Feasibility and Efficacy of a Virtual Reality Social Prediction Training in Children and Young Adults with Congenital Cerebellar Malformations.

This study tested the feasibility and efficacy of a Virtual Reality (VR) social prediction training (VR-Spirit) specifically designed for patients with congenital cerebellar malformation. The study is a randomised controlled trial in which 28 cerebellar patients aged 7-25 yo were randomly allocated to the VR-Spirit or to a control intervention in VR. The VR-Spirit required participants to compete with different avatars in scenarios that prompted them to form predictions about avatars' intentions. The control intervention consisted of games currently adopted for motor rehabilitation. Social prediction as well as secondary neuropsychological and behavioural outcomes were assessed at the beginning (T0), at the end (T2) and after 2 months (T3). The experimental group showed a significant increase, compared to the control participants, in social prediction assessed through a VR task. Moreover, at least at T3, the VR-Spirit enhanced the use of contextual predictions in a computer-based action prediction task. Importantly, these effects were generalized to secondary neuropsychological outcomes, specifically theory of mind and, only at T2, inhibition. No differences between the interventions were detected on emotional-behavioural problems. Lastly, both interventions showed high feasibility and acceptability. These findings confirm that it is possible to develop condition-specific rehabilitative training on the basis of neurocognitive functions impaired in case of congenital malformation. The VR-Spirit demonstrated to generalize its effects to theory of mind abilities, and it might be thus extended to other neurodevelopmental disorders that present social perception deficits and alterations of predictive processing.Trial registration: ISRCTN, ID: ISRCTN22332873. Retrospectively registered on 12 March 2018.

Neurorestorative effects of cerebellar transcranial direct current stimulation on social prediction of adolescents and young adults with congenital cerebellar malformations.

BACKGROUND: Converging evidence points to impairments of the predictive function exerted by the cerebellum as one of the causes of the social cognition deficits observed in patients with cerebellar disorders. OBJECTIVE: We tested the neurorestorative effects of cerebellar transcranial direct current stimulation (ctDCS) on the use of contextual expectations to interpret actions occurring in ambiguous sensory sceneries in a sample of adolescents and young adults with congenital, non-progressive cerebellar malformation (CM). METHODS: We administered an action prediction task in which, in an implicit-learning phase, the probability of co-occurrence between actions and contextual elements was manipulated to form either strongly or moderately informative expectations. Subsequently, in a testing phase, we probed the use of these contextual expectations for predicting ambiguous (i.e., temporally occluded) actions. In a sham-controlled, within-subject design, participants received anodic or sham ctDCS during the task. RESULTS: Anodic ctDCS, compared to sham, improved patients' ability to use contextual expectations to predict the unfolding of actions embedded in moderately, but not strongly, informative contexts. CONCLUSIONS: These findings corroborate the role of the cerebellum in using previously learned contextual associations to predict social events and document the efficacy of ctDCS to boost social prediction in patients with congenital cerebellar malformation. The study encourages the further exploration of ctDCS as a neurorestorative tool for the neurorehabilitation of social cognition abilities in neurological, neuropsychiatric, and neurodevelopmental disorders featured by macro- or micro-structural alterations of the cerebellum.

Hormonal Dysfunction in Paediatric Patients Admitted to Rehabilitation for Severe Traumatic Brain Injury: Analysis of the Associations with Rehabilitation Outcomes.

Traumatic brain injury is often accompanied by defects in hormone levels, caused by either peripheral gland dysfunctions or by an insufficient central stimulation of hormone production. The epidemiology of endocrinological defects after traumatic brain injury is quite well described, but the consequences of hormone defects are largely unknown, especially in paediatric patients undergoing neurological rehabilitation. Only one previous study reported on a cohort of 20 children with traumatic brain injury and found a low incidence of hormone defects and a correlation between some hormone levels and neurological recovery. In this study, we performed a retrospective chart review on patients affected by severe subacute traumatic brain injury. Their levels of cortisol, ACTH, IGF-1, TSH, free T4, free T3, and prolactin were collected and compared with reference ranges; we then used regression models to highlight any correlation among them and with clinical variables; last, we probed with regression models whether hormone levels could have any correlation with clinical and rehabilitation outcomes. We found eligible data from the records of 52 paediatric patients with markedly severe traumatic brain injury, as shown by an average GCS of 4.7; their age was 10.3 years, on average. The key results of our study are that 32% patients had low IGF-1 levels and in multiple regression models, IGF-1 levels were correlated with neurological recovery, indicating a possible role as a biomarker. Moreover, 69% of patients had high prolactin levels, possibly due to physical pain and high stress levels. This study is limited by the variable timing of the IGF-1 sampling, between 1 and 2 months after injury. Further studies are required to confirm our exploratory findings.

