Voxel-based analysis of diffusion tensor imaging in mild traumatic brain injury in adolescents.

BACKGROUND AND PURPOSE: DTI of normal-appearing WM as evaluated by conventional MR imaging in mTBI has the potential to identify important regional abnormalities that relate to PCS. VBA was used to examine WM changes in acute mTBI. MATERIALS AND METHODS: WM was assessed between 1 and 6 days postinjury with voxel-based DTI analyses in 10 adolescent patients with mTBI and 10 age-matched control participants. In addition to the voxel-based group, analysis used to identify brain pathology across all patients with mTBI, 2 voxel-based linear regressions were performed. These analyses investigated the relation between 1) the ADC and PCS severity scores, and 2) ADC and scores on the BSI of emotional symptoms associated with mTBI. We hypothesized that frontotemporal WM changes would relate to symptoms associated with PCS and endorsed on the BSI. RESULTS: Patients with mTBI demonstrated significant reductions in ADC in several WM regions and in the left thalamus. As expected, no increases in ADC were found in any region of interest. All injury-affected regions showed decreased radial diffusivity, unchanged AD, and increased FA, which is consistent with axonal cytotoxic edema, reflective of acute injury. CONCLUSIONS: Whole-brain WM DTI measures can detect abnormalities in acute mTBI associated with PCS symptoms in adolescents.

Diffusion tensor imaging of acute mild traumatic brain injury in adolescents.

BACKGROUND: Despite normal CT imaging and neurologic functioning, many individuals report postconcussion symptoms following mild traumatic brain injury (MTBI). This dissociation has been enigmatic for clinicians and investigators. METHODS: Diffusion tensor imaging tractography of the corpus callosum was performed in 10 adolescents (14 to 19 years of age) with MTBI 1 to 6 days postinjury with Glasgow Coma Scale score of 15 and negative CT, and 10 age- and gender-equivalent uninjured controls. Subjects were administered the Rivermead Post Concussion Symptoms Questionnaire and the Brief Symptom Inventory to assess self-reported cognitive, affective, and somatic symptoms. RESULTS: The MTBI group demonstrated increased fractional anisotropy and decreased apparent diffusion coefficient and radial diffusivity, and more intense postconcussion symptoms and emotional distress compared to the control group. Increased fractional anisotropy and decreased radial diffusivity were correlated with severity of postconcussion symptoms in the MTBI group, but not in the control group. CONCLUSIONS: In adolescents with mild traumatic brain injury (MTBI) with Glasgow Coma Scale score of 15 and negative CT, diffusion tensor imaging (DTI) performed within 6 days postinjury showed increased fractional anisotropy and decreased diffusivity suggestive of cytotoxic edema. Advanced MRI-based DTI methods may enhance our understanding of the neuropathology of TBI, including MTBI. Additionally, DTI may prove more sensitive than conventional imaging methods in detecting subtle, but clinically meaningful, changes following MTBI and may be critical in refining MTBI diagnosis, prognosis, and management.

The neurobehavioural rating scale-revised: sensitivity and validity in closed head injury assessment.

OBJECTIVES: To investigate the factor structure and psychometric properties of the neurobehavioural rating scale-revised (NRS-R) and to determine its usefulness in clinical trials. METHODS: A consecutive series of patients sustaining severe closed head injury were evacuated to one of 11 large regional North American trauma centres and entered into a randomised, phase III, multicentre clinical trial investigating the therapeutic use of moderate hypothermia. Acute care personnel were blinded to outcome and outcome personnel were blinded to treatment condition. The Glasgow outcome scale (GOS) was the primary outcome measure. Secondary outcome measures included the disability rating scale (DRS) and the NRS-R. RESULTS: Exploratory factor analysis of NRS-R data collected at 6 months after injury (n=210) resulted in a five factor model including: (1) executive/cognition, (2) positive symptoms, (3) negative symptoms, (4) mood/affect, and (5) oral/motor. These factors showed acceptable internal consistency (0.62 to 0.88), low to moderate interfactor correlations (0.19 to 0.61), and discriminated well between GOS defined groups. Factor validity was demonstrated by significant correlations with specific neuropsychological domains. Significant change was measured from 3 to 6 months after injury for the total score (sum of all 29 item ratings) and all factor scores except mood/affect and positive symptoms. The total score and all factor scores correlated significantly with concurrent GOS and DRS scores. CONCLUSIONS: The NRS-R is well suited as a secondary outcome measure for clinical trials as its completion rate exceeds that of neuropsychological assessment and it provides important neurobehavioural information complementary to that provided by global outcome and neuropsychological measures.

