Predicting models for arm impairment: External validation of the Scandinavian models and identification of new predictors in post-acute stroke settings.

BACKGROUND: Post-stroke arm impairment at rehabilitation admission as predictor of discharge arm impairment was consistently reported as extremely useful. Several models for acute prediction exist (e.g. the Scandinavian), though lacking external validation and larger time-window admission assessments. OBJECTIVES: (1) use the 33 Fugl-Meyer Assessment-Upper Extremity (FMA-UE) individual items to predict total FMA-UE score at discharge of patients with ischemic stroke admitted to rehabilitation within 90 days post-injury, (2) use eight individual items (seven from the Scandinavian study plus the top predictor item from objective 1) to predict mild impairment (FMA-UE≥48) at discharge and (3) adjust the top three models from objective 2 with known confounders. METHODS: This was an observational study including 287 patients (from eight settings) admitted to rehabilitation (2009-2020). We applied regression models to candidate predictors, reporting adjusted R2, odds ratios and ROC-AUC using 10-fold cross-validation. RESULTS: We achieved good predictive power for the eight item-level models (AUC: 0.70-0.82) and for the three adjusted models (AUC: 0.85-0.88). We identified finger mass flexion as new item-level top predictor (AUC:0.88) and time to admission (OR = 0.9(0.9;1.0)) as only common significant confounder. CONCLUSION: Scandinavian item-level predictors are valid in a different context, finger mass flexion outperformed known predictors, days-to-admission predict discharge mild arm impairment.

Long-term trajectories of community integration: identification, characterization, and prediction using inpatient rehabilitation variables.

BACKGROUND: Community integration (CI) is often regarded as the foundation of rehabilitation endeavors after stroke; nevertheless, few studies have investigated the relationship between inpatient rehabilitation (clinical and demographic) variables and long-term CI. OBJECTIVES: To identify novel classes of patients having similar temporal patterns in CI and relate them to baseline features. METHODS: Retrospective observational cohort study analyzing (n = 287) adult patients with stroke admitted to rehabilitation between 2003 and 2018, including baseline Functional Independence Measure (FIM) at discharge, follow-ups (m = 1264) of Community Integration Questionnaire (CIQ) between 2006 and 2022. Growth mixture models (GMMs) were fitted to identify CI trajectories, and baseline predictors were identified using multivariate logistic regression (reporting AUC) with 10-fold cross validation. RESULTS: Each patient was assessed at 2.7 (2.2-3.7), 4.4 (3.7-5.6), and 6.2 (5.4-7.4) years after injury, 66% had a fourth assessment at 7.9 (6.8-8.9) years. GMM identified three classes of trajectories.Lowest CI (n=105, 36.6%): The lowest mean total CIQ; highest proportion of dysphagia (47.6%) and aphasia (46.7%), oldest at injury, largest length of stay (LOS), largest time to admission, and lowest FIM.Highest CI (n=63, 21.9%): The highest mean total CIQ, youngest, shortest LOS, highest education (27% university) highest FIM, and Intermediate CI (n=119, 41.5%): Intermediate mean total CIQ and FIM scores. Age at injury OR: 0.89 (0.85-0.93), FIM OR: 1.04 (1.02-1.07), hypertension OR: 2.86 (1.25-6.87), LOS OR: 0.98 (0.97-0.99), and high education OR: 3.05 (1.22-7.65) predicted highest CI, and AUC was 0.84 (0.76-0.93). CONCLUSION: Novel clinical (e.g. hypertension) and demographic (e.g. education) variables characterized and predicted long-term CI trajectories.

The impact of COVID-19 on home, social, and productivity integration of people with chronic traumatic brain injury or stroke living in the community.

