Differences in brain structure and cognitive performance between patients with long-COVID and those with normal recovery.

BACKGROUND: The pathophysiology of protracted symptoms after COVID-19 is unclear. This study aimed to determine if long-COVID is associated with differences in baseline characteristics, markers of white matter diffusivity in the brain, and lower scores on objective cognitive testing. METHODS: Individuals who experienced COVID-19 symptoms for more than 60 days post-infection (long-COVID) (n = 56) were compared to individuals who recovered from COVID-19 within 60 days of infection (normal recovery) (n = 35). Information regarding physical and mental health, and COVID-19 illness was collected. The National Institute of Health Toolbox Cognition Battery was administered. Participants underwent magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). Tract-based spatial statistics were used to perform a whole-brain voxel-wise analysis on standard DTI metrics (fractional anisotropy, axial diffusivity, mean diffusivity, radial diffusivity), controlling for age and sex. NIH Toolbox Age-Adjusted Fluid Cognition Scores were used to compare long-COVID and normal recovery groups, covarying for Age-Adjusted Crystallized Cognition Scores and years of education. False discovery rate correction was applied for multiple comparisons. RESULTS: There were no significant differences in age, sex, or history of neurovascular risk factors between the groups. The long-COVID group had significantly (p < 0.05) lower mean diffusivity than the normal recovery group across multiple white matter regions, including the internal capsule, anterior and superior corona radiata, corpus callosum, superior fronto-occiptal fasciculus, and posterior thalamic radiation. However, the effect sizes of these differences were small (all ß<|0.3|) and no significant differences were found for the other DTI metrics. Fluid cognition composite scores did not differ significantly between the long-COVID and normal recovery groups (p > 0.05). CONCLUSIONS: Differences in diffusivity between long-COVID and normal recovery groups were found on only one DTI metric. This could represent subtle areas of pathology such as gliosis or edema, but the small effect sizes and non-specific nature of the diffusion indices make pathological inference difficult. Although long-COVID patients reported many neuropsychiatric symptoms, significant differences in objective cognitive performance were not found.

Criterion validity of a single-item measure of fear avoidance behavior following mild traumatic brain injury.

Maladaptive coping such as fear avoidance behavior can prolong recovery from mild traumatic brain injury (mTBI). Routine assessment of fear avoidance may improve management of mTBI. This study aimed to validate a single-item measure of fear avoidance to make its assessment more pragmatic. The present study is a secondary analysis of a clinical trial that involved adults with persistent post-concussion symptoms (N = 90, 63% female). Participants completed the single-item fear avoidance rating, a validated legacy measure of fear avoidance (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and measures of anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), post-concussion symptoms (Rivermead Postconcussion Symptoms Questionnaire), and disability (World Health Organization Disability Assessment Schedule 12.0). Questionnaires were completed twice, at baseline (mean 18.1 weeks post injury) and again 12-16 weeks later following study-delivered rehabilitation in addition to usual care. We analyzed the associations (Spearman's correlations) and agreement (weighted Kappa) between the single-item and FAB-TBI at baseline, posttreatment, individual FAB-TBI item scores, and the change in scores between baseline and posttreatment. In addition, we examined correlations between the single-item fear avoidance measure and related constructs, including anxiety, depression, post-concussion symptoms, and disability. The single-item fear avoidance measure correlated strongly with the FAB-TBI both at baseline and following treatment (ρ = 0.63 - 0.67, p < .001), and moderately with FAB-TBI item scores (ρ = 0.4 - 0.6). The correlation between the change in these scores from baseline to posttreatment was moderate (ρ = 0.45, p < .001). Agreement between the single-item fear avoidance measure and discretized FAB-TBI scores was moderate (κ = 0.45 - 0.51). Before and after treatment, the single-item fear avoidance measure correlated moderately with anxiety (ρ = 0.34), depression (ρ = 0.43), post-concussion symptoms (ρ = 0.50), and disability (ρ = 0.43). The FAB-TBI was more strongly correlated with these measures (ρ = 0.53 - 0.73). In summary, the present study supports the criterion validity of the single-item fear avoidance measure. This measure may be a useful screening and monitoring tool for patients with mTBI but is not a substitute for the FAB-TBI questionnaire.

Graded exposure therapy for adults with persistent symptoms after mTBI: A historical comparison study.

