Cost-effectiveness of neuropsychological rehabilitation for acquired brain injuries: Update of Stolwyk et al.'s (2019) review.

Acquired brain injuries (ABI), resulting from stroke or traumatic brain injury, cause a range of neuropsychological impairments and many patients continue to experience neuropsychological deficits years after onset. The increasing average age of the population highlights the importance of effective management strategies for the consequences of ABI. Despite the well-documented impact of rehabilitation interventions, the cost-effectiveness of neuropsychological rehabilitation remains largely unknown. This study conducted a scoping review to update the findings of Stolwyk et al. (Neuropsychological Rehabilitation, 2021, 31, 316), focusing on the economic evaluations of neuropsychological rehabilitation for individuals with ABI. Following the PIO framework, PRISMA ScR guidelines, and systematic review reporting checklist, the review screened 1027 articles and included eight studies published between 2019 and 2024. The studies encompassed either language rehabilitation or general neuropsychological programs, including neuropsychological interventions. The economic analyses, including two cost-effectiveness, five cost-utility, and one cost-benefit study, mostly adhered to CHEERS guidelines, enhancing the transparency and methodological rigour of their reporting. These studies demonstrated varying degrees of cost-effectiveness for interventions targeting post-stroke language disorders and neuropsychological rehabilitation for ABI, with significant cost savings and health benefits observed, particularly for home-based rehabilitation interventions. The included studies suffered from a short time horizon, limiting the ability to capture the long-term economic impacts and effectiveness of the interventions. Future research should focus on longer-term follow-up data and include broader search strategies to enhance understanding and optimise health care interventions. A comprehensive implementation of these economic analyses is crucial for informing policymakers, enabling them to introduce rehabilitative interventions based on solid evidence.

Does pain influence cognitive performance in patients with mild traumatic brain injury?

OBJECTIVES: Pain is still a neglected problem in mild traumatic brain injury (mTBI). In this cross-sectional study, we examined the frequency of musculoskeletal pain in a sample of adult patients with persistent cognitive symptoms after mTBI and whether pain level affected cognition. METHODS: The participants were 23 adult patients aged 18-50 referred to brain injury rehabilitation clinics for neuropsychological assessment after having sustained an mTBI. A non-injured control group (n = 29) was recruited through advertisements. The patients were, on average, assessed 22 months after trauma. All participants completed a comprehensive neuropsychological test battery and completed the Örebro Musculoskeletal Pain Screening Questionnaire, The Rivermead Post-Concussion Symptoms Questionnaire, and the State-Trait Anxiety Inventory. RESULTS: Patients reported high levels of current pain and significantly more frequent neck and shoulder pain than the non-injured controls. Patients also reported high post-concussive symptoms and anxiety levels and performed less well on several neuropsychological tests. Pain level was associated with slower processing speed among the controls but not related to performance in the mTBI group. CONCLUSION: We conclude that musculoskeletal pain is frequent in mTBI patients referred to rehabilitation settings. Furthermore, the results indicate that the interaction between pain and cognitive functioning differs in mTBI compared to controls. Our results implicate that pain screening should be an integrated part of neuropsychological rehabilitation after mTBI to identify conditions that run the risk of becoming chronic. The study was approved by the Regional Ethical Board in Stockholm, Sweden (04-415/2).

Fatigue and cognitive fatigability in patients with chronic pain.

OBJECTIVES: Fatigue is common in patients with chronic pain. Still, there is a lack of studies examining objectively measurable cognitive aspects of fatigue: cognitive fatigability (CF). We aimed to investigate the presence of CF in patients with chronic pain and its relation to self-rated fatigue, attention, pain characteristics, sleep disturbance, depression, and anxiety. METHODS: Two hundred patients with chronic pain and a reference group of 36 healthy subjects underwent a comprehensive neuropsychological test battery, including measurement of CF with the Wechsler Adult Intelligence Scale-III Coding subtest, and self-assessment of trait and state fatigue. RESULTS: The patients with chronic pain did not show more CF as compared to the reference group. There was an association between CF and processing speed on a test of sustained and selective attention in the chronic pain group, while self-rated fatigue measures and pain characteristics were not associated with CF. Self-rated fatigue measures were highly correlated with self-rated pain intensity, spreading of pain, depression, anxiety, and sleep disturbance. CONCLUSIONS: The findings highlight the distinction between objective and subjective aspects of fatigue in chronic pain, and that the underlying causes of these different aspects of fatigue need to be studied further.