ABSTRACT: Compare community integration of people with stroke or traumatic brain injury (TBI) living in the community before and during the coronavirus severe acute respiratory syndrome coronavirus 2 disease (COVID-19) when stratifying by injury: participants with stroke (G1) and with TBI (G2); by functional independence in activities of daily living: independent (G3) and dependent (G4); by age: participants younger than 54 (G5) and older than 54 (G6); and by gender: female (G7) and male (G8) participants.Prospective observational cohort studyIn-person follow-up visits (before COVID-19 outbreak) to a rehabilitation hospital in Spain and on-line during COVID-19.Community dwelling adults (≥18 years) with chronic stroke or TBI.Community integration questionnaire (CIQ) the total-CIQ as well as the subscale domains (ie, home-CIQ, social-CIQ, productivity CIQ) were compared before and during COVID-19 using the Wilcoxon ranked test or paired t test when appropriate reporting Cohen effect sizes (d). The functional independence measure was used to assess functional independence in activities of daily living.Two hundred four participants, 51.4% with stroke and 48.6% with TBI assessed on-line between June 2020 and April 2021 were compared to their own in-person assessments performed before COVID-19.When analyzing total-CIQ, G1 (d = -0.231), G2 (d = -0.240), G3 (d = -0.285), G5 (d = -0.276), G6 (d = -0.199), G7 (d = -0.245), and G8 (d = -0.210) significantly decreased their scores during COVID-19, meanwhile G4 was the only group with no significant differences before and during COVID-19.In productivity-CIQ, G1 (d = -0.197), G4 (d = -0.215), G6 (d = -0.300), and G8 (d = -0.210) significantly increased their scores, meanwhile no significant differences were observed in G2, G3, G5, and G7.In social-CIQ, all groups significantly decreased their scores: G1 (d = -0.348), G2 (d = -0.372), G3 (d = -0.437), G4 (d = -0.253), G5 (d = -0.394), G6 (d = -0.319), G7 (d = -0.355), and G8 (d = -0.365).In home-CIQ only G6 (d = -0.229) significantly decreased, no significant differences were observed in any of the other groups.The largest effect sizes were observed in total-CIQ for G3, in productivity-CIQ for G6, in social-CIQ for G3 and in home-CIQ for G6 (medium effect sizes).Stratifying participants by injury, functionality, age or gender allowed identifying specific CIQ subtotals where remote support may be provided addressing them.

Long-term trajectories of motor functional independence after ischemic stroke in young adults: Identification and characterization using inpatient baseline assessments.

BACKGROUND: Stroke is a major worldwide cause of serious long-term disability. Most previous studies addressing functional independence included only inpatients with limited follow-up. OBJECTIVE: To identify novel classes of patients having similar temporal patterns in motor functional independence and relate them to baseline clinical features. METHODS: Retrospective observational cohort study, data were obtained for n = 428 adult patients with ischemic stroke admitted to rehabilitation (March 2005-March 2020), including baseline clinical features and follow-ups of motor Functional Independence Measure (mFIM) categorized as poor, fair or good. Growth mixture models (GMMs) were fitted to identify classes of patients with similar mFIM trajectories. RESULTS: GMM identified three classes of trajectories (1,664 mFIM assessments):C1 (11.2 %), 97.9% having poor admission mFIM, at 4.93 years 61.1% still poor, with the largest percentage of hypertension, neglect, dysphagia, diabetes and dyslipidemia of all three classes.C2 (23.1%), 99% had poor admission mFIM, 25% poor discharge mFIM, the largest percentage of aphasia and greatest mFIM gain, at 4.93 years only 6.2% still poor.C3 (65.7%) the youngest, lowest NIHSS, 37.7% poor admission mFIM, 73% good discharge mFIM, only 4.6% poor discharge mFIM, 90% good at 4.93 years. CONCLUSIONS: GMM identified novel motor functional classes characterized by baseline features.

The impact of coronavirus disease 2019 on emotional and behavioral stress of informal family caregivers of individuals with stroke or traumatic brain injury at chronic phase living in a Mediterranean setting.

INTRODUCTION: Even in nonpandemic times, persons with disabilities experience emotional and behavioral disturbances which are distressing for them and for their close persons. We aimed at comparing the levels of stress in emotional and behavioral aspects, before and during coronavirus disease 2019 (COVID-19), as reported by informal family caregivers of individuals with chronic traumatic brain injury (TBI) or stroke living in the community, considering two different stratifications of the recipients of care (cause and injury severity). METHODS: We conducted a STROBE-compliant prospective observational study analyzing informal caregivers of individuals with stroke (IC-STROKE) or traumatic brain injury (IC-TBI). IC-STROKE and IC-TBI were assessed in-person before and during COVID-19 online, using the Head Injury Behavior Scale (HIBS). The HIBS comprises behavioral and emotional subtotals (10 items each) and a total-HIBS. Comparisons were performed using the McNemar's test, Wilcoxon signed-rank test or t-test. Recipients of care were stratified according to their injury severity using the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS). RESULTS: One hundred twenty-two informal caregivers (62.3% IC-STROKE and 37.7% IC-TBI) were assessed online between June 2020 and April 2021 and compared to their own assessments performed in-person 1.74 ± 0.88 years before the COVID-19 lockdown. IC-STROKE significantly increased their level of stress during COVID-19 in five emotional items (impatience, frequent complaining, often disputes topics, mood change and overly sensitive) and in one behavioral item (overly dependent). IC-TBI stress level only increased in one behavioral item (impulsivity). By injury severity, (i) mild (14.7%) showed no significant differences in emotional and behavioral either total-HIBS (ii) moderate (28.7%) showed significant emotional differences in two items (frequent complaining and mood change) and (iii) severe (56.6%) showed significant differences in emotional (often disputes topics) and behavioral (impulsivity) items. CONCLUSIONS: Our results suggest specific items in which informal caregivers could be supported considering cause or severity of the recipients of care.

