Rehabilitation of working memory after acquired brain injury and multiple sclerosis: A systematic review.

The objective is to study the effectiveness of working memory (WM) rehabilitation after Acquired brain injury (ABI) and multiple sclerosis (MS). A systematic database search of published studies, following PRISMA recommendations, with assessment of methodological quality and risk of bias, was conducted. The results were analysed according to the rehabilitation method used. 31 studies (including 14 class I) were included, and 11 different training programs were identified. Despite great variability in training methodology and outcome measures, the results were positive overall. However, only three rehabilitation programs showed a transfer effect to WM (near) and daily life with long-term maintenance. The results were more variable for protocols limited to the use of computerized n-back training tasks. Overall, the current evidence supports multi-task WM training rather than single-task-limited program. It also supports early and long duration training, with some therapist support. However, it is not possible, to date, to make strong recommendations regarding the rehabilitation program to be used preferentially. Although results are encouraging, level of evidence remains modest, particularly regarding the maintenance of the therapeutic effect after the end of training, and the transfer to everyday life skills. The influence of rehabilitation parameters (training duration, therapist involvement … ) remains difficult to assess.

Co-existence of depression and post-concussion syndrome one month after mild traumatic brain injury.

BACKGROUND: Previous studies suggest an association between Post-concussion syndrome (PCS) and depression, both highly prevalent after mTBI. OBJECTIVE: To assess the prevalence and risk-factors of depression among patients with PCS 1 month after mTBI. METHODS: We prospectively screened 372 mTBI patients admitted in two academic Emergency Departments between 2017 and 2019. One month after mTBI, we administered the Rivermead Post-concussion symptoms Questionnaire (RPQ) and the Patient Health Questionnaire (PHQ-9) questionnaires over the telephone. PCS and depression were defined by RPQ ≥ 12 and PHQ-9 ≥ 10. Multivariate multinomial regression identified baseline factors associated with PCS and depression. RESULTS: Two hundred and eight completed RPQ and PHQ-9. Forty-seven patients (22.5%) met criteria for PCS, among which 22 (46.8%) met criteria for depression (PCS+D+). Patients with PCS but without depression were less likely to present with an associated injury (Coefficient = -1.6, p = 0.047) and to report initial sadness (Coefficient = -2.5, p = 0.03). Initial sadness (Coefficient = -1.3, p = 0.047), associated injury (Coefficient = -1.9, p = 0.008), as well as initial nausea (Coefficient = -1.8, p = 0.002), and male sex (Coefficient = 1.8, p = 0.002), were associated with the absence of depression and PCS in comparison with PCS+D+ patients. CONCLUSION: Among patients with PCS 1 month after mTBI, those with depression are more likely to present with initial sadness and with an associated injury.

Assessment of impaired self-awareness after moderate-to-severe traumatic brain injury: a comparison of assessment tools.

OBJECTIVE: To compare different assessment methods of impaired self-awareness (ISA). METHODS: We included 37 patients with moderate-to-severe traumatic brain injury (TBI) at a subacute/chronic stage, and 33 healthy controls. ISA was assessed with three methods: discrepancy scores (comparison between patient and proxy ratings) on three scales (Patient Competency Rating Scale (PCRS), Awareness Questionnaire (AQ) and Dysexecutive Questionnaire (DEX)); clinician rating with the Self-Awareness of Deficits Interview (SADI); and the difference between prediction or estimation of performance and actual performance on two cognitive tasks. RESULTS: Clinician-patient discrepancy scores appeared more sensitive than relative-patient discrepancy. The AQ was the most sensitive. The discrepancy scores were strongly correlated one with each other. Correlations with the SADI were weaker. Patients did not overestimate their performance on cognitive tasks, and the prediction did not significantly correlate with other measures of ISA. DISCUSSION/CONCLUSION: Results support the multidimensional nature of ISA: discrepancy scores assess meta-cognitive knowledge (understanding that a function/skill is affected), while the SADI takes into account anticipatory awareness (ability to set realistic goals) and estimation of performance assesses anticipatory and situational awareness. Assessment of these different domains may provide a comprehensive overview of an individual's self-awareness.

Discriminative value of different combinations of tests to detect unilateral neglect in patients with right hemisphere damage.

