It has been long assumed that following the resolution of acute injuries, traumatic brain injury and stroke represent stable neural entities. However, there is growing evidence from our lab and elsewhere, that brain injury may instead trigger an ongoing neurodegenerative process that can be measured well into the chronic stages of injury.
For scientists and clinicians, it is critical to examine this body of evidence and to explore its implications. Does such a degenerative process occur in moderate-severe TBI or can findings to date be alternatively explained? If it does occur, what are the risk-factors, causal mechanisms and the neural, behavioural and functional characteristics? Such information will be needed to develop treatments to mitigate or preempt neurodegeneration, and to much better inform clinical care of TBI patients.
The majority of recovery studies have assumed that recovery, once achieved, persists (e.g., Holbrook et al., 1999). However, there is some past evidence from animal and human studies that recovery is not invariably maintained. As far back as 1988, in a little-cited study by Wilson et al., 25 human adults with TBI underwent MRI at two time-points, once immediately post-injury and then again anywhere from 5 to 18 months later. Ventricular enlargement was observed in some patients, and was moreover correlated with neuropsychological function. While an intriguing finding, an important limitation is that edema early post-injury may have enlarged the brain, making volume loss inevitable on later measurement, even in the absence of actual atrophy.
A small number of more recent studies have been undertaken. For example, 7 mildly and moderately impaired patients were administered MRIs more than 3 months apart in a retrospective study by MacKenzie et al., (2002). Volume of brain parenchyma decreased significantly over time, and moreover correlated with longer loss of consciousness. Bendlin et al (2008), too, found evidence of decline within the first year of injury. Recent studies, however, have suffered the same edema confound as the original study by Wilson and colleagues. In research conducted in our own lab (Greenberg et al; Ng et al; Green et al, 2009; Adnan et al 2010) we extended previous research, examining more brain regions as well as visible lesion progression, and obviating the edema confound by making our first measurement at 4.5 months post-injury, long after the acute events of injury would have resolved.
This topic is of pressing clinical concern and scientific interest. We must understand these processes in order to design effective, mechanism-based treatments, and to provide prognostic information for appropriate care-planning. Scientifically, there are intriguing parallels to other dementias. For example, chronic traumatic encephalopathy, is another putative neurodegenerative disorder triggered by brain trauma, multiple mild ones. TBI is largely a disorder of white matter. The speculated mechanisms of this disorder may show parallels to and shed light on the mechanisms of progression of other white matter disorders, such as multiple sclerosis. Lastly, given that current research and clinical practice widely rest on the assumption that TBI is a non-progressive disorder, we must carefully explore this assumption in order to be able to move in a very different direction if need be.
It has been long assumed that following the resolution of acute injuries, traumatic brain injury and stroke represent stable neural entities. However, there is growing evidence from our lab and elsewhere, that brain injury may instead trigger an ongoing neurodegenerative process that can be measured well into the chronic stages of injury.
For scientists and clinicians, it is critical to examine this body of evidence and to explore its implications. Does such a degenerative process occur in moderate-severe TBI or can findings to date be alternatively explained? If it does occur, what are the risk-factors, causal mechanisms and the neural, behavioural and functional characteristics? Such information will be needed to develop treatments to mitigate or preempt neurodegeneration, and to much better inform clinical care of TBI patients.
The majority of recovery studies have assumed that recovery, once achieved, persists (e.g., Holbrook et al., 1999). However, there is some past evidence from animal and human studies that recovery is not invariably maintained. As far back as 1988, in a little-cited study by Wilson et al., 25 human adults with TBI underwent MRI at two time-points, once immediately post-injury and then again anywhere from 5 to 18 months later. Ventricular enlargement was observed in some patients, and was moreover correlated with neuropsychological function. While an intriguing finding, an important limitation is that edema early post-injury may have enlarged the brain, making volume loss inevitable on later measurement, even in the absence of actual atrophy.
A small number of more recent studies have been undertaken. For example, 7 mildly and moderately impaired patients were administered MRIs more than 3 months apart in a retrospective study by MacKenzie et al., (2002). Volume of brain parenchyma decreased significantly over time, and moreover correlated with longer loss of consciousness. Bendlin et al (2008), too, found evidence of decline within the first year of injury. Recent studies, however, have suffered the same edema confound as the original study by Wilson and colleagues. In research conducted in our own lab (Greenberg et al; Ng et al; Green et al, 2009; Adnan et al 2010) we extended previous research, examining more brain regions as well as visible lesion progression, and obviating the edema confound by making our first measurement at 4.5 months post-injury, long after the acute events of injury would have resolved.
This topic is of pressing clinical concern and scientific interest. We must understand these processes in order to design effective, mechanism-based treatments, and to provide prognostic information for appropriate care-planning. Scientifically, there are intriguing parallels to other dementias. For example, chronic traumatic encephalopathy, is another putative neurodegenerative disorder triggered by brain trauma, multiple mild ones. TBI is largely a disorder of white matter. The speculated mechanisms of this disorder may show parallels to and shed light on the mechanisms of progression of other white matter disorders, such as multiple sclerosis. Lastly, given that current research and clinical practice widely rest on the assumption that TBI is a non-progressive disorder, we must carefully explore this assumption in order to be able to move in a very different direction if need be.