Loss of smell in patients with traumatic brain injury is associated with neuropsychiatric behavioral alterations.

OBJECTIVE: We sought to identify and correlate the severity of traumatic brain injuries (TBIs) associated with olfactory dysfunction with cognitive and behavioral profiles. PARTICIPANTS AND SETTING: Patients with TBI undergoing treatment in a specialized neuro-rehabilitation hospital. DESIGN: Prospective study. MAIN MEASURES: Glasgow Coma Scale (GCS) at the time of injury and during posttraumatic amnesia. Motor functions were assessed with the Functional Instrument Measure and Disability Rating Scales. The Wechsler Adult Intelligence test was used for neuropsychologic assessment and the Neuropsychiatric Inventory was used to assess behavioral changes. The Barcelona Smell Test-24 was used to study subjective smell loss. RESULTS: A total of 111 patients with TBI were enrolled (33 females; mean age 32.86 years); 38.73% exhibited smell loss. Patients with no olfactory impairment (OI) had worse TBIs than those with OI (GCS scores 5.65 and 7.74, respectively); no significant differences in cognitive behaviors, such as attention memory, visuoperception, and visuoconstruction, were observed. However, patients with TBI and olfactory dysfunction showed statistically significant alterations in neuropsychiatric behavioral performances such as feeding when compared with patients with TBI without smell loss. CONCLUSION: Olfactory dysfunction in patients with a TBI correlates with altered neuropsychiatric behavioral performances such as feeding, sleeping, and motor behavior.

Predictive models for independence after stroke rehabilitation: Maugeri external validation and development of a new model.

BACKGROUND: Many efforts have been devoted to identify predictors of functional outcomes after stroke rehabilitation. Though extensively recommended, there are very few external validation studies. OBJECTIVE: To externally validate two predictive models (Maugeri model 1 and model 2) and to develop a new model (model 3) that estimate the probability of achieving improvement in physical functioning (primary outcome) and a level of independence requiring no more than supervision (secondary outcome) after stroke rehabilitation. METHODS: We used multivariable logistic regression analysis for validation and development. Main outcome measures were: Functional Independence Measure (FIM) (primary outcome), Functional Independence Staging (FIS) (secondary outcome) and Minimal Clinically Important Difference (MCID). RESULTS: Patients with stroke admitted to a rehabilitation center from 2006 to 2019 were retrospectively studied (N = 710). Validation of Maugeri models confirmed very good discrimination: for model 1 AUC = 0.873 (0.833-0.915) and model 2 AUC = 0.803 (0.749-0.857). The Hosmer-Lemeshow χ2 was 6.07(p = 0.63) and 8.91(p = 0.34) respectively. Model 3 yielded an AUC = 0.894 (0.857-0.929) (primary outcome) and an AUC = 0.769 (0.714-0.825) (MCID). CONCLUSIONS: Discriminative power of both Maugeri models was externally confirmed (in a 20 years younger population) and a new model (incorporating aphasia) was developed outperforming Maugeri models in primary outcome and MCID.

Neuropsychological Assessments of Patients With Acquired Brain Injury: A Cluster Analysis Approach to Address Heterogeneity in Web-Based Cognitive Rehabilitation.

