Traumatic Microbleeds in the Hippocampus and Corpus Callosum Predict Duration of Posttraumatic Amnesia.

OBJECTIVE: Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. SETTING: Academic, tertiary medical center. PARTICIPANTS: Adults with traumatic brain injury (TBI). DESIGN: We identified 65 TBI patients with acute GRE MRI. PTA duration was determined with the Galveston Orientation and Amnesia Test, Orientation Log, or chart review. TMBs were identified within memory regions (hippocampus, corpus callosum, fornix, thalamus, and temporal lobe) and control regions (internal capsule and global). Regression tree analysis was performed to identify radiologic predictors of PTA duration, controlling for clinical PTA predictors. MAIN MEASURES: TMB distribution, PTA duration. RESULTS: Sixteen patients (25%) had complicated mild, 4 (6%) had moderate, and 45 (69%) had severe TBI. Median PTA duration was 43 days (range, 0-240 days). In univariate analysis, PTA duration correlated with TMBs in the corpus callosum (R = 0.29, P = .02) and admission Glasgow Coma Scale (GCS) score (R = -0.34, P = .01). In multivariate regression analysis, admission GCS score was the only significant contributor to PTA duration. However, in regression tree analysis, hippocampal TMBs, callosal TMBs, age, and admission GCS score explained 26% of PTA duration variance and distinguished a subgroup with prolonged PTA. CONCLUSIONS: Hippocampal and callosal TMBs are potential radiologic predictors of PTA duration.

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal.

BACKGROUND: Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as "grade 3 diffuse axonal injury," but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome. METHODS: Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients. RESULTS: Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mm3. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R = 0.37, p = 0.02, and R = 0.36, p = 0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes. CONCLUSIONS: These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

Risk Factors for Institutionalization After Traumatic Brain Injury Inpatient Rehabilitation.

OBJECTIVE: To create a profile of individuals with traumatic brain injury (TBI) who received inpatient rehabilitation and were discharged to an institutional setting using characteristics measured at rehabilitation discharge. METHODS: The Traumatic Brain Injury Model Systems National Database is a prospective, multicenter, longitudinal database for people with moderate to severe TBI. We analyzed data for participants enrolled from January 2002 to June 2012 who had lived in a private residence before TBI. This cross-sectional study used logistic regression analyses to identify sociodemographic factors, lengths of stay, and cognitive and physical functioning levels that differentiated patients discharged to institutional versus private settings. RESULTS: Older age, living alone before TBI, and lower levels of function at rehabilitation discharge (independence in locomotion, bladder management, comprehension, and social interaction) were significantly associated with higher institutionalization rates and provided the best models identifying factors associated with institutionalization. Institutionalization was also associated with decreased independence in bed-chair-wheelchair transfers and increased duration of posttraumatic amnesia. CONCLUSIONS: Individuals institutionalized after inpatient rehabilitation for TBI were older, lived alone before injury, had longer posttraumatic amnesia durations, and were less independent in specific functional characteristics. Research evaluating the effect of increasing postdischarge support and improving treatment effectiveness in these functional areas is recommended.

Diffusion tensor imaging in acute-to-subacute traumatic brain injury: a longitudinal analysis.

BACKGROUND: Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. METHODS: From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. RESULTS: FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/-0.07 vs. 0.49+/-0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = -0.78, p = 0.02) and splenium (R = -0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = -0.63, p < 0.05) and no inverse correlations were observed. CONCLUSIONS: White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period.

Longitudinal Diffusion Tensor Imaging Detects Recovery of Fractional Anisotropy Within Traumatic Axonal Injury Lesions.

BACKGROUND: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome. METHODS: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation. RESULTS: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores. CONCLUSIONS: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

Predicting institutionalization after traumatic brain injury inpatient rehabilitation.