Randomized clinical trial on the effects of a computerized cognitive training for pediatric patients with acquired brain injury or congenital malformation.

Both acquired injuries and congenital malformations often cause lifelong disabilities in children, with a significant impact on cognitive abilities. Remote computerized cognitive training (CCT) may be delivered in ecological settings to favour rehabilitation continuity. This randomized clinical trial (RCT) evaluated the efficacy of an 8-week multi-domain, home-based CCT in a sample of patients aged 11-16 years with non-progressive acquired brain injury (ABI), brain tumor (BT) and congenital brain malformation (CBM). Following a stepped-wedge research design, patients were randomized into two groups: Training-first group, which started the CCT immediately after baseline assessment and Waiting-first group, which started the CCT after a period of time comparable to that required by the training (8 weeks). Post-training and long-term (6 months) changes were assessed. Both groups improved on visual-spatial working memory after the CCT, with benefits maintained after 6 months, while no other changes in cognitive or psychological measures were found. These findings suggest that a multi-domain CCT can generate benefits in visual-spatial working memory, in accordance with data from extant literature reporting that computer games heavily engage visuo-spatial abilities. We speculate that is tapping on the same cognitive ability with a prolonged training that may generate the greatest change after a CCT.

Long-Term Vocational Outcome at 15 Years from Severe Traumatic and Non-Traumatic Brain Injury in Pediatric Age.

BACKGROUND: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. METHODS: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical and functional details ("Glasgow Outcome Scale", "Functional Independent Measure" and Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. RESULTS: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability of being partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working-taking into account limitations due to the traumatic event-versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. CONCLUSIONS: Rehabilitation should adequately emphasize "vocational rehabilitation" because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

Prelinguistic intersubjective and socio-communicative skills in infants with neurodevelopmental disabilities aged 0-36 months: A new assessment and parent support tool.

Background: Although children with neurodevelopmental disability (NDD) present with several deficits, they partially share developmental impairments in prelinguistic intersubjective and socio-communicative skills, which are not easily assessed by conventional tests during the first years of life. Aim: The current paper presents a new procedure to assess the prelinguistic intersubjective and socio-communicative skills of NDD children aged 0-36 months. A specific observation form template, called the Observation of Prelinguistic Intersubjective and Socio-Communicative Skills (OPISCoS) form, has been designed to systematically detect infant skills during daily routines (e.g., mealtime, playtime, desk activities). The OPISCoS form helps speech therapists to provide parents support to better perceive and understand early communicative signals from their children, avoiding the risk of excessive or reduced social stimulation. Methods: The OPISCoS form is composed of three sections, namely, "Pragmatics and Communication," "Decoding," and "Expression," which are useful to delineate the communication abilities of children with NDD and are not tapped by traditional batteries. Vignettes from clinical practice illustrate and provide exemplifications for using the OPISCoS form with NDD infants and their parents. Results: The OPISCoS form was reported for two children and showed potential in detecting disrupted communicative behaviors and planning specific early interventions. Further, we observed an improvement not only in children's communicative abilities improve but also in their interactions with parents. From a clinical point of view, the OPISCoS form (1) offers an observational perspective of prelinguistic intersubjective and socio-communicative skills in infants with NDD and (2) may be useful to practitioners to enhance parents' sensitivity to their infants' communicative behavior. Conclusion: The OPISCoS form was developed in clinical practice and is based on a very preliminary description of a new observational procedure as integration for the assessment of NDD children. The OPISCoS form appears to be a useful tool for the clinical assessment of prelinguistic intersubjective and socio-communicative skills in NDD infants as well as for promoting the quality of early parenting.