We aimed to (1) apply cluster analysis techniques to mixed-type data (numerical and categorical) from baseline neuropsychological standard and widely used assessments of patients with acquired brain injury (ABI) (2) apply state-of-the-art cluster validity indexes (CVI) to assess their internal validity (3) study their external validity considering relevant aspects of ABI rehabilitation such as functional independence measure (FIM) in activities of daily life assessment (4) characterize the identified profiles by using demographic and clinically relevant variables and (5) extend the external validation of the obtained clusters to all cognitive rehabilitation tasks executed by the participants in a web-based cognitive rehabilitation platform (GNPT). We analyzed 1,107 patients with ABI, 58.1% traumatic brain injury (TBI), 21.8% stroke and 20.1% other ABIs (e.g., brain tumors, anoxia, infections) that have undergone inpatient GNPT cognitive rehabilitation from September 2008 to January 2021. We applied the k-prototypes algorithm from the clustMixType R package. We optimized seven CVIs and applied bootstrap resampling to assess clusters stability (fpc R package). Clusters' post hoc comparisons were performed using the Wilcoxon ranked test, paired t-test or Chi-square test when appropriate. We identified a three-clusters optimal solution, with strong stability (>0.85) and structure (e.g., Silhouette > 0.60, Gamma > 0.83), characterized by distinctive level of performance in all neuropsychological tests, demographics, FIM, response to GNPT tasks and tests normative data (e.g., the 3 min cut-off in Trail Making Test-B). Cluster 1 was characterized by severe cognitive impairment (N = 254, 22.9%) the mean age was 47 years, 68.5% patients with TBI and 22% with stroke. Cluster 2 was characterized by mild cognitive impairment (N = 376, 33.9%) mean age 54 years, 53.5% patients with stroke and 27% other ABI. Cluster 3, moderate cognitive impairment (N = 477, 43.2%) mean age 33 years, 83% patients with TBI and 14% other ABI. Post hoc analysis on cognitive FIM supported a significant higher performance of Cluster 2 vs. Cluster 3 (p < 0.001), Cluster 2 vs. Cluster 1 (p < 0.001) and Cluster 3 vs. Cluster 1 (p < 0.001). All patients executed 286,798 GNPT tasks, with performance significantly higher in Cluster 2 and 3 vs. Cluster 1 (p < 0.001).

Cognition assessments to predict inpatient falls in a subacute stroke rehabilitation setting.

Background: Stroke-related falls occur at especially high rates in rehabilitation settings. Inpatient-hospital falls have been identified as one of the most common medical complications after stroke, negatively influencing recovery, nevertheless, the role of cognition in relation to falls during inpatient rehabilitation is largely unexplored. Objective. We aim to predict inpatient falls in a subacute stroke rehabilitation setting using previously reported variables such as stroke severity, gender, age, ataxia, hemiparesis, and functionality in activities of daily living, further extending them with specific cognition variables assessing memory, verbal fluency, attention, and orientation. Methods: This observational study included 158 stroke patients admitted to a rehabilitation center between 2007 and 2019, with less than 30 days since stroke onset to admission. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Four logistic regressions were performed including NIHSS, age, sex, ataxia, and hemiparesis plus one of the following: (1) Functional Independence Measure cognitive (C-FIM) and motor (M-FIM) subtests. (2) individual C-FIM items, (3) Ray Auditory Verbal Memory Test (RAVLT) and (4) verbal fluency test (PMR), Digit Span from Wechsler Adult Intelligence Scale (WAIS III), and Orientation from Test Barcelona. Results: Neither NIHSS, age, sex, ataxia nor hemiparesis predicted falls. C-FIM was a significant predictor (AUC:0.891), but not M-FIM. The problem solving C-FIM item (AUC:0.836), the RAVLT learning subtest (AUC:0.879), and PMR verbal fluency (AUC:0.871) were significant predictors for each model, respectively. Conclusions: Cognition assessments, i.e., one FIM item, one RAVLT item, or a one-minute verbal fluency test are significant falls predictors.

The impact of Body Mass Index on functional rehabilitation outcomes of working-age inpatients with stroke.

BACKGROUND: Stroke is the most relevant cause of acquired persistent disability in adulthood. The relationship between patient's weight during rehabilitation and stroke functional outcome is controversial, previous research reported positive, negative and no effects, with scarce studies specifically addressing working-age patients. AIM: To evaluate the association between Body Mass Index (BMI) and the functional progress of adult (<65 years) patients with stroke admitted to a rehabilitation hospital. DESIGN: Retrospective observational cohort study. SETTING: Inpatient rehabilitation center. POPULATION: 178 stroke patients (ischemic or hemorrhagic). METHODS: Point-biserial and Spearman's correlations, multivariate linear regressions and analysis of covariance were used to describe differences in functional outcomes after adjusting for age, sex, severity, dysphagia, depression and BMI category. Functional Independence Measure (FIM), FIM gain, efficiency and effectiveness were assessed. RESULTS: Participants were separated in 3 BMI categories: normal weight (47%), overweight (33%) and obese (20%). There were no significant differences between BMI categories in any functional outcome (total FIM [T-FIM], cognitive [C-FIM]), motor [M-FIM]) at discharge, admission, gain, efficiency or effectiveness. In regression models BMI (as continuous variable) was not significant predictor of T-FIM at discharge after adjusting for age, sex, severity, dysphagia, depression and ataxia (R2=0.4813), significant predictors were T-FIM at admission (ß=0.528) and NIHSS (ß=-0.208). M-FIM efficiency did not significantly differ by BMI subgroups, neither did C-FIM efficiency. Length of stay (LOS) and T-FIM effectiveness were associated for normal (r=0.33) and overweight (r=0.43), but not for obese. LOS and T-FIM efficiency were strongly negatively associated only for obese (r=-0.50). CONCLUSIONS: FIM outcomes were not associated to BMI, nevertheless each BMI category when individually considered (normal weight, overweight or obese) was characterized by different associations involving FIM outcomes and clinical factors. CLINICAL REHABILITATION IMPACT: In subacute post-stroke working-age patients undergoing rehabilitation, BMI was not associated to FIM outcomes (no obesity paradox was reported in this sample). Distinctive significant associations emerged within each BMI category, (supporting their characterization) such as length of stay and T-FIM effectiveness were associated for normal weight and overweight, but not for obese. Length of stay and T-FIM efficiency were strongly negatively associated only for obese.

