Scale and pattern of atrophy in the chronic stages of moderate-severe TBI

Abstract

Background: Moderate-severe traumatic brain injury (TBI) is increasingly being understood as a progressive disorder, with growing evidence of reduced brain volume and white matter (WM) integrity as well as lesion expansion in the chronic phases of injury. The scale of these losses has yet to be investigated, and pattern of change across structures has received limited attention.Objectives: (1) To measure the percentage of patients in our TBI sample showing atrophy from 5 to 20 months post-injury in the whole brain and in structures with known vulnerability to acute TBI, and (2) To examine relative vulnerability and patterns of volume loss across structures.Methods: Fifty-six TBI patients [complicated mild to severe, with mean Glasgow Coma Scale (GCS) in severe range] underwent MRI at, on average, 5 and 20 months post-injury; 12 healthy controls underwent MRI twice, with a mean gap between scans of 25.4 months. Mean monthly percent volume change was computed for whole brain (ventricle-to-brain ratio; VBR), corpus callosum (CC), and right and left hippocampi (HPC).Results: (1) Using a threshold of 2 z-scores below controls, 96% of patients showed atrophy across time points in at least one region; 75% showed atrophy in at least 3 of the 4 regions measured. (2) There were no significant differences in the proportion of patients who showed atrophy across structures. For those showing decline in VBR, there was a significant association with both the CC and the right HPC (P < 0.05 for both comparisons). There were also significant associations between those showing decline in (i) right and left HPC (P < 0.05); (ii) all combinations of genu, body and splenium of the CC (P < 0.05), and (iii) head and tail of the right HPC (P < 0.05 all sub-structure comparisons).Conclusions: Atrophy in chronic TBI is robust, and the CC, right HPC and left HPC appear equally vulnerable. Significant associations between the right and left HPC, and within substructures of the CC and right HPC, raise the possibility of common mechanisms for these regions, including transneuronal degeneration. Given the 96% incidence rate of atrophy, a genetic explanation is unlikely to explain all findings. Multiple and possibly synergistic mechanisms may explain findings. Atrophy has been associated with poorer functional outcomes, but recent findings suggest there is potential to offset this. A better, understanding of the underlying mechanisms could permit targeted therapy enabling better long-term outcomes.

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

“…Rather, demyelination and delayed atrophy of white matter tracts develops for over one year post-TBI in rodents [30–33] and progresses for decades in TBI patients [34, 35]. This temporal pattern of delayed white matter injury may therefore provide an amendable therapeutic window; however, the mechanisms that occur between the initial traumatic event and the manifestation of white matter loss remain poorly defined.…”

“…The corpus callosum is particularly susceptible to injury due to a rigid attachment to the falx cerebri, a fold of dura mater that descends into the longitudinal fissure, and due to connections with the two independently mobile cerebral hemispheres [21]. A separate study determined that 96% of moderate-severe TBI patients showed atrophy of at least one brain region and 76.8% of TBI patients showed significant loss of corpus callosum volume [34]. Although the mechanisms remain poorly defined, white matter degradation, including a 25% reduction in corpus callosum thickness, was correlated with inflammatory activation at one-year after a single TBI [37].…”

Delayed voluntary exercise does not enhance cognitive performance after hippocampal injury: an investigation of differentially distributed exercise protocols

“…Cancer studies have shown that therapeutic doses of irradiation can cause neurotoxic effects – especially affecting hippocampal neurogenesis, cell proliferation, differentiation and apoptosis (Dietrich et al, 2008; Monje, 2008). Stroke or traumatic brain injuries generally produce more widespread and diffuse cerebral pathologies (Bramlett and Dietrich, 2004), although hippocampal atrophy is a common finding in human survivors of traumatic brain injury (Ariza et al, 2006; Green et al, 2014; Tomaiuolo et al, 2004). The injury model used in the present study (fimbria-fornix transection) is a focal mechanical injury specifically targeting hippocampal functioning.…”

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques

“…However, it takes weeks for stabilization of the frontal pathology to emerge as encephalomalacia, focal atrophy and loss of parenchyma. Longitudinal studies in those with TBI have shown that it takes a minimum of 6 weeks for prominent encephalomalacia consistently to be apparent in imaging studies (Blatter et al 1995), with dynamic changes in lesion size, volume and regional atrophy extending across the first year to even longer timeframes post-injury (Farbota et al 2012;Green et al 2014;Ng et al 2008). As visualized in Fig.…”

“…Nonetheless, an enduring marker of global atrophy is a derivative of the Evans' index or ratio -the ventricle-to-brain ratio (VBR) where total ventricular volume is divided by brain volume and multiplied by 100 so that whole numbers are used in the quantification metric. The VBR is not only an established measure of overall brain integrity, but as a ratio it automatically adjusts (partially) for head size variation (Mathalon et al 1993) and commonly relates to neuropsychological status Green et al 2014;Olesen et al 2011;Tate et al 2011). Like all quantitative image techniques it is not without its drawbacks and there are circumstances where it may be best to adjust or correct for head size statistically (e.g., regression or covariance) rather than using a ratio like the VBR (Arndt et al (Arndt et al 1991).…”