Thursday, August 4, 2011

Longitudinal changes of structural connectivity in traumatic axonal injury

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

+ Author Affiliations

1. From the Department of Cognition and Neuroscience (J.Y.W., K.B., H.A., M.D.D.) and Center for Brain Health (C.D.M.d.l.P.), University of Texas at Dallas, Richardson; and Departments of Radiology (H.A., M.D.D.), Neurology (C.M., R.D.-A.), and Neurosurgery (C.J.M.), University of Texas Southwestern Medical Center, Dallas. Dr. Diaz-Arrastia is currently with the Center for Neuroscience and Regenerative Medicine, Uniformed Services University for the Health Sciences, Rockville, MD.

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.

Wednesday, August 3, 2011

Blast-induced phenotypic switching in cerebral vasospasm

+ Author Affiliations

1. Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard School of Engineering and Applied Science, Pierce Hall #321, 29 Oxford Street, Cambridge, MA 02138

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.

Thursday, July 7, 2011

Widespread Tau and Amyloid-Beta Pathology Many Years After a Single Traumatic Brain Injury in Humans.

Brain Pathol. 2011 Jun 29;

Authors: Johnson VE, Stewart W, Smith DH

Whilst a history of single traumatic brain injury (TBI) is associated with the later development of syndromes of cognitive impairment, such as Alzheimer's disease (AD), the long-term pathology evolving after single TBI is poorly understood. However, a progressive tauopathy, chronic traumatic encephalopathy, is described in selected cohorts with a history of repetitive concussive / mild head injury. Here, post-mortem brains from long-term survivors of just a single TBI (1 to 47 years survival; n = 39) versus uninjured, age-matched controls (n = 47) were examined for neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques using immunohistochemistry and thioflavin-S staining. Detailed maps of findings permitted classification of pathology using semi-quantitative scoring systems.NFTs were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one third of TBI cases. In addition, Aβ-plaques were found in a greater density following TBI versus controls. Moreover, thioflavin-S staining revealed that while all plaque-positive control cases displayed predominantly diffuse plaques, 64% of plaque-positive TBI cases, displayed predominantly thioflavin-S positive plaques or a mixed thioflavin-S positive / diffuse pattern. These data demonstrate widespread NFT and Aβ plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease.

PMID: 21714827 [PubMed - as supplied by publisher]

Dan Gardner, M.D.

www.dangardnermd.com

dgardner@ucsd.edu 858-560-5609

Assessment and treatment of common persistent sequelae following blast induced mild traumatic brain injury.

NeuroRehabilitation. 2011 Jan 1;28(4):309-20

Authors: Schultz BA, Cifu DX, McNamee S, Nichols M, Carne W

The ongoing wars in Iraq and Afghanistan and terrorist activity worldwide have been associated with an increased incidence of blast injuries. While blast injuries share similarities with blunt or penetrating traumatic injuries, there are unique mechanistic elements of blast injury that create increased vulnerability to damage of specific organs. This review highlights the mechanism of blast-related injury, describes the common sequelae of blast exposure that may impact rehabilitation care, and summarizes the intervention strategies for these blast-related sequelae.

PMID: 21725164 [PubMed - in process]

Dan Gardner, M.D.

www.dangardnermd.com

dgardner@ucsd.edu 858-560-5609

Optic radiation injury following traumatic epidural hematoma: Diffusion tensor imaging study.

NeuroRehabilitation. 2011 Jan 1;28(4):383-7

Authors: Kwon HG, Jang SH

Little is known about optic radiation (OR) injury in patients with traumatic brain injury (TBI). We report on a patient who showed an OR injury on diffusion tensor imaging (DTI) following traumatic epidural hematoma (EDH). A 38 year-old man with TBI and 7 age-matched normal subjects were enrolled in this study. The patient had fallen down stairs while in an alcohol intoxicated state. He underwent a craniotomy following diagnosis of traumatic EDH in the left temporo-parietal lobe on brain CT. He complained of right bilateral homonymous hemianopsia, which was confirmed on the Humphrey visual field test. No lesion on the left OR was observed during brain MRI. We were not able to reconstruct the fiber tractography for the left OR in this patient. We found that the left OR had been injured most severely around the midportion between the lateral geniculate body and occipital pole. We determined that DTI would be a useful technique for detection of an OR injury in patients with TBI. Therefore, we believe that DTI should be performed along with conventional brain MRI for patients with visual field defects following TBI.

PMID: 21725172 [PubMed - in process]

Dan Gardner, M.D.

www.dangardnermd.com

dgardner@ucsd.edu 858-560-5609

Friday, July 1, 2011

Evidence-Based Cognitive Rehabilitation: Updated Review of the Literature From 2003 Through 2008

Abstract

Cicerone KD, Langenbahn DM, Braden C, Malec JF, Kalmar K, Fraas M, Felicetti T, Laatsch L, Harley JP, Bergquist T, Azulay J, Cantor J, Ashman T. Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008.

Objective

To update our clinical recommendations for cognitive rehabilitation of people with traumatic brain injury (TBI) and stroke, based on a systematic review of the literature from 2003 through 2008.