Fear avoidance behaviour is associated with slow recovery from mild traumatic brain injury (mTBI). This study is a preliminary evaluation of graded exposure therapy (GET), which directly targets fear avoidance behaviour, for reducing post-concussion symptoms (PCS) and disability following mTBI. In a historical comparison design, we compared two groups from independent randomized trials. The GET + UC group (N = 34) received GET (delivered over 16 videoconference sessions) in addition to usual care (UC). The historical comparison group (N = 71) received UC only. PCS severity (Rivermead Post Concussion Symptoms Questionnaire; RPQ) and disability (World Health Organization Disability Assessment Schedule; WHODAS 2.0 12-item) were measured at clinic intake (M = 2.7, SD = 1.1 months after injury) and again at M = 4.9 (SD = 1.1) months after injury. Between-group differences were estimated using linear mixed effects regression, with a sensitivity analysis controlling for injury-to-assessment intervals. The estimated average change on the RPQ was -14.3 in the GET + UC group and -5.3 in the UC group. The estimated average change on the WHODAS was -5.3 in the GET + UC group and -3.2 in the UC group. Between-group differences post-treatment were -5.3 on the RPQ and -1.5 on the WHODAS. Treatment effects were larger in sensitivity analyses. Findings suggest that a randomized controlled trial is warranted.

Management of Psychological Complications Following Mild Traumatic Brain Injury.

PURPOSE OF REVIEW: It has been clear for decades that psychological factors often contribute to mild traumatic brain injury (mTBI) outcome, but an emerging literature has begun to clarify which specific factors are important, when, for whom, and how they impact recovery. This review aims to summarize the contemporary evidence on psychological determinants of recovery from mTBI and its implications for clinical management. RECENT FINDINGS: Comorbid mental health disorders and specific illness beliefs and coping behaviors (e.g., fear avoidance) are associated with worse recovery from mTBI. Proactive assessment and intervention for psychological complications can improve clinical outcomes. Evidence-based treatments for primary mental health disorders are likely also effective for treating mental health disorders after mTBI, and can reduce overall post-concussion symptoms. Broad-spectrum cognitive-behavioral therapy may modestly improve post-concussion symptoms, but tailoring delivery to individual psychological risk factors and/or symptoms may improve its efficacy. Addressing psychological factors in treatments delivered primarily by non-psychologists is a promising and cost-effective approach for enhancing clinical management of mTBI. Recent literature emphasizes a bio-psycho-socio-ecological framework for understanding mTBI recovery and a precision rehabilitation approach to maximize recovery. Integrating psychological principles into rehabilitation and tailoring interventions to specific risk factors may improve clinical management of mTBI.

Attachment and Clinical Outcomes Among Treatment-Seeking Adults With Persistent Symptoms After Mild Traumatic Brain Injury.

OBJECTIVE: Interpersonal attachment influences the development and course of disease. Overreliance on insecure attachment strategies may increase risk for poor disease outcomes. This study aimed to investigate largely unexplored relationships between attachment strategies and clinical outcomes among adults with persistent symptoms after mild traumatic brain injury (mTBI). METHODS: Participants with persistent symptoms after mTBI (N=83) completed measures assessing dimensions of insecure attachment (Relationship Scales Questionnaire [RSQ]), persistent symptoms (Rivermead Post-Concussion Symptoms Questionnaire), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), and health-related quality of life (HRQOL) (Quality of Life After Brain Injury-Overall Scale). Questionnaires were administered at clinic intake (mean=18.1 weeks postinjury) and again 3-4 months later (mean=32.2 weeks postinjury), except the RSQ, which was administered only in the follow-up assessment. Treatment response for each outcome was calculated as the difference between scores at clinic intake and follow-up. Generalized linear models were fitted for each clinical outcome, with RSQ variables as predictors. RESULTS: Higher attachment anxiety was associated with greater persistent symptom severity, greater depression and anxiety symptoms, and worse HRQOL at follow-up. Higher attachment anxiety was also associated with less improvement in depression and HRQOL over time. In contrast, attachment avoidance was unrelated to any of the clinical outcomes. CONCLUSIONS: Attachment anxiety, the fear that a significant other will not be available in stressful circumstances, may be a particularly important social factor associated with health among adults with persistent symptoms after mTBI. Greater consideration of the attachment system is warranted in mTBI care and research.

Three-month Practice Effect of the National Institutes of Health Toolbox Cognition Battery in Young Healthy Adults.

The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test-retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen's d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Litigation, Performance Validity Testing, and Treatment Outcomes in Adults With Mild Traumatic Brain Injury.

