Close proximity to blast: No long-term or lasting effect on cognitive performance in service members with and without TBI during blast exposure.

OBJECTIVE: Blast related characteristics may contribute to the diversity of findings on whether mild traumatic brain injury sustained during war zone deployment has lasting cognitive effects. This study aims to evaluate whether a history of blast exposure at close proximity, defined as exposure within 30 feet, has long-term or lasting influences on cognitive outcomes among current and former military personnel. METHOD: One hundred participants were assigned to one of three groups based on a self-report history of blast exposure during combat deployments: 47 close blast, 14 non-close blast, and 39 comparison participants without blast exposure. Working memory, processing speed, verbal learning/memory, and cognitive flexibility were evaluated using standard neuropsychological tests. In addition, assessment of combat exposure and current post-concussive, posttraumatic stress, and depressive symptoms, and headache was performed via self-report measures. Variables that differed between groups were controlled as covariates. RESULTS: No group differences survived Bonferroni correction for family-wise error rate; the close blast group did not differ from non-close blast and comparison groups on measures of working memory, processing speed, verbal learning/memory, or cognitive flexibility. Controlling for covariates did not alter these results. CONCLUSION: No evidence emerged to suggest that a history of close blast exposure was associated with decreased cognitive performance when comparisons were made with the other groups. Limited characterization of blast contexts experienced, self-report of blast distance, and heterogeneity of injury severity within the groups are the main limitations of this study.

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

An fMRI study of executive functioning after severe diffuse TBI.

PRIMARY OBJECTIVE: Preliminary study of whether severe diffuse traumatic brain injury (TBI) increases extent of frontal tissue recruited by cognitive control tasks. RESEARCH DESIGN: Functional magnetic resonance imaging (fMRI) on N-back working memory (WM)and arrows inhibition tasks in a 46 year old man who had severe diffuse TBI 1 year earlier, a 44 year old man (inhibition task) and three women (working memory task), age 20-26 years. Images were acquired by 1.5 T magnet with BOLD method and PRESTO pulse sequence and analysed using SPM. MAIN OUTCOMES AND RESULTS: Frontal activation increased under 2-back relative to 1-back condition of working memory in all participants with more extensive activation in the TBI patient relative to controls. Frontal activation increased with inhibition on the arrows task, but was greater in the TBI patient. CONCLUSION: Severe diffuse TBI results in recruitment of additional neural resources for cognitive control.

Excessive daytime sleepiness in adults with brain injuries.

OBJECTIVES: To determine the prevalence, demographics, and causes of excessive daytime sleepiness in adults with brain injuries after the acute phase of their injury and to investigate the relations between self-report and objective measures of hypersomnolence. DESIGN: A case series of patients enrolled consecutively into a residential rehabilitation program. SETTING: University sleep laboratory, live-in rehabilitation center. PATIENTS: Adults with brain injuries (n = 71); mean time +/- standard deviation from injury to study, 38 +/- 60 months. INTERVENTIONS: A polysomnogram and Multiple Sleep Latency Test (MSLT) were performed in each subject. Each subject also completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. MAIN OUTCOME MEASURES: Sleep patterns, by polysomnogram. Daytime hypersomnolence, diagnosed by mean sleep latency on the MSLT

Virtual reality in the assessment of selected cognitive function after brain injury.

OBJECTIVE: To assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. STUDY DESIGN: A computer-simulated virtual kitchen was used to assess the ability of 30 patients with brain injury and 30 volunteers without brain injury to process and sequence information. The overall assessment score was based on the number of correct responses and the time needed to complete daily living tasks. Identical daily living tasks were tested and scored in participants with and without brain injury. Each subject was evaluated twice within 7 to 10 days. A total of 30 tasks were categorized as follows: information processing, problem solving, logical sequencing, and speed of responding. RESULTS: Persons with brain injuries consistently demonstrated a significant decrease in the ability to process information (P = 0.04-0.01), identify logical sequencing (P = 0.04-0.01), and complete the overall assessment (P < 0.01), compared with volunteers without brain injury. The time needed to process tasks, representing speed of cognitive responding, was also significantly different between the two groups (P < 0.01). CONCLUSION: A computer-generated virtual reality environment represents a reproducible tool to assess selected cognitive functions and can be used as a supplement to traditional rehabilitation assessment in persons with acquired brain injury.

Levels of self-awareness after acute brain injury: how patients' and rehabilitation specialists' perceptions compare.