Risk factors contributing to institutionalization after inpatient rehabilitation for people with traumatic brain injury (TBI) have not been well studied and need to be better understood to guide clinicians during rehabilitation. We aimed to develop a prognostic model that could be used at admission to inpatient rehabilitation facilities to predict discharge disposition. The model could be used to provide the interdisciplinary team with information regarding aspects of patients' functioning and/or their living situation that need particular attention during inpatient rehabilitation if institutionalization is to be avoided. The study population included 7219 patients with moderate-severe TBI in the Traumatic Brain Injury Model Systems (TBIMS) National Database enrolled from 2002-2012 who had not been institutionalized prior to injury. Based on institutionalization predictors in other populations, we hypothesized that among people who had lived at a private residence prior to injury, greater dependence in locomotion, bed-chair-wheelchair transfers, bladder and bowel continence, feeding, and comprehension at admission to inpatient rehabilitation programs would predict institutionalization at discharge. Logistic regression was used, with adjustment for demographic factors, proxy measures for TBI severity, and acute-care length-of-stay. C-statistic and predictiveness curves validated a five-variable model. Higher levels of independence in bladder management (adjusted odds ratio [OR], 0.88; 95% CI 0.83, 0.93), bed-chair-wheelchair transfers (OR, 0.81 [95% CI, 0.83-0.93]), and comprehension (OR, 0.78 [95% CI, 0.68, 0.89]) at admission were associated with lower risks of institutionalization on discharge. For every 10-year increment in age was associated with a 1.38 times higher risk for institutionalization (95% CI, 1.29, 1.48) and living alone was associated with a 2.34 times higher risk (95% CI, 1.86, 2.94). The c-statistic was 0.780. We conclude that this simple model can predict risk of institutionalization after inpatient rehabilitation for patients with TBI.

Fractional anisotropy helps predicts memory rehabilitation outcome after traumatic brain injury.

Traumatic brain injury (TBI) commonly results in residual memory difficulties. Such deficits are amenable to cognitive rehabilitation, but optimal selection of rehabilitation interventions remains a challenge. We hypothesized that diffusion tensor imaging (DTI) could be used to predict which individuals were likely to benefit from a specific memory rehabilitation intervention. Thirty-seven individuals with TBI, of all severities, first underwent DTI scanning, along with 18 matched controls. Participants with TBI then attended a 12-session memory intervention emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of DTI scanning, and both immediately and one month post-therapy. In contrast to typical neuroimaging analysis, fractional anisotropy (FA) was used to predict long-term outcome scores, adjusting for typical predictors (injury severity, age, education, time since injury, pretest score). FA of the parahippocampal white matter was a significant negative predictor of HVLT, while the anterior corpus callosum, left anterior internal capsule, and right anterior corona radiata were negative predictors of RBMT outcome. The importance of these predictors rivaled those of pretest scores. Thus, FA measures may provide substantial predictive value for other cognitive interventions as well. The reason why higher FA was associated with less successful response to cognitive intervention remains unclear and will require further study.

Test-re-test reliability of the Hopkins Verbal Learning Test-Revised in individuals with traumatic brain injury.

PRIMARY OBJECTIVE: To determine test-re-test reliability of the Hopkins Verbal Learning Test-Revised (HVLT-R) in a group of individuals with traumatic brain injury (TBI). RESEARCH DESIGN: Single-group repeated measures design. METHODS AND PROCEDURES: Seventy-five individuals with TBI were administered the HVLT-R twice, with 6-8 weeks between the two test sessions. MAIN OUTCOMES AND RESULTS: Test-re-test reliability on HVLT-R scoring parameters ranged from 0.537-0.818, with seven of the eight scoring parameters exhibiting r > 0.6. At re-test, scores did not significantly change on any of the eight HVLT-R scoring parameters. CONCLUSIONS: HVLT-R use with individuals with TBI is supported. Test-re-test reliability of total recall and delayed recall sub-scores was particularly high.

Electronic reminding technology following traumatic brain injury: effects on timely task completion.