Remote cognitive training for children with congenital brain malformation or genetic syndrome: a scoping review.

Increased attention is arising on the delivery of remote cognitive interventions, which allow performing exercises in everyday settings, favouring rehabilitation continuity. The present study offers an overview of remote cognitive training programs for children with congenital brain malformation or genetic syndrome affecting the central nervous system, included in papers published in the time period 2011-2021. A total of 13 records was found and discussed including efficacy studies, feasibility studies and study protocols. Many studies have focused on a specific diagnosis, such as cerebral palsy, Down Syndrome, Fragile X Syndrome, while no or little evidence has been gathered on more rare diseases or brain malformations. Interventions were found to generate benefits on some cognitive functions, but problems with adherence were highlighted, especially due to excessive cognitive load from the training or clinical comorbidities. Conclusions remain tentative due to heterogeneity in training, study and patients characteristics, and methodological limitations of studies.

Neuropsychological assessment through Coma Recovery Scale-Revised and Coma/Near Coma Scale in a sample of pediatric patients with disorder of consciousness.

BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) has become a standard tool in assessing Disorders of consciousness (DoC) in adults. However, its measurement validity in pediatrics has only been ascertained in healthy cases. Increasing use of CRS-R in children with DoC imposes appropriate comparison against previously validated tools. The aims of the study were to describe the emergence to a conscious state (eMCS) in pediatric acquired brain injury (ABI); to explore the agreement between the CRS-R and Coma Near Coma Scale (CNCS) and to discuss the advantage of administering the CRS-R in pediatric age. MATERIALS AND METHODS: In this observational prospective study, 40 patients were recruited. Inclusion criteria were age 5 to 18 years, Glasgow Coma Scale (GCS) score ≤ 8 at the insult, and unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) at admission. Patients were assessed with CRS-R, and CNCS was used as standard. RESULTS: The agreement between scales was moderate (r = - 0.71). The analysis of the CRS-R domain scores also confirmed that decreasing CNCS levels (from a coma to eMCS) corresponded to concurrent increas of CRS-R scores in all domains. Moreover, CRS-R better defined patients' status in the emergency phase from MCS. Conversely, CRS-R had lower DoC scoring ability in the presence of severe motor impairment. CONCLUSION: We show that CRS-R can track changes in DoC in children as young as 5 years old, and we provide evidence that the agreement with CNCS scores is good.

Visual Feedback and Virtual Reality in Gait Rehabilitation of Hemiparetic Children and Teenagers after Acquired Brain Injury: A Pilot Study.

Hemiparesis as a term refers to a neurological disorder that can be extremely variable, especially with regard to walking abilities. Few works have assessed the use of virtual reality and biofeedback in children and adolescents with hemiparesis. The aim of this study is to provide insights about the rehabilitation of hemiparetic children and teenagers with visual biofeedback in a virtual reality environment. Six hemiparetic subjects (mean age 13.13 years, age range (7-18), 4 males) received 20 personalized rehabilitation GRAIL (Gait Real-time Analysis Interactive Lab) sessions plus 20 sessions of traditional physiotherapy. After an initial evaluation of rehabilitation needs, training focused on gait pattern correction (GP), walking endurance (WE), or gross motor functions (GMFs). All subjects were assessed for their gait analysis by GRAIL, the Gross Motor Function Measure (GMFM), and the 6-Minute Walking Test (6MWT) before and after rehabilitation. All subjects reached their rehabilitation goals, save for one who showed reduced collaboration. In addition, 4 subjects reached a better GP, 3 subjects reported improvements in WE, and 2 subjects improved in GMF. This personalized training with visual biofeedback delivered in a VR setting appears to be effective in modifying motor control and improving gait pattern, in addition to resistance and functional activities, in subjects with hemiparesis.

Body Processing in Children and Adolescents with Traumatic Brain Injury: An Exploratory Study.