OBJECTIVE: To examine self-awareness regarding performance on 4 daily living tasks and to test theoretical predictions for a model of self-awareness in persons with acquired brain injury. DESIGN: A comparative design examining the level of self-awareness recorded by patients and actual patient performance as judged by rehabilitation clinicians. SETTING: A community-based residential center providing comprehensive rehabilitation services to persons with acquired brain injury. PARTICIPANTS: Fifty-five persons with acquired brain injury and the identified potential to return to independent function in the community. Ten subjects without brain injury provided comparison data. INTERVENTION: Information was collected by using patient self-report, clinician rating of patient performance, patient rating of non-brain-injured subjects, and clinician rating of non-brain-injured subjects. MAIN OUTCOME MEASURES: Three self-awareness criteria were examined: intellectual, emergent, and anticipatory. Self-awareness was rated for 3 tasks: dressing, meal planning, and money management. RESULTS: Statistically significant differences (p <.05) were found for all levels of self-awareness across the 3 tasks. Persons with brain injury judged their abilities higher than clinician ratings of actual performance. No statistical support was found for a hierarchy among intellectual, emergent, and anticipatory self-awareness. CONCLUSIONS: No evidence was found supporting a hierarchy among levels of self-awareness as defined and measured in the present study. New methods for operationally defining intellectual, emergent, and anticipatory self-awareness are necessary to examine the relationship between self-awareness and performance.

Neuropsychological assessment and the Disability Rating Scale (DRS): a concurrent validity study.

Assessment of current level of functioning among clients with traumatic brain injury (TBI) often guides the establishment of realistic outcome goals for post-acute rehabilitation. Further, data generated from neuropsychological testing provide a clinician with a better understanding of a client's pattern of cognitive strengths and weaknesses. The Disability Rating Scale (DRS) is commonly used by TBI rehabilitation facilities to assess a client's general level of functioning in terms of impairment, disability, and handicap. Previous studies have used clients' neuropsychological test results to predict future level of functioning. These studies have shown mixed results regarding the predictive validity of the test findings; however, they usually employ only a limited number of tests for prediction representing a limited number of cognitive domains. Using a concurrent validity design, the present study investigated the bivariate associations between various neuropsychological testing domains (i.e. intellectual, academic, language, visuoperceptual, memory, and executive functioning) and level of functioning as indexed by the DRS. Participants were administered the DRS and the neuropsychological evaluation during the initial part of post-acute rehabilitation. Composite scores were derived for each of the neuropsychological domains. Most participants were categorized as sustaining a severe TBI. The mean age and education of this predominately male sample was 28.84 years (SD = 9.13) and 11.83 years (SD = 1.7), respectively. Results revealed a significant positive relationship between performances in intellectual, executive, academic, and visuoperceptual domains and level of functioning.

Volume of focal brain lesions and hippocampal formation in relation to memory function after closed head injury in children.

OBJECTIVES: (1) A study of verbal learning and memory in children who had sustained a closed head injury (CHI) at least 3 months earlier. (2) To relate memory function to focal brain lesion and hippocampal formation volumes using morphometric analysis of MRI. METHODS: A group of 245 children who had been admitted to hospital for CHI graded by the Glasgow coma scale (GCS), including 161 patients with severe and 84 with mild CHI completed the California verbal learning test (CVLT) and underwent MRI which was analysed for focal brain lesion volume independently of memory test data. Brain MRI with 1.5 mm coronal slices obtained in subsets of 25 patients with severe and 25 patients with mild CHI were analysed for hippocampal formation volume. Interoperator reliability in morphometry was satisfactory. RESULTS: Severity of CHI and age at study significantly affected memory performance. Regression analysis showed that bifrontal, left frontal, and right frontal lesion volumes incremented prediction of various learning and memory indices after entering the GCS score and age into the model. Extrafrontal lesion volume did not contribute to predicting memory performance. CONCLUSIONS: Prefrontal lesions contribute to residual impairment of learning and memory after severe CHI in children. Although effects of CHI on hippocampal formation volume might be difficult to demonstrate in non-fatal paediatric CHI, further investigation using functional brain imaging could potentially demonstrate hippocampal dysfunction.

Predictive validity of the Neurobehavioural Cognitive Status Examination (NCSE) in a post-acute rehabilitation setting.

