Moderate–severe traumatic brain injury causes delayed loss of white matter integrity: Evidence of fornix deterioration in the chronic stage of injury

Adnan, Areeba; Crawley, Adrian P.; Mikulis, David J.; Moscovitch, Morris; Colella, Brenda; Green, Robin

doi:10.3109/02699052.2013.823659

Cited by 55 publications

(44 citation statements)

References 49 publications

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“…Similar to animal data showing a temporal progression of axonal injury, measured as changes of DTI parameters (Mac Donald et al, 2007a), clinical studies of TBI patients at different stages also report different DTI findings, suggesting a temporal progress of TBI pathology. Adnan et al (2013) prospectively scanned 29 moderate to severe TBI patients at two time points: 5 months and 29 months after injury. Adnan et al (2013) prospectively scanned 29 moderate to severe TBI patients at two time points: 5 months and 29 months after injury.…”

Section: Temporal Progression Of Dti Signature In Tbi Patientsmentioning

confidence: 99%

Traumatic white matter injury and glial activation: From basic science to clinics

Kou

VandeVord

2014

Glia

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An improved understanding and characterization of glial activation and its relationship with white matter injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination after brain trauma. Traumatic brain injury (TBI) is a significant public healthcare burden and a leading cause of death and disability in the United States. Particularly, traumatic white matter (WM) injury or traumatic axonal injury has been reported as being associated with patients' poor outcomes. However, there is very limited data reporting the importance of glial activation after TBI and its interaction with WM injury. This article presents a systematic review of traumatic WM injury and the associated glial activation, from basic science to clinical diagnosis and prognosis, from advanced neuroimaging perspective. It concludes that there is a disconnection between WM injury research and the essential role of glia which serve to restore a healthy environment for axonal regeneration following WM injury. Particularly, there is a significant lack of non-invasive means to characterize the complex pathophysiology of WM injury and glial activation in both animal models and in humans. An improved understanding and characterization of the relationship between glia and WM injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination.

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Section: Temporal Progression Of Dti Signature In Tbi Patientsmentioning

confidence: 99%

Traumatic white matter injury and glial activation: From basic science to clinics

Kou

VandeVord

2014

Glia

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“…Moreover, one must distinguish clinically and pathologically between static, non-progressive cumulative effects of multiple concussions vs. progressive findings of symptomatic neurodegenerative disease. Complicating the situation are cases of a single, but more serious TBI associated with increased risk of dementia (Blennow et al, 2012; Sayed et al, 2013) as well as atrophy and loss of white matter integrity in the sub-acute and chronic stages of injury (Greenberg et al, 2008; Ng et al, 2008; Whitwell and Josephs, 2011; Adnan et al, 2013)…”

Section: Summary and Conclusion: Much Remains To Be Knownmentioning

confidence: 99%

Chronic traumatic encephalopathy and other neurodegenerative proteinopathies

Tartaglia

Hazrati

Davis

et al. 2014

Front. Hum. Neurosci.

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“Chronic traumatic encephalopathy” (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this “perspective” is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

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“…Evidence is accumulating from several laboratories including our own that following early cognitive recovery, many patients show statistically and clinically significant cognitive decline in the ensuing months (Ruff et al, 1991) and years (Millis et al, 2001; Till et al, 2008). We and others have also demonstrated that the brain's structure is not static after resolution of acute injuries, with TBI patients showing volume loss and reduced white matter (WM) integrity during the sub-acute and chronic stages of injury (Bendlin et al, 2008; Greenberg et al, 2008; Ng et al, 2008; Sidaros et al, 2009; Farbota et al, 2012; Adnan et al, 2013). Given that such atrophy is observed in some studies well after the resolution of acute events (Greenberg et al, 2008; Ng et al, 2008; Ross et al, 2012), and that sub-acute structural deterioration has been correlated with functional and behavioral outcomes (Bendlin et al, 2008; Sidaros et al, 2009), these changes cannot be attributed simply to encephalomalacia (i.e., scar formation associated with gliosis) or to resolution of edema.…”

Section: Introductionmentioning

confidence: 96%

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

Green

Colella

Maller

et al. 2014

Front. Hum. Neurosci.

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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.

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Moderate–severe traumatic brain injury causes delayed loss of white matter integrity: Evidence of fornix deterioration in the chronic stage of injury

Cited by 55 publications

References 49 publications

Traumatic white matter injury and glial activation: From basic science to clinics

Traumatic white matter injury and glial activation: From basic science to clinics

Chronic traumatic encephalopathy and other neurodegenerative proteinopathies

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

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