Published online before print August 3, 2011, doi: 10.1212/WNL.0b013e31822c61d7 Neurology WNL.0b013e31822c61d7

1. J.Y. Wang, PhD,
2. K. Bakhadirov, MD,
3. H. Abdi, PhD,
4. M.D. Devous Sr., PhD,
5. C.D. Marquez de la Plata, PhD,
6. C. Moore, MA,
7. C.J. Madden, MD and
8. R. Diaz-Arrastia, MD, PhD

+ Author Affiliations

1. Address correspondence and reprint requests to Dr. Ramon Diaz-Arrastia, Center for Neuroscience and Regenerative Medicine, Uniformed Services University for the Health Sciences, 12725 Twinbrook Parkway, Rockville, MD 20852 Ramon.Diaz-Arrastia@usuhs.mil

Abstract

Objectives: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome.

Methods: The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0–9 days postinjury for acute scans and 6–14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used.

Results: Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function.

Conclusions: Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome.

• Received December 13, 2010.
• Accepted March 22, 2011.

1. Patrick W. Alford¹,
2. Borna E. Dabiri,
3. Josue A. Goss,
4. Matthew A. Hemphill,
5. Mark D. Brigham, and
6. Kevin Kit Parker²

+ Author Affiliations

1.      Edited* by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 20, 2011 (received for review April 14, 2011)

Abstract

Vasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased incidence. Here, using theoretical and in vitro models, we show that a single rapid mechanical insult can induce vascular hypercontractility and remodeling, indicative of vasospasm initiation. We employed high-velocity stretching of engineered arterial lamellae to simulate the mechanical forces of a blast pulse on the vasculature. An hour after a simulated blast, injured tissues displayed altered intracellular calcium dynamics leading to hypersensitivity to contractile stimulus with endothelin-1. One day after simulated blast, tissues exhibited blast force dependent prolonged hypercontraction and vascular smooth muscle phenotype switching, indicative of remodeling. These results suggest that an acute, blast-like injury is sufficient to induce a hypercontraction-induced genetic switch that potentiates vascular remodeling, and cerebral vasospasm, in bTBI patients.

Endocr Rev, Vol. 32 (03_MeetingAbstracts): OR16-4
Copyright © 2011 by The Endocrine Society

Charles W Wilkinson, PhD², Elaine R Peskind, MD², Elizabeth A Colasurdo² and Jane B Shofer, MS¹

Department of Psychiatry and Behavioral Sciences (JBS), University of Washington, Seattle, WA
Geriatric Research, Education and Clinical Center (CWW,ERP,EAC), Veterans Affairs Puget Sound Health Care System, Seattle, WA

Studies of civilian traumatic brain injury (TBI) from all causes have found evidence of chronic hypopituitarism, as defined by deficient production of one or more pituitary hormones measured at least one year after injury, in 33-50% of cases (1). Its occurrence has not been found to be related to trauma severity (1,2). Hypopituitarism is associated with non-specific behavioral symptoms that can be mistaken for PTSD, including fatigue, anxiety, depression, irritability, insomnia, poor concentration and memory, and decreased quality of life (1). Despite these findings, the prevalence of hypopituitarism after blast concussion mild TBI, the signature injury of combat in Iraq and Afghanistan, has not yet been investigated. Mild TBI (mTBI) is characterized by brief loss of consciousness or loss of memory for events surrounding the trauma or any alteration of mental state (disorientation, confusion). In order to determine the frequency of pituitary dysfunction after blast concussion mTBI, we are measuring pituitary and target organ hormones in blood samples from Iraq/Afghanistan Veterans with mTBI taken at least one year subsequent to their last blast exposure. Most have experienced multiple blast exposures. Criteria for identifying abnormal circulating levels of LH, FSH, total testosterone, prolactin, ACTH, cortisol, TSH, free thyroxine, GH, IGF-I, and arginine vasopressin (AVP) were derived from RIA or EIA measurement of basal morning concentrations in a large group of male non-Veteran control subjects. In general, values below the 5th percentile or above the 95th percentile were defined as abnormal. When both pituitary and target organ hormones were measured for a given axis, a specific combination of criteria signaled dysfunction of that axis. Using the criteria defined in controls, 10 of 26 Veterans with blast mTBI were found to have abnormal hormone levels in one or more pituitary axes. Seven mTBI subjects exhibited deviant plasma AVP concentrations, either above or below the 5th-95th percentile normal range. The frequency of abnormally low or abnormally elevated AVP levels has been found to be relatively high in the acute stage of non-blast TBI, but it tends to decline with time. These preliminary findings suggest that the prevalence of hypopituitarism after blast concussion mTBI is similar to that in other forms of TBI, and that recovery and rehabilitation of blast-exposed Veterans may be facilitated by comprehensive screening for pituitary dysfunction.

(1) Ghigo E et al., Brain Inj, 2005; 19:711(2) Lieberman SA et al., J Clin Endocrinol Metab 2001; 86:2752

Nothing to Disclose: CWW, E

PLoS One. 2011 May 4;6(5):e19214.

Newcombe V, Chatfield D, Outtrim J, Vowler S, Manktelow A, Cross J, Scoffings D, Coleman M, Hutchinson P, Coles J, Carpenter TA, Pickard J, Williams G, Menon D.

Source

University Division of Anaesthesia, University of Cambridge, Cambridge, United Kingdom.

Abstract

BACKGROUND:

Traumatic brain injury is a major cause of morbidity and mortality worldwide. Ameliorating the neurocognitive and physical deficits that accompany traumatic brain injury would be of substantial benefit, but the mechanisms that underlie them are poorly characterized. This study aimed to use diffusion tensor imaging to relate clinical outcome to the burden of white matter injury.

METHODOLOGY/PRINCIPAL FINDINGS:

Sixty-eight patients, categorized by the Glasgow Outcome Score, underwent magnetic resonance imaging at a median of 11.8 months (range 6.6 months to 3.7 years) years post injury. Control data were obtained from 36 age-matched healthy volunteers. Mean fractional anisotropy, apparent diffusion coefficient (ADC), and eigenvalues were obtained for regions of interest commonly affected in traumatic brain injury. In a subset of patients where conventional magnetic resonance imaging was completely normal, diffusion tensor imaging was able to detect clear abnormalities. Significant trends of increasing ADC with worse outcome were noted in all regions of interest. In the white matter regions of interest worse clinical outcome corresponded with significant trends of decreasing fractional anisotropy.

CONCLUSIONS/SIGNIFICANCE:

This study found that clinical outcome was related to the burden of white matter injury, quantified by diffusivity parameters late after traumatic brain injury. These differences were seen even in patients with the best outcomes and patients in whom conventional magnetic resonance imaging was normal, suggesting that diffusion tensor imaging can detect subtle injury missed by other techniques. An improved in vivo understanding of the pathology of traumatic brain injury, including its distribution and extent, may enhance outcome evaluation and help to provide a mechanistic basis for deficits that remain unexplained by other approaches.