Free Thyroxine (fT4) as a Potential Biomarker of Neurological and Functional Outcome in Acquired Brain Injury: A Prospective Multicenter Cohort Study.

The potential involvement of thyroid hormones (THs) in the neurological and functional recovery of patients with brain damage has been hypothesized. We aimed at investigating the role of THs and their variations during the rehabilitation process as predictive biomarkers of neurological and functional outcome in patients with acquired brain injury (ABI). This prospective, multicenter cohort study included 220 patients with ABI consecutively admitted for a 6-month neurorehabilitation program. Data on the etiology of the brain injury, occurrence of seizures, neurosurgical procedures, and death during hospitalization were collected. Both at the baseline (T0) and at the end of the rehabilitation process (T1), the following variables were evaluated: thyroid function (TSH, fT4, and fT3) and outcome measure including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale-Extended (GOS-E), and Functional Independence Measure (FIM) scale. During neurorehabilitation, a significant decrease in fT4 levels was documented in the population as a whole and in patients with severe ABI (p < 0.0001), whereas no significant variations were found in TSH and fT3 levels. No significant associations were found between THs and seizure occurrence, while the neurological and functional outcomes were associated with the variation in fT4 levels during rehabilitation. In particular, a higher magnitude of decrease in fT4 levels emerged as an independent predictor of more severe neurological damage (OR = 3.48, CI 95% 1.04-11.69, p = 0.04) and a lower functional recovery (ß = -0.22, p = 0.01). In conclusion, serum fT4 variation during neurorehabilitation could represent a potential biomarker of neurological and functional outcome in patients with ABI. Further studies are needed to investigate the mechanisms underlying this association.

Investigating microRNAs as biomarkers in disorders of consciousness: a longitudinal multicenter study.

MicroRNAs (miRNAs) are involved in gene regulation and may affect secondary brain injury and recovery in patients with disorders of consciousness (DoC). This study investigated the role of five miRNAs (150-5p, 132-3p, 23b-3p, 451a, and 16-5p) in prolonged DoC. miRNA levels were assessed in serum samples from 30 patients with unresponsive wakefulness syndrome or minimally conscious state due to traumatic or hypoxic-ischemic brain injury (TBI, HIBI) at baseline (1-3 months) and 6 months post-injury. Patients' diagnoses were determined using the Coma Recovery Scale revised, and functional outcomes were evaluated 6 months after injury with the Glasgow Outcome Scale Extended (GOSE) and the Functional Independence Measure (FIM). Compared to healthy controls, patients with TBI had lower levels of miRNAs 150-5p, 132-3p, and 23b-3p at baseline, while patients with HIBI had lower levels of miRNA 150-5p at baseline and 6 months post-injury and a reduction of miRNA 451a at baseline. Higher levels of miRNAs 132-3p and 23b-3p were associated with better outcomes in TBI patients as indicated by GOSE and FIM scores. This study highlights distinct miRNA dysregulated patterns in patients with prolonged DoC, dependent on etiology and post-injury time, and suggests that miRNAs 132-3p and 23b-3p may serve as prognostic biomarkers.

The structure of the Early Rehabilitation Barthel Index (ERBI) should be modified: evidence from a Rasch analysis study.

