Neurological outcome scale for traumatic brain injury: III. Criterion-related validity and sensitivity to change in the NABIS hypothermia-II clinical trial.

The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16-45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the glasgow outcome scale (GOS), GOS-extended (GOS-E), disability rating scale (DRS), and neurobehavioral rating scale-revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.

Centrum semiovale and corpus callosum integrity in relation to information processing speed in patients with severe traumatic brain injury.

OBJECTIVES: This study investigated white matter alterations in the corpus callosum (CC) and centrum semiovale (CSO), using diffusion tensor imaging and magnetization transfer imaging, in participants with severe traumatic brain injury (TBI) and related these changes to processing speed measures. PARTICIPANTS AND METHODS: Fourteen adult participants with severe TBI underwent neuroimaging and assessment, using the Symbol Digit Modalities Test and Trail-Making Test, Part B, at approximately 6 months postinjury. Thirteen demographically similar, neurologically intact adults were imaged for comparison. RESULTS: The TBI group demonstrated lower fractional anisotropy (FA) for the right CSO and higher apparent diffusion coefficient (ADC) for the CSO bilaterally than the control group. Lower FA and higher ADC were noted in all CC regions. Magnetization transfer imaging revealed smaller magnetization transfer ratios (MTRs) in the right and left CSO and CC genu and splenium. Written Symbol Digit Modalities Test performance was related to right CSO FA, bilateral CSO ADC, CC FA, and right CSO MTR, whereas oral Symbol Digit Modalities Test was related to right CSO FA, ADC, and MTR. Trail-Making Test, Part B, was related to right CSO FA and MTR. CONCLUSIONS: Advanced neuroimaging modalities such as diffusion tensor imaging and magnetization transfer imaging demonstrate significant alterations in white matter, which are related to processing speed. These techniques may be useful in quantifying the extent of injury even in normal appearing white matter after TBI.

Alterations in white matter pathways in Angelman syndrome.

AIM: Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity. METHOD: DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. RESULTS: The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p < 0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p < 0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p < 0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p < 0.05). INTERPRETATION: Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning.

Cerebral and cerebellar volume loss in children and adolescents with systemic lupus erythematosus: a review of clinically acquired brain magnetic resonance imaging.

OBJECTIVE: Cerebral atrophy is a prominent feature in adults with systemic lupus erythematosus (SLE). We assessed cerebral and cerebellar volume loss on clinically acquired brain magnetic resonance imaging (MRI) scans of children and adolescents with SLE. METHODS: We abstracted information on disease course for patients who underwent clinical brain MRI during the period 2002-2008. We completed qualitative assessments of volume loss and measured corpus callosum thickness and ventricular enlargement for patients with lupus and controls. RESULTS: Forty-nine children underwent brain MRI during the review period due to clinical indications. The lupus cohort was predominantly female and ethnically diverse. Mean age at imaging was 15.3 +/- 2.6 years and mean disease duration was 30.6 +/- 33.3 months. Findings suggestive of cerebral and cerebellar volume loss were seen respectively in 89.8% and 91.8% of lupus patients. Cerebral volume loss was moderate or severe in 26.5% of children. Cerebellar volume loss was moderate in 20.4% of these patients. Linear measurement means reflected corpus callosum thinning and ventricular enlargement in lupus patients. Volume loss was observed in newly diagnosed patients prior to corticosteroid use. Disease duration and corticosteroid use did not predict the severity of volume loss. There were statistically significant differences in linear imaging measurements comparing lupus patients to 14 similar-age controls. CONCLUSION: Regional volume loss was observed in most adolescents with lupus undergoing clinical brain MRI scans. As in other pediatric conditions with inflammatory or vascular etiologies, these findings may be reflecting disease-associated neuronal loss and not solely the effects of corticosteroid.

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus.

BACKGROUND: Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. OBJECTIVE: We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. MATERIALS AND METHODS: We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. RESULTS: Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. CONCLUSION: MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.

Age-related, regional, hemispheric, and medial-lateral differences in myelin integrity in vivo in the normal adult brain.

BACKGROUND AND PURPOSE: Clinical validation of magnetization transfer (MT) imaging is important for investigating clinical disease and organization of normal brain function. We determined whether an in vivo quantitative measure sensitive to white matter is distributed in functionally important ways. METHODS: Axial 1.5-T MR images with and those without MT were obtained. MT ratios (MTRs) were computed for 33 regions of interest (ROIs) in 27 healthy adults (aged 18-69 years) without evidence of cognitive or radiographic abnormalities. Three tests of reliability yielded coefficients above 0.97. MTRs for the whole brain, groups of structures, and individual ROIs were calculated. Low standard errors confirmed the consistency of the technique. RESULTS: Age, education, sex, and hand dominance were not correlated with whole-brain MTR (mean = 37.35, SD = 1.25), but age was associated with the cerebellum and some lobes at a trend level. MTRs were as follows, in descending order: corpus callosum, cingulate, white matter, brain stem, subcortical nuclei, and cerebellum. MTRs were selectively higher in the prefrontal lobe versus the posterior frontal lobe and in the lateral temporal lobe versus medial temporal lobe. MTR was higher in the left hemisphere than in the right hemisphere for the whole brain, frontal and temporal lobes, and lenticular nuclei. CONCLUSION: MT imaging showed selective age, medial-lateral, and hemispheric differences, giving evidence of normal aging effects on the white matter in the absence of T2- weighted hyperintensities. These differences support neurocognitive theories of the organization of brain function. MT imaging appears to be a robust technique for use in cognitive neuroscience.