Data Sources

PubMed and Infotrieve literature searches were conducted using the terms attention, awareness, cognitive, communication,executive, language, memory, perception, problem solving, and/or reasoning combined with each of the following terms:rehabilitation, remediation, and training for articles published between 2003 and 2008. The task force initially identified citations for 198 published articles.

Study Selection

One hundred forty-one articles were selected for inclusion after our initial screening. Twenty-nine studies were excluded after further detailed review. Excluded articles included 4 descriptive studies without data, 6 nontreatment studies, 7 experimental manipulations, 6 reviews, 1 single case study not related to TBI or stroke, 2 articles where the intervention was provided to caretakers, 1 article redacted by the journal, and 2 reanalyses of prior publications. We fully reviewed and evaluated 112 studies.

Thursday, June 16, 2011

Chronic Hypopituitarism after Blast Concussion Mild Traumatic Brain Injury in Iraq/Afghanistan Combat Veterans

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

Tuesday, June 14, 2011

DOD Unveils New Traumatic Brain Injury Application

Matthew Andres, Chicago Veterans Policy Examiner

Posted:06/11/2011 3:08 PM

In a June seventh press release, The Department of Defense announced the release of a mobile application for health care professionals: the Mild Traumatic Brain Injury Pocket Guide. The app was developed by the National Center for Telehealth and Technology, and gives doctors a complete and quick reference to traumatic brain injury. In addition, the app includes assessment and treating directions. The application is aimed at treating military personnel and veterans who have suffered traumatic brain injuries, a common injury sustained in Iraq and Afghanistan.

Katherine Helmick, the deputy director for traumatic brain injury at the National Center for Telehealth and Technology, was quoted in the press release as saying: “This new tool is about providing clinicians with quick and convenient access to clinical guidelines for concussion care. It not only allows the clinician to provide evidenced-based care but maximizes time spent with the patient.”

The mobile application is free of charge, and available for download on Android smart phones via:https://market.android.com/details?id=org.t2health.mtbi . Hard copies of the pocket guide can also be ordered by contacting the Defense and Veterans Brain Injury Center at info@dvbic.org or 1-800-870-9244.

Dan Gardner, M.D.

www.dangardnermd.com

dgardner@ucsd.edu 858-560-5609

Saturday, June 11, 2011

The Association between Apolipoprotein E and Traumatic Brain Injury Severity and Functional Outcome

J Neurotrauma. 2011 Jun 8;

Authors: Ponsford J, McLaren A, Schönberger M, Burke R, Rudzki D, Olver J, Ponsford M

Traumatic Brain Injury can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. This study aimed to examine whether possession of the Apolipoprotein E 4 allele was associated with greater acute injury severity and poorer long-term outcome in patients referred for rehabilitation following TBI. Apolipoprotein E genotype was determined for 648 patients with traumatic brain injury, who were prospectively followed up a mean of 1.9 years post-injury. Hypotheses that 4 carriers would have lower Glasgow Coma Scale scores and longer post-traumatic amnesia duration were not supported. Prediction of worse Glasgow Outcome Scale-Extended scores for 4 carriers was supported, with greater susceptibility in females. Results indicate the Apolipoprotein E 4 allele may be associated with poorer long-term outcome but not acute injury severity. Possible mechanisms include differential effects of the 4 allele on inflammatory and cellular repair processes and /or amyloid deposition.

PMID: 21651315 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=21651315&dopt=Abstract

Wednesday, May 18, 2011

Mapping traumatic axonal injury using diffusion tensor imaging: correlations with functional outcome.

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.

Thursday, May 12, 2011

Amantadine Found to Improve Prolonged Disorders of Consciousness After TBI

Amantadine Found to Improve Prolonged Disorders of Consciousness After TBI

via Traumatic Brain Injury News and Information on 5/10/11

Amantadine hydrochloride effectively improved functional recovery in patients in a vegetative or minimally conscious state after traumatic brain injury, results from a 6-week, randomized, multicenter study showed. "The improvements with amantadine were clinically significant in that they were associated with more frequent emergence of functionally meaningful behaviors [that are] associated with returning to full consciousness," Dr. Douglas I. Katz said at the annual meeting of the American Academy of Neurology.

Wednesday, March 23, 2011

Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports.

Authors

Naeser MA, et al. Show all

Affiliation

1 VA Boston Healthcare System , Boston, Massachusetts.

Journal

Photomed Laser Surg. 2010 Dec 23. [Epub ahead of print]

Abstract

Abstract Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1″ diameter, 61 diodes (9 × 633 nm, 52 × 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.

PMID

21182447 [PubMed - as supplied by publisher]

Full text: Mary Ann Liebert, Inc.

Monday, March 7, 2011

Role of low-level laser therapy in neurorehabilitation.

PM R. 2010 Dec;2(12 Suppl 2):S292-305

Authors: Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR

This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered.

PMID: 21172691 [PubMed - in process]

Saturday, January 1, 2011

Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumati

Photomed Laser Surg. 2010 Dec 23;

Authors: Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA

PMID: 21182447 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=21182447&dopt=Abstract

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Dan Gardner, M.D.

www.danielgardner.yourmd.com

dgardner@ucsd.edu 858-560-5609