Dysfunctions in body processing have been documented in adults with brain damage, while limited information is available for children. This study aimed to investigate body processing in children and adolescents with traumatic brain injury (TBI) (N = 33), compared to peers with typical development. Two well-known computerized body-representation paradigms, namely Visual Body Recognition and Visuo-spatial Imagery, were administered. Through the first paradigm, the body inversion and composite illusion effects were tested with a matching to sample task as measures of configural and holistic processing of others' bodies, respectively. The second paradigm investigated with a laterality judgement task the ability to perform first-person and object-based mental spatial transformations of own body and external objects, respectively. Body stimuli did not convey any emotional contents or symbolic meanings. Patients with TBI had difficulties with mental transformations of both body and object stimuli, displaying deficits in motor and visual imagery abilities, not limited to body processing. Therefore, cognitive rehabilitation of body processing in TBI might benefit from the inclusion of both general training on visuo-spatial abilities and specific exercises aimed at boosting visual body perception and motor imagery.

Emerging Treatments for Disorders of Consciousness in Paediatric Age.

The number of paediatric patients living with a prolonged Disorder of Consciousness (DoC) is growing in high-income countries, thanks to substantial improvement in intensive care. Life expectancy is extending due to the clinical and nursing management achievements of chronic phase needs, including infections. However, long-known pharmacological therapies such as amantadine and zolpidem, as well as novel instrumental approaches using direct current stimulation and, more recently, stem cell transplantation, are applied in the absence of large paediatric clinical trials and rigorous age-balanced and dose-escalated validations. With evidence building up mainly through case reports and observational studies, there is a need for well-designed paediatric clinical trials and specific research on 0-4-year-old children. At such an early age, assessing residual and recovered abilities is most challenging due to the early developmental stage, incompletely learnt motor and cognitive skills, and unreliable communication; treatment options are also less explored in early age. In middle-income countries, the lack of rehabilitation services and professionals focusing on paediatric age hampers the overall good assistance provision. Young and fast-evolving health insurance systems prevent universal access to chronic care in some countries. In low-income countries, rescue networks are often inadequate, and there is a lack of specialised and intensive care, difficulty in providing specific pharmaceuticals, and lower compliance to intensive care hygiene standards. Despite this, paediatric cases with DoC are reported, albeit in fewer numbers than in countries with better-resourced healthcare systems. For patients with a poor prospect of recovery, withdrawal of care is inhomogeneous across countries and still heavily conditioned by treatment costs as well as ethical and cultural factors, rather than reliant on protocols for assessment and standardised treatments. In summary, there is a strong call for multicentric, international, and global health initiatives on DoC to devote resources to the paediatric age, as there is now scope for funders to invest in themes specific to DoC affecting the early years of the life course.

Virtual-Reality Performance-Based Assessment of Cognitive Functions in Adult Patients With Acquired Brain Injury: A Scoping Review.

Individuals with acquired brain injury (ABI) commonly present with impairments in cognitive abilities. As these competencies seem to be predictive of patients' abilities to reintegrate into the everyday settings, it is crucial to assess them properly. However, previous research has indicated that patients may perform relatively well on standard tests of cognitive functioning, but may nonetheless encounter significant difficulties in organizing and executing everyday tasks. In order to overcome this issue, virtual reality (VR) methods have been introduced in clinical practice with the aim of creating assessments that simulate real-world activities and thus, provide a clearer picture of patients' functioning in everyday settings. This review offers an overview of VR assessment tools described in the scientific literature between 2010 and 2019. Overall, 38 relevant records describing 31 different tools were found. Among these tools, 16 assessed executive functions and prospective memory, while the other 15 assessed visuo-spatial abilities. Although promising results have been reported, our analysis indicated that about half of the tools deliver tasks that differ from everyday activities, thus limiting the generalizability of patients' performance to the real-world. Moreover, a variety of methodological shortfalls related to study Internal and External Validity have been highlighted, which hamper the possibility of drawing definite recommendations on tool choice. These limitations suggest the importance of putting considerable efforts into the improvement or development of VR tools for patients with ABI for both research and clinical purposes, considering the great potential of this form of assessment.

Oxcarbazepine for Behavioral Disorders after Brain Injury: Factors Influencing Efficacy.

