS and VR-based therapy and 30 minutes of conventional physical therapy, or a control group, who exclusively received conventional physical therapy focusing on passive and active assistive range of motion exercises. The sensorimotor function of all participants was assessed before and after 25 one-hour sessions, administered three to five times a week, using the upper extremity subscale of the Fugl-Meyer Assessment, the time and ability subscales of the Wolf Motor Function Test, and the Nottingham Sensory Assessment. RESULTS: A clinically meaningful improvement of the upper limb motor function was consistently revealed in all motor measures after the experimental intervention, but not after conventional physical therapy. Similar limited effects were detected in the sensory function in both groups. CONCLUSION: The combined tDCS and VR-based paradigm provided not only greater but also clinically meaningful improvement in the motor function (and similar sensory effects) in comparison to conventional physical therapy.

Time since injury limits but does not prevent improvement and maintenance of gains in balance in chronic stroke.

OBJECTIVE: To determine the influence of time since injury on the efficacy and maintenance of gains of rehabilitation of balance after stroke. METHOD: Forty-seven participants were assigned to a least (6-12 months), a moderate (12-24 months), or a most chronic (>24 months) group. Participants trained for 20 one-hour sessions, administered three to five times a week, combining conventional physical therapy and visual feedback-based exercises that trained the ankle and hip strategies. Participants were assessed before, after the intervention, and one month later with a posturography test (Sway Speed and Limits of Stability) and clinical scales. RESULTS: In contrast to other subjects, the most chronic participants failed to improve their sway and to maintain the benefits detected in the Limits of Stability after the intervention. Although all the participants improved in those clinical tests that better matched the trained skills, time since injury limited the improvement, and over all, the maintenance of gains. CONCLUSION: Time since injury limits but does not prevent improvement in chronic stages post-stroke, and this effect appears to be more pronounced with maintaining gains. These findings support that training duration and intensity as well as type of therapy may need to be adjusted based on time post-stroke.

Combined Transcranial Direct Current Stimulation and Virtual Reality-Based Paradigm for Upper Limb Rehabilitation in Individuals with Restricted Movements. A Feasibility Study with a Chronic Stroke Survivor with Severe Hemiparesis.

Impairments of the upper limb function are a major cause of disability and rehabilitation. Most of the available therapeutic options are based on active exercises and on motor and attentional inclusion of the affected arm in task oriented movements. However, active movements may not be possible after severe impairment of the upper limbs. Different techniques, such as mirror therapy, motor imagery, and non-invasive brain stimulation have been shown to elicit cortical activity in absence of movements, which could be used to preserve the available neural circuits and promote motor learning. We present a virtual reality-based paradigm for upper limb rehabilitation that allows for interaction of individuals with restricted movements from active responses triggered when they attempt to perform a movement. The experimental system also provides multisensory stimulation in the visual, auditory, and tactile channels, and transcranial direct current stimulation coherent to the observed movements. A feasibility study with a chronic stroke survivor with severe hemiparesis who seemed to reach a rehabilitation plateau after two years of its inclusion in a physical therapy program showed clinically meaningful improvement of the upper limb function after the experimental intervention and maintenance of gains in both the body function and activity. The experimental intervention also was reported to be usable and motivating. Although very preliminary, these results could highlight the potential of this intervention to promote functional recovery in severe impairments of the upper limb.

Altered postural control and stability in cirrhotic patients with minimal hepatic encephalopathy correlate with cognitive deficits.

BACKGROUND & AIMS: Cognitive dysfunction in cirrhotic patients with minimal hepatic encephalopathy (MHE) is associated with falls. Alterations in postural control and stability could contribute to increase falls risk in these patients. We aimed to assess whether postural control and direction-specific limits of stability are altered in cirrhotic patients with MHE compared to patients without MHE and controls. We also assessed if alterations in postural control correlate with neurological impairment and/or blood biomarkers. METHODS: Posturography analysis, attention Stroop test and bimanual and visuo-motor coordination tests were performed in 18 controls, 19 patients with cirrhosis without MHE and 17 with MHE, diagnosed by PHES. Posturography was assessed by NedSVE® /IBV system under four sensory conditions. Limits of stability and rhythmic weight-shifting tests were also performed. Blood ammonia and serum interleukins were also measured. Falls were assessed after 12-24 months follow-up. RESULTS: MHE patients show impaired balance, mainly on unstable surface with eyes open, with longer reaction and confinement times and lower success in Limits of Stability test compared to patients without MHE. Performance in attention and motor coordination tests correlated with most posturography parameters alterations. Logistic regression analysis shows that posturography parameters and bimanual coordination test are good predictors of falls. CONCLUSION: Balance patterns and limits of stability in MHE patients are impaired compared to patients without MHE and controls. This seems to contribute to a higher falls risk. Attention and motor coordination deficits could contribute to balance impairment in patients with MHE.

Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke.

BACKGROUND: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. METHODS: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). RESULTS: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. CONCLUSIONS: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.

Feasibility of a walking virtual reality system for rehabilitation: objective and subjective parameters.

BACKGROUND: Even though virtual reality (VR) is increasingly used in rehabilitation, the implementation of walking navigation in VR still poses a technological challenge for current motion tracking systems. Different metaphors simulate locomotion without involving real gait kinematics, which can affect presence, orientation, spatial memory and cognition, and even performance. All these factors can dissuade their use in rehabilitation. We hypothesize that a marker-based head tracking solution would allow walking in VR with high sense of presence and without causing sickness. The objectives of this study were to determine the accuracy, the jitter, and the lag of the tracking system and its elicited sickness and presence in comparison of a CAVE system. METHODS: The accuracy and the jitter around the working area at three different heights and the lag of the head tracking system were analyzed. In addition, 47 healthy subjects completed a search task that involved navigation in the walking VR system and in the CAVE system. Navigation was enabled by natural locomotion in the walking VR system and through a specific device in the CAVE system. An HMD was used as display in the walking VR system. After interacting with each system, subjects rated their sickness in a seven-point scale and their presence in the Slater-Usoh-Steed Questionnaire and a modified version of the Presence Questionnaire. RESULTS: Better performance was registered at higher heights, where accuracy was less than 0.6 cm and the jitter was about 6 mm. The lag of the system was 120 ms. Participants reported that both systems caused similar low levels of sickness (about 2.4 over 7). However, ratings showed that the walking VR system elicited higher sense of presence than the CAVE system in both the Slater-Usoh-Steed Questionnaire (17.6 ± 0.3 vs 14.6 ± 0.6 over 21, respectively) and the modified Presence Questionnaire (107.4 ± 2.0 vs 93.5 ± 3.2 over 147, respectively). CONCLUSIONS: The marker-based solution provided accurate, robust, and fast head tracking to allow navigation in the VR system by walking without causing relevant sickness and promoting higher sense of presence than CAVE systems, thus enabling natural walking in full-scale environments, which can enhance the ecological validity of VR-based rehabilitation applications.

Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial.

OBJECTIVES: First, to evaluate the clinical effectiveness of a virtual reality (VR)-based telerehabilitation program in the balance recovery of individuals with hemiparesis after stroke in comparison with an in-clinic program; second, to compare the subjective experiences; and third, to contrast the costs of both programs. DESIGN: Single-blind, randomized, controlled trial. SETTING: Neurorehabilitation unit. PARTICIPANTS: Chronic outpatients with stroke (N=30) with residual hemiparesis. INTERVENTIONS: Twenty 45-minute training sessions with the telerehabilitation system, conducted 3 times a week, in the clinic or in the home. MAIN OUTCOME MEASURES: First, Berg Balance Scale for balance assessment. The Performance-Oriented Mobility Assessment balance and gait subscales, and the Brunel Balance Assessment were secondary outcome measures. Clinical assessments were conducted at baseline, 8 weeks (posttreatment), and 12 weeks (follow-up). Second, the System Usability Scale and the Intrinsic Motivation Inventory for subjective experiences. Third, cost (in dollars). RESULTS: Significant improvement in both groups (in-clinic group [control] and a home-based telerehabilitation group) from the initial to the final assessment in the Berg Balance Scale (ηp(2)=.68; P=.001), in the balance (ηp(2)=.24; P=.006) and gait (ηp(2)=.57, P=.001) subscales of the Tinetti Performance-Oriented Mobility Assessment, and in the Brunel Balance Assessment (control: χ(2)=15.0; P=.002; experimental: χ(2)=21.9; P=.001). No significant differences were found between the groups in any balance scale or in the feedback questionnaires. With regard to subjective experiences, both groups considered the VR system similarly usable and motivating. The in-clinic intervention resulted in more expenses than did the telerehabilitation intervention ($654.72 per person). CONCLUSIONS: First, VR-based telerehabilitation interventions can promote the reacquisition of locomotor skills associated with balance in the same way as do in-clinic interventions, both complemented with a conventional therapy program; second, the usability of and motivation to use the 2 interventions can be similar; and third, telerehabilitation interventions can involve savings that vary depending on each scenario.

