Randall S. Scheibel

Diffusion Tensor Imaging of Mild to Moderate Blast-Related Traumatic Brain Injury and Its Sequelae

To evaluate the effects of mild to moderate blast-related traumatic brain injury (TBI) on the microstructure of brain white matter (WM) and neurobehavioral outcomes, we studied 37 veterans and service members (mean age 31.5 years, SD = 7.2; post-injury interval 871.5 days; SD = 343.1), whose report of acute neurological status was consistent with sustaining mild to moderate TBI due to blast while serving in Iraq or Afghanistan. Fifteen veterans without a history of TBI or exposure to blast (mean age 31.4 years, SD = 5.4) served as a comparison group, including seven subjects with extracranial injury (post-injury interval 919.5 days, SD = 455.1), and eight who were uninjured. Magnetic resonance imaging disclosed focal lesions in five TBI participants. Post-concussion symptoms (Neurobehavioral Symptom Inventory), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist-Civilian), and global distress and depression (Brief Symptom Inventory) were worse in the TBI participants than the comparison group, but no group differences were found in perceived physical or mental functioning (SF-12). Verbal memory (Selective Reminding) was less efficient in the TBI group, but there were no group differences in nonverbal memory (Selective Reminding) or decision making (Iowa Gambling Task). Verbal memory in the TBI group was unrelated to PTSD severity. Diffusion tensor imaging (DTI) using tractography, standard single-slice region-of-interest measurement, and voxel-based analysis disclosed no group differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC). However, FA of the left and right posterior internal capsule and left corticospinal tract was positively correlated with total words consistently recalled, whereas ADC for the left and right uncinate fasciculi and left posterior internal capsule was negatively correlated with this measure of verbal memory. Correlations of DTI variables with symptom measures were non-significant and inconsistent. Our data do not show WM injury in mild to moderate blast-related TBI in veterans despite their residual symptoms and difficulty in verbal memory. Limitations of the study and implications for future research are also discussed.

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. NEUROLOGY 1991;41:672‐676

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

SummaryThis 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.

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.

Altered brain activation during cognitive control in patients with moderate to severe traumatic brain injury.

Background. Persistent deficits in cognitive control have been documented following traumatic brain injury (TBI) but are inconsistently related to the presence and location of focal lesions. Objective. Functional magnetic resonance imaging (fMRI) was used to examine brain activation during a cognitive control task in patients with moderate to severe TBI or orthopedic injury (OI). Methods. Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury using a stimulus-response compatibility task in which response accuracy and reaction time were measured. Performance between the groups was equated by individually adjusting the amount of training. Groups did not differ in age, gender, or education. Results. Brain activation during stimulus-response incompatibility was greater in TBI patients than in OI patients within the cingulate, medial frontal, middle frontal, and superior frontal gyri. However, the positive regression of activation with response accuracy during stimulus-response incompatibility indicated a stronger relationship for OI patients than the TBI group within the anterior cingulate gyrus, medial frontal, and parietal regions, as well as deep brain structures (eg, brainstem). The number of focal lesions within either the whole brain or within prefrontal areas was not related to brain activation, but there was a relationship between activation and TBI severity. Conclusions. These findings suggest that neural networks mediating cognitive control are altered after moderate to severe TBI, possibly as a result of diffuse axonal injury, and that the typical relationship of brain activation to performance is disrupted.

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

Zhang L, Abreu BC, Masel B, Scheibel RS, Christiansen CH, Huddleston N, Ottenbacher KJ: Virtual reality in the assessment of selected cognitive function after brain injury. Am J Phys Med Rehabil 2001;80:597–604. ObjectiveTo assess selected cognitive functions of persons with traumatic brain injury using a computer-simulated virtual reality environment. Study DesignA 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. ResultsPersons 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). ConclusionA 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.

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate-to-severe traumatic brain injury.

While closed head injury frequently results in damage to the frontal and temporal lobes, damage to deep cortical structures, such as the hippocampus, amygdala, and basal ganglia, has also been reported. Five deep central structures (hippocampus, amygdala, globus pallidus, putamen, and caudate) were examined in 16 children (eight males, eight females; aged 9–16y), imaged 1 to 10 years after moderate‐to‐severe traumatic brain injury (TBI), and in 16 individually‐matched uninjured children. Analysis revealed significant volume loss in the hippocampus, amydala, and globus pallidus of the TBI group. Investigation of relative volume loss between these structures and against five cortical areas (ventromedial frontal, superomedial frontal, lateral frontal, temporal, and parieto‐occipital) revealed the hippocampus to be the most vulnerable structure following TBI (i.e. greatest relative difference between the groups). In a separate analysis excluding children with focal hippocampal abnormalities (e.g. lesions), group differences in hippocampal volume were still evident, suggesting that hippocampal damage may be diffuse rather than focal.

Psychosocial outcome of TBI in children with unilateral frontal lesions

To evaluate effects of unilateral frontal lesions on psychosocial and global outcome of traumatic brain injury (TBI) in children, Study 1 compared matched groups of 22 school aged children who had sustained TBI either with or without unilateral frontal lesions. Study 2 evaluated effects of unilateral extrafrontal lesions in 18 TBI patients as compared with 18 nonlesional TBI patients. Communication, Daily Living, and Socialization domains and the Maladaptive Behavior Scale of the Vineland Adaptive Behavior Scales (VABS) were used to assess psychosocial outcome, and the Glasgow Outcome Scale (GOS) measured global outcome. All patients underwent magnetic resonance imaging at least 3 months post injury. Children with frontal lesions had worse scores on the Daily Living and Socialization domains and a higher frequency of maladaptive behavior than those without frontal lesions, but there was no difference in cognitive function. Disability was twice as common in the frontal lesion group relative to children without frontal lesions. Volume of frontal lesion was related to the Socialization domain. Side of lesion had no effect, nor did presence of an extrafrontal lesion (Study 2). Unilateral frontal lesions adversely affect late psychosocial outcome of TBI in children.

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.

Diffusion Tensor Imaging of the Cingulum Bundle in Children After Traumatic Brain Injury

Structural damage to the prefrontal-cingulate network has been implicated in cognitive and neurobehavioral deficits associated with traumatic brain injury (TBI). Forty-six children who had sustained moderate-to-severe TBI and 43 children with extracranial injury were imaged using diffusion tensor imaging (DTI). Decreased fractional anisotropy (FA) and increased apparent diffusion coefficient (ADC) values were found in the cingulum bundles bilaterally in the TBI group. Cingulum ADC was related to frontal lesion volume, injury severity, and injury mechanism. Finally, cingulum DTI parameters were related to cognitive control measures. DTI detects TBI-related injury to the cingulum, which may facilitate advances in assessment and treatment.