Two Coarse Spatial Patterns of Altered Brain Microstructure Predict Post-traumatic Amnesia in the Subacute Stage of Severe Traumatic Brain Injury.

Introduction: Diffuse traumatic axonal injury (TAI) is one of the key mechanisms leading to impaired consciousness after severe traumatic brain injury (TBI). In addition, preferential regional expression of TAI in the brain may also influence clinical outcome. Aim: We addressed the question whether the regional expression of microstructural changes as revealed by whole-brain diffusion tensor imaging (DTI) in the subacute stage after severe TBI may predict the duration of post-traumatic amnesia (PTA). Method: Fourteen patients underwent whole-brain DTI in the subacute stage after severe TBI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for five bilateral brain regions: fronto-temporal, parieto-occipital, and midsagittal hemispheric white matter, as well as brainstem and basal ganglia. Region-specific calculation of mean FA and MD only considered voxels that showed no tissue damage, using an exclusive mask with all voxels that belonged to local brain lesions or microbleeds. Mean FA or MD of the five brain regions were entered in separate partial least squares (PLS) regression analyses to identify patterns of regional microstructural changes that account for inter-individual variations in PTA. Results: For FA, PLS analysis revealed two spatial patterns that significantly correlated with individual PTA. The lower the mean FA values in all five brain regions, the longer that PTA lasted. A pattern characterized by lower FA values in the deeper brain regions relative to the FA values in the hemispheric regions also correlated with longer PTA. Similar trends were found for MD, but opposite in sign. The spatial FA changes as revealed by PLS components predicted the duration of PTA. Individual PTA duration, as predicted by a leave-one-out cross-validation analysis, correlated with true PTA values (Spearman r = 0.68, p permutation = 0.008). Conclusion: Two coarse spatial patterns of microstructural damage, indexed as reduction in FA, were relevant to recovery of consciousness after TBI. One pattern expressed was consistent with diffuse microstructural damage across the entire brain. A second pattern was indicative of a preferential damage of deep midline brain structures.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

BACKGROUND: Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [18F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. NEW METHOD: The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [18F]FDG-PET scan and venous blood sampling. RESULTS: Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. COMPARISON WITH EXISTING METHODS: Our study demonstrates that the analysis method of the [18F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. CONCLUSION: We recommend supplementing a static [18F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc.

Increasing Incidence of Hospitalization for Stroke and Transient Ischemic Attack in Young Adults: A Registry-Based Study.

BACKGROUND: Studies have reported increasing incidence of ischemic stroke in adults younger than 50 to 55 years. Information on temporal trends of other stroke subtypes and transient ischemic attack (TIA) is sparse. The aim of this study was to investigate temporal trends of the incidence of hospitalizations for TIA and stroke including sex- and subtype-specific trends in young adults aged 15 to 30 years. METHODS AND RESULTS: From the Danish National Patient Register, we identified all cases of first-ever stroke and TIA (age 15-30 years) in Denmark, who were hospitalized during the study period of 1994 to 2012. Incidence rates and estimated annual percentage changes (EAPCs) were estimated by using Poisson regression. During the study period, 4156 cases of first-ever hospitalization for stroke/TIA were identified. The age-standardized incidence rates of hospitalizations for stroke increased significantly (EAPC 1.83% [95% CI 1.11-2.55%]) from 11.97/100 000 person-years (PY) in 1994 to 16.77/100 000 PY in 2012. TIA hospitalizations increased from 1.93/100 000 PY in 1994 to 5.81/100 000 PY in 2012 and after 2006 more markedly in men than in women (EAPC 16.61% [95% CI 10.45-23.12%]). The incidence of hospitalizations for ischemic stroke was markedly lower among men, but increased significantly from 2006 (EAPC 14.60% [95% CI 6.22-23.63%]). The incidences of hospitalizations for intracerebral hemorrhage and subarachnoid hemorrhage remained stable during the study period. CONCLUSIONS: The incidence rates of first-time hospitalizations for ischemic stroke and TIA in young Danish adults have increased substantially since the mid 1990s. The increase was particularly prominent in the most recent years.