Recovery at One Year Following Isolated Traumatic Brain Injury: A Western Trauma Association Prospective Multicenter Trial

Livingston, David H.; Lavery, Robert F.; Mosenthal, Anne C.; Knudson, M. Margaret; Lee, Seong; Morabito, Diane; Manley, Geoffrey T.; Nathens, Avery B.; Jurkovich, Gregory J.; Hoyt, David B.; Coimbra, Raúl

doi:10.1097/01.ta.0000196002.03681.18

Cited by 118 publications

(68 citation statements)

References 29 publications

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“…Confirmed factors of poor prognosis for patients with GCS 3 or 4 and older than 65 years are closed basal cisterns and midline shift > 15 mm on the first CT (Brazinova et al, 2010). The worse outcomes in elderly human subjects occur despite what appears to be less severe TBI, as measured by a higher GCS upon admission (Livingston et al, 2005;Susman et al, 2002). …”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, increasing age is strongly associated with a poor prognosis both in experimental trauma models and following TBI in humans (Livingston et al, 2005;Onyszchuk et al, 2008;Rothweiler et al, 1998;Sendroy-Terrill et al, 2010;Susman et al, 2002). Confirmed factors of poor prognosis for patients with GCS 3 or 4 and older than 65 years are closed basal cisterns and midline shift > 15 mm on the first CT (Brazinova et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…T raumatic brain injury (TBI) is a significant problem in senior citizens, with old age being associated with a poor recovery from brain injury (Hukkelhoven et al, 2003;Livingston et al, 2005;Thompson et al, 2006). The poorer prognosis has prompted some investigators to advocate a more conservative approach in elderly patients with moderate and severe TBI (Gan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Mellergård

Sjögren

Hillman

2012

Journal of Neurotrauma

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Old age is associated with a poor recovery from traumatic brain injury (TBI). In a retrospective study we investigated if the biochemical response following TBI is age dependent. Extracellular fluids were continuously sampled by microdialysis in 69 patients admitted to our NSICU following severe TBI. The concentrations of glycerol, glutamate, lactate, pyruvate, and eight different cytokines (IL-1b, IL-6, IL-10, IL-8, MIP-1b, RANTES, FGF2, and VEGF) were determined by fluorescence multiplex bead technology. Patients in the oldest age group ( ‡ 65 years) had significantly higher microdialysate concentrations of glycerol and glutamate compared to younger patients: the mean microdialysate concentration of glycerol increased from 55.9 lmol/L (25-44 year) to 252 lmol/L ( ‡ 65 years; p < 0.0001); similarly glutamate increased from 15.8 mmol/L to 92.2 mmol/L ( p < 0.0001). The lactate-pyruvate ratio was also significantly higher in the patients ‡ 65 years of age (63.9) compared with all the other age groups. The patterns of cytokine responses varied. For some cytokines (IL-1b, IL-10, and IL-8) there were no differences between age groups, while for others (MIP-1b, RANTES, VEGF, and IL-6) some differences were observed, but with no clear correlation with increasing age. For FGF2 the mean microdialysate concentration was 43 pg/mL in patients ‡ 65 years old, significantly higher compared to all other age groups ( p < 0.0001). Increased concentrations of glycerol and glutamate would indicate more extensive damaging processes in the elderly. An increase in concentration of FGF2 could serve a protective function, but could also be related to a dysregulation of the timing in the cellular response in elderly patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Mellergård

Sjögren

Hillman

2012

Journal of Neurotrauma

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“…11,12 These findings lend credibility to previous retrospective and shorter-term longitudinal studies suggesting a risk for dementia and continued functional decline (some of it perhaps, due to dementing illness) among older individuals, as longitudinal data were utilized for this investigation. 11,12,[18][19][20] Interestingly, TBI survivors who improved over time were slightly younger (though not significantly), and had worse disability ratings at admission to and discharge from rehabilitation services than patients who did not improve, and therefore had more room for improvement. While this may explain the potential for greater improvement among the young as compared to older patients, actual improvement over time reflected by the DRS is less understood.…”

Section: Discussionmentioning

confidence: 99%

Impact of Age on Long-Term Recovery From Traumatic Brain Injury

Plata

Hart

Hammond³

et al. 2008

Archives of Physical Medicine and Rehabilitation

196

117

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Objective-To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). Design-Longitudinal cohort study. Setting-Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers.Participants-Subjects enrolled in the TBIMS national dataset. Interventions-Not applicable.Main Outcome Measures-Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended.Results-Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (≥40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. While DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. Additionally, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model demonstrated that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates.Conclusions-This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. Additionally, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.Reprint requests to Ramon Diaz-Arrastia, MD, PhD, 5323 Harry Hines Blvd, Dallas, TX 75390-9036, e-mail: ramon.diazarrastia@utsouthwestern.edu. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. The resulting injuries range from mild disability to longterm disabilities or death. 3 It has been observed that particular subpopulations recover differently from similar injuries. One characteristic felt to have an impact on the degree of recovery is age: in general, the older the patient the worse the outcome. 7-12 Issues of TBI and aging are important to study because of the large and growing number of older people who are affected by TBI, which has a bimodal age distribution peaking in late adolescence/early adulthood and again after age 70. 3 NIH Public AccessTBI may interact negatively with aging in at least 2 ways: (1) recovery after TBI is more limited for older than younger survivors; and (2) older individuals who have suffered a TBI are at higher risk for progressive cognitive decline. First, advanced age at the time of injury may result in less complete recovery comp...

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“…54 In that study of 236 patients, the TBI patients above 60 years who were discharged with a Glasgow Outcome Score (GOS) of less than 4 showed lower FIM Scores at 1 year, compared with younger patients. In the clinical trial reported by Temkin et al, 1 no data on GOS (or any other scoring system) upon discharge were reported.…”

Section: Efficacy Studies With Magnesiummentioning

confidence: 96%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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Summary: Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI.

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Recovery at One Year Following Isolated Traumatic Brain Injury: A Western Trauma Association Prospective Multicenter Trial

Cited by 118 publications

References 29 publications

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

The Cerebral Extracellular Release of Glycerol, Glutamate, and FGF2 Is Increased in Older Patients following Severe Traumatic Brain Injury

Impact of Age on Long-Term Recovery From Traumatic Brain Injury

Use of Magnesium in Traumatic Brain Injury

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