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Background/Objectives: Stroke remains a major cause of disability and death, with survivors facing significant physical, cognitive, and emotional challenges. Rehabilitation is crucial for recovery, but outcomes can vary widely. Cognitive reserve (CR) has emerged as a factor influencing these outcomes. This systematic review evaluates the role of CR in post-stroke rehabilitation, examining whether higher CR is associated with better outcomes. Methods: A systematic search of PubMed, Google Scholar, Scopus, and Cochrane Library databases was conducted for studies published between 2004 and 2024. Studies examining social-behavior CR proxies (e.g., education, bilingualism) and their impact on post-stroke outcomes were included. Data were analyzed using descriptive statistics. The study quality was assessed using the Methodological Index for NOn-Randomized Studies (MINORS) scale. Results: Among 3851 articles screened, 27 met the inclusion criteria. Higher education levels, bilingualism, and engagement in cognitively stimulating activities were associated with better cognitive outcomes and functional recovery. Lower socioeconomic status (SES) correlated with poorer outcomes. Early rehabilitation and dynamic CR proxies showed stronger associations with cognitive recovery than static ones. Conclusions: CR may predict post-stroke rehabilitation outcomes, with education, bilingualism, and active engagement in cognitive activities showing potential benefits. Future research should explore CR’s role alongside factors like lesion location and severity in enhancing recovery.

Abstract 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.

Abstract 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.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96-0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89-0.96; P < 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications.

Background/Objectives: Stroke remains a major cause of disability and death, with survivors facing significant physical, cognitive, and emotional challenges. Rehabilitation is crucial for recovery, but outcomes can vary widely. Cognitive reserve (CR) has emerged as a factor influencing these outcomes. This systematic review evaluates the role of CR in post-stroke rehabilitation, examining whether higher CR is associated with better outcomes. Methods: A systematic search of PubMed, Google Scholar, Scopus, and Cochrane Library databases was conducted for studies published between 2004 and 2024. Studies examining social-behavior CR proxies (e.g., education, bilingualism) and their impact on post-stroke outcomes were included. Data were analyzed using descriptive statistics. The study quality was assessed using the Methodological Index for NOn-Randomized Studies (MINORS) scale. Results: Among 3851 articles screened, 27 met the inclusion criteria. Higher education levels, bilingualism, and engagement in cognitively stimulating activities were associated with better cognitive outcomes and functional recovery. Lower socioeconomic status (SES) correlated with poorer outcomes. Early rehabilitation and dynamic CR proxies showed stronger associations with cognitive recovery than static ones. Conclusions: CR may predict post-stroke rehabilitation outcomes, with education, bilingualism, and active engagement in cognitive activities showing potential benefits. Future research should explore CR's role alongside factors like lesion location and severity in enhancing recovery. [ABSTRACT FROM AUTHOR]

Abstract 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.

PurposeA 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).MethodsThis 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.ResultsLower 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 (β=0.655, p=0.002) and cognitive functions (β=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes.ConclusionsSerum 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.

Patients suffering from rheumatic inflammatory diseases, e.g., systemic sclerosis, rheumatoid arthritis, and ankylosing spondylitis, are at risk of low bone mass. Dual-energy X-ray Absorptiometry (DXA) is the traditional radiological measurement technique for bone mineral density (BMD). The recently developed trabecular bone score (TBS) enhances the skeletal information provided by standard BMD. It re-analyzes the spatial dynamics of pixel intensity changes in lumbar spine DXA images, defining a quantitative index, characterizing trabecular bone microarchitecture. It has been demonstrated that low TBS values are associated with an increased incidence of fractures in patients with rheumatic diseases. These methods used together for bone damage evaluation can be of value to identify individuals who will potentially fracture. The main scientific literature on the clinical aspects of osteoporosis, including the use of TBS in evaluating this pathology, are herein reported aimed at shedding light on the role trabecular bone score plays in chronic inflammatory rheumatic diseases.

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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

(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.

Although comorbidities have a well-known impact on the functional recovery of patients with disorders of consciousness, including coma, vegetative state (VS), and minimally conscious state (MCS), a specific tool for their assessment in this challenging group of patients is lacking. For this aim, a multistep process was used to develop and validate the Comorbidities Coma Scale (CoCoS) in a sample of 162 patients with a diagnosis of coma, VS or MCS admitted to four Acute Inpatient Rehabilitation Units. To establish the psychometric properties of the scale, content validity, and internal consistency were investigated through Exploratory Factor Analysis in the whole sample (n = 162). Interrater reliability, assessed by the weighted Cohen's kappa (Kw), and concurrent validity of the scale as compared to the Greenfield Scale, assessed by ρ Spearman's correlation coefficient, were investigated in a subsample of patients (n = 52) within two of the above units. Our findings provided evidence of a good content validity of the scale, with the identification of a 12-factor structure representing the different comorbid dimensions of the target population. Inter-rater reliability was excellent in both the rehabilitation units where the assessment was made [Kw 0.98 (95% CI 0.96–0.99)]. CoCoS total scores correlated significantly with total scores of the Greenfield Scale (ρ = 0.932, 95% CI 0.89–0.96; P < 0.0001) indicating that CoCoS has concurrent validity while being more informative about the specific pattern of comorbidities of these challenging patients. The CoCos is a new tool which standardizes the approach to assessment of comorbid conditions and reliably identifies the category and severity of each comorbidity detected. It may be used for both clinical and research applications.