Investigating cognitive reserve, symptom resolution and brain connectivity in mild traumatic brain injury.

BACKGROUND: A proportion of patients with mild traumatic brain injury (mTBI) suffer long-term consequences, and the reasons behind this are still poorly understood. One factor that may affect outcomes is cognitive reserve, which is the brain's ability to maintain cognitive function despite injury. It is often assessed through educational level or premorbid IQ tests. This study aimed to explore whether there were differences in post-concussion symptoms and symptom resolution between patients with mTBI and minor orthopedic injuries one week and three months after injury. Additional aims were to explore the relationship between cognitive reserve and outcome, as well as functional connectivity according to resting state functional magnetic resonance imaging (rs-fMRI). METHOD: Fifteen patients with mTBI and 15 controls with minor orthopedic injuries were recruited from the emergency department. Assessments, including Rivermead Post-Concussion Questionnaire (RPQ), neuropsychological testing, and rs-fMRI scans, were conducted on average 7 days (SD = 2) and 122 days (SD = 51) after injury. RESULTS: At the first time point, significantly higher rates of post-concussion symptoms (U = 40.0, p = 0.003), state fatigue (U = 56.5, p = 0.014), and fatigability (U = 58.5, p = 0.025) were observed among the mTBI group than among the controls. However, after three months, only the difference in post-concussion symptoms remained significant (U = 27.0, p = 0.003). Improvement in post-concussion symptoms was found to be significantly correlated with cognitive reserve, but only in the mTBI group (Spearman's rho = -0.579, p = .038). Differences in the trajectory of recovery were also observed for fatigability between the two groups (U = 36.5, p = 0.015). Moreover, functional connectivity differences in the frontoparietal network were observed between the groups, and for mTBI patients, functional connectivity differences in an executive control network were observed over time. CONCLUSION: The findings of this pilot study suggest that mTBI, compared to minor orthopedic trauma, is associated to both functional connectivity changes in the brain and concussion-related symptoms. While there is improvement in these symptoms over time, a small subgroup with lower cognitive reserve appears to experience more persistent and possibly worsening symptoms over time. This, however, needs to be validated in larger studies. TRIAL REGISTRATION: NCT05593172. Retrospectively registered.

Cognitive and mental fatigue in chronic pain: cognitive functions, emotional aspects, biomarkers and neuronal correlates-protocol for a descriptive cross-sectional study.

INTRODUCTION: Chronic pain (CP) is one of the most frequently presenting conditions in health care and many patients with CP report mental fatigue and a decline in cognitive functioning. However, the underlying mechanisms are still unknown. METHODS AND ANALYSIS: This study protocol describes a cross-sectional study aimed at investigating the presence of self-rated mental fatigue, objectively measured cognitive fatigability and executive functions and their relation to other cognitive functions, inflammatory biomarkers and brain connectivity in patients with CP. We will control for pain-related factors such as pain intensity and secondary factors such as sleep disturbances and psychological well-being. Two hundred patients 18-50 years with CP will be recruited for a neuropsychological investigation at two outpatient study centres in Sweden. The patients are compared with 36 healthy controls. Of these, 36 patients and 36 controls will undergo blood sampling for inflammatory markers, and of these, 24 female patients and 22 female controls, between 18 and 45 years, will undergo an functional MRI investigation. Primary outcomes are cognitive fatigability, executive inhibition, imaging and inflammatory markers. Secondary outcomes include self-rated fatigue, verbal fluency and working memory. The study provides an approach to study fatigue and cognitive functions in CP with objective measurements and may demonstrate new models of fatigue and cognition in CP. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethics Review Board (Dnr 2018/424-31; 2018/1235-32; 2018/2395-32; 2019-66148; 2022-02838-02). All patients gave written informed consent to participate in the study. The study findings will be disseminated through publications in journals within the fields of pain, neuropsychology and rehabilitation. Results will be spread at relevant national and international conferences, meetings and expert forums. The results will be shared with user organisations and their members as well as relevant policymakers. TRIAL REGISTRATION NUMBER: NCT05452915.