BACKGROUND AND PURPOSE: This study was undertaken to assess the most sensitive combination of tests to detect peripersonal unilateral neglect (UN) after stroke. METHODS: The present study is a secondary analysis of a previously reported multicentric study of 203 individuals with right hemisphere damage (RHD), mainly subacute stroke, 11 weeks postonset on average, and 307 healthy controls. A battery of seven tests, providing 19 age- and education-adjusted z-scores, were given: the bells test, line bisection, figure copying, clock drawing, overlapping figures test, and reading and writing. Statistical analyses used a logistic regression and a receiver operating characteristic (ROC) curve after adjustment on demographic variables. RESULTS: A combination of four z-scores based on the following three tests provided good discrimination of patients with RHD from matched healthy controls: the starting point and the difference between the number of omissions on left and right sides from the bells test, rightward deviation in bisection of long lines (20 cm), and left-sided omissions in a reading task. The area under the ROC curve was 0.865 (95% confidence interval = 0.83-0.901), with sensitivity = 0.68, specificity = 0.95, accuracy = 0.85, positive predictive value = 0.90, and negative predictive value = 0.82. CONCLUSIONS: The most sensitive and parsimonious combination of tests to detect UN after stroke relies on four scores from three simple tests (bells test, line bisection, and reading). Future study is warranted to assess its ability to account for the functional difficulties of UN in daily life in the patient's actual environment.

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study.

BACKGROUND: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. METHODS: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale - Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. RESULTS: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. CONCLUSIONS: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

A Systematic Review of Treatments of Post-Concussion Symptoms.

Approximately 10−20% of patients who have sustained a mild Traumatic Brain Injury (mTBI) show persistent post-concussion symptoms (PCS). This review aims to summarize the level of evidence concerning interventions for PCS. Following the PRISMA guidelines, we conducted a systematic review regarding interventions for PCS post-mTBI until August 2021 using the Medline, Cochrane, and Embase databases. Inclusion criteria were the following: (1) intervention focusing on PCS after mTBI, (2) presence of a control group, and (3) adult patients (≥18 y.o). Quality assessment was determined using the Incog recommendation level, and the risk of bias was assessed using the revised Cochrane risk-of-bias tool. We first selected 104 full-text articles. Finally, 55 studies were retained, including 35 that obtained the highest level of evidence. The risk of bias was high in 22 out of 55 studies. Cognitive training, psycho-education, cognitive behavioral therapy, and graded return to physical activity demonstrated some effectiveness on persistent PCS. However, there is limited evidence of the beneficial effect of Methylphenidate. Oculomotor rehabilitation, light therapy, and headache management using repetitive transcranial magnetic stimulation seem effective regarding somatic complaints and sleep disorders. The preventive effect of early (<3 months) interventions remains up for debate. Despite its limitations, the results of the present review should encourage clinicians to propose a tailored treatment to patients according to the type and severity of PCS and could encourage further research with larger groups.

Factors influencing the length of stay in a unit with mixed rehabilitation and psychiatric care after a suicide attempt by jumping: a cohort observational retrospective study.

BACKGROUND: Persons who have attempt suicide by jumping often require intensive treatment for their somatic injuries and the high risk of future completed suicide. The FSEF (French Student Health Foundation) developed a Transdisciplinary unit specifically designed for these people. AIM: The aim of this study was to investigate psychiatric and somatic factors associated with Length Of Stay (LOS) in this unit. DESIGN: Cohort observational retrospective study. SETTING: The Transdisciplinary unit provide a dual approach, combining rehabilitation (physiotherapy, balneotherapy, occupational therapy, speech therapy, cognitive rehabilitation, social and family support) and psychiatric care. POPULATION: Men and women admitted into the Transdisciplinary unit, after a suicide attempt by jumping from a height with severe somatic injuries. METHODS: We examined the associations between potential predictors and LOS with Stepwise regressions: model 1 included all variables assessed at admission (age, sex, occupational status, psychiatric disorder history, height of the fall, type of injury, LOS in acute care units and dependences at admission); model 2: all variables at discharge (main psychiatric diagnosis, orientation at discharge, psychotropic treatments, pain treatments, arms mobility limitation, legs mobility limitation, sphincter disorders and dependences at discharge); final model: all significant variables in models 1 and 2. RESULTS: One hundred ninety-seven subjects were included (49.7% of men; mean age: 25.6 years, ±6.21). Most factors associated with LOS were related to injuries due to the suicide attempt. LOS in the Transdisciplinary unit increased with longer LOS in acute care (ß=0.589; P=0.003), higher dependence for continence at admission (ß=44.640; P<0.001) and sphincter disorders at discharge (ß=78.034; P<0.001). LOS was also longer with higher dependence for behavior at discharge (ß=30.182; P=0.042) and unemployed status (ß=59.496; P=0.008), which could reflect psychiatric disorders severity. LOS was shorter when subjects had arms mobility limitation at discharge (ß=-42.591; P=0.018). CONCLUSIONS: The persons admitted into this unit have serious physical injuries due to their fall. These injuries require intensive rehabilitation and their severity is the largest contributing factor to the LOS. Some findings also advocate for influence of psychiatric factors on LOS, underlying the need for both concomitant psychiatric and somatic care for these people. CLINICAL REHABILITATION IMPACT: People should ideally receive both psychiatric and rehabilitation care after a suicide attempt by jumping.