BACKGROUND: The Early Rehabilitation Barthel Index (ERBI) comprises seven items of the Early Rehabilitation Index and ten items of the Barthel Index. The ERBI is usually used to measure functional changes in patients with severe acquired brain injury (sABI), but its measurement properties have yet to be extensively assessed. AIM: To study the unidimensionality and internal construct validity (ICV) of the ERBI through Confirmatory Factor Analysis (CFA), Mokken Analysis (MA), and Rasch Analysis (RA). DESIGN: Multicenter prospective study. SETTING: Inpatients from five intensive rehabilitation centers. POPULATION: Two hundred and forty-seven subjects with sABI. METHODS: ERBI was administered on admission and discharge to study its unidimensionality through CFA and MA and its ICV, reliability, and targeting through RA. RESULTS: The preliminary analyses showed a lack of unidimensionality (RMSEA=0.460 >0.06; SRMR=0.176 >0.06; CFI=1.000 >0.950; TLI=1.000 >0.950). According to CFA, "Confusional state" and "Behavioral disturbance" items showed low factor loadings (<0.40), whereas these two items composed a separate scale within the MA. Furthermore, the baseline RA showed that three items misfitted ("Mechanical ventilation," "Confusional state," "Behavioral disturbances") and a lack of conformity of several ICV requirements. After deletion of three misfitting items and further non-structural modifications (i.e., testlets creation to absorb local dependence between items and item misfit), the solution obtained showed adequate ICV, adequate reliability for measurements at the individual level (PSI>0.85), although with a frank floor effect. This final solution was successfully replicated in a total sample of the subjects. After post-hoc modifications of the score structure of two out of three misfitting items, the subsequent CFA (RMSEA=0.044 <0.06; SRMR=0.056 <0.06; CFI=1.000 >0.950 TLI=1.000 >0.950) and MA showed the resolution of the unidimensional issues. CONCLUSIONS: Although the ERBI is a potentially valuable tool for measuring functioning in the coma-to-community continuum, our analyses suggested its lack of ICV, partly due to an incorrect scoring design of some items. A new perspective multicenter study is proposed to validate a modified version of the ERBI that overcomes the problems highlighted in this analysis. CLINICAL REHABILITATION IMPACT: Our results do not support the use of the original structure of the ERBI in clinical practice and research, as a lack of ICV was highlighted.

When the practice does not meet the theory: results from an Italian survey on the clinical and pathway management of inpatients with decompressive craniectomy or cranioplasty admitted to rehabilitation.

BACKGROUND: Cranioplasty (CP) is supposed to improve the functional outcome of severe acquired brain injury (sABI) patients with decompressive craniectomy (DC). However, ongoing controversies exist regarding its indications, optimum materials, timing, complications, and relationships with hydrocephalus (HC). For these reasons, an International Consensus Conference (ICC) on CP in traumatic brain injury (TBI) was held in June 2018 to issue some recommendations. AIM: The aims of this study were: to investigate cross-sectionally before the ICC the prevalence of DC/CP in sABI inpatients admitted to neurorehabilitation units in Italy; to assess the perception of Italian clinicians working in the sABI neurorehabilitation settings on the management of inpatients with DC/CP during their rehabilitation stay. DESIGN: Cross-sectional. SETTING AND POPULATION: Physiatrists or neurologists working in 38 Italian rehabilitation centers involved in the care of sABI, giving a pooled sample of 599 inpatients. METHODS: Survey questionnaire consisting of 21 closed-ended questions with multiple-choice answers. Sixteen questions regarded the respondents' opinions and experiences regarding the clinical and management aspects of patients. Survey data were collected via e-mail between April and May 2018. RESULTS: About 1/3 of the 599 inpatients had either a DC (18.9%) or a CP (13.5%). TBI and cerebral hemorrhage were strongly associated with DC/CP, although the association was much stronger for TBI. Significant discrepancies were uncovered between some of the recommendations of the ICC and the corresponding perceptions of the respondents, especially regarding the clinical management of patients (i.e., CP timing). Clear guidelines were perceived as the most crucial factor in improving clinical pathways. CONCLUSIONS: Early collaboration between the neurosurgical and the neurorehabilitation teams is crucial to optimize all clinical and organizational factors, which could expedite CP and minimize the risk of complications, such as infections and HC, to ensure the best possible outcome for DC patients, regardless of the etiology of the sABI. CLINICAL REHABILITATION IMPACT: There may be different attitudes and perceptions, if not controversies, between neurorehabilitation physicians and neurosurgeons regarding the optimal clinical and care pathway management of patients with DC/CP in Italy. Therefore, an Italian Consensus Conference involving all stakeholders on the clinical and management pathways of DC/CP patients admitted to neurorehabilitation is advocated.

Modeling outcome trajectories in patients with acquired brain injury using a non-linear dynamic evolution approach.

