Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury

Abstract

Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as ‘frontal-temporal’ in nature, suggesting a possible link between acute metabolic crisis related-brain atrophy and neurocognitive impairment in this population. While focal lesions and diffuse axonal injury have a well-established role in the neuropsychological deficits observed following traumatic brain injury, no studies to date have examined the possible contribution of acute metabolic crisis-related atrophy in the neuropsychological sequelae of traumatic brain injury. In the current study we employed positron emission tomography, magnetic resonance imaging, and neuropsychological assessments to ascertain the relationship between acute metabolic crisis related-brain atrophy and neurocognitive outcome in a sample of 14 right-handed traumatic brain injury survivors. We found that acute metabolic crisis related-atrophy in the frontal and temporal lobes was associated with poorer attention, executive functioning, and psychomotor abilities at 12 months post-injury. Furthermore, participants with gross frontal and/or temporal lobe atrophy exhibited numerous clinically significant neuropsychological deficits in contrast to participants with other patterns of brain atrophy. Our findings suggest that interventions that reduce acute metabolic crisis may lead to improved functional outcomes for traumatic brain injury survivors.

A prospective study of gray matter abnormalities in mild traumatic brain injury

“…Atrophy has been observed within weeks of injury in more severe TBI. 8,9 Previous work with symptomatic (81.3% with posttraumatic stress disorder), mixed injury cohorts (mild and moderate TBI) reported longitudinal differences 1 to 2 years postinjury in wholebrain parenchyma as well as cerebral white matter. 17 Others reported atrophic whole-brain changes for patients with complicated mTBI 6 months postinjury, with typical mTBI patients showing no evidence of atrophy.…”

“…Additionally, recent animal models indicate increased anisotropy within the thalamus and hippocampus during acute and more chronic injury phases. 6,7 Although evidence of atrophy has been found as early as 1 to 3 weeks postinjury in moderate to severe TBI,8,9 it becomes more prevalent at 6 to 12 months, 10-13 even in the absence of macroscopically detectable lesions.…”

“…Additionally, recent animal models indicate increased anisotropy within the thalamus and hippocampus during acute and more chronic injury phases. 6,7 Although evidence of atrophy has been found as early as 1 to 3 weeks postinjury in moderate to severe TBI, 8,9 it becomes more prevalent at 6 to 12 months, [10][11][12][13] even in the absence of macroscopically detectable lesions. 14,15 Studies of patients with complicated 16 and symptomatic mild to moderate 17 TBI indicate atrophy as a function of disease progression approximately 6 months 16 or 1 year 17 postinjury.…”

Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain

“…Our results of global changes in bioenergetic function occurring in the contralateral hemisphere following focal injury in a large animal model correlates with rodent data depicting global alterations in oxidative metabolism (Scafidi et al, 2009) and neuropathology (Hall et al, 2008), as well as human imaging data utilizing positron emission tomography (Vespa et al, 2005). Compensatory increases in contralateral mitochondrial respiration post-CCI may represent an increase in mitochondrial respiration stimulated after injury that may be necessary to limit secondary cascades of TBI in face of increased metabolic demand (Marcoux et al, 2008a; Robertson et al, 2006; Wright et al, 2013). Therefore, there remains a significant difference between the contralateral and ipsilateral sides of the injured brain for maximal coupled and uncoupled oxidative phosphorylation by all measures; as well as, a significant evolving lesion volume beyond 24 h (evaluated with neuropathology and significant behavioral changes in our model; data not shown); and other limited studies in rodents (Vespa et al, 2005; Watson et al, 2013).…”

Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury

“…Numerous studies have determined that the presence of DAI and focal lesions, frequently located in the frontal and temporal lobes, are associated with poorer cognitive outcomes following TBI (Auerbach, 1986; Bigler, 2001; Fork et al 2005; Kraus et al, 2007; Lehtonen et al, 2005; Levine et al, 2002; Wallesch et al, 2001; Williamson et al, 1996). Interestingly, our group found a relationship between long-term cognitive outcomes and frontal and temporal lobe atrophy associated ACMC following TBI (Wright et al, 2013). Specifically, ACMC-related brain atrophy correlated with attention, executive function, and psychomotor speed at 12 months post-TBI.…”