Five-year mortality after hospitalisation for suicide attempt with a violent method.

OBJECTIVE: This study aimed to estimate the 5-year mortality among people admitted into a transdisciplinary unit providing combined psychiatric and somatic rehabilitation treatment. METHODS: In this retrospective study, we analyzed the clinical records of all individuals admitted into the transdisciplinary unit from 01/01/2011 to 12/31/2017 after a suicide attempt using violent means. Vital status was ascertained for these 215 people, a standardized mortality ratio (SMR) was calculated and Log-rank tests were used to identify factors associated with mortality. RESULTS: The crude mortality rate was 5.12% (11 deaths) and the SMR was 15.45 (95% CI = [7.71-27.65]; p < 0.001) 5.40 years after admission into the transdisciplinary unit. Factors associated with mortality were: older age (29.91 years versus 25.30 years, p < 0.001), a longer stay in acute care (p = 0.002) and a shorter stay in the transdisciplinary unit (p < 0.001). CONCLUSION: Long-term mortality among people who have attempted suicide using violent means is 15 times higher than in the corresponding general young adult population. This study supports the hypothesis that the severity of a suicide attempt is associated with subsequent excess mortality. Therefore, there is a need to consolidate outpatient facilities that provide appropriate support for this specific population after discharge. These programmes need to ensure the continuity of coordinated psychiatric and somatic care and psychosocial rehabilitation in order to prevent the risk of suicide.

The ICEBERG: A score and visual representation to track the severity of traumatic brain injury: Design principles and preliminary results.

BACKGROUND: Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Scale score at 3 years). In addition, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. METHODS: This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included six variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure, intracranial pressure, body temperature, sedation depth, arterial partial pressure of CO 2 , and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and Extended Glasgow Outcome Score. RESULTS: The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and computed tomography parameters at admission were combined with the ICEBERG score at 48 hours using a multimodal approach, the predictive value was significantly increased (area under the curve = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation ( p < 0.05). CONCLUSION: The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. In addition, ICEBERG representation could enhance the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level III.

Relationships between neuropsychological impairments and functional outcome eight years after severe traumatic brain injury: Results from the PariS-TBI study.

BACKGROUND/OBJECTIVES: The objective was to assess the relationships between neuropsychological impairments, functional outcome and life satisfaction in a longitudinal study of patients after a severe traumatic brain injury (TBI) (PariS-TBI study). PATIENTS: Out of 243 survivors, 86 were evaluated 8 years post-injury. They did not significantly differ from patients lost-to-follow up except for the latter being more frequently students or unemployed before the injury. METHODS: Outcome measures included the Glasgow Outcome Scale-Extended (GOS-E), a functional independence questionnaire, employment, mood, fatigue and satisfaction with life. Neuropsychological outcome was assessed by two ways: performance-based outcome measures, using neuropsychological tests and patient and relative-based measures. RESULTS: Neuropsychological measures were not significantly related to initial injury severity nor to gender, but were significantly related to age and education. After statistical correction for multiple comparisons, cognitive testing and cognitive questionnaires were significantly correlated with most outcome measures. By contrast, satisfaction with life was only related with patient-rated questionnaires. A regression analysis showed that the Trail-Making-Test-A was the best predictor of functional outcome, in addition to education duration. CONCLUSIONS: Cognitive measures, particularly slowed information processing speed, were significant indicators of functional outcome at a long-term post-injury, beyond and above demographics or injury severity measures.

Impaired self-awareness after traumatic brain injury: A systematic review. Part 2. Consequences and predictors of poor self-awareness.