Subacute ischemic stroke rehabilitation outcomes in working-age adults: The role of aphasia in cognitive functional independence.

BACKGROUND: About one-third of adult stroke patients suffer from aphasia when they are discharged from hospital. Aphasia seems to be a negative predictive factor affecting post-stroke functional recovery after rehabilitation, but this association has been scarcely addressed in previous research. OBJECTIVES: We aim to evaluate the impact of aphasia in cognitive functional outcomes in working-age first-ever ischemic stroke adults. METHODS: Retrospective observational cohort study. One hundred and thirty ischemic (≤ 64 years old) adult stroke patients (43.07% with aphasia) admitted to a rehabilitation center between 2007 and 2019 were analyzed. Univariate and multivariate linear regressions were performed using state-of-the-art variables (stroke severity, gender, age) extending them with potential confounders (e.g. diabetes, medication for depression). The cognitive subtest (C-FIM) of the Functional Independence Measure (FIM) at discharge and C-FIM gain were the dependent variables. RESULTS: Patients with aphasia (PWA) had lower C-FIM scores at admission and at discharge. No significant differences were observed in relation to C-FIM gain, C-FIM efficiency, C-FIM effectiveness and length of stay (LOS).C-FIM gain was remarkably higher though non-significant (p = .059) in PWA. Regression analysis identifies C-FIM at admission and aphasia as significant predictors of C-FIM at discharge (R2 = 0.72). The same variables plus taking medication for depression predicted C-FIM gain (R2 = 0.38). CONCLUSIONS: We identified no significant differences in C-FIM outcomes (gain, efficiency and effectiveness) either in LOS between PWA and patients without aphasia, though C-FIM differences were significant at admission and discharge. Aphasia was a significant predictor of C-FIM gain and C-FIM at discharge.

Predicting length of stay in patients admitted to stroke rehabilitation with severe and moderate levels of functional impairments.

Severe stroke patients are known to be associated with larger rehabilitation length of stay (LOS) but other factors besides severity may be contributing. We aim to identify LOS predictors within a population of mostly severe patients and analyze the impact of socioeconomic situation in functionality at admission.A retrospective observational cohort study was conducted including 172 inpatients admitted to a rehabilitation center between 2007 and 2019. Associations with LOS were examined among 30 potential predictor variables using bivariate correlations. Significantly correlated (P < .002, Bonferroni adjustment) variables were entered into 9 different multiple linear regression models.No mild participants were included, 63.37% severe and 36.63% moderate. Most significant LOS determinants were: 1) total functional independence measure (FIM) (P < .001) and hemiparesis (P = .0108) (adjusted R = 0.24), 2) cognitive FIM (P = .002) and severity (P = .001) (adjusted R = 0.22), and 3) home accessibility (P = .043) and hemiparesis (P = 0.032) (adjusted R = 0.19).Known LOS predictors (e.g., depression, ataxia) within the full stroke severities were not found significant in our dataset.Socioeconomic situation was found moderately correlated with total FIM (r = -0.32, P < .0001).When stratifying the patients' socioeconomic situation into mild, important, and severe social risk, their respective median total FIM at admission were 61.5, 50, and 41, with significant differences between the mild and important group (P < .001); also significant differences were found between mild and severe groups (P < .001).A few of the variables identified in the literature as significant predictors of LOS within the full stroke population were also significant for our dataset (National Institutes of Health Stroke Scale, FIM, home accessibility) explaining less than 25% of the LOS variance. Most of the 30 analyzed known predictors were not significant (e.g., depression, age, recurrent stroke, ataxia, orientation, verbal communication, etc) suggesting that factors outside functional, socioeconomic, medical, and demographics not included in this study (e.g., rehabilitation sessions intensity) have important influences on LOS for severe patients.Patients at mild social risk obtained significantly higher total FIM at admission than patients at important and severe social risk. The importance of socioeconomic situation has been scarcely studied in the literature in relation to functionality at admission; our results suggest that it requires to be considered.