OBJECTIVE: To determine whether automated reminders from 2 contemporary personal digital assistant (PDA) devices produce higher rates of timely task completion in people with traumatic brain injury (TBI). SETTING: Outpatient and community rehabilitation settings. PARTICIPANTS: Thirty-six adults aged 18 to 66 years with TBI and self-determined complaints of memory impairment. MEASURES: Timely completion rates for assigned memory tasks under 4 randomly assigned memory aid conditions. RESULTS: Significantly, higher completion rates were found when using either PDA device when compared with a combined baseline and paper memory aid condition (for Palm OS device, Incidence Rate Ratio [IRR] = 2.14, P < .0005, CI [confidence interval] = 1.77-2.59; for Microsoft Pocket PC OS device, IRR = 1.47, P < .001, CI = 1.18-1.82). A significant difference in completion rates was also found between the 2 PDA devices (IRR = 1.46, P < .0005, CI = 1.26-1.70), with the Palm version producing the better scores. CONCLUSIONS: Substantially higher rates of task completion (more than double in some cases) when using either PDA device suggest that rehabilitation clinicians can make productive use of PDA-based memory aids in their TBI patient populations. The strength of the effects of PDA device usage argues for further investigation of the impact of device usage on quality-of-life and costs of care, and of personal and caregiver factors predictive of successful and sustained device usage.

Regional brain morphometry predicts memory rehabilitation outcome after traumatic brain injury.

Cognitive deficits following traumatic brain injury (TBI) commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of the MRI scan, immediately following therapy, and again at 1-month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores). We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

Test-re-test reliability of the virtual planning test in individuals with traumatic brain injury.

PRIMARY OBJECTIVE: To determine test-re-test reliability of the VIrtual Planning Test (VIP) in a group of individuals with traumatic brain injury (TBI). RESEARCH DESIGN: Single-group repeated measures design. METHODS AND PROCEDURES: Seventy-five individuals with TBI were administered the VIP, with 6-8 weeks between the two test sessions. MAIN OUTCOMES AND RESULTS: Test-re-test reliability on VIP scoring parameters--as measured by Pearson correlation coefficients--ranged from 0.341-0.855, with five of the seven scoring parameters exhibiting r > 0.6. CONCLUSIONS: Based on the findings of the current study, the VIP has overall moderate test-re-test reliability when administered to individuals with TBI. Some VIP scoring parameters, i.e. Total correct/accuracy and Total absence, demonstrated high test-re-test reliability. Others, i.e. Planning time and Total wrong order, demonstrated low test-re-test reliability.

A controlled treatment study of internal memory strategies (I-MEMS) following traumatic brain injury.

OBJECTIVE: To evaluate the effects of participation in a memory group intervention focusing on internal strategy use on persons with traumatic brain injury-related memory impairment. PARTICIPANTS: Ninety-four adults with traumatic brain injury (54 in the experimental group and 40 controls) and resulting memory impairment, with severities ranging from mild to severe. All participants were at least 18 years of age at the time of injury and at least 1 year post injury at the time of study. DESIGN: Non randomized pre/posttest group comparison design. MAIN OUTCOME MEASURES: Hopkins Verbal Learning Test-Revised and Rivermead Behavioral Memory Test II. RESULTS: Participation in the memory group intervention was associated with improved memory performance immediately postintervention, and improvements were maintained 1 month postintervention. Severe injury was associated with less improvement in memory outcomes than mild and moderate injuries. Age and preinjury education were not related to outcome. CONCLUSIONS: Individuals with traumatic brain injury may benefit from memory group intervention focusing on internal strategy use. Study hypotheses should be retested using a randomized, controlled design, and further research is needed to better delineate influences on intervention candidacy and outcomes.

Neurophysiological alterations during strategy-based verbal learning in traumatic brain injury.

BACKGROUND: Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood. METHODS: We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (>1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition). RESULTS: Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional-but not anatomical-breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy. CONCLUSION: After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation.

Prediction of memory rehabilitation outcomes in traumatic brain injury by using functional magnetic resonance imaging.

OBJECTIVE: To evaluate the ability of functional magnetic resonance imaging (fMRI) measures collected from people with traumatic brain injury (TBI) to provide predictive value for rehabilitation outcomes over and above standard predictors. DESIGN: Prospective study. SETTING: Academic medical center. PARTICIPANTS: Persons (N=54) with TBI greater than 1 year postinjury. INTERVENTION: A novel 12-session group rehabilitation program focusing on internal strategies to improve memory. MAIN OUTCOME MEASURE: The Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall score. RESULTS: fMRI measures were collected while participants performed a strategically directed word memorization task. Prediction models were multiple linear regressions with the following primary predictors of outcome: age, education, injury severity, preintervention HVLT-R, and task-related fMRI activation of the left dorsolateral and left ventrolateral prefrontal cortex (VLPFC). Baseline HVLT-R was a significant predictor of outcome (P=.007), as was injury severity (for severe vs mild, P=.049). We also found a significant quadratic (inverted-U) effect of fMRI in the VLPFC (P=.007). CONCLUSIONS: This study supports previous evidence that left prefrontal activity is related to strategic verbal learning, and the magnitude of this activation predicted success in response to cognitive memory rehabilitation strategies. Extreme under- or overactivation of VLPFC was associated with less successful learning after rehabilitation. Further study is necessary to clarify this relationship and to expand and optimize the possible uses of functional imaging to guide rehabilitation therapies.