Within the context of a post-acute rehabilitation setting, association and agreement between results from the Neurobehavioural Cognitive Status Examination (NCSE) and from the neuropsychological (NP) evaluation are examined. All participants (n = 48) had sustained a severe traumatic brain injury and NCSE testing preceded NP testing by an average of 1 month. A significant relationship and fair classification agreement (i.e. presence or absence of cognitive impairment) was found between the overall results from NCSE and NP evaluation. Significant relationships were also observed between most NCSE subtests and paired NP tests thought to be assessing the same cognitive domains. However, the classification agreement (i.e. the presence or absence of deficient performance) between most NCSE subtests and paired NP tests was poor. The findings are discussed from the standpoint of individual treatment planning.

Dissociation of frequency and recency processing from list recall after severe closed head injury in children and adolescents.

To investigate judgment of the frequency and recency of events relative to word list recall in children following closed head injury (CHI), 124 children and adolescents, including 79 severe CHI patients (mean age at test = 13.2 years), 27 mild CHI cases (mean age at test = 12.1 years), and 18 uninjured comparison subjects (mean age = 12.8 years) were studied. The mean postinjury interval was 63.6 months for the severe and 46.7 months for the mild CHI groups. The experimental tasks included estimation of the frequency of presentation of words and designs and recency judgment to select the most recently presented of two stimuli on verbal (words) and nonverbal (faces) tasks. To compare frequency and recency judgments to performance on a task which has been shown to be sensitive to CHI severity and age at test, verbal recall was tested using the California Verbal Learning Test-Children's Version. Severity of CHI (group) affected verbal recall across trials and after delays, but had no effect on estimating frequency and isolated effects on judgment of recency. Age was also primarily related to verbal recall. A subgroup of severe CHI patients with frontal lesions was impaired on delayed recall. The results are discussed in relation to previous research on the effects of CHI on processing the frequency and recency of events.

Corpus callosum damage and interhemispheric transfer of information following closed head injury in children.

We evaluated the relationship of corpus callosum atrophy and/or lesions on magnetic resonance imaging (MRI) to functional hemispheric disconnection following closed head injury (CHI) in 51 pediatric patients, including mild CHI, moderate to severe CHI with extracallosal lesions, and moderate to severe CHI with callosal atrophy and/or lesions. Interhemispheric transfer of information was assessed using auditory, motor, tactile, and visual tests in patients and in 16 uninjured children. Total and regional callosal areas were measured from the midsagittal MRI slice by morphometry. The corpus callosum lesion group demonstrated a greater right ear advantage on verbal dichotic listening than all other groups. Areas of the posterior corpus callosum were negatively correlated with laterality indices of verbal dichotic listening performance and tachistoscopic identification of verbal material. The relationship of corpus callosum atrophy and/or lesions to asymmetry in dichotic listening is consistent with previous investigation of posttraumatic hemispheric disconnection effects in adults.

Completion rates and feasibility of outcome measures: experience in a multicenter clinical trial of systemic hypothermia for severe head injury.

The National Acute Brain Injury Study: Hypothermia (NABIS:H) is an ongoing multicenter trial of systemic hypothermia for the treatment of severe head injury. Follow-up rates for the study's 3-and 6-month outcome assessments have been maintained at high levels by establishing close contact with family members, by reimbursing cost of travel, and by sending examiners to the subject's location whenever necessary. Two years into the study, global disability data (e.g., Glasgow Outcome Scale) have been obtained on 86% of patients due for 3-month assessment (n = 131) and for all subjects due at 6 months (n = 100). Over half of the patients have completed neuropsychological testing with high reliability ratings. These preliminary findings suggest that the procedures used to document data quality and increase follow-up and completion rates are being successful.

Magnetic resonance imaging in relation to functional outcome of pediatric closed head injury: a test of the Ommaya-Gennarelli model.

