GFAP out-performs S100ß in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions.

Both glial fibrillary acidic protein (GFAP) and S100ß are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100ß as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100ß to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT, 20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who sustained extracranial fractures below the head to the torso and extremities. Levels of S100ß were significantly higher in patients with fractures, compared with those without fractures (p<0.001) whether MMTBI was present or not. However, GFAP levels were not significantly affected by the presence of fractures (p>0.05). The area under the receiver operating characteristics curve (AUC) for predicting intracranial lesions on CT for GFAP was 0.84 (0.73-0.95) and for S100ß was 0.78 (0.67-0.89). However, in the presence of extracranial fractures, the AUC for GFAP increased to 0.93 (0.86-1.00) and for S100ß decreased to 0.75 (0.61-0.88). In a general trauma population, GFAP out-performed S100ß in detecting intracranial CT lesions, particularly in the setting of extracranial fractures.

Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention.

STUDY OBJECTIVE: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

Operating characteristics of executive functioning tests following traumatic brain injury.

The primary purposes of this study were to determine if controls, and mild and moderate/severe traumatic brain injury (TBI) patients performed differently on a battery of executive functioning (EF) tests, and to identify the operating characteristics of EF tests in this population. Participants consisted of 46 brain-injured individuals and 24 healthy controls. All participants completed an extensive battery of EF tests. Results showed that mild TBI participants performed worse than controls on the Trail Making Test Part B, and that moderate/severe TBI participants consistently performed worse than either group on a variety of EF measures. Tests of EF exhibited a wide range of operating characteristics, suggesting that some EF tests are better than others in identifying TBI-related neurocognitive impairment. Predictive values were better for individuals with moderate/severe TBI than mild TBI. Overall, the Digit Span Backward Test showed the best positive predictive power in differentiating TBI. Our results provide useful data that may guide test selection in evaluating EF in patients with traumatic brain injury.

Cardiac resynchronization therapy: a pilot study examining cognitive change in patients before and after treatment.

BACKGROUND: Cardiovascular patients with reduced cardiovascular output and capacity such as those with congestive heart failure (CHF) have demonstrated cognitive-related dysfunction. The use of cardiac resynchronization therapy (CRT) is considered standard care for CHF patients who do not improve despite optimal medical therapy. Cardiac resynchronization therapy may improve neurocognitive and psychosocial functioning in patients by increasing cardiac output and cerebral perfusion. METHODS: A total of 20 patients were examined before and 3 months after CRT device implantation, via administration of standard neurocognitive and psychosocial testing measures. RESULTS: Significant improvements in neurocognitive measures of attention (Digit Span: t[20] = - 2.695 [55.94+/-9.27-62.31+/-10.05], P = 0.015) and information processing (Digit Symbol: t[20] = - 4.577, P < 0.001; Controlled Oral Word Association Test: t[20] = - 3.338, P = 0.004) were demonstrated. Improvements in cardiac-specific quality of life were also significant (Minnesota Living with Heart Failure Questionnaire: t[16] = 3.544, P = 0.005 [55.17+/-18.23-36.75+/-18.00]; The Left Ventricular Dysfunction Questionnaire: t[16] = 3.544, P = 0.003 [63.43+/-23.35-43.29+/-21.62]). CONCLUSION: These results represent clinically significant, qualitative, and quantitative cognitive functional benefits for patients from a neurocognitive and psychosocial perspective. Results suggest that biventricular pacing improves cardiovascular outcome and psychosocial functioning in patients with CHF. The future investigation of a larger sample would be beneficial in establishing the depth and breadth of this improvement.

Measurement of patient fears about implantable cardioverter defibrillator shock: an initial evaluation of the Florida Shock Anxiety Scale.

BACKGROUND: Psychological distress is both a precipitant and a consequence of ICD shock. Therefore, the assessment of patient anxiety and concerns related to receiving an ICD shock may prompt appropriate psychological referrals and treatment. METHODS: The purpose of this study is to assess the initial validity and clinical utility of the Florida Shock Anxiety Scale (FSAS). Seventy-two ICD recipients completed the FSAS. RESULTS: Exploratory factor analysis revealed a two-factor structure with items loading such that Factor 1 could be conceptualized as a Consequence Factor (e.g., fearing creating a scene if the device were to fire) and Factor 2 as a Trigger Factor (e.g., fearing sexual activity). Alpha coefficients suggest good reliability (Cronbach's alpha= 0.91, split-half = 0.92), and FSAS Total Score was moderately correlated (r =-0.65) with total score on the Multidimensional Fear of Death Scale. CONCLUSIONS: Two subscales, labeled consequence of shock and trigger of shock, were established via factor analysis. Collectively the FSAS demonstrates potential utility to assess shock distress and warrants additional investigation.

Parametric manipulation of working memory load in traumatic brain injury: behavioral and neural correlates.

Traumatic brain injury (TBI) is often associated with enduring impairments in high-level cognitive functioning, including working memory (WM). We examined WM function in predominantly chronic patients with mild, moderate and severe TBI and healthy comparison subjects behaviorally and, in a small subset of moderate-to-severe TBI patients, with event-related functional magnetic resonance imaging (fMRI), using a visual n-back task that parametrically varied WM load. TBI patients showed severity-dependent and load-related WM deficits in performance accuracy, but not reaction time. Performance of mild TBI patients did not differ from controls; patients with moderate and severe TBI were impaired, relative to controls and mild TBI patients, but only at higher WM-load levels. fMRI results show that TBI patients exhibit altered patterns of activation in a number of WM-related brain regions, including the dorsolateral prefrontal cortex and Broca's area. Examination of the pattern of behavioral responding and the temporal course of activations suggests that WM deficits in moderate-to-severe TBI are due to associative or strategic aspects of WM, and not impairments in active maintenance of stimulus representations. Overall, results demonstrate that individuals with moderate-to-severe TBI exhibit WM deficits that are associated with dysfunction within a distributed network of brain regions that support verbally mediated WM.

Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia.

BACKGROUND: Schizophrenic patients show deficits in working memory (WM) and inhibition of prepotent responses. We examined brain activity while subjects performed tasks that placed demands on WM and overriding prepotent response tendencies, testing predictions that both processes engage overlapping prefrontal cortical (PFC) regions and that schizophrenic patients show reduced PFC activity and performance deficits reflecting both processes. METHODS: Functional magnetic resonance imaging data were acquired while 16 schizophrenic and 15 healthy subjects performed the N-Back task that varied WM load and a version of the AX-CPT that required overriding a prepotent response tendency. RESULTS: Both tasks engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's area, parietal cortex). Increased WM load monotonically increased activity; preparation to override a prepotent response produced greater and more enduring activity. Group differences on each task emerged in a right dorsolateral PFC region: schizophrenic subjects showed lesser magnitude increases under conditions of high WM and prepotent response override demands, with concomitant performance impairments. CONCLUSIONS: Schizophrenic patients exhibit PFC-mediated deficits in WM and preparation to override prepotent responses. Findings are consistent with the operation of a single underlying PFC-mediated cognitive control mechanism and with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients reflecting impairments in this mechanism.