Rehabilitation Considerations for Traumatic Brain Injury in the Geriatric Population: Epidemiology, Neurobiology, Prognosis, and Management

Crownover, James; Galang, Gary; Wagner, Amy K.

doi:10.1007/s13670-012-0021-6

Cited by 12 publications

(6 citation statements)

References 99 publications

(94 reference statements)

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“…The first mechanism , age effects independent of inflammation, is well documented in TBI (Crownover et al , 2012; De Guise et al , 2015; Røe et al , 2013). The single greatest predictor of TBI-related deaths is older age, with nearly a 6% increase in risk of death for each year increase in age after injury (Harrison-Felix et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Kumar

Rubin

Berger

et al. 2016

Brain, Behavior, and Immunity

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Studies have characterized absolute levels of multiple inflammatory agents as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 versus 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Kumar

Rubin

Berger

et al. 2016

Brain, Behavior, and Immunity

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“…; Crownover et al . ), which has its own patterns of neurochemical alterations and genetic influences on DA neurotransmission (Massucci et al . ; Wagner et al .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, adjuvant treatments with other DAergic agents like D2 agonists are common in PD subjects, and they produce long-lasting changes in the DAergic system as well (Ahlskog et al 1999, Marek et al 2002Parkinson Study, G 2002). Although L-DOPA is mostly utilized in the context of PD, it has beneficial effects in other conditions like traumatic brain injury (Lal et al 1988;Haig and Ruess 1990;Krimchansky et al 2004;Crownover et al 2012), which has its own patterns of neurochemical alterations and genetic influences on DA neurotransmission (Massucci et al 2004;Wagner et al 2005Wagner et al , 2009aWagner et al ,b, 2014Bales et al 2009;Shin et al 2011;Failla et al 2015). The specific region, pathology, genetic influences, and drug interactions are all important contributors to understanding how even the same agent differentially affects DA neurotransmission between individuals and in different regions of the same individual.…”

Section: Discussionmentioning

confidence: 99%

Fast‐scan cyclic voltammetry demonstrates that L‐DOPA produces dose‐dependent, regionally selective bimodal effects on striatal dopamine kinetics in vivo

Harun

Hare

Brough

et al. 2016

Journal of Neurochemistry

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Parkinson’s disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. Levodopa (L-Dopa) was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L-Dopa to augment striatal DA production are well known, little is actually known about how L-Dopa alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L-Dopa administration (100mg/kg carbidopa/250mg/kg L-Dopa) on regional electrically stimulated DA response kinetics using fast-scan cyclic voltammetry (FSCV) in anesthetized rats. We demonstrate that L-Dopa enhances DA release in both the dorsal striatum (D-STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D-STR, a finding that may be related to high-dose L-Dopa effects. In both regions, L-Dopa progressively attenuated reuptake kinetics through a decrease in Vmax and an increase in Km. This finding is consistent with recent clinical studies suggesting that L-Dopa chronically down-regulates the DA transporter (DAT), which may relate to the common development of L-Dopa induced dyskinesias (LID) in PD subjects.

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“…Our findings revealed age to be a significant predictor for greater cognitive impairment; likely explanations include age-related exacerbation of secondary injury mechanisms [89], other premorbid medical conditions and functional impairments, and limitations with cognitive reserve often observed in older individuals with TBI [91]. Of note, the effect of age on cognitive impairment was small; in contrast, the difference in cognitive impairment between G-homozygotes and C-carriers in our cohort was substantial, roughly the equivalent of a 45 year age difference in cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury

Markos

Failla

Ritter

et al. 2017

Journal of Head Trauma Rehabilitation

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Introduction Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter 2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2’s role in monoaminergic neurotransmission. Objective Evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. Methods We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment [cognitive composite T-scores (Comp-Cog)] to influence functional cognition [Functional Independence Measure Cognitive subscale (FIM-Cog)] 6 and 12 months post-injury. Results Multivariate analyses at 6-months post-injury showed rs363226 genotype was associated with Comp-Cog (p=0.040) and interacted with Comp-Cog to influence functional cognition (p<0.001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. Discussion We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes following TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes.

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Rehabilitation Considerations for Traumatic Brain Injury in the Geriatric Population: Epidemiology, Neurobiology, Prognosis, and Management

Cited by 12 publications

References 99 publications

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury

Fast‐scan cyclic voltammetry demonstrates that L‐DOPA produces dose‐dependent, regionally selective bimodal effects on striatal dopamine kinetics in vivo

Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury

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