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.

Highlights

  • In 2013, emergency departments in the US recorded a total of 2.8 million visits related to traumatic brain injuries; 280,000 resulted in hospitalization and 56,000 in deaths.[56]

  • Throughout months, years, or even decades, these events may result in structural and functional changes of the brain associated with cerebral atrophy, the gradual loss of neurons and the connections between them, and neurodegeneration, the gradual functional decline.[45]

  • We propose to simulate focal atrophy in selected regions of the gray matter including the bilateral thalamus, bilateral hippocampus, cerebellum, bilateral putamen, bilateral pallidum, and insula, and regions of the white matter including the corpus callosum, corona radiata, capsule, brainstem, and inferior and superior fascicules

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Summary

Introduction

In 2013, emergency departments in the US recorded a total of 2.8 million visits related to traumatic brain injuries; 280,000 resulted in hospitalization and 56,000 in deaths.[56]. Throughout months, years, or even decades, these events may result in structural and functional changes of the brain associated with cerebral atrophy, the gradual loss of neurons and the connections between them, and neurodegeneration, the gradual functional decline.[45] Figure 1 highlights the characteristic features of cerebral atrophy following traumatic brain injury: a widening of the cortical sulci, a gradual enlargement of the ventricles, a pronounced cortical thinning, and a shrinking of the hippocampus

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