This study describes a dynamic non-linear mathematical approach for modeling the course of disease in acquired brain injury (ABI) patients. Data from a multicentric study were used to evaluate the reliability of the Michaelis-Menten (MM) model applied to well-known clinical variables that assess the outcome of ABI patients. The sample consisted of 156 ABI patients admitted to eight neurorehabilitation subacute units and evaluated at baseline (T0), 4 months after the event (T1) and at discharge (T2). The MM model was used to characterize the trend of the first Principal Component Analysis (PCA) dimension (represented by the variables: feeding modality, RLAS, ERBI-A, Tracheostomy, CRS-r and ERBI-B) in order to predict the most plausible outcome, in terms of positive or negative Glasgow outcome score (GOS) at discharge. Exploring the evolution of the PCA dimension 1 over time, after day 86 the MM model better differentiated between the time course for individuals with a positive and negative GOS (accuracy: 85%; sensitivity: 90.6%; specificity: 62.5%). The non-linear dynamic mathematical model can be used to provide more comprehensive trajectories of the clinical evolution of ABI patients during the rehabilitation period. Our model can be used to address patients for interventions designed for a specific outcome trajectory.

Cognitive and psychological outcomes and follow-up in severely affected COVID-19 survivors admitted to a rehabilitation hospital.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents the most recent severe pandemic resulting in coronavirus disease 2019 (COVID-19). COVID-19 can damage the central nervous system, requiring admission to intensive care units (ICU) and aggressive treatments (long-term ventilatory assistance and sedation) to stabilize vitals. Most post-COVID-19 patients experience cognitive impairments and mood or stress disorders. We aimed to study the frequency of cognitive deficits in COVID-19 survivors, the relationship between clinical factors in the acute phase and cognitive outcomes, affective states, and quality of life. We explored cognitive reserve (CR) role, as a post-COVID-19 resilience factor. METHODS: Twenty-nine COVID-19 inpatients were assessed using a neuropsychological battery, mood scales, quality of life, and social integration questionnaires. Twenty-five were retained through telephone follow-up to monitor cognitive sequelae, affective states, and reintegration levels roughly 8 months after hospital discharge. We administered the Cognitive Reserve Index questionnaire. RESULTS: We found most patients display no cognitive deficits. When they did, multi-domain impairment occurred most frequently, especially involving executive functions. Results revealed a significant correlation between depression levels and the interval between ICU admission and tracheal tube removal. We found increased levels of depression and anxiety at follow-up, a significant relationship between resuming daily life activities, high CR, and executive functions. CONCLUSIONS: These findings suggest the importance of psychological support in the long term and the modulating role of cognitive reserve in quality of life after infection.

Cognition in COVID-19 infected patients undergoing invasive ventilation: results from a multicenter retrospective study.

A growing number of scientific contributions suggest that COVID-19 infection can lead to impairment of cognition, mainly in executive functions and memory domains, even in the absence of frank neurological pathologies.The primary objective of this retrospective study is to evaluate the frequency and type of inefficiencies in a selection of cognitive tests administered to a sample of subjects who, following infection, required invasive assisted ventilation and were admitted to rehabilitation wards for the treatment of functional impairment.Fifty-seven subjects were enrolled. The recruited patients undergone an assessment of verbal and visuospatial memory and executive functions, upon entry into the rehabilitation department, after discharge from intensive care. The following tests were administered: Rey Auditory Verbal Learning Test (AVLT) (immediate and delayed recall), Rey-Osterrieth Complex Figure Test (ROCFT) (copy and delayed recall), Stroop Color-Word Test, and Trail Making Test (TMT, A and B).Deficient scores, in beyond 25% of subjects, were found in the copy of the ROCFT (32.1% of subjects), and in the delayed recall of ROCFT (27.2%). Between 10 and 20% of patients presented an abnormal result in delayed recall of AVLT (16.07%), and Stroop Test (time, 15.6%, error, 11.5%). Less than 10% of the sample had abnormal performances on TMT (A, 3.5%, and B, 9.4%), and in AVLT immediate recall (8.9%). Correlations of the performances with age, sex, and education were also found.This paper highlights the high incidence of abnormal cognitive performances in this specific subpopulation of patients with COVID-19 infection.

Long term effects of severe acquired brain injury: A follow-up investigation on the role of cognitive reserve on cognitive outcomes.