Improvement in balance using a virtual reality-based stepping exercise: a randomized controlled trial involving individuals with chronic stroke.

OBJECTIVE: To study the clinical effectiveness and the usability of a virtual reality-based intervention compared with conventional physical therapy in the balance recovery of individuals with chronic stroke. DESIGN: Randomized controlled trial. SETTING: Outpatient neurorehabilitation unit. PARTICIPANTS: A total of 20 individuals with chronic stroke. INTERVENTIONS: The intervention consisted of 20 one-hour sessions, five sessions per week. The experimental group combined 30 minutes with the virtual reality-based intervention with 30 minutes of conventional training. The control group underwent one hour conventional therapy. MAIN MEASURES: Balance performance was assessed at the beginning and at the end of the trial using the Berg Balance Scale, the balance and gait subscales of the Tinetti Performance-Oriented Mobility Assessment, the Brunel Balance Assessment, and the 10-m Walking Test. Subjective data of the virtual reality-based intervention were collected from the experimental group, with a feedback questionnaire at the end of the trial. RESULTS: The results revealed a significant group-by-time interaction in the scores of the Berg Balance Scale (p < 0.05) and in the 10-m Walking Test (p < 0.05). Post-hoc analyses showed greater improvement in the experimental group: 3.8 ±2.6 vs. 1.8 ±1.4 in the Berg Balance Scale, -1.9 ±1.6 seconds vs. 0.0 ±2.3 seconds in the 10-m Walking Test, and also in the number of participants who increased level in the Brunel Balance Assessment (χ(2) = 2.5, p < 0.01). CONCLUSIONS: Virtual reality interventions can be an effective resource to enhance the improvement of balance in individuals with chronic stroke.

Videogame-based group therapy to improve self-awareness and social skills after traumatic brain injury.

BACKGROUND: This study determines the feasibility of different approaches to integrative videogame-based group therapy for improving self-awareness, social skills, and behaviors among traumatic brain injury (TBI) victims and retrieves participant feedback. METHODS: Forty-two adult TBI survivors were included in a longitudinal study with a pre- and post-assessments. The experimental intervention involved weekly one-hour sessions conducted over six months. Participants were assessed using the Self-Awareness Deficits Interview (SADI), Patient Competency Rating Scale (PCRS), the Social Skills Scale (SSS), the Frontal Systems Behavior Scale (FrSBe), the System Usability Scale (SUS). Pearson's chi-squared test (χ (2)) was applied to determine the percentage of participants who had changed their clinical classification in these tests. Feedback of the intervention was collected through the Intrinsic Motivation Inventory (IMI). RESULTS: SADI results showed an improvement in participant perceptions of deficits (χ (2) = 5.25, p < 0.05), of their implications (χ (2) = 4.71, p < 0.05), and of long-term planning (χ (2) = 7.86, p < 0.01). PCRS results confirm these findings (χ (2) = 5.79, p < 0.05). SSS results were also positive with respect to social skills outcomes (χ (2) = 17.52, p < 0.01), and FrSBe results showed behavioral improvements (χ (2) = 34.12, p < 0.01). Participants deemed the system accessible (80.43 ± 8.01 out of 100) and regarded the intervention as interesting and useful (5.74 ± 0.69 out of 7). CONCLUSIONS: Integrative videogame-based group therapy can improve self-awareness, social skills, and behaviors among individuals with chronic TBI, and the approach is considered effective and motivating.

Tracking systems for virtual rehabilitation: objective performance vs. subjective experience. A practical scenario.

Motion tracking systems are commonly used in virtual reality-based interventions to detect movements in the real world and transfer them to the virtual environment. There are different tracking solutions based on different physical principles, which mainly define their performance parameters. However, special requirements have to be considered for rehabilitation purposes. This paper studies and compares the accuracy and jitter of three tracking solutions (optical, electromagnetic, and skeleton tracking) in a practical scenario and analyzes the subjective perceptions of 19 healthy subjects, 22 stroke survivors, and 14 physical therapists. The optical tracking system provided the best accuracy (1.074 ± 0.417 cm) while the electromagnetic device provided the most inaccurate results (11.027 ± 2.364 cm). However, this tracking solution provided the best jitter values (0.324 ± 0.093 cm), in contrast to the skeleton tracking, which had the worst results (1.522 ± 0.858 cm). Healthy individuals and professionals preferred the skeleton tracking solution rather than the optical and electromagnetic solution (in that order). Individuals with stroke chose the optical solution over the other options. Our results show that subjective perceptions and preferences are far from being constant among different populations, thus suggesting that these considerations, together with the performance parameters, should be also taken into account when designing a rehabilitation system.

Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study.

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤ 24 h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose >200mg versus ≤ 200 mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.

Progression of posturographic findings after acquired brain injury.

OBJECTIVE: To study the characteristics of balance performance in a sample of patients with increasing postural instability after acquired brain injury (ABI) and to establish the clinical utility of a new computerized posturographic system (NedSVE/IBV). METHODS: This study included 108 patients with ABI divided into five groups from minimal to severe postural impairment. All patients were assessed with the NedSVE/IBV system and with traditional balance measures. Posturographic analyses included the modified clinical test of sensory interaction on balance, the limits of stability and the weight-shifting test. Sensitivity to detect changes and reproducibility were evaluated in 63 patients who were followed-up for 6 months and in 20 patients who were evaluated on two separate occasions during the same week, respectively. RESULTS: The patients showed reduced stability limits, abnormal postural responses and an increased reliance on visual input with differences in intensity directly related to their degree of balance impairment. Posturographic study showed excellent convergent validity, reproducibility and sensitivity to detect changes. CONCLUSION: The data suggests that, regardless of the intensity of postural instability, there is a common mechanism of sensory processing to maintain balance after ABI. The NedSVE-IBV system is a valid tool to quantify balance after ABI.

Medical comorbidities in patients with prolonged disorder of consciousness: A narrative review.

BACKGROUND: A few studies specifically addressed medical comorbidities (MCs) in patients with severe acquired traumatic or non-traumatic brain injury and prolonged disorders of consciousness (pDoC; i.e., patients in vegetative state/unresponsive wakefulness syndrome, VS/UWS, or in minimally conscious state, MCS). OBJECTIVE: To provide an overview on incidence of MCs in patients with pDoC. METHODS: Narrative review on most impacting MCs in patients with pDoC, both those directly related to brain damage (epilepsy, neurosurgical complications, spasticity, paroxysmal sympathetic hyperactivity, PSH), and those related to severe disability and prolonged immobility (respiratory comorbidities, endocrine disorders, metabolic abnormalities, heterotopic ossifications). RESULTS: Patients with pDoC are at high risk to develop at least one MC. Moderate or severe respiratory and musculoskeletal comorbidities are the most common MCs. Epilepsy and PSH seem to be more frequent in patients in VS/UWS compared to patients in MCS, likely because of higher severity in the brain damage in VS. Endocrine metabolic, PSH and respiratory complications are less frequent in traumatic etiology, whereas neurogenic heterotopic ossifications are more frequent in traumatic etiology. Spasticity did not significantly differ between VS/UWS and MCS and in the three etiologies. MCs are associated with higher mortality rates, worse clinical improvement and can impact accuracy in the clinical diagnosis. CONCLUSIONS: The frequent occurrence of several MCs requires a specialized rehabilitative setting with high level of multidisciplinary medical expertise to prevent, appropriately recognize and treat them. Comprehensive rehabilitation could avoid possible progression to more serious complications that can negatively impact clinical outcomes.

Neurobehavioral Progress and Signs of Transition in Children With Prolonged Disorders of Consciousness: A Retrospective Longitudinal Study With the Coma Recovery Scale-Revised.

BACKGROUND: Research on disorders of consciousness in children is scarce and includes disparate and barely comparable participants and assessment instruments and therefore provides inconclusive information on the clinical progress and recovery in this population. This study retrospectively investigated the neurobehavioral progress and the signs of transition between states of consciousness in a group of children admitted to a rehabilitation program either with an unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS). METHODS: Systematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. RESULTS: Twenty-one children, nine admitted with a UWS and 12 admitted in an MCS, were included in the study. Four children with a UWS transitioned to an MCS with a CRS-R of 10 (9.2 to 12.2) by showing visual pursuit, visual fixation, or localization to noxious stimulation. Twelve children emerged from the MCS with a CRS-R of 20.5 (19 to 21.7). Children who emerged from the MCS had had a shorter time postinjury and higher CRS-R at admission, compared with those who did not emerge. CONCLUSIONS: Almost half of the children who were admitted with a UWS transitioned to an MCS, and almost all who were admitted in an MCS emerged from this state. Children who emerged had shorter times since injury and higher scores on the CRS-R at admission, compared with those who did not emerge.