Evidence of chronic stroke rehabilitation interventions in activities and participation outcomes: systematic review of meta-analyses of randomized controlled trials.

INTRODUCTION: Stroke is a leading cause of long-term disabilities worldwide. A great deal of meta-analyses of randomized controlled trials (RCTs) address rehabilitation in chronic stroke, several of them with focus on activities and participation, considered critical outcomes of successful rehabilitation. Nevertheless, substantial heterogeneity might exist between studies, the reported associations may be causal, but they might also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of interventions in chronic phase. Furthermore, most RCTs might focus on specific rehabilitation domains, not paying the same attention to others. EVIDENCE ACQUSITION: Formal evaluation of published systematic reviews of meta-analyses (January 2008 to November 2018) of rehabilitation in chronic phase to 1) assess the strength of evidence: participants, publication biases, heterogeneity, prediction intervals (PIs) 2) grade the evidence to perform qualitative analysis on effects sizes and heterogeneity, 3) perform meta-regressions and sensitivity analysis on relevant covariates 4) map outcomes to activities and participation domain of the World Health Organization's International Classification of Functioning, Disability and Health (ICF). Systematic review on meta-analyses of RCTs addressing activities and participation will be performed in Medline, Web of Science, Scopus, Cochrane and Google Scholar. EVIDENCE SYNTHESIS: A total of 97 meta-analyses on 31 different rehabilitation interventions involving 25,275 participants were included. Thirty-nine meta-analyses (40.74%) reported statistically significant findings (P<0.05) in both fixed and random effects sizes. Their magnitude was small in 62.96% cases, moderate in 19.75% and large in 17.28%. Heterogeneity was low in 48,48%, moderate and high in 21.2%. The mean number of participants is 815, far away from the convincing, highly suggestive, or suggestive required evidence levels. All PIs include the null value. Mobility is addressed by 87% of the identified meta-analyses, with 75% of them focusing exclusively in mobility. CONCLUSIONS: The findings of this study show a clear need for high quality RCTs examining the effectiveness of rehabilitation interventions addressing activities and participation. The ICF framework may contribute to a holistic approach in chronic stroke rehabilitation, including not only motor functioning but also the ability to participate in everyday life activities.

Olfactory Training Prevents Olfactory Dysfunction Induced by Bulbar Excitotoxic Lesions: Role of Neurogenesis and Dopaminergic Interneurons.

Glutamatergic excitotoxicity is involved in pathologies affecting the central nervous system, including traumatic brain injury (TBI) and neurodegenerative diseases, such as Parkinson's disease (PD), in which olfactory dysfunction is an early symptom. Interestingly, our group has recently shown that bilateral administration of the glutamate agonist, N-methyl-D-aspartate (NMDA) in the olfactory bulbs (OBs) induces an olfactory dysfunction 1 week after lesions. Although a wide range of treatments have been attempted, no standard therapy has been established to treat olfactory disorders. Increasing evidence suggests a beneficial effect of olfactory training (OT) in olfactory function. However, the mechanisms underlying OT effects remain unknown. We investigated the effects of OT on the olfactory dysfunction induced by excitotoxicity in bilateral OB NMDA-lesioned animals. We compared OT effects with the ones obtained with neuroprotective therapies (pramipexole and MK801). We studied the underlying mechanisms involved in OT effects investigating the changes in the subventricular zone (SVZ) neurogenesis and in the number of periglomerular dopaminergic interneurons. One week after lesion, NMDA decreased the number of correct trials in the olfactory discrimination tests in the non-trained group (p < 0.01). However, OT performed for 1 week after lesions prevented olfactory dysfunction (p < 0.01). Pramipexole did not prevent olfactory dysfunction, whereas MK801 treatment showed a partial recovery (p < 0.05). An increase in SVZ neurogenesis (p < 0.05) associated with an increase in OB dopaminergic interneurons (p < 0.05) was related to olfactory function prevention induced by OT. The present results suggest a role for dopaminergic OB interneurons underlying the beneficial effects of OT improving olfactory dysfunction in bilaterally OB NMDA-lesioned animals.

Quality of Life After Brain Injury: Psychometric Properties of the Spanish Translation of the QoLIBRI.