The impact of visuospatial and executive function on activity performance and outcome after robotic or conventional gait training, long-term after stroke-as part of a randomized controlled trial.

INTRODUCTION: Visuospatial and executive impairments have been associated with poor activity performance sub-acute after stroke. Potential associations long-term and in relation to outcome of rehabilitation interventions need further exploration. AIMS: To explore associations between visuospatial and executive function and 1) activity performance (mobility, self-care and domestic life) and 2) outcome after 6 weeks of conventional gait training and/or robotic gait training, long term (1-10 years) after stroke. METHODS: Participants (n = 45), living with stroke affecting walking ability and who could perform the items assessing visuospatial/executive function included in the Montreal Cognitive Assessment (MoCA Vis/Ex) were included as part of a randomized controlled trial. Executive function was evaluated using ratings by significant others according to the Dysexecutive Questionnaire (DEX); activity performance using 6-minute walk test (6MWT), 10-meter walk test (10MWT), Berg balance scale, Functional Ambulation Categories, Barthel Index and Stroke Impact Scale. RESULTS: MoCA Vis/Ex was significantly associated with baseline activity performance, long-term after stroke (r = .34-.69, p < .05). In the conventional gait training group, MoCA Vis/Ex explained 34% of the variance in 6MWT after the six-week intervention (p = 0.017) and 31% (p = 0.032) at the 6 month follow up, which indicate that a higher MoCA Vis/Ex score enhanced the improvement. The robotic gait training group presented no significant associations between MoCA Vis/Ex and 6MWT indicating that visuospatial/executive function did not affect outcome. Rated executive function (DEX) presented no significant associations to activity performance or outcome after gait training. CONCLUSION: Visuospatial/executive function may significantly affect activity performance and the outcome of rehabilitation interventions for impaired mobility long-term after stroke and should be considered in the planning of such interventions. Patients with severely impaired visuospatial/executive function may benefit from robotic gait training since improvement was seen irrespective of visuospatial/executive function. These results may guide future larger studies on interventions targeting long-term walking ability and activity performance. TRIAL REGISTRATION: clinicaltrials.gov (NCT02545088) August 24, 2015.

Assessing time processing ability and daily time management in persons with dementia: Psychometric properties of three instruments.

INTRODUCTION: Persons with dementia experience time-related problems, but there is a lack of instruments evaluating their time processing ability and daily time management. This study aimed to evaluate the psychometric properties of the instruments KaTid®-Senior measuring time processing ability, and Time-S© Senior and Time-Proxy© measuring daily time management for persons with dementia. METHODS: Persons with dementia (n = 53) and their significant others (n = 49) participated in the study. Rasch analyses were used to evaluate the instruments' rating scale functioning; internal scale validity; person-response validity; unidimensionality; person-separation reliability; and internal consistency. Versions excluding items with poor fit to the Rasch model were also evaluated. RESULTS: Overall, the Rasch analyses showed acceptable psychometric properties. All instruments met the criteria for unidimensionality and the reliability was good. More challenging items should be added in KaTid-Senior for better targeting of persons with mild dementia. Person-response validity issues in Time-S Senior need to be addressed. CONCLUSION: The instruments can validly and reliably be used to assess time processing ability and daily time management in persons with dementia in clinical research and healthcare settings. In turn, this can contribute to the development of methods to compensate for impaired time processing ability and daily time management. The assessments can also increase the possibility of early detection of impaired time processing ability and daily time management, thereby facilitating adequate timing of interventions and enhanced occupational performance.