In a recent study we showed that Cognitive Reserve (CR) did not significantly predict the neuropsychological outcomes of patients with severe Acquired Brain Injury (sABI), after a rehabilitation program. The present study aims to extend the previous results by assessing the role of CR on long-term neuropsychological outcomes of a subgroup (N = 27) of that same population. Patients took part in a telephone interview, where Tele-Global Examination Mental State (Tele-GEMS) and Glasgow Outcome Scale Extended (GOS-E) were administered. A linear regression model was conducted considering Tele-GEMS and GOS-E as dependent variables, while the scores on Cognitive Reserve Index questionnaire (CRIq), Disability Rating Scale (DRS), and Level of Cognitive Functioning (LCF), administered at discharge, were considered as predictors. Results show that higher levels of CR and LCF, significantly predicted cognitive performance 4 years later. However, in the same follow-up, CR did not predict functional outcome, which was only predicted by lower disability scores at discharge. Thus, even if CR seems not showing an effect on cognitive efficiency when tested after the first rehabilitation intervention, current results show that CR has significant effects on long-term cognitive outcomes.

Robot-assisted rehabilitation for children with neurological disabilities: Results of the Italian consensus conference CICERONE.

BACKGROUND: The use of robotic technologies in pediatric rehabilitation has seen a large increase, but with a lack of a comprehensive framework about their effectiveness. OBJECTIVE: An Italian Consensus Conference has been promoted to develop recommendations on these technologies: definitions and classification criteria of devices, indications and limits of their use in neurological diseases, theoretical models, ethical and legal implications. In this paper, we present the results for the pediatric age. METHODS: A systematic search on Cochrane Library, PEDro and PubMed was performed. Papers published up to March 1st, 2020, in English, were included and analyzed using the methodology of the Centre for Evidence-Based Medicine in Oxford, AMSTAR2 and PEDro scales for systematic reviews and RCT, respectively. RESULTS: Some positives aspects emerged in the area of gait: an increased number of children reaching the stance, an improvement in walking distance, speed and endurance. Critical aspects include the heterogeneity of the studied cases, measurements and training protocols. CONCLUSION: Many studies demonstrate the benefits of robotic training in developmental age. However, it is necessary to increase the number of trials to achieve greater homogeneity between protocols and to confirm the effectiveness of pediatric robotic rehabilitation.

Six-month outcomes in patients with hemorrhagic and non-hemorrhagic traumatic disorders of consciousness.

BACKGROUND: Intracranial hematomas (IHs) occur commonly after severe traumatic brain injury, but their effects on outcomes in patients with prolonged disorders of consciousness (DoC) following coma (i.e., unresponsive wakefulness syndrome and minimally conscious state) are unknown. METHODS: In this multicenter longitudinal study, we compared clinical outcomes and serum neurofilament light chain (NFL) levels of 52 patients with traumatic DoC with (n = 35) and without (n = 17) IH in the acute phase. Patients were evaluated with the Coma Recovery Scale-Revised (CRS-R) at enrollment (1-3 months post-injury) and with the CRS-R, extended Glasgow Outcome Scale (GOSE), and Functional Independence Measure (FIM) at 6 months post-injury. At the same timepoints, serum NFL levels were compared between patients with and without IHs and with those of 52 sex- and age-matched healthy controls. RESULTS: Patients with and without IH did not differ in terms of DoC or CRS-R scores at admission, or clinical outcomes (death, unresponsive wakefulness syndrome, minimally conscious state, or emergence from minimally conscious state) or CRS-R, GOSE, or FIM scores 6 months post-injury. NFL levels were significantly higher in patients than in controls at admission and 6 months post-injury (both p < 0.0001), but they did not differ between patients with and without IH. CONCLUSIONS: This study showed that IHs do not affect clinical outcomes or markers of axonal degeneration in patients with traumatic DoC.

Thyrotropic Axis and Disorders of Consciousness in Acquired Brain Injury: A Potential Intriguing Association?

Purpose: A potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI). Methods: This retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients. Results: Lower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (ß=0.655, p=0.002) and cognitive functions (ß=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes. Conclusions: Serum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

Redefining a minimal rehabilitation assessment protocol for severe acquired brain injuries.

