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BR A IN INJURY professional vol. 10 issue 3

The official publication of the North American Brain Injury Society

Advanced Neuroimaging Hypermetabolic Neural Activity in People with Post Concussion Syndrome Revealed by Functional Imaging Structural Magnetic Resonance Imaging in Concussion Functional Imaging for Concussion Assessment and Research A Historical Perspective on Advanced Neuroimaging in Clinics and Courts Imaging for TBI: Current and Future Prospects Imaging for Brain Trauma: Questions to Be Answered BRAIN INJURY PROFESSIONAL

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contents

BRAIN INJURY professional vol. 10 issue 3

The official publication of the North American Brain Injury Society

north american brain injury society

32 legal spotlight

chairman Mariusz Ziejewski, PhD VICE CHAIR Debra Braunling-McMorrow, PhD Immediate Past Chair Ronald C. Savage, EdD treasurer Bruce H. Stern, Esq. family Liaison Skye MacQueen executive director/administration Margaret J. Roberts executive director/operations J. Charles Haynes, JD marketing manager Megan Bell graphic designer Nikolai Alexeev administrative assistant Benjamin Morgan administrative assistant Bonnie Haynes

34 bip expert interview

brain injury professional

departments 4 editor in chief’s message 6 guest editor’s message

35 literature review 36 non-profit news 38 legislative roundup

features 8 Hypermetabolic Neural Activity in People with Post Concussion

Syndrome Revealed by Functional Imaging by Barry Willer, PhD and John Leddy, MD 10 Structural Magnetic Resonance Imaging in Concussion By Paul Polak, MASc 14 Functional Imaging for Concussion Assessment and Research by David S. Wack, PhD 18 A Historical Perspective on Advanced Neuroimaging in Clinics and

Courts by Hal S. Wortzel, MD

publisher J. Charles Haynes, JD Editor in Chief Ronald C. Savage, EdD Editor, Legal Issues Frank Toral, Esq. Editor, Legislative Issues Susan L. Vaughn Editor, Literature Review Debra Braunling-McMorrow, PhD Editor, Technology Tina Trudel, PhD founding editor Donald G. Stein, PhD design and layout Nick Alexeev advertising sales Megan Bell

EDITORIAL ADVISORY BOARD Michael Collins, PhD Walter Harrell, PhD Chas Haynes, JD Cindy Ivanhoe, MD Ronald Savage, EdD Elisabeth Sherwin, PhD Donald Stein, PhD Sherrod Taylor, Esq. Tina Trudel, PhD Robert Voogt, PhD Mariusz Ziejewski, PhD

editorial inquiries Managing Editor Brain Injury Professional PO Box 131401 Houston, TX 77219-1401 Tel 713.526.6900 Website: www.nabis.org Email: contact@nabis.org

advertising inquiries 24 Imaging for TBI: Current and Future Prospects by Katherine H. Taber, PhD and Robin A. Hurley, md 28 Imaging for Brain Trauma: Questions to Be Answered By Jonathan M. Silver, MD

Megan Bell Brain Injury Professional HDI Publishers PO Box 131401 Houston, TX 77219-1401 Tel 713.526.6900 Email: mbell@hdipub.com

national office

North American Brain Injury Society PO Box 1804 Alexandria, VA 22313 Tel 703.960.6500 Fax 703.960.6603 Website: www.nabis.org Brain Injury Professional is a quarterly publication published jointly by the North American Brain Injury Society and HDI Publishers. © 2013 NABIS/HDI Publishers. All rights reserved. No part of this publication may be reproduced in whole or in part in any way without the written permission from the publisher. For reprint requests, please contact, Managing Editor, Brain Injury Professional, PO Box 131401, Houston, TX 77219-1400, Tel 713.526.6900, Fax 713.526.7787, e-mail mbell@hdipub.com

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editor in chief’s message “Now, as humans, we can identify galaxies light years away. We can study particles smaller than an atom, but we still haven’t unlocked the mystery of the three pounds of matter that sits between our ears.” —President Barack Obama announcing The BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) on April 2, 2013.

Ronald Savage, EdD

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Neuroimaging is the cornerstone to not only understanding the mysteries of the human brain, but also what happens to the brain when it is injured. Today, however, it is like playing a brain memory game trying to recall all the neuroimaging technologies that have been entering our medical-clinical world over the past two decades. Think about it: computed axial tomography (CT), diffuse optical imaging (DOI), event-related optical signal EOS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and still more to come. In this issue of BIP, Drs. Willer, Leddy and Silver help us to sift and sort through this maze of neuroimaging technology and provide us with a sense of what this all means in brain injury research and treatment. They have also provided NABIS Conference participants with a symposium on neuroimaging to coincide with this issue. Although still a relatively young field, neuroimaging has rapidly advanced over