Carbamazepine and oxcarbazepine are used for behavioral disorders following organic diseases. After severe acquired brain injury, patients may develop frontal symptoms. In our neurological rehabilitation routine, oxcarbazepine is used for better safety over carbamazepine, although its efficacy is not clarified. We aimed to improve knowledge on this use of oxcarbazepine, by probing clinical factors associated with response. We retrospectively examined the clinical records of our patients, collecting clinical variables and outcomes of efficacy, both clinician-rated and caregiver/self-rated. We described the distribution of clinical variables and examined their associations via logistic regressions. Patients in our cohort were predominantly pediatric, with frontal lobe damage and irritable/reactive. With an oxcarbazepine median dose of 975 mg, almost half of patients improved. We found several clinical factors associated with clinician-rated efficacy: absence of frontal damage and absence of irritability/reactivity symptoms; clinical factors associated with caregivers/patients-rated efficacy were: higher DRS score at baseline and higher patient age. In this retrospective study, we observed that oxcarbazepine was differentially efficacious in patients with specific characteristics. Our study could not examine drug therapy separately from neuropsychological therapy, nor the influence of dose. Our associative results should be verified experimentally, also assessing causality and establishing dose-related efficacy and safety.

Individualized Prognostic Prediction of the Long-Term Functional Trajectory in Pediatric Acquired Brain Injury.

In pediatric acquired brain injury, heterogeneity of functional response to specific rehabilitation treatments is a key confound to medical decisions and outcome prediction. We aimed to identify patient subgroups sharing comparable trajectories, and to implement a method for the early prediction of the long-term recovery course from clinical condition at first discharge. 600 consecutive patients with acquired brain injury (7.4 years ± 5.2; 367 males; median GCS = 6) entered a standardized rehabilitation program. Functional Independent Measure scores were measured yearly, until year 7. We classified the functional trajectories in clusters, through a latent class model. We performed single-subject prediction of trajectory membership in cases unseen during model fitting. Four trajectory types were identified (post.prob. > 0.95): high-start fast (N = 92), low-start fast (N = 168), slow (N = 130) and non-responders (N = 210). Fast responders were older (chigh = 1.8; clow = 1.1) than non-responders and suffered shorter coma (chigh = -14.7; clow = -4.3). High-start fast-responders had shorter length of stay (c = -1.6), and slow responders had lower incidence of epilepsy (c = -1.4), than non-responders (p < 0.001). Single-subject trajectory could be predicted with high accuracy at first discharge (accuracy = 0.80). In conclusion, we stratified patients based on the evolution of their response to a specific treatment program. Data at first discharge predicted the response over 7 years. This method enables early detection of the slow responders, who show poor post-acute functional gains, but achieve recovery comparable to fast responders by year 7. Further external validation in other rehabilitation programs is warranted.

The Effectiveness of Robot- vs. Virtual Reality-Based Gait Rehabilitation: A Propensity Score Matched Cohort.

Robot assisted gait training (RAGT) and virtual reality plus treadmill training (VRTT) are two technologies that can support locomotion rehabilitation in children and adolescents affected by acquired brain injury (ABI). The literature provides evidence of their effectiveness in this population. However, a comparison between these methods is not available. This study aims at comparing the effectiveness of RAGT and VRTT for the gait rehabilitation of children and adolescents suffering from ABI. This is a prospective cohort study with propensity score matching. Between October 2016 and September 2018, all patients undergoing an intensive gait rehabilitation treatment based on RAGT or VRTT were prospectively observed. To minimize selection bias associated with the study design, patients who underwent RAGT or VRTT were retrospectively matched for age, gender, time elapsed from injury, level of impairment, and motor impairment using propensity score in a matching ratio of 1:1. Outcome measures were Gross Motor Function Mesure-88 (GMFM-88), six-min walking test (6MWT), Gillette Functional Assessment Questionnaire (FAQ), and three-dimensional gait analysis (GA). The FAQ and the GMFM-88 had a statistically significant increase in both groups while the 6MWT improved in the RAGT group only. GA highlighted changes at the proximal level in the RAGT group, and at the distal district in the VRTT group. Although preliminary, this work suggests that RAGT and VRTT protocols foster different motor improvements, thus recommending to couple the two therapies in the paediatric population with ABI.