OBJECTIVE: To investigate whether involvement in litigation and performance validity test (PVT) failure predict adherence to treatment and treatment outcomes in adults with persistent symptoms after mild traumatic brain injury (mTBI). SETTING: Outpatient concussion clinics in British Columbia, Canada. Participants were assessed at intake (average 12.9 weeks postinjury) and again following 3 to 4 months of rehabilitation. PARTICIPANTS: Adults who met the World Health Organization Neurotrauma Task Force definition of mTBI. Litigation status was known for 69 participants (n = 21 reported litigation), and 62 participants completed a PVT (n = 13 failed the Test of Memory Malingering) at clinic intake. DESIGN: Secondary analysis of a clinical trial (ClinicalTrials.gov #NCT03972579). MAIN MEASURES: Outcomes included number of completed sessions, homework adherence, symptoms (Rivermead Post Concussion Symptoms Questionnaire), disability ratings (World Health Organization Disability Assessment Schedule 2.0), and patient-rated global impression of change. RESULTS: We did not observe substantial differences in session and homework adherence associated with litigation or PVT failure. Disability and postconcussion symptoms generally improved with treatment. Involvement in litigation was associated with a smaller improvement in outcomes, particularly disability (B = 2.57, 95% confidence interval [CI] [0.25-4.89], P = .03) and patient-reported global impression of change (odds ratio [OR] = 4.19, 95% CI [1.40-12.57], P = .01). PVT failure was not associated with considerable differences in treatment outcomes. However, participants who failed the PVT had a higher rate of missing outcomes (31% vs 8%) and perceived somewhat less global improvement (OR = 3.47, 95% CI [0.86-14.04]; P = .08). CONCLUSION: Adults with mTBI who are in litigation or who failed PVTs tend to adhere to and improve following treatment. However, involvement in litigation may be associated with attenuated improvements, and pretreatment PVT failure may predict lower engagement in the treatment process.

Psychological Contributions to Symptom Provocation Testing After Concussion.

OBJECTIVE: Following concussion, symptoms such as headache, dizziness, and fatigue may transiently worsen or reemerge with increased exertion or activity. Standardized tests have been developed to assess symptom increases following aerobic, cognitive, or vestibular/oculomotor challenge. Although neurophysiological mechanisms are proposed to underlie symptom increases following exertion, psychological factors such as anxiety and misinterpretation of normal bodily sensations may also play a role. In this study, we examined the contribution of psychological factors to symptom provocation testing outcomes. SETTING: Two outpatient concussion clinics in British Columbia, Canada. PARTICIPANTS: Adults with persistent symptoms following concussion ( N = 79; 62% women). DESIGN: In a single session, participants completed self-report questionnaires measuring the psychological factors of interest and underwent symptom provocation testing including aerobic (Buffalo Concussion Bike Test; BCBT), cognitive (National Institutes of Health Toolbox-Cognition Battery; NIHTB-CB), and vestibular/oculomotor (Vestibular/Ocular Motor Screening for Concussion; VOMS) challenge. MAIN MEASURES: Psychological factors of interest included premorbid and current anxiety (Generalized Anxiety Disorder-7; GAD-7), catastrophizing (Pain Catastrophizing Scale-Adapted; PCS-A), fear avoidance behavior (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and somatization (Patient Health Questionnaire-15; PHQ-15). Our primary outcome variables were self-reported symptom change during each symptom provocation test. RESULTS: We found that current anxiety ( B = 0.034; 95% CI = 0.003, 0.065), symptom catastrophizing ( B = 0.013; 95% CI = 0.000, 0.026), fear avoidance behavior ( B = 0.029; 95% CI = 0.008, 0.050), and somatization ( B = 0.041; 95% CI = 0.007, 0.075) were associated with increased symptoms during the VOMS in univariate models adjusted for time postinjury but not in a multivariable model that included all covariates. The psychological variables of interest were not significantly related to symptom change during the BCBT or NIHTB-CB. CONCLUSION: Our findings suggest that symptom provocation test failure should be interpreted with caution because it might indicate psychological maladjustment rather than lingering brain injury or incomplete neurophysiological recovery.

Responsiveness and trajectory of changes in the rating of everyday arm-use in the community and home (REACH) scale over the first-year post-stroke.

OBJECTIVE: To examine the trajectory of the Rating of Everyday Arm-use in the Community and Home (REACH) scores over the first-year post-stroke, determine if REACH scores are modified by baseline impairment level and explore the responsiveness of the REACH scale through hypothesis testing. DESIGN: Consecutive sample longitudinal study. SETTING: Participants were recruited from an acute stroke unit and followed up at three, six, and 12 months post-stroke. PARTICIPANTS: Seventy-three participants with upper limb weakness (Shoulder Abduction and Finger Extension score ≤ 8). MAIN MEASURES: The REACH scale is a six-level self-report classification scale that captures how the affected upper limb is being used in one's own environment. The Fugl-Meyer Upper Limb Assessment (FMA-UL), Stroke Upper Limb Capacity Scale (SULCS), accelerometer-based activity count ratio and Global Rating of Change Scale (GRCS) were used to capture upper limb impairment, capacity, and use. RESULTS: The following proportions of participants improved at least one REACH level: 64% from baseline to three months, 37% from three to six months and 13% from six to 12 months post-stroke. The trajectory of REACH scores over time was associated with baseline impairment. Change in REACH had a moderate correlation to change in SULCS and the GRCS but not FMA-UL or the activity count ratio. CONCLUSIONS: Results of hypothesis testing provide preliminary evidence of the responsiveness of the REACH scale. On average, individuals with severe impairment continued to show improvement in use over the first year, while those with mild/moderate impairment plateaued and a small proportion decreased in the early chronic phase.