BACKGROUND: The assessment of patients with severe Acquired Brain Injury (sABI) is mandatory in every phase and setting of care, and requires a multidimensional and interdisciplinary approach, to develop the individual rehabilitation project, and monitor long-term functional outcomes. In 2001 the Italian Society of Physical and Rehabilitation Medicine (SIMFER) published the minimal assessment protocol for traumatic sABI, providing a comprehensive, standardized functional assessment based on the International Classification of Functioning, Disability and Health (ICF), 2001. In 2007, a new protocol was published, extended to all sABI patients (PMGCA). In 2019, the SIMFER appointed a working group to provide a revised, updated version: the PMGCA2020. AIM: The purpose of this study was to describe the minimal assessment protocol to be applied at every stage and setting of the care process of patients with sABI. METHODS: The working group, including one neurologist and 11 physiatrists experts in sABI rehabilitation, performed a review of the international recommendations for sABI assessment focusing on the following key words: "sABI assessment," "sABI rehabilitation," "sABI prognostic factors," "sABI rehabilitation assessment," "sABI outcome," in MEDLINE. Revision and integration proposals by each member were written and motivated, discussed and voted. RESULTS: The PMGCA2020 is addressed to sABI adult patients. It investigates the main clinical problems of sABI at any time of the rehabilitation pathway. It includes a demographic/anamnestic section, a clinical/functional assessment section and an outcome measures section following the ICF model of functioning and the model of the construction of the rehabilitation project. CONCLUSIONS: The PMGCA2020 provides an updated tool for the multidimensional rehabilitation assessment of sABI patients, at any stage of the rehabilitation pathway. Further studies will allow the validation of this minimum set of variables paving the way to an assessment standardization of patients with sABI in the rehabilitation settings. CLINICAL REHABILITATION IMPACT: This minimum set of variables, defining patient's functioning and clinical status and outcomes, at every stage and setting of the care process to provide a framework for the standardization of the clinical evaluation of patients with sABI in rehabilitation settings.

Effectiveness of action observation therapy based on virtual reality technology in the motor rehabilitation of paretic stroke patients: a randomized clinical trial.

BACKGROUND: The rehabilitation of paretic stroke patients uses a wide range of intervention programs to improve the function of impaired upper limb. A new rehabilitative approach, called action observation therapy (AOT) is based on the discovery of mirror neurons and has been used to improve the motor functions of adult stroke patients and children with cerebral palsy. Recently, virtual reality (VR) has provided the potential to increase the frequency and effectiveness of rehabilitation treatment by offering challenging and motivating tasks.  METHODS: The purpose of the present project is to design a randomized controlled six-month follow-up trial (RCT) to evaluate whether action observation (AO) added to standard VR (AO + VR) is effective in improving upper limb function in patients with stroke, compared with a control treatment consisting of observation of naturalistic scenes (CO) without any action content, followed by VR training (CO + VR). DISCUSSION: AO + VR treatment may provide an addition to the rehabilitative interventions currently available for recovery after stroke and could be utilized within standard sensorimotor training or in individualized tele-rehabilitation. TRIAL REGISTRATION: The trial has been prospectively registered on ClinicalTrials.gov. NCT05163210 . 17 December 2021.

Cognitive reserve index and functional and cognitive outcomes in severe acquired brain injury: A pilot study.

BACKGROUND: Many variables affect outcome after brain injury. Cognitive reserve (CR) is a subjective factor that reflects a set of personal characteristics and that differentiates individuals. It may influence an individual's capacity to react to brain injury. OBJECTIVE: To study the effects of cognitive reserve on functional and cognitive outcome at the end of rehabilitation, in patients with severe acquired brain injury (sABI), by means of the Cognitive Reserve Index questionnaire (CRIq). METHODS: We report a retrospective study of a continuous series of sABI patients on first admission to a rehabilitation center. Disability and cognitive outcomes were recorded. RESULTS: In the 94 patients enrolled, the assessments after rehabilitation showed a significant gain measured with the disability Rating Scale for patients with a higher CR (CRIq≥ 85). A significant negative correlation was found: between CRIq scores and the interval elapsing before first access to neuropsychological assessment, between CRIq scores, especially level of education, and tests that measure the same domain (attention). CONCLUSIONS: Improvements in overall and cognitive disability emerged, but CR did not seem to substantially influence outcome in this sample of patients. This result may be partly due to the clinical severity of the population studied and the sample's dimension, although quantitatively representative of the population.

The importance of assessing parent stress in families with children with severe neuromotor and intellectual disability - a pilot study.