Use of the Disability Rating Scale Recovery curve as a predictor of psychosocial outcome following closed-head injury.

Rapid rate of recovery has been associated with better outcome following closed-head injuries, but few studies have compellingly demonstrated this. This study used growth curve analyses of Disability Rating Scale (DRS) scores at acute hospitalization discharge, 1, 3, and 6 months post injury in a sample of 55 patients with a closed-head injury. Six month post-injury outcome measures were taken from significant other (SO) responses on the NYU Head Injury Family Interview (NYU-HIFI) including severity and burden ratings of affective/neurobehavioral disturbance, cognitive deficits, and physical/dependency status. Rate of recovery (linear and curvilinear recovery curve components) was significantly related to the level of affective/neurobehavioral severity, and the severity and burden of SO-perceived cognitive deficits. Only the intercept of the DRS recovery curve was associated with the SO-perceived severity and burden of physical/dependency status. Growth curve modeling is a meaningful and powerful tool in predicting head injury outcome.

Factor analysis of an outcome interview for use in clinical trials of traumatically brain-injured patients: a preliminary study.

OBJECTIVE: To study the factor structure, internal consistency, concurrent validity, and sensitivity to detect change in patient report of problems of a structured interview in relationship with accepted outcome measures. DESIGN: Outcome status of patients with severe traumatic brain injury participating in a randomized, phase III, multicenter clinical trial was assessed at 6 mo postinjury using the Glasgow Outcome Scale, the Disability Rating Scale, and the Severe Traumatic Brain Injury Outcome Interview. RESULTS: Exploratory factor analysis of the Severe Traumatic Brain Injury Outcome Interview produced a meaningful five-factor model: (1) activities of daily living; (2) cognitive; (3) affective; (4) behavioral; and (5) instrumental activities of daily living. The internal consistency of the factors ranged from moderate (0.61 instrumental activities of daily living) to high (0.94 activities of daily living); the interfactor correlations were moderate. The summed factor scores were significantly correlated with measures of global outcome: the Glasgow Outcome Scale (r = 0.66; P < 0.0001) and the Disability Rating Scale (r = 0.61; P < 0.0001). Patient report of cognitive problems correlated moderately with the neuropsychological tests. The summed factor scores were sensitive to change over time. CONCLUSIONS: Overall, the interview assessed the major important features of outcome pertinent to traumatic brain injury and demonstrated greater sensitivity to subtle changes over time than the unidimensional approaches, such as the Glasgow Outcome Scale and Disability Rating Scale.

Depression and posttraumatic stress disorder at three months after mild to moderate traumatic brain injury.

To investigate the frequency and risk factors of major depressive disorder (MDD) after mild to moderate traumatic brain injury (TBI), 69 TBI and 52 general trauma (GT) patients were prospectively recruited and studied at 3-months postinjury. There was a nonsignificant difference in the proportion of MDD patients in the TBI and GT groups. Therefore, a composite MDD group (TBI and GT patients) was compared to patients who were nondepressed. Female gender was related to MDD, but no other risk factors were identified. MDD was associated with disability (Glasgow Outcome Scale, Community Integration Questionnaire) and cognitive impairment. MDD was comorbid with posttraumatic stress disorder. Implications for postacute management of mild to moderate TBI are discussed.

Postconcussional disorder following mild to moderate traumatic brain injury: anxiety, depression, and social support as risk factors and comorbidities.

Previous studies of postconcussional disorder (PCD) have utilized a dimensional approach (i.e., number and/or severity ratings of symptoms) to study postconcussional symptoms. This study used a syndromal approach (modified form of the DSM-IV criteria) for investigating risk factors for developing PCD, 3-months postinjury. The head trauma requirement was waived in order to determine specificity of symptoms to traumatic brain injury. Preliminary results from this ongoing study indicated significant risk factors including female gender, poor social support, and elevated self-reported depressive symptoms at 1-month postinjury. Comorbidities included concurrent diagnosis of major depressive disorder and/or posttraumatic stress disorder. Hispanics were significantly less likely to develop PCD than other racial/ethnic groups. PCD resulted more frequently from motor vehicle accidents and assaults. Screening tests for PCD risk factors/comorbidities performed shortly after injury (i.e., during routine follow-up clinic appointments) coupled with appropriate referrals for psychoeducational interventions and support groups may avoid prolonged loss of productivity and poor perceived quality of life in these patients.