The ineffectiveness of the Hospital Anxiety and Depression Scale for diagnosis in an Omani traumatic brain injured population.

BACKGROUND: The rehabilitation of the traumatic brain injury (TBI) patient is especially challenging in non-western populations as the phenotypic indicators as well as the neurobehavioral assessments for the survivors of brain injury are limited. OBJECTIVE: The study screened for the prevalence of anxiety and depressive states among patients with TBI and examined the validity of the Hospital Anxiety and Depression Scale (HADS) to identify TBI patients with comorbid affective dysfunctions, specifically anxiety and depressive disorders, in an Omani population. METHODS: Sixty-eight survivors of TBI were screened with the semi-structured, Composite International Diagnostic Interview (CIDI) and the HADS. A receiver operating characteristics (ROC) curve was calculated to discriminate the power of the HADS for every possible threshold score. RESULTS: The semi-structured interview revealed the prevalence rate of 57.4% for depressive disorder and 50% for anxiety disorder. The sensitivity (53.8%) and specificity 75.9%, gave the best compromise using the cut-off score of 4, suggesting HADS is not a useful screening tool for this particular population. CONCLUSIONS: Phenotypic indicators as detected by CIDI revealed that prevalence of affective dysfunctionality is common among this TBI population. Although the HADS is the most widely used screening instrument in other clinical populations, it does not appear to be a reliable resource in identifying depression and anxiety in people with traumatic brain injury in Oman.

Characteristics of home-based community integration programmes for adults with brain injury.

OBJECTIVES: To conduct a nationwide telephone survey in order to gather data on some of the quantifiable characteristics of home-based community integration programmes available in the US to adults with brain injury. DESIGN: Survey. METHODS: The Community Integration Programme Questionnaire (CIPQ) was used to interview 13 home-based community integration programmes. This study then used descriptive statistics to analyse the characteristics of the programmes. OUTCOME: There was a good deal of variability in client and programmatic characteristics. CONCLUSIONS: There is considerable variability in characteristics among home-based community integration programmes.

Characteristics of residential community integration programs for adults with brain injury.

OBJECTIVES: To gather data on some quantifiable characteristics of residential community integration programs available to adults with brain injury. PARTICIPANTS: Directors, assistant directors, or coordinators of community integration programs for people with brain injury. MEASUREMENT TOOLS: The Community Integration Program Questionnaire (CIPQ). DESIGN: Nationwide telephone survey of 30 residential community integration programs between June 2002 and June 2003. RESULTS: There was tremendous variability in the areas of staffing, client, and programmatic characteristics. Staff-to-client ratio varied from 0.77 to 3.3. Lengths of stay ranged from 0.13 to 288 months. Times from injury to admission varied from 0.2 to 180 months. CONCLUSIONS: The considerable variability in characteristics of residential community integration programs for adults with brain injury presents significant challenges to researchers seeking to identify vital program components and to consumers attempting to compare programs.

Twenty years of pharmacology.

During the past 20 years in pharmacology, a number of innovations have appeared that have resulted in significant changes in the drugs available for people with traumatic brain injury. Among the anticonvulsants, antidepressants, and antipsychotics, new drugs have appeared with fewer cognitive side effects. In these classes of drugs, as well as among central nervous system stimulants, once-daily or other sustained-release preparations have been introduced that make it considerably more likely that the patient will take his or her medication, with smaller fluctuations in drug levels as well. New drugs have also resulted in a greater number of medications for the clinician to choose from. The overall effect has been a dramatic change in pharmacology that has benefited people with traumatic brain injury.