Parent-related stress represents the level of dysfunction in the parent-child system related to the parents' functioning. The aim of this retrospective pilot study was to assess the degree of stress perceived by mothers and fathers, in the framework of a family-centred approach to rehabilitation.We considered 43 parents of 29 children with cerebral palsy, genetic disorders or brain injury admitted to a neurological rehabilitation center. Parenting stress was assessed with the Parenting Stress Index - Short Form (PSI-SF) self-report questionnaire and a semi-structured investigation of situational stress factors of the family. The cognitive and motor disability of the children were assessed with the Diagnostic and Statistical Manual of Mental Disorders 5(DSM-5) and the Gross Motor Function Classification System-(GMFCS), respectively.The results showed that parental stress is directly correlated with the level of cognitive and behavioral disability and not with motor disability. No significant difference was found in the level of stress perceived by mothers and fathers. The effect of a worsening occupational situation seemed to influence the perception of stress more than a change in the formal relationship of the couple, but neither was statistically significant.

Development of a generic version of the multiple errands test for severe acquired brain injuries.

BACKGROUND: Impairment of executive functions is a frequent and disabling consequence of brain injury. In 1991, Shallice and Burgess elaborated the Multiple Errand Test (MET) to assess everyday troubles associated with this impairment. OBJECTIVE: Our first aim was to create a generic version of MET (MET-G) readily adaptable to different settings and for retesting. The second aim was to validate the revised version to detect executive impairment in individuals with severe ABI. METHODS: An inter-professional team of experts in neurorehabilitation created a revised version of MET. Twenty-one patients with sABI (severe Acquired Brain Injury) and a control group of 20 neurologically healthy subjects, took part in the testing of MET-G. RESULTS: MET-G clearly distinguished people with sABI from healthy controls based on Total error score, task completion, and rule breaking. The test showed good inter-rater reliability and internal consistency. CONCLUSIONS: The new, generic version of MET was able to differentiate adults with sABI from controls and proved to be a good tool for evaluating executive functions in these patients in daily-life contexts. Indications on how to adapt the test to different contexts and different scoring modalities are provided.

User-centered practices in the eyes of informal caregivers of in-patients with severe acquired brain injury: needs, caring experience, and satisfaction.

OBJECTIVE: This study examines the perceived needs, experience, and satisfaction of informal caregivers (ICGs) in in-hospital settings, related to their involvement in the design and delivery of services together with hospital staff, namely co-production. DESIGN: To obtain a picture of current ICG-staff relationship, a multicenter observational study was carried out. Participants were 75 ICGs recruited in five dedicated in-patient neurorehabilitation wards. Participants answered a self-report questionnaire tapping perceived information/communication needs, emotional/social needs, and their satisfaction; family-centered practices implemented by the staff (namely involving practices and cooperative communication); and ICGs' satisfaction with the service. RESULTS: Need satisfaction related positively to staff practices aimed at involving IGCs in treatment and training, but not in decision-making. Involving practices concerning treatment also related positively to ICGs' information/communication needs. In addition, the more the staff involved ICGs in decision-making and promoted cooperative communication regarding treatment, the more ICGs felt that their collaboration in the healthcare process was valuable. Finally, all involvement practices and cooperative communication were positively related to ICGs' overall satisfaction with the service. CONCLUSION: The results of the study help to identify gaps in meeting ICGs' needs and to promote strategies to implement family participation toward co-production in in-hospital settings.

Sustained Axonal Degeneration in Prolonged Disorders of Consciousness.

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1-3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients' serum NFL levels were significantly higher than those of controls at 1-3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1-3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

Rehabilitation in a rare case of coffin-siris syndrome with major cognitive and behavioural disorders.

BACKGROUND: Coffin-Siris syndrome is a rare genetic disease with heterozygous variants in the ARID1A, ARID1B, ARID2, DPF2, SMARCA4, SMARCB1, SMARCE1 or SOX11 genes. It may manifest with somatic anomalies, deafness, urogenital malformations, recurrent infections, mental retardation, speech deficit, agenesis of the corpus callosum, convulsions, hypotonia, developmental delay, and scoliosis. CASE REPORT: A 14-year-old boy with Coffin-Siris syndrome due to variants in the ARID1A gene was referred to the clinic. His rehabilitation over a 9-year period was described. The problem of assessment and the approach to rehabilitation was discussed, enabling a progressive remodelling of the cognitive-behavioural disorders that most hindered the possibility of his acquiring new skills and achieving social and family integration. CLINICAL REHABILITATION: A protracted, customised, multiprofessional rehabilitation approach, centred on realistic functional objectives, implemented with the direct involvement of the family and school, was the only way to achieve the maximum independence and social and family integration permitted by his residual disability.