OBJECTIVE: To characterize late neuropathological findings of pediatric closed head injury (CHI), to assess depth of brain lesion in relation to acute severity, and to assess long-term outcome to test the Ommaya-Gennarelli model. METHODS: Magnetic resonance imaging (MRI) at least 3 months postinjury in a prospective sample (n 5 169) and at least 3 years after CHI in a retrospective sample (n 5 82) was studied. Lesion volume was measured by planimetry. Acute CHI severity was measured by the Glasgow Coma Scale. Patients were classified according to the depth of the deepest parenchymal lesion into no lesion, subcortical, and deep central gray/brain stem groups. The outcomes were assessed by the Glasgow Outcome Scale and the Vineland Adaptive Behavior Scale, which were performed at the time of the MRI in the retrospective sample and up to 3 years postinjury in the prospective sample. RESULTS: Focal brain lesions were present in 55.4% of the total sample. Depth of brain lesion was directly related to severity of acute impairment of consciousness and inversely related to outcome, as measured by both the Glasgow Outcome Scale and the Vineland Adaptive Behavior Scale. A rostrocaudal gradient of hemispheric lesion frequency was observed, whereas the posterior lesions of the corpus callosum were particularly common. Total lesion volume could not explain the depth of lesion effect. CONCLUSION: Our findings extend support for the Ommaya-Gennarelli model to pediatric CHI, indicating that depth of brain lesion is related to functional outcome. The relative frequency of focal brain lesions revealed by late MRI is higher than that of previous findings using acute computed tomography. Future investigations could explore whether depth of lesion observed using late MRI is sensitive to neuroprotective interventions.

Concept formation and problem-solving following closed head injury in children.

To further investigate the usefulness of 3 purported measures of executive function (EF) in head injured children, we administered the Twenty Questions Test (TQT), Tower of London (TOL), and the Wisconsin Card Sorting Test (WCST) to 151 children who had sustained a closed head injury (CHI) of varying severity about 3 years earlier. In addition, we tested 89 normal controls. Fifty-seven of the patients were included in a longitudinal study that compared performance at 3 months and 36 months. All of the head injured children underwent magnetic resonance imaging for investigational purposes. Severity of CHI, as defined by the lowest Glasgow Coma Scale (GCS) score, affected performance on all 3 EF measures. Focal lesion volume incremented prediction of performance on TOL and WCST, but not TQT. Moderate intercorrelations of the test variables were obtained. Although all three EF measures depicted changes in performance over 3 years, a ceiling effect detracted from the sensitivity of the TOL to the impact of CHI on development. Implications of the findings for clinical applications are discussed.

Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment.

This study examined the relationship between cognitive function, tumor malignancy, adjunctive therapy, and lesion lateralization following surgery for intracerebral glioma. Neuropsychological test battery results showed no difference between patients with highly malignant gliomas and those with less malignant gliomas, but differences were found for tumor lateralization and type of therapy. Scores on a test of graphomotor speed were lowest for patients who had received radiation or a combination of radiation and chemotherapy, regardless of lesion location. Other test results did not differ according to type of prior treatment but were related instead to tumor lateralization. Left hemisphere lesions were associated with lower scores on verbal tests, while right hemisphere lesions were related to lower scores on a test of facial recognition. These findings suggest that neuropsychological tests may be useful for distinguishing between the diffuse side effects of brain tumor therapy and the focal effects of tumors and surgery on brain functions. In addition, it appears that any differences in cognitive function due to tumor malignancy are eliminated or reduced following surgical intervention.

Case report: acquired antisocial personality disorder associated with unilateral left orbital frontal lobe damage.

We report on our analysis of a patient who developed personality changes which strongly resembled an antisocial personality disorder after surgical resection of a pituitary tumor. Despite behavioral changes that were obvious to friends, family and health care professionals, formal neuropsychological and personality testing revealed no specific cognitive deficits or psychopathology. We hypothesize that damage to a circumscribed region of the left orbitofrontal cortex, illustrated by magnetic resonance imaging, underlies these personality alterations. In contrast to previous reports, which ascribe such personality changes to bilateral frontal lobe injury, we suggest that unilateral frontal lobe damage alone may have resulted in the development of this syndrome.

Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease.

Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment.

Persistent neurotoxicity of systemically administered interferon-alpha.

Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible.

Early detection and diagnosis of neurobehavioral disorders associated with cancer and its treatment.

The cognitive and behavioral disorders associated with cancer and its treatments can have a tremendous impact on patients' quality of life. Brain tumors, leptomeningeal disease, and paraneoplastic syndromes have all been shown to cause specific neurobehavioral abnormalities. In addition, cancer patients frequently develop cognitive and behavioral alterations during or after radiation therapy, chemotherapy, or immunotherapy. Although some impairments are acute and reversible, others may persist after the cessation of treatment or have a delayed onset. These neurobehavioral disorders can range from profound intellectual decline (dementia) to subtle deficits evident only on sensitive neuropsychological tests. Even mild cognitive impairments may compromise an individual's ability to return to work or other activities.