We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed.

In this paper, we propose a new automated procedure for lesion identification from single images based on the detection of outlier voxels. We demonstrate the utility of this procedure using artificial and real lesions. The scheme rests on two innovations: First, we augment the generative model used for combined segmentation and normalization of images, with an empirical prior for an atypical tissue class, which can be optimised iteratively. Second, we adopt a fuzzy clustering procedure to identify outlier voxels in normalised gray and white matter segments. These two advances suppress misclassification of voxels and restrict lesion identification to gray/white matter lesions respectively. Our analyses show a high sensitivity for detecting and delineating brain lesions with different sizes, locations, and textures. Our approach has important implications for the generation of lesion overlap maps of a given population and the assessment of lesion-deficit mappings. From a clinical perspective, our method should help to compute the total volume of lesion or to trace precisely lesion boundaries that might be pertinent for surgical or diagnostic purposes.

Objective:To image β-amyloid (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer disease (AD).Methods:Patients 11 months to 17 years after moderate–severe TBI underwent 11C-Pittsburgh compound B (11C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of 11C-PiB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with 11C-PiB BPND.Results:Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased 11C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum.Conclusions:Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.

Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson's disease. Although both pre- and post-synaptic mechanisms seem to be implicated in their development, the precise physiopathology of these disabling involuntary movements remains to be fully elucidated. Abnormalities in glutamate transmission (over expression and phosphorylation of N-methyl-D-aspartate receptors) have been associated with the development of levodopa-induced dyskinesias in animal models of Parkinsonism. The role of glutamate function in dyskinetic patients with Parkinson's disease, however, is unclear. We used (11)C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-D-aspartate receptor ion channels, to compare in vivo glutamate function in parkinsonian patients with and without levodopa-induced dyskinesias. Each patient was assessed with positron emission tomography twice, after taking and withdrawal from levodopa. Striatal and cortical tracer uptake was calculated using a region of interest approach. In the 'OFF' state withdrawn from levodopa, dyskinetic and non-dyskinetic patients had similar levels of tracer uptake in basal ganglia and motor cortex. However, when positron emission tomography was performed in the 'ON' condition, dyskinetic patients had higher (11)C-CNS 5161 uptake in caudate, putamen and precentral gyrus compared to the patients without dyskinesias, suggesting that dyskinetic patients may have abnormal glutamatergic transmission in motor areas following levodopa administration. These findings are consistent with the results of animal model studies indicating that increased glutamatergic activity is implicated in the development and maintenance of levodopa-induced dyskinesias. They support the hypothesis that blockade of glutamate transmission may have a place in the management of disabling dyskinesias in Parkinson's disease.