Feasibility and Acceptability of a Real-Time Telerehabilitation Intervention for Children and Young Adults with Acquired Brain Injury During the COVID-19 Pandemic: An Experience Report.

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care.

Drug Use in Pediatric Patients Admitted to Rehabilitation For Severe Acquired Brain Injury: Analysis of the Associations With Rehabilitation Outcomes.

INTRODUCTION: Patients with severe acquired brain injuries require drug therapies in intensive care for life support and injury treatment. Patients who then access rehabilitation usually maintain their drug treatments long term, with a potential influence on the rehabilitation course. Whereas drug effects have been reported for specific drugs and clinical issues in adults, comprehensive data on pediatric patients with traumatic and non-traumatic injuries are scant. OBJECTIVES: The aims of this study were to describe the therapeutic classes and groups of drugs prescribed to pediatric inpatients recovering from severe acquired brain injury when they enter rehabilitation; to assess whether clinical variables may determine the use of drug classes; and to assess whether the use of drug classes may be associated with differences in rehabilitation outcomes. METHODS: We carried out a retrospective chart review, following a previous study on the clinical-epidemiological characteristics of our patients. We collected information on drug therapies present at admittance to rehabilitation and analyzed their distribution according to therapeutic classes and groups. We verified the associations of drug groups with clinical variables (putatively antecedents to drug use) and with rehabilitation outcomes (putatively resultant of drug use and of clinical variables) in regression models. The clinical variables considered were injury etiology, Glasgow Outcome Score (GOS) at admittance to rehabilitation, sex, age at injury, plus two aggregate factors resulting from the previous work, 'neurological dysfunction' regarding the use of devices and 'injury severity' regarding the neurological status. The rehabilitation outcomes used were death after rehabilitation, persistence of a vegetative/minimally conscious state, coma duration, duration of the rehabilitation stay, rehabilitation efficiency (GOS at discharge minus GOS at admittance, divided by the length of rehabilitation stay). RESULTS: We described the distribution of drug classes and groups among pediatric patients with severe acquired brain injuries. Regarding the associations between drug classes and clinical variables, we found greater use of cardiovascular agents with higher patient age, 'neurological dysfunction' score, and with an etiology of hypoxic brain injury. The use of antithrombotic agents was greater with higher patient age and 'neurological dysfunction' score. Glucocorticoid use was greater with higher GOS at admittance and with several etiologies: brain tumor, infective encephalitis, and autoimmune encephalitis. Regarding drug classes and rehabilitation outcomes, we found that the use of cardiovascular drugs was associated with increased occurrence of death after rehabilitation. The use of antispastic drugs was associated with a more frequent permanence in vegetative/minimally conscious states. The use of antispastic drugs and melatonin was associated with longer coma duration. The use of glucocorticoid drugs was associated with decreased rehabilitation efficiency. CONCLUSIONS: We provided a description of drug use in pediatric rehabilitation after severe acquired brain injuries, which was lacking in the literature. Prospective studies should verify our associative observations regarding clinical variables, drugs use, and outcomes, to assess causality.

Feasibility Randomized Trial for an Intensive Memory-Focused Training Program for School-Aged Children with Acquired Brain Injury.

(1) Background: Memory deficits are common sequelae of pediatric Acquired Brain Injury (ABI). Only methods for non-focused cognitive remediation are available to the pediatric field. The aims of this feasibility trial are the description, implementation, and test of an intensive program specific to the training and re-adaptation of memory function in children, called Intensive Memory-Focused Training Program (IM-FTP); (2) Methods: Eleven children and adolescents with ABI (mean age at injury = 12.2 years, brain tumor survivors excluded) were clinically assessed and rehabilitated over 1-month through IM-FTP, including physio-kinesis/occupational, speech, and neuropsychology treatments. Each patient received a psychometric evaluation and a brain functional MRI at enrollment and at discharge. Ten pediatric controls with ABI (mean age at injury = 13.8 years) were clinically assessed, and rehabilitated through a standard program; (3) Results: After treatment, both groups had marked improvement in both immediate and delayed recall. IM-FTP was associated with better learning of semantically related and unrelated words, and larger improvement in immediate recall in prose memory. Imaging showed functional modification in the left frontal inferior cortex; (4) Conclusions: We described an age-independent reproducible multidisciplinary memory-focused rehabilitation protocol, which can be adapted to single patients while preserving inter-subject comparability, and is applicable up to a few months after injury. IM-FTP will now be employed in a powered clinical trial.

