Cognition and post-concussive symptom status after pediatric mild traumatic brain injury.

Cognitive impairment and post-concussive symptoms (PCS) represent hallmark sequelae of pediatric mild traumatic brain injury (pmTBI). Few studies have directly compared cognition as a function of PCS status longitudinally. Cognitive outcomes were therefore compared for asymptomatic pmTBI, symptomatic pmTBI, and healthy controls (HC) during sub-acute (SA; 1-11 days) and early chronic (EC; approximately 4 months) post-injury phases. We predicted worse cognitive performance for both pmTBI groups relative to HC at the SA visit. At the EC visit, we predicted continued impairment from the symptomatic group, but no difference between asymptomatic pmTBI and HCs. A battery of clinical (semi-structured interviews and self-report questionnaires) and neuropsychological measures were administered to 203 pmTBI and 139 HC participants, with greater than 80% retention at the EC visit. A standardized change method classified pmTBI into binary categories of asymptomatic or symptomatic based on PCS scores. Symptomatic pmTBI performed significantly worse than HCs on processing speed, attention, and verbal memory at SA visit, whereas lower performance was only present for verbal memory for asymptomatic pmTBI. Lower performance in verbal memory persisted for both pmTBI groups at the EC visit. Surprisingly, a minority (16%) of pmTBI switched from asymptomatic to symptomatic status at the EC visit. Current findings suggest that PCS and cognition are more closely coupled during the first week of injury but become decoupled several months post-injury. Evidence of lower performance in verbal memory for both asymptomatic and symptomatic pmTBI suggests that cognitive recovery may be a process separate from the resolution of subjective symptomology.

Investigating the diagnostic accuracy of a paper-and-pencil and a computerized cognitive test battery for pediatric mild traumatic brain injury.

OBJECTIVE: This study assessed classification accuracy of paper-and-pencil and computerized cognitive batteries at subacute (SA; 1-11 days) and early chronic (EC; ∼4 months) phases of pediatric mild traumatic brain injury (pmTBI). Two statistical approaches focused on single-subject performance (individual task scores, total impairments) were used to maximize clinical utility. METHOD: Two hundred thirty-five pmTBI and 169 healthy controls (HC) participants aged 8-18 were enrolled, with a subset (190 pmTBI; 160 HC) returning for the EC visit. The paper-and-pencil battery included several neuropsychological tests selected from recommended common data elements, whereas computerized testing was performed with the Cogstate Brief Battery. Hierarchical logistic regressions (base model: Parental education and premorbid reading abilities; full model: Base model and cognitive testing variables) were used to examine sensitivity/specificity, with diagnosis as the dependent variable. RESULTS: Number Sequencing and Cogstate One-Card Learning accuracy significantly predicted SA diagnosis (full model accuracy = 71.6%-71.7%, sensitivity = 80.6%-80.8%, specificity = 59.1%-59.6%), while only immediate recall was significant at EC visit (accuracy = 68.5%, sensitivity = 74.6%, specificity = 61.5%). Other measures (Letter Fluency, Cogstate Detection, and One-Card Learning accuracy) demonstrated higher proportions of impairment for pmTBI subacutely (pmTBI: 11.5%-19.8%; HC: 3.7%-6.1%) but did not improve classification accuracy. Evidence of multiple impairments across the entire testing battery significantly predicted diagnosis at both visits (full model accuracy = 66.2%-68.6%, sensitivity = 71.2%-78.9%, specificity = 54.3%-61.5%). CONCLUSIONS: Current results suggest similar modest diagnostic accuracy for computerized and paper-and-pencil batteries across multiple pmTBI phases. Moreover, findings suggest the total number of impairments may be more clinically useful than any single test or cognitive domain in terms of diagnostic accuracy at both assessment points. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Influence of age and education on a performance-based measure of everyday functioning.

Sociodemographic variables, such as age and education, influence the determination of impairment on neuropsychological tests, but their influence on impairment determinations for tests of everyday functioning is less well defined. Existing studies suggest that older age and lower education levels are associated with worse everyday functioning when assessed by self- or collateral-report. This relationship, however, has not been thoroughly investigated with performance-based methods of everyday functioning. This study aimed to determine the influence of sociodemographic factors on the Functional Impact Assessment (FIA), a performance-based measure of everyday functioning that includes measures of both accuracy and speed. Seventy-three healthy individuals, ages 42 - 88 years, completed the FIA and an additional everyday functioning self-report questionnaire (Functional Activities Questionnaire). Using a multiple regression statistical approach, age and education predicted overall FIA accuracy, while age alone predicted FIA speed. Sociodemographic variables continued to predict FIA performance when controlling for overall cognitive functioning. Sociodemographic variables were unrelated to FAQ scores. These findings indicate that age and education are associated with scores on a performance-based test of everyday functioning. Demographic corrections may improve accuracy in determining functional impairment, but more research is needed given the complex relationships among demographic factors, healthy aging, and dementia risk.