BACKGROUND: Impaired self-awareness (ISA) has frequently been found both frequent and deleterious in patients with moderate to severe traumatic brain injury (TBI). OBJECTIVES: This is the second of a two-part systematic review on ISA after TBI, focusing on the consequences and predictors of ISA after TBI. METHODS: Following the PRISMA guidelines, 95 articles meeting the inclusion criteria were included; 46 were specifically related to this second part of the review. RESULTS: Among 16 studies that investigated the effect of ISA on outcome, most (n=13) found poor self-awareness associated with poor rehabilitation, functional, social and vocational outcome and with increased burden on relatives. Multiple factors have been found associated with increased frequency of ISA. ISA was found significantly related to injury severity in 8 of 10 studies, impaired executive functions in 12 of 15 studies, and poor social cognition in 3 studies, but paradoxically inverse associations were repeatedly found between self-awareness and emotional status (11 of 12 studies). Finally, although research in the field is still scarce, ISA seems associated with a dysfunction within brain networks involving the anterior cingulate cortex, anterior insula and fronto-parietal control network. CONCLUSIONS: ISA is a complex and multifaceted disorder associated with poor rehabilitation outcome, severe injuries, and deficits of executive functions and social cognition but has an inverse association with mood impairments.

Unmet Rehabilitation Needs after Traumatic Brain Injury across Europe: Results from the CENTER-TBI Study.

This study aims to assess rehabilitation needs and provision of rehabilitation services for individuals with moderate-to-severe disability and investigate factors influencing the probability of receiving rehabilitation within six months after traumatic brain injury (TBI). Overall, the analyses included 1206 individuals enrolled in the CENTER-TBI study with severe-to-moderate disability. Impairments in five outcome domains (daily life activities, physical, cognition, speech/language, and psychological) and the use of respective rehabilitation services (occupational therapy, physiotherapy, cognitive and speech therapies, and psychological counselling) were recorded. Sociodemographic and injury-related factors were used to investigate the probability of receiving rehabilitation. Physiotherapy was the most frequently provided rehabilitation service, followed by speech and occupational therapy. Psychological counselling was the least frequently accessed service. The probability of receiving a rehabilitative intervention increased for individuals with greater brain injury severity (odds ratio (OR) 1.75, CI 95%: 1.27-2.42), physical (OR 1.92, CI 95%: 1.21-3.05) and cognitive problems (OR 4.00, CI 95%: 2.34-6.83) but decreased for individuals reporting psychological problems (OR 0.57, CI 95%: 1.21-3.05). The study results emphasize the need for more extensive prescription of rehabilitation services for individuals with disability. Moreover, targeted rehabilitation programs, which aim to improve outcomes, should specifically involve psychological services to meet the needs of individuals recovering from TBI.

Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients.

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (Cmax [1 h] = 2.2 ng mL-1 ; approximately) after a single dose of 1 mg.

Long-Term Disabilities of Survivors of Out-of-Hospital Cardiac Arrest: The Hanox Study.

BACKGROUND: Long-term outcomes of awakened survivors of out-of-hospital cardiac arrest (OHCA) are poorly known. RESEARCH QUESTION: What are the month (M) 18 outcomes of survivors of out-of-hospital cardiac arrest (OHCA) who awakened during the first 2 weeks' post-OHCA and their poor-outcome risk factors? STUDY DESIGN AND METHODS: All OHCA survivors with a Glasgow Coma Scale score ≥12 during the first 2 weeks' post-OHCA were enrolled in six ICUs and followed up at M3, M6, M12, and M18. The primary outcome measure was Glasgow Outcome Scale-Extended (GOS-E) score at M18. Secondary outcome measures included evaluation at M18 of neurologic, behavioral, and cognitive disabilities; health-related quality of life (HR-QOL), anxiety and depression; and poor-outcome risk factors (GOS-E score ≤ 6). RESULTS: Among the 139 included patients, 98 were assessable for the primary outcome measure. At M18, 64 (65%) had full recovery or minor disabilities (GOS-E score > 6), 18 (18%) had moderate disabilities but were autonomous for daily-life activities (GOS-E score = 6), 12 (12%) had poor autonomy (GOS-E score < 6 but > 1), and four had died. Percentages of patients with GOS-E scores > 6 increased significantly over the 18-month study period. At M18, no patients had major neurologic disabilities, 20% had cognitive disabilities, 32% had anxiety symptoms, 25% had depression symptoms, and their HR-QOL was impaired compared with a sex- and age-matched population. Low-flow time, Sequential Organ Failure Assessment score at admission, coma duration > 3 days after cardiac arrest, and mechanical ventilation on days 3 and 7 were associated with poor functional outcome. INTERPRETATION: Among patients who awoke (Glasgow Coma Scale score ≥12) in the 14 days following OHCA, 35% had moderate to severe disabilities or had died at M18. Interestingly, patients improved until M18 post-OHCA. Risk factors associated with poor functional outcome were low-flow time, clinical severity at ICU admission, prolonged coma duration, and mechanical ventilation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02292147; URL: www.clinicaltrials.gov.