Regional brain tissue composition in children with hydrocephalus. Relationships with cognitive development.

OBJECTIVE: To determine whether children with shunted hydrocephalus show variations in regional brain tissue composition that relate to cognitive functions. DESIGN: Nonequivalent control group. PATIENTS AND METHODS: Magnetic resonance imaging (MRI) and cognitive skills assessments were obtained on 28 children, 6 to 9 years of age, with shunted hydrocephalus and 13 normal control subjects comparable in age, gender, ethnicity, and socioeconomic status. Three consecutive MRI slices below the vertex were segmented using a fuzzy clustering algorithm to separate pixels into gray matter, white matter, and cerebrospinal fluid (CSF) in quadrants representing left and right anterior and posterior brain regions. The cognitive skills assessments included the Wechsler Intelligence Scale for Children-Revised verbal and performance IQ scores, neuropsychological composites of language and visuospatial skills, a measure of visuomotor dexterity, and 2 measures of problem-solving abilities. The MRI data were analyzed in a group x tissue x hemisphere x region analysis of variance. Spearman rho correlations were computed within the hydrocephalus group between the MRI and cognitive measures. RESULTS: Children with hydrocephalus showed reductions in overall gray matter percentages and corresponding increased CSF percentages that were more pronounced in posterior than anterior regions of both hemispheres. White matter percentages were reduced in children with hydrocephalus only in the left posterior quadrant. Correlations of posterior, but not anterior, CSF and gray matter percentages were significant with verbal and performance IQ scores and language, visuospatial, and visuomotor dexterity skills, but not with problem-solving abilities. Children with hydrocephalus who had proportionately greater posterior than anterior CSF percentages had significantly poorer visuomotor dexterity and visuospatial skills than did hydrocephalic children with proportionate CSF percentages. CONCLUSION: Regional variations in brain tissue composition in children with shunted hydrocephalus correlate with a variety of cognitive and visuomotor functions.

Morphometric evaluation of the hydrocephalic brain: relationships with cognitive development.

The effects of early hydrocephalus and related brain anomalies on cognitive skills are not well understood. In this study, magnetic resonance scans were obtained from 99 children aged from 6 to 13 years with either shunted hydrocephalus (n = 42) or arrested (unshunted) hydrocephalus (n = 19), from patient controls with no hydrocephalus (n = 23), and from normal, nonpatient controls (n = 15). Lateral ventricle volumes and area measurements of the internal capsules and centra semiovale in both hemispheres were obtained from these scans, along with area measurements of the corpus callosum. Results revealed reductions in the size of the corpus callosum in the shunted hydrocephalus group. In addition, lateral ventricle volumes were larger and internal capsule areas were smaller in both hemispheres in children with shunted and arrested hydrocephalus. The centra semiovale measurements did not differentiate the groups. Correlating these measurements with concurrent assessments of verbal and nonverbal cognitive skills, motor abilities, and executive functions revealed robust relationships only between the area of the corpus callosum and nonverbal cognitive skills and motor abilities. These results support the theory of a prominent role for the corpus callosum defects characteristic of many children with shunted hydrocephalus in the spatial cognition deficits commonly observed in these children.

Reliability of brain structure morphometry in hydrocephalic children using MR images.

To assess the ability of human operators to make decisions about region boundaries in significantly malformed brains, we performed a study of the reliability of morphometric measurements of specific brain structures from MRI in children with hydrocephalus and controls. Cross-sectional area measures of the corpus callosum, internal capsules and centrum semiovale, and volumes of the lateral ventricles were made in 50 children. Independent measurements were made by two raters on T1 and T2-weighted MR images. Pearson's correlation coefficients (r) and intraclass correlation coefficients (ICC) between the two rater's sets of measures were computed for each structure across all subjects. ICCs ranged from a low of 0.7502 to a high of 0.9895. All ICCs were significant at the p < .0001 level and were generally less than or equal to the corresponding Pearson's r value in every case. Therefore, the Pearson's r may overestimate the reliability. The results of this study support the claim that the ICC should be used rather than the Pearson's r when assessing interater reliability in situations where large between-group differences are present. In addition, the results show that brains malformed by disorders, such as hydrocephalus, can be reliably assessed using morphometric measures of MR images.