Test-Retest Reliability of a Semi-Structured Interview to Aid in Pediatric Traumatic Brain Injury Diagnosis.

OBJECTIVE: Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test-retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI. METHOD: One-hundred and eight-four mTBI (aged 8-18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC). RESULTS: The test-retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test-retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI. CONCLUSIONS: Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test-retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).

Predictors of Caregiver Burden in Huntington's Disease.

OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative condition that is characterized by cognitive, motor, and psychiatric dysfunction. The purpose of this study was to explore which disease characteristics influence caregiver burden in HD. METHODS: Fifty participants with HD and 50 of their caregivers participated in the study at the University of South Florida. Participants were administered a neuropsychological battery, the Unified Huntington's Disease Rating Scale (UHDRS) motor exam, and the Frontal Systems Behavior Scale (FrSBe) self-report. Caregivers completed the Caregiving Appraisal Scale and the FrSBe family-report. RESULTS: There were significant correlations between caregiver burden and caregiver age and sex, UHDRS motor scores, cognitive functioning, and self and caregiver-reported FrSBe scores. The significant variables were entered into a regression model and explained 63.1% of the variance in caregiver burden scores. Caregiver age, cognitive functioning, and caregiver-reported FrSBe scores continued to be significant predictors of caregiver burden, whereas the other variables were no longer significant. CONCLUSIONS: There were significant relationships between caregiver burden, cognitive functioning, and frontally mediated behaviors, but not motor scores. The results suggest that possible interventions for caregivers may include education to caregivers on how to cope with apathy/executive dysfunction and cognitive decline. Caregiver age was associated with burden, with younger age being associated with increased burden when controlling for symptom severity. This has implications for this population in that HD typically has a younger age of onset than other neurodegenerative diseases and therefore, these caregivers may be particularly at risk for caregiver burden.

Use of Medical Cannabis to Treat Traumatic Brain Injury.

There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option. Pre-clinical TBI research suggests that cannabinoids have neuroprotective and psychotherapeutic properties. In contrast, recreational cannabis use has consistently shown to have detrimental effects. Our review identified a paucity of high-quality studies examining the beneficial and adverse effects of medical cannabis on TBI, with only a single phase III randomized control trial. However, observational studies demonstrate that TBI patients are using medical and recreational cannabis to treat their symptoms, highlighting inconsistencies between public policy, perception of potential efficacy, and the dearth of empirical evidence. We conclude that randomized controlled trials and prospective studies with appropriate control groups are necessary to fully understand the efficacy and potential adverse effects of medical cannabis for TBI.

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.

OBJECTIVE: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. METHOD: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase. RESULTS: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. CONCLUSIONS: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

Resting-State Power and Regional Connectivity After Pediatric Mild Traumatic Brain Injury.

BACKGROUND: Physiological recovery from pediatric mild traumatic brain injury (pmTBI) as a function of age remains actively debated, with the majority of studies relying on subjective symptom report rather than objective markers of brain physiology. PURPOSE: To examine potential abnormalities in fractional amplitude of low-frequency fluctuations (fALFF) or regional homogeniety (ReHo) during resting-state fMRI following pmTBI. STUDY TYPE: Prospective cohort. POPULATION: Consecutively recruited pmTBI (N = 105; 8-18 years old) and age- and sex-matched healthy controls (HC; N = 113). FIELD STRENGTH/SEQUENCE: 3T multiecho gradient T1 -weighted and single-shot gradient-echo echo-planar imaging. ASSESSMENT: All pmTBI participants were assessed 1 week and 4 months postinjury (HC assessed at equivalent timepoints after the first visit). Comprehensive demographic, clinical, and cognitive batteries were performed in addition to primary investigation of fALFF and ReHo. All pmTBI were classified as "persistent" or "recovered" based on both assessment periods. STATISTICAL TESTS: Chi-square, nonparametric, and generalized linear models for demographic data. Generalized estimating equations for clinical and cognitive data. Voxelwise general linear models (AFNI's 3dMVM) for fALFF and ReHo assessment. RESULTS: Evidence of recovery was observed for some, but not all, clinical and cognitive measures at 4 months postinjury. fALFF was increased in the left striatum for pmTBI relative to HC both at 1 week and 4 months postinjury; whereas no significant group differences (P > 0.001) were observed for ReHo. Age-at-injury did not moderate either resting-state metric across groups. In contrast to analyses of pmTBI as a whole, there were no significant (P > 0.001) differences in either fALFF or ReHo in patients with persistent postconcussive symptoms compared to recovered patients and controls at 4 months postinjury. DATA CONCLUSIONS: Our findings suggest prolonged clinical recovery and alterations in the relative amplitude of resting-state fluctuations up to 4 months postinjury, but no clear relationship with age-at-injury or subjective symptom report. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 2 J. MAGN. RESON. IMAGING 2020;52:1701-1713.