Which information derived from the Coma Recovery Scale-Revised provides the most reliable prediction of clinical diagnosis and recovery of consciousness? A comparative study using machine learning techniques.

BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) is the most recommended clinical tool to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. AIM: This study investigates which information derived from the CRS-R provides the most reliable prediction of both the clinical diagnosis and recovery of consciousness at the discharge of a long-term neurorehabilitation program. DESIGN: Retrospective observational multisite study. SETTING: The enrollment was performed in three neurorehabilitation facilities of the same hospital network. POPULATION: A total of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were enrolled. METHODS: Machine learning classifiers were trained to predict the clinical diagnosis and recovery of consciousness at discharge using clinical confounders and different metrics extracted from the CRS-R scale. RESULTS: Results showed that the neurobehavioral state at discharge was predicted with acceptable and comparable predictive value with all the indices and measures derived from the CRS-R, but for the clinical diagnosis and the Consciousness Domain Index, and the recovery of consciousness was predicted with higher accuracy and similarly by all the investigated measures, with the exception of initial clinical diagnosis. CONCLUSIONS: Interestingly, the total score in the CRS-R and, especially, the total score in its subscales provided the best overall results, in contrast to the clinical diagnosis, which could indicate that a comprehensive measure of the clinical diagnosis rather than the condition of the individuals could provide a more reliable prediction of the neurobehavioral progress of individuals with prolonged DOC. CLINICAL REHABILITATION IMPACT: The results of this work have important implications in clinical practice, offering a more accurate prognosis of patients and thus giving the possibility to personalize and optimize the rehabilitation plan of patients with DoC using low-cost and easily collectable information.

Minimally conscious state plus versus minus: Likelihood of emergence and long-term functional independence.

OBJECTIVE: Severe brain injuries can result in disorders of consciousness, such as the Minimally Conscious State (MCS), where individuals display intermittent yet discernible signs of conscious awareness. The varied levels of responsiveness and awareness observed in this state have spurred the progressive delineation of two subgroups within MCS, termed "plus" (MCS+) and "minus" (MCS-). However, the clinical validity of these classifications remains uncertain. This study aimed to investigate and compare the likelihood of emergence from MCS, as well as the functional independence after emergence, in individuals categorized as in MCS+ and MCS-. METHODS: Demographic and behavioral data of 80 participants, admitted as either in MCS+ (n = 30) or MCS- (n = 50) to a long-term neurorehabilitation unit, were retrospectively analyzed. The neurobehavioral condition of each participant was evaluated weekly until discharge, demise, or emergence from MCS. The functional independence of those participants who emerged from MCS was assessed 6 months after emergence. RESULTS: While only about half of the individuals classified as in MCS- (n = 24) emerged from the MCS, all those admitted as in MCS+ did, and in a shorter postinjury period. Despite these differences, all individuals who emerged from the MCS demonstrated similar high disability and low functional independence 6 months after emergence, regardless of their state at admission. INTERPRETATION: Individuals classified as MCS+ exhibited a higher likelihood of emergence and a shorter time to emergence compared to those in MCS-. However, the level of functional independence 6 months after emergence was found to be unrelated to the initial state at admission.

Nociception Coma Scale-Revised with Personalized Painful Stimulus Versus Standard Stimulation in Persons with Disorders of Consciousness: An International Multicenter Study.

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale-Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management.

Validation of a low-cost virtual reality system for training street-crossing. A comparative study in healthy, neglected and non-neglected stroke individuals.

Unilateral spatial neglect is a common consequence of stroke that directly affects the performance of activities of daily living. This impairment is traditionally assessed with paper-and-pencil tests that can lack correspondence to real life and are easily compensated. Virtual reality can immerse patients in more ecological scenarios, thus providing therapists with new tools to assess and train the effects of this impairment in simulated real tasks. This paper presents the clinical validation and convergent validity of a low-cost virtual reality system for training street-crossing in stroke patients with and without neglect. The performance of neglect patients was significantly worse than the performance of non-neglect and healthy participants. In addition, several correlations between the scores in the system and in the traditional scales were detected.