The Shrinking Brain: Cerebral Atrophy Following Traumatic Brain Injury

Abstract

Cerebral atrophy in response to traumatic brain injury is a well-documented phenomenon in both primary investigations and review articles. Recent atrophy studies focus on exploring the region-specific patterns of cerebral atrophy; yet, there is no study that analyzes and synthesizes the emerging atrophy patterns in a single comprehensive review. Here we attempt to fill this gap in our current knowledge by integrating the current literature into a cohesive theory of preferential brain tissue loss and by identifying common risk factors for accelerated atrophy progression. Our review reveals that observations for mild traumatic brain injury remain inconclusive, whereas observations for moderate-to-severe traumatic brain injury converge towards robust patterns: brain tissue loss is on the order of 5% per year, and occurs in the form of generalized atrophy, across the entire brain, or focal atrophy, in specific brain regions. The most common regions of focal atrophy are the thalamus, hippocampus, and cerebellum in gray matter and the corpus callosum, corona radiata, and brainstem in white matter. We illustrate the differences of generalized and focal gray and white matter atrophy on emerging deformation and stress profiles across the whole brain using computational simulation. The characteristic features of our atrophy simulations—a widening of the cortical sulci, a gradual enlargement of the ventricles, and a pronounced cortical thinning—agree well with clinical observations. Understanding region-specific atrophy patterns in response to traumatic brain injury has significant implications in modeling, simulating, and predicting injury outcomes. Computational modeling of brain atrophy could open new strategies for physicians to make informed decisions for whom, how, and when to administer pharmaceutical treatment to manage the chronic loss of brain structure and function.

Prognostic-factors for neurodegeneration in chronic moderate-to-severe traumatic brain injury: a systematic review protocol

“…However, there is now extensive evidence that moderate-to-severe TBI is a progressive and deteriorative disorder. Our lab and others have found extensive evidence of progressive lesion expansion, grey and white matter atrophy, and loss of white matter integrity in the months and years following injury [12][13][14][15][16][17][18][19][20][21][22][23]. For example, our group observed significant atrophy from 5 to 20 months post-injury in at least one region of interest in 96% of 56 moderate-to-severe brain injury patients studied [13].…”

Fifty Shades of Brain: A Review on the Mechanical Testing and Modeling of Brain Tissue

“…To model the biochemical effects of neurodegeneration, we could introduce the atrophy tensor F a as a function of the toxic protein concentration c [175]. To model the biomechanical effects of neurodegeneration, we recommend using a finite hyperelastic model and assume that viscoelastic and poro-elastic effects are negligible on the relevant time scales on the order of several decades [75]. While the computational modeling of neurodegeneration is still in its infancy, there seems to be a general agreement that a more quantitative understanding of the spatio-temporal spreading of neurodegenerative diseases is necessary to establish a prognostic timeframe of disease progression.…”

“…During traumatic brain injury, external mechanical load leads to damage of the highly delicate brain tissue and ultimately loss of brain function [116]. Clinically, traumatic brain injury can be classified into mild, moderate, and severe, and repetitive mild traumatic brain injuries are now more commonly referred to as chronic traumatic encephalopathy [75]. While computational models can help estimate injury risk and advance injury prevention [38], correct predictions of the deformation field during impact critically depends on the accurate representation of the nonlinear, loading-mode-, and region-dependent stressstrain relationship of brain tissue.…”

Translating research findings into clinical practice: a systematic and critical review of neuroimaging-based clinical tools for brain disorders

“…A tool (Icobrain 40 ) is therefore designed for intracranial lesion segmentation, cistern segmentation and the evaluation of midline shift. However, mild TBI is not associated with gross brain lesions but with subtle progressive atrophy 58 . Accordingly, a different tool (NeuroQuant 46,[49][50][51] ) has been validated to detect atrophy, structures asymmetry and/or progressive atrophy in patients with TBI.…”