Traumatic brain injury (TBI) is frequently followed by a variety of physical, emotional, and cognitive symptoms, which affect the patient's daily life, their social relations, and their work/educational status. In addition to function measures, health-related quality of life (HRQoL) has received increasing attention as an important outcome after TBI, as it may guide rehabilitation and evaluate treatment success. Here, we report on psychometric properties of a Spanish translation of the quality of life after brain injury (QoLIBRI) questionnaire, a disease-specific instrument to assess HRQoL in patients after TBI. Classical test theory, item response theory, and structural equation modeling were used to evaluate psychometric properties of the Spanish QoLIBRI translation in a convenience sample of N = 155 patients with TBI. A subset of n = 23 patients were tested twice with a test-retest interval of ≤2 weeks. Internal consistency and test-retest reliabilities were high (Cronbach's α: 0.78-0.96; ICCs: 0.81-0.96). Rasch analysis infit (range 0.52-1.20) and outfit indices (range 0.50-1.17) supported unidimensionality of subscales, whereas SEM analysis tended to support a correlated six-factor model (CFI = .88, RMSEA = .068, 95% confidence interval [.061, .075]). Results show favorable psychometric properties of the Spanish translation of the QoLIBRI, comparable to the international version. It is, thus, a useful instrument for clinicians and researchers assessing the impact of TBI on quality of life, the outcomes of rehabilitation, and may be included in epidemiological surveys.

Feasibility of Aerobic Exercise in the Subacute Phase of Recovery From Traumatic Brain Injury: A Case Series.

BACKGROUND AND PURPOSE: Aerobic exercise is as important for individuals with traumatic brain injury (TBI) as for the general population; however, the approach to aerobic training may require some adaptation. The objective of the trial program was to examine the feasibility of introducing aerobic physical exercise programs into the subacute phase of multidisciplinary rehabilitation from moderate to severe TBI, which includes computerized cognitive training. CASE DESCRIPTION: Five individuals undergoing inpatient rehabilitation with moderate or severe TBIs who also have concomitant physical injuries. All of these individuals were in the subacute phase of recovery from TBIs. INTERVENTION: An 8-week progressive aerobic physical exercise program. Participants were monitored to ensure that they could both adhere to and tolerate the exercise program. In addition to the physical exercise, individuals were undergoing their standard rehabilitation procedures that included cognitive training. Neuropsychological testing was performed to gain an understanding of each individual's cognitive function. OUTCOMES: Participants adhered to both aerobic exercise and cognitive training. Poor correlations were noted between heart rate reserve and ratings of perceived effort. Two minor adverse events were reported. DISCUSSION: Despite concomitant physical injuries and cognitive impairments, progressive aerobic exercise programs seem feasible and well tolerated in subacute rehabilitation from moderate to severe TBI. Findings highlight the difficulty in measuring exercise intensity in this population.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A235).

Olfactory Training in Post-Traumatic Smell Impairment: Mild Improvement in Threshold Performances: Results from a Randomized Controlled Trial.

Traumatic Brain Injury (TBI) can be associated with partial or total smell loss. Recent studies have suggested that olfactory outcome can be positively modulated after olfactory training (OT). This study's aim was to investigate OT's potential role in smell recovery after TBI-induced olfactory loss. A prospective, randomized, and controlled study was developed. Patients with TBI-induced olfactory dysfunction (n = 42) were randomized into an experimental group with OT and a control group without (nOT). OT was performed twice daily with a six odor training set during 12 weeks. Olfactory loss was assessed using subjective olfactometry (Barcelona Smell Test [BAST] 24), a visual analogue scale (VAS), and n-butanol threshold (n-BTt) at baseline at 4, 12, and 24 weeks. Additionally, patients underwent MRI of the olfactory brain and olfactory bulbs (OB). Based on the MRI results, an overall score (0-16) was developed to associate the structural neurological damage with olfactory outcomes. The primary outcome was the change in olfactory measurements (VAS and BAST-24) between baseline and 12 weeks. The secondary outcome was the association of the MRI score with olfactory outcomes at baseline, and the impact on quality of life (QoL). After 12 weeks of training, OT patients showed a significant improvement in n-BTt (0.6 ± 1.7 OT vs. -0.6 ± 1.8 nOT, p < 0.05), but not in the smell VAS and BAST-24 scores. Olfactory outcomes (VAS, BAST-24, and n-BTt) were significantly associated with MRI structural findings (p < 0.001), but not with the OB volume or olfactory sulcus length. The present study suggests that 12 weeks of OT mildly improves the olfactory threshold in TBI, whereas the overall MRI score may be used as an imaging marker of olfactory dysfunction and disease severity in TBI patients.