Preliminary Findings on Cognitive Dysfunction in University-Educated Patients After Mild COVID-19 Disease.

Objective: To investigate cognitive functioning in patients with higher education having post COVID-19 condition. Design: Prospective cohort study. Setting: Outpatient rehabilitation clinic. Participants: Patients (N=38; mean age, 48.5y; 71% women) at the Cognitive Post COVID-19 Clinic at Danderyd University Hospital in Stockholm, Sweden, who sought health care because of self-experienced cognitive problems. All had at least 4 years of university education and an initially mild infection (ie, most were not hospital admitted, none were admitted to intensive care). Interventions: Not applicable. Main Outcome Measures: Cognitive test performance assessed with a comprehensive neuropsychological test battery including Information, Matrix Reasoning, Coding, and Digit Span from Wechsler's Adult Intelligence Scale-IV, Buschke Selective Reminding Test, Rey Complex Figure Test, Ruff 2&7, Color-Word Interference Test, Verbal Fluency, and Trail Making Test. The mean time between the infection and the assessment was 18 months. Results: Cognitive deficits were evident on tests of verbal learning and memory (Buschke Selective Reminding Test) and selective attention (Ruff 2&7). Approximately 50% of the participants had scores lower than 1 SD below the mean in the norm group on the measures of verbal learning and memory. When estimated premorbid cognitive functioning was accounted for, deficits were suggested in most cognitive domains. Conclusions: Post COVID-19 condition seems to be associated with cognitive deficits, even in patients with high education and an initially mild infection.

Cognitive Reserve, Early Cognitive Screening, and Relationship to Long-Term Outcome after Severe Traumatic Brain Injury.

The objective was to investigate the relationship between early global cognitive functioning using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and cognitive flexibility (Trail Making Test (TMT), TMT B-A), with long-term outcome assessed by the Mayo-Portland Adaptability Index (MPAI-4) in severe traumatic brain injury (sTBI) controlling for the influence of cognitive reserve, age, and injury severity. Of 114 patients aged 18-65 with acute Glasgow Coma Scale 3-8, 41 patients were able to complete (BNIS) at 3 months after injury and MPAI-4 5-8 years after injury. Of these, 33 patients also completed TMT at 3 months. Global cognition and cognitive flexibility correlated significantly with long-term outcome measured with MPAI-4 total score (rBNIS = 0.315; rTMT = 0.355). Global cognition correlated significantly with the participation subscale (r = 0.388), while cognitive flexibility correlated with the adjustment (r = 0.364) and ability (r = 0.364) subscales. Adjusting for cognitive reserve and acute injury severity did not alter these relationships. The effect size for education on BNIS and TMT scores was large (d ≈ 0.85). Early screenings with BNIS and TMT are related to long-term outcome after sTBI and seem to measure complementary aspects of outcome. As early as 3 months after sTBI, educational level influences the scores on neuropsychological screening instruments.

Monthlong Intubated Patient with Life-Threatening COVID-19 and Cerebral Microbleeds Suffers Only Mild Cognitive Sequelae at 8-Month Follow-up: A Case Report.

OBJECTIVE: To elaborate on possible cognitive sequelae related to COVID-19, associated cerebrovascular injuries as well as the general consequences from intensive care. COVID-19 is known to have several, serious CNS-related consequences, but neuropsychological studies of severe COVID-19 are still rare. METHODS: M., a 45-year-old man, who survived a severe COVID-19 disease course including Acute Respiratory Distress Syndrome (ARDS), cerebral microbleeds, and 35 days of mechanical ventilation, is described. We elaborate on M's recovery and rehabilitation process from onset to the 8-month follow-up. The cognitive functions were evaluated with a comprehensive screening battery at 4 weeks after extubation and at the 8-month follow-up. RESULTS: Following extubation, M. was delirious, reported visual hallucinations, and had severe sleeping difficulties. At about 3 months after COVID-19 onset, M. showed mild to moderate deficits on tests measuring processing speed, working memory, and attention. At assessments at 8 months, M. performed better, with results above average on tests measuring learning, memory, word fluency, and visuospatial functions. Minor deficits were still found regarding logical reasoning, attention, executive functioning, and processing speed. There were no lingering psychiatric symptoms. While M. had returned to a part-time job, he was not able to resume previous work-tasks. CONCLUSION: This case-study demonstrates possible cognitive deficits after severe COVID-19 and emphasizes the need of a neuropsychological follow-up, with tests sensitive to minor deficits. The main findings of this report provide some support that the long-term prognosis for cognition in severe COVID-19 may be hopeful.