Evaluation of a performance-rating method to assess awareness of cognitive functioning in Huntington's disease.

Objective: Anosognosia, or lack of awareness of symptoms, is commonly observed in Huntington's disease (HD) using patient/informant-report discrepancy methods. The purpose of this study was to examine the utility of a performance-rating method for assessing awareness of cognitive performance in HD.Method: Persons with manifest HD (n = 54) rated their performance on the daily living tests from the Neuropsychological Assessment Battery (NAB) using a bell curve. We also examined patient/informant-report discrepancies of executive functioning (FrSBe) in a subset (n = 47) of patients and their informants.Results: Patients were able to reliably use our method of categorizing their performance as evidenced by significant correlations between verbal descriptions of their performance and the percentile ratings they indicated on the bell curve. Patients across the range of observed Unified HD Rating Scale motor scale scores rated their performance on the NAB tasks significantly higher than actual performance for both pretest prediction and posttest evaluation ratings. Only patients with more severe motor impairment underestimated their problems relative to informant report on the FrSBe.Conclusions: This is the first study to use a performance-rating method for examining awareness in HD. Patients could reliably use this performance-based bell curve method to provide accurate estimations of their performance and as a group they tended to overestimate performance as has been demonstrated in previous studies. Unlike previous studies using self-report methodology, we also demonstrated decreased awareness in the persons with HD with less severe motor impairment using the performance-rating method, suggesting the two methods may measure different constructs of awareness.

Awareness of Chorea in Huntington's Disease.

BACKGROUND: Anosognosia, or unawareness of illness of deficits, has been observed in Huntington's disease (HD) in relation to motor and cognitive signs and symptoms. Most studies of awareness in HD have used self-report questionnaire methodology rather than asking patients to report on their symptoms in real-time. The two studies in which patients were asked about their chorea in real-time had small sample sizes and only examined patients early in disease progression. OBJECTIVE: To examine awareness of chorea in real-time in HD patients across a broad range of disease progression. METHODS: Fifty HD patients across motor and cognitive impairment severity were asked if they noticed any involuntary movements after completing a simple working memory task used to elicit chorea. A movement disorders specialist rated the presence or absence of chorea while the patients completed the task. Disagreement between the patient and movement disorders specialist's ratings was considered to be an indicator of unawareness. RESULTS: Approximately 46% of patients who exhibited chorea did not report chorea. Eighty-eight percent of participants who acknowledged chorea did not report chorea in all parts of the body that chorea was observed. CONCLUSIONS: HD patients demonstrate unawareness of chorea across cognitive and motor sign severity.

Examining Huntington's disease patient and informant concordance on frontally mediated behaviors.

INTRODUCTION: Huntington's disease (HD) is a genetic, neurodegenerative disease that affects cognitive, psychiatric and motor functioning. Frontal subcortical circuits are impacted by disease pathology, resulting in frontally mediated behavioral dysfunction. The purpose of this study was (a) to examine the relationship between both patient and informant reports of frontally mediated behaviors and disease progression and (b) to determine rate of agreement between patient and informant reports of these behaviors in relation to disease progression. METHOD: Twenty-six HD patients and their informants participated in the study at the University of South Florida. Patient-informant pairs completed the Frontal Systems Behavior Scale (FrSBe) Self and Family ratings forms, respectively. UHDRS (Unified Huntington's Disease Rating Scale) motor scores were obtained from medical records as an index of disease progression. RESULTS: Only informant report of frontally mediated behaviors of apathy, disinhibition, and executive dysfunction was related to neurological examination results. On average, ratings by patients with less severe motor symptoms were comparable to informant ratings, suggesting intact awareness of deficits. In contrast, ratings of patients with more severe motor symptoms were discrepant from informant data, with informants providing more severe ratings than patients. CONCLUSIONS: HD patients may show intact awareness of frontally mediated behaviors in less severe stages but become increasingly unaware in more severe stages of the disease. This underscores the importance of clinical decisions regarding patient versus informant report at various stages of the disease.