Minimum Clinically Important Difference of Gross Motor Function and Gait Endurance in Children with Motor Impairment: A Comparison of Distribution-Based Approaches.

OBJECTIVE: The minimum clinically important difference (MCID) is a standard way of measuring clinical relevance. The objective of this work was to establish the MCID for the 6-minute walking test (6minWT) and the Gross Motor Function Measure (GMFM-88) in pediatric gait disorders. METHODS: A cohort, pretest-posttest study was conducted in a hospitalized care setting. A total of 182 patients with acquired brain injury (ABI) or cerebral palsy (CP) performed 20 robot-assisted gait training sessions complemented with 20 sessions of physical therapy over 4 weeks. Separate MCIDs were calculated using 5 distribution-based approaches, complemented with an anonymized survey completed by clinical professionals. RESULTS: The MCID range for the 6minWT was 20-38 m in the ABI cohort, with subgroup ranges of 20-36 m for GMFCS I-II, 23-46 m for GMFCS III, and 24-46 m for GMFCS IV. MCIDs for the CP population were 6-23 m, with subgroup ranges of 4-28 m for GMFCS I-II, 9-19 m for GMFCS III, and 10-27 m for GMFCS IV. For GMFM-88 total score, MCID values were 1.1%-5.3% for the ABI cohort and 0.1%-3.0% for the CP population. For dimension "D" of the GMFM, MCID ranges were 2.3%-6.5% and 0.8%-5.2% for ABI and CP populations, respectively. For dimension "E," MCID ranges were 2.8%-6.5% and 0.3%-4.9% for ABI and CP cohorts, respectively. The survey showed a large interquartile range, but the results well mimicked the distribution-based methods. CONCLUSIONS: This study identified for the first time MCID ranges for 6minWT and GMFM-88 in pediatric patients with neurological impairments, offering useful insights for clinicians to evaluate the impact of treatments. Distribution-based methods should be used with caution: methods based on pre-post correlation may underestimate MCID when applied to patients with small improvements over the treatment period. Our results should be complemented with estimates obtained using consensus- and anchor-based approaches.

Joint Neuropsychological Assessment through Coma/Near Coma and Level of Cognitive Functioning Assessment Scales Reduces Negative Findings in Pediatric Disorders of Consciousness.

The present study aimed to: (a) characterize the emergence to a conscious state (CS) in a sample of children and adolescents with severe brain injury during the post-acute rehabilitation and through two different neuropsychological assessment tools: the Rappaport Coma/Near Coma Scale (CNCS) and Level of Cognitive Functioning Assessment Scale (LOCFAS); (b) compare the evolution in patients with brain lesions due to traumatic and non-traumatic etiologies; and (c) describe the relationship between the emergence to a CS and some relevant clinical variables. In this observational prospective longitudinal study, 92 consecutive patients were recruited. Inclusion criteria were severe disorders of consciousness (DOC), Glasgow Coma Scale (GCS) score ≤8 at insult, age 0 to 18 years, and direct admission to inpatient rehabilitation from acute care. The main outcome measures were CNCS and LOCFAS, both administered three and six months after injury. The cohort globally shifted towards milder DOC over time, moving from overall 'moderate/near coma' at three months to 'near/no coma' at six months post-injury. The shift was captured by both CNCS and LOCFAS. CNCS differentiated levels of coma at best, while LOCFAS was superior in characterizing the emergence from coma. Agreement between scales was fair, and reduced negative findings at less than 10%. Patients with traumatic brain injury (TBI) vs. non-traumatic brain injury (NTBI) were older and had neurosurgical intervention more frequently. No relation between age and the level of consciousness was found overall. Concurrent administration of CNCS and LOCFAS reduced the rate of false negatives and better detected signs of arousal and awareness. This provides indication to administer both tools to increase measurement precision.