Does Intensive Training of Attention Influence Cognitive Fatigability in Patients With Acquired Brain Injury?

RESEARCH OBJECTIVES: Impairments in attention and the speed of information processing are central to the experience of cognitive fatigue in patients with acquired brain injury (ABI). Attention may be improved through intensive training in a rehabilitation setting. The aim of the study was to investigate the feasibility of reducing cognitive fatigability (CF) using attention training and to explore the effect of two different approaches to attention training. DESIGN: Randomised controlled study in a rehabilitation setting. PARTICIPANTS: 59 patients (age 19-59 years) with mild to moderate stroke or traumatic brain injury in the early (<4 month) phase. INTERVENTIONS: Patients were randomly assigned to intensive specific training with Attention Process Training (APT) or Activity-Based Attention Training (ABAT) for 3-5 days per week for a period of 5-6 weeks with a total of 20 h, in addition to traditional interdisciplinary rehabilitation. MAIN OUTCOME MEASURE: CF was conceptualised as performance decline in terms of an increased number of incorrect responses between the first and the last quintiles of the Paced Auditory Serial Addition Test (PASAT). A negative result was defined as fatigability. The evaluator of fatigability was blinded to treatment. RESULTS: At baseline, there were no differences between the groups in age, education, reasoning, anxiety or depression. After training, a significant treatment effect was found (p = 0.020), as the APT-group, but not the ABAT-group, had improved. However, after controlling for baseline differences regarding CF on the PASAT-f, the difference was no longer significant. CONCLUSION: The results indicate that cognitive training might be a feasible method for reducing CF through attention training and that patients with high levels of CF benefit most from attention training. The type of intervention provided, whether specific or activity-based attention training, appears to be of less importance, as there was no treatment effect after controlling for the baseline level of CF. Future studies are required to confirm the validity of the findings.

Methodological aspects of using a wearable eye-tracker to support diagnostic clinical evaluation of prolonged disorders of consciousness.

OBJECTIVE: To evaluate the feasibility of using a wearable eye-tracker when assessing patients with prolonged disorders of consciousness using the Coma Recovery Scale Revised (CRS-R), focusing on technical challenges. DESIGN: A methodological investigation with descriptive and analytical elements. SUBJECTS: Four patients with prolonged disorders of consciousness were recruited from the rehabilitation clinic of a regional rehabilitation unit. METHODS: A selection of subtests in the CRS-R were performed while recording eye movements with a wearable eye-tracker. RESULTS: No major adverse reactions were observed, suggesting likely patient acceptability. Calibration was not always possible. However, distinct eye movements were discernible from the recorded data even without calibration, and analysis of these produced results with the potential to support clinical assessment. CONCLUSION: Eye tracking was feasible during clinical assessment for this patient group. Recording eye movement responses in these easily fatigued patients has the potential to add sensitivity for detection of conscious responses and to complement clinical examination. Further study is merited. Current hardware and software limitations can be overcome with manual data processing and analysis; however, significant developments in automating data processing will be required for broader clinical application.