Olfactory function in an excitotoxic model for secondary neuronal degeneration: Role of dopaminergic interneurons.

Secondary neuronal degeneration (SND) occurring in Traumatic brain injury (TBI) consists in downstream destructive events affecting cells that were not or only marginally affected by the initial wound, further increasing the effects of the primary injury. Glutamate excitotoxicity is hypothesized to play an important role in SND. TBI is a common cause of olfactory dysfunction that may be spontaneous and partially recovered. The role of the glutamate excitotoxicity in the TBI-induced olfactory dysfunction is still unknown. We investigated the effects of excitotoxicity induced by bilateral N-Methyl-D-Aspartate (NMDA) OB administration in the olfactory function, OB volumes, and subventricular zone (SVZ) and OB neurogenesis in rats. NMDA OB administration induced a decrease in the number of correct choices in the olfactory discrimination tests one week after lesions (p<0.01), and a spontaneous recovery of the olfactory deficit two weeks after lesions (p<0.05). A lack of correlation between OB volumes and olfactory function was observed. An increase in SVZ neurogenesis (Ki67+ cells, PSANCAM+ cells (p<0.01) associated with an increase in OB glomerular dopaminergic immunostaining (p<0.05) were related to olfactory function recovery. The present results show that changes in OB volumes cannot explain the recovery of the olfactory function and suggest a relevant role for dopaminergic OB interneurons in the pathophysiology of recovery of loss of smell in TBI.

tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which can modulate cortical excitability and combined with rehabilitation therapies may improve motor recovery after stroke. OBJECTIVE: Our aim was to study the feasibility of a 4-week robotic gait training protocol combined with tDCS, and to study tDCS to the leg versus hand motor cortex or sham to improve walking ability in patients after a subacute stroke. METHODS: Forty-nine subacute stroke patients underwent 20 daily sessions (5 days a week for 4 weeks) of robotic gait training combined with tDCS. Patients were assigned either to the tDCSleg group (n = 9), receiving 2 mA anodal tDCS over the motor cortex leg representation (vertex), or an active control group (n = 17) receiving anodal tDCS over the hand motor cortex area (tDCShand). In addition, we studied 23 matched patients in a control group receiving gait training without tDCS (notDCS). Study outcomes included gait speed (10-meter walking test), and quality of gait, using the Functional Ambulatory Category (FAC) before and after the 4-week training period. RESULTS: Only one patient did not complete the treatment because he presented a minor side-effect. Patients in all three groups showed a significantly improvement in gait speed and FAC. The tDCSleg group did not perform better than the tDCShand or notDCS group. CONCLUSION: Combined tDCS and robotic training is a safe and feasible procedure in subacute stroke patients. However, adding tDCS to robot-assisted gait training shows no benefit over robotic gait training alone.

ICF profiling of patients with traumatic brain injury: an international professional survey.

PURPOSE: A worldwide internet survey was conducted (1) to identify problems of individuals with traumatic brain injury (TBI) addressed by health professionals and (2) to summarize these problems using the International Classification of Functioning, Disability and Health (ICF). METHOD: A pool of professionals involved in the TBI rehabilitation process that included physicians, nurses, physical therapists, occupational therapists, social workers and psychologists were surveyed to identify problems in functioning and contextual factors of individuals with TBI using open-ended questions. All answers were translated ("linked") to the ICF based on established rules. The frequencies of the linked ICF categories were reported stratified based on context. RESULTS: One-hundred thirty seven professionals from the six World Health Organization regions identified 5656 concepts. 92.66% could be linked to the ICF; 33.03% were related to the domain of body functions, 27.28% to activities and participation, 10.98% to structures and 21.38% to environmental factors. CONCLUSIONS: The complexity of TBI was described through the identification of a wide variety of ICF categories. ICF language proved to be a neutral framework allowing the comparison of answers between different professionals in different world regions. IMPLICATIONS FOR REHABILITATION: People that suffered a traumatic brain injury (TBI) may have a variety of sequelae that impair functioning. The International Classification of Functioning, Disability and Health (ICF) can help in providing information regarding the identification of patients problems and needs as well as planning, implementing and coordinating the rehabilitation process. The ICF provides a frame of reference process illustrated as the rehabilitation cycle that can help during the rehabilitation process in goal setting bringing together the clinicians' and patient's perspectives in a patient oriented biopsychosocial approach. In the field of TBI rehabilitation, activity limitations and participation restrictions are broadly affected as reported by the professionals interviewed and highly influenced by cognitive and moreover behavioral problems.