Late recovery of consciousness in vegetative state is considered as an exceptional outcome and has been reported prevalently in patients who suffered a traumatic brain injury. In these patients, the benefits of prolonging the rehabilitation, aimed at the recovery of autonomy in basic everyday activities, has been demonstrated. Here, we describe the application of an intensive multi-professional rehabilitation program carried out on a young female patient, with exceptionally late recovery of consciousness, specifically, after 7 years of vegetative state due to severe brain hemorrhage. Neuropsychological and functional assessment was conducted before and after the end of the rehabilitation program. In addition, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)-based probabilistic tractography were performed. Two follow-up neuropsychological and functional assessments were also conducted 6 and 29 months after the conclusion of the program. Functional results showed an improvement, maintained over time, in walking with assistance, cognitive efficiency, visual acuity and visual field, dysarthria, and execution of activities of daily living. Moreover, functional and structural magnetic resonance imaging (MRI) data documented the existence of preserved neural networks involved in sensory, motor, and linguistic tasks, which in all likelihood support the recovery process. This report suggests the possibility of undertaking an intensive rehabilitation program in patients who remain for long periods in altered states of consciousness, in spite of early negative prognosis.

Objective: The Bells Test is a cancelation task that is widely used for the diagnosis of unilateral spatial neglect (USN). With the aim of fostering more reliable use of this instrument, we set out to develop new norms adjusted for the possible influence of age, gender and education. We worked on the original version of the test.Methods: Normative data were collected from 401 healthy participants aged between 20 and 80 years. Individual factors that could affect performance (i.e., gender, age, and years of education) were considered. We computed several indices on the Bells Test including an asymmetry score, an accuracy score and execution time. Multiple regression analyses (for time measures) and generalized linear models (for accuracy measures) were used to check for the influence of individual predictors of performance on the Bells Test.Results: Data indicated a significant influence of age on the accuracy score and execution time variables and a marginally significant effect of education on the accuracy score variable. Wherever appropriate, cut-offs are provided for the three dependent scores on the Bells Test corrected for age and education.Conclusion: Based on a large normative sample, the present study provides new normative data on the Bells Test, which could lead to its reliable use in the diagnosis of USN.

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 (β = −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. [ABSTRACT FROM AUTHOR]

Nosocomial or hospital acquired pneumonia (HAP) is an illness contracted during a hospital stay, generally with onset 48 hours or more after admission to hospital, or within 14 days of discharge from hospital. HAP is divided into subgroups: Ventilator-associated pneumonia (VAP), accounting for 86% of hospital acquired pneumonia, and stroke-associated pneumonia (SAP). The incidence of SAP in neurological intensive care units (NICUs) is 4.1-56.6%, in medical intensive care units (MICUs) it is 17-50%, in stroke units it is 3.9-44% and in rehabilitation it is 3.2-11%, whereas in intensive rehabilitation following severe cranial trauma, the reported incidence of HAP is between 3.9 and 12% of cases. The aim of this study is to evaluate the cases of HAP occurring in a continuous series of patients with severe acquired brain injury (sABI) admitted to intensive rehabilitation units. The data collected can help evaluate the growing complexity of early rehabilitation of these patients, starting from how lung infections interfere with hospital stays and rehabilitation outcomes. This prospective observational cohort study evaluates, from 01/01/2015 to 31/12/2015, for patients with sABI on first admission to intensive neurological rehabilitation, the frequency of HAP and its impact on patient outcomes and complexity of care. A total of 61 patients were enrolled: 39 males and 22 females, average age 59.5 years (17-88 yrs, SD 3.53), coming from critical care (n=52), medical units (n=5), neurosurgery (n=3) and surgical units (n=1). The aetiology of hospital admission was haemorrhagic in 36% of cases, traumatic in 36%, anoxic in 13.1%, infectious in 6.5%, ischaemic in 4.9%, and other causes in 3.2%. Among the patients, 93.44% had received antibiotic therapy in their unit of provenance, and in 61.27% of cases a multidrug resistant (MDR) bacterium was isolated. On enrolment, 26 patients presented respiratory insufficiency, 29 subjects were in oxygen therapy, and 4 under invasive mechanical ventilation. There were 54 tracheostomized patients, 33 patients with percutaneous endoscopic gastrostomy (PEG) tubes, and 23 with nasogastric (NG) tubes. In 2015, among these subjects admitted to neurological rehabilitation, the incidence of HAP was 13.1%. For these 8 pneumonia cases, it was possible to isolate the bacterium in 62.5% of cases, and the detected microorganisms were K. pneumoniae (n=2), P. aeruginosa (n=1), P. mirabilis (n=1), S. maltophilia (n=1), E. cloacae + MRSCoN (n=1). Compared to the literature data, the results of the first year of monitoring show a slight increase in HAP cases (13.1%) in severe brain injury patients on first admission to neurological rehabilitation. These preliminary results need to be further confirmed and monitored over time. The findings moreover confirm the criticality and complexity of care for these patients admitted to neurological rehabilitation units.

The complexity of simultaneous impairments in persons with severe acquired brain injury calls for coordinated work by a team of specialists in order to optimise residual potential and deal immediately with aspects that interfere with recovery. Here we propose a review of the main critical aspects that can interfere with neuropsychological rehabilitation in these subjects in the post-acute intensive rehabilitation stage: associated damage, complications, sensory and motor impairment and pharmacological treatment.