Effectiveness of specialized rehabilitation after mild traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness of specialized rehabilitation in adults with prolonged symptoms, or risk of prolonged symptoms, following mild traumatic brain injury. DATA SOURCES: Randomized controlled trials or non-randomized controlled studies published between 1 Jan 2000 and 10 Mar 2019 in Cochrane Controlled Register of Trials, PubMed, EMBASE, CINAHL or PsycINFO. Meta-analyses were performed for studies of similar interventions when identical or comparable outcomes were reported. STUDY SELECTION AND DATA EXTRACTION: Screening, data extraction, and risk of bias assessment were carried out by 2 independent researchers. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: A total of 9 studies were identified, which were divided into 3 subgroups. Results from meta-analyses implied that problem-solving therapy and cognitive behavioural therapy reduce residual symptoms, improve psychological functioning, decrease depression, increase activity and participation, and improve quality of life, compared with usual care. The meta-analyses also suggested that specialized interdisciplinary rehabilitation reduces residual symptoms. CONCLUSION: Persons with mild traumatic brain injury who are at risk of, or who experience, prolonged symptoms should be considered for specialist treatment, as they may experience positive effects from cognitive behavioural therapy, problem-solving therapy, or interdisciplinary team rehabilitation. Further research is required to strengthen the evidence.

Tolerability and psychological effects of a multimodal day-care rehabilitation program for persons with Huntington's disease.

OBJECTIVE: To determine whether the psychological benefits of intense, inpatient, multimodal rehabilitation for persons with Huntingtons disease (HD), as found in earlier studies, also apply in a shorter, day-care setting. DESIGN: Prospective, non-randomized cohort study. SUBJECTS: Twenty patients attending a group-based 8-week (3 days/week) rehabilitation programme aimed at persons in early stages of HD. METHODS: An explorative cohort study on register data from a specialized rehabilitation centre, includ-ing descriptive data, number of cancellations, a self-reported evaluation, and measures of psychiatric symptoms, health-related quality of life, sense of coherence and physical function at baseline and at the end of rehabilitation. RESULTS: Patients' attendance rate was almost 90%. Patients were satisfied, and displayed significantly reduced anxiety and depression and improved health-related quality of life after rehabilitation. Baseline measures of sense of coherence showed significant negative correlation with the number of cancelled days of rehabilitation. Physical function improved, but did not correlate significantly with psychological outcome measures. CONCLUSION: These results indicate that an 8-week multimodal day-care rehabilitation programme can be tolerable, reduce psychiatric symptoms, and improve health-related quality of life for people with HD. A higher sense of coherence seems to promote attendance rates. Further larger studies, including the impact of cognition and disease progression on the treatment effect, are warranted.

Lack of time and dependence on significant others: Occupational therapists´ experiences of prescribing time assistive technology for persons with dementia.

Background: There is lack of knowledge on how occupational therapists (OTs) assess daily time management (DTM) for persons with dementia (PwDs) and on which aspects affect prescription of time assistive technology (AT).Aim: To explore OTs' experiences of assessing the need for and prescribing time AT for PwDs.Material and methods: Focus group interviews with OTs that prescribe time AT for PwDs analyzed via qualitative content analysis.Results: A main category and four categories were identified. The categories illustrated a complex and time-consuming prescription process, which was facilitated if the PwD was supported by a significant other (SO). Support from a SO was especially important during implementation and follow-up. OTs had to take individual responsibility for staying informed about time AT. Organizational limitations and time constraints were barriers for OTs striving to work according to national prescription guidelines.Conclusions and significance: High demands are made on SO's participation during the prescription process. PwDs with no support from SOs are at risk not receiving or fully benefitting from time AT. To avoid inequalities, specific forms of support need to be developed and targeted at PwDs without SOs to ensure that they have sufficient opportunities to access and use time AT.

An observational study of trait and state fatigue, and their relation to cognitive fatigability and saccade performance.

AIM: Different fatigue measurements and their relation to saccadic functions were investigated in 15 patients with a mild traumatic brain injury (mTBI) and 15 orthopedic controls. MATERIALS & METHODS: State fatigue was measured with the Fatigue Severity Scale and trait fatigue with the question on fatigue in the Rivermead Post Concussion Questionnaire and fatigability as decreased performance over time on a neuropsychological measure. RESULTS: Patients with an mTBI scored significantly higher in state fatigue and showed more fatigability compared with the orthopedic controls. Among patients with mTBI, state fatigue correlated with prosaccade latency and cognitive fatigability, while trait fatigue correlated with anxiety and antisaccade latency and variability. CONCLUSION: This pilot study indicates that saccade measurements might, in the future, be useful in the understanding of fatigue and in the search for prognostic factors after mTBI.

Relationship between fatigue after acquired brain injury and depression, injury localization and aetiology: An explorative study in a rehabilitation setting.

OBJECTIVE: Fatigue after acquired brain injury may be related to the subcortico-frontal attention network. Depression is also strongly related to fatigue. This study investigates whether injury localization, diagnosis and depression are related to self-rated mental fatigue in patients with an acquired brain injury. DESIGN: Retrospective cross-sectional cohort study. SUBJECTS: Sixty-one patients diagnosed with stroke, subarachnoidal haemorrhage, traumatic brain injury, or brain tumour were included in the study. METHODS: Patients who underwent a multidisciplinary team assessment during September 2011 to June 2012, and who were assessed with the Mental Fatigue Scale, were included in the study. RESULTS: A significantly higher number of patients with posterior and non-specific lesions experienced fatigue compared with those with subcortical/frontal injuries. Fewer stroke patients experienced fatigue compared with the other patient groups. How-ever, after logistic regression, only depression remained as an explanatory variable for self-rated fatigue. Nevertheless, although all patients with depression were fatigued, not all fatigued patients were depressed. CONCLUSION: Although depression explains a high degree of fatigue after an acquired brain injury, mental fatigue after brain injury should be viewed as a condition partly separate from depression. Future extensive comparative studies are required, preferably including neuropsychological measures.

The value of incorporating personally relevant stimuli into consciousness assessment with the Coma Recovery Scale - Revised: A pilot study.

OBJECTIVE: To explore whether the use of personally relevant stimuli, for some tasks in the Coma Recovery Scale - Revised (CRS-R), generates more responses in patients with prolonged disorders of consciousness compared with neutral stimuli. DESIGN: Multiple single-case design. SUBJECTS: Three patients with prolonged disorders of consciousness recruited from an inpatient department at a regional brain injury rehabilitation clinic in Stockholm, Sweden. METHODS: Patients were repeatedly assessed with the CRS-R. Randomization tests (bootstrapping) were used to compare the number of responses generated by personally relevant and neutral stimuli on 5 items in the CRS-R. RESULTS: Compared with neutral stimuli, photographs of relatives generated significantly more visual fixations. A mirror generated visual pursuit to a significantly greater extent than other self-relevant stimuli. On other items, no significant differences between neutral and personally relevant stimuli were seen. CONCLUSION: Personally relevant visual stimuli may minimize the risk of missing visual fixation, compared with the neutral stimuli used in the current gold standard behavioural assessment measure (CRS-R). However, due to the single-subject design this conclusion is tentative and more research is needed.

Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance.

INTRODUCTION: Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI. MATERIAL AND METHODS: Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT. RESULTS: The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period. DISCUSSION: This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.

Effects of testosterone and estrogen replacement on memory function.

OBJECTIVE: Testosterone insufficiency has been associated with psychosexual problems, reduced psychological well-being, and negative metabolic consequences, whereas less is known about the effects on cognition. The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women. METHODS: In a randomized, double-blind, placebo-controlled design, women with surgically induced menopause (n = 50; mean [SD] age, 54.0 [2.9] y) received estradiol valerate in combination with testosterone undecanoate or placebo. The women were assessed with a self-report questionnaire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline, at the time of crossover, and after completion of treatment. RESULTS: Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks. Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline. This was not observed in the women in the estrogen + testosterone treatment. Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment. However, there was no significant treatment effect between the two groups. CONCLUSIONS: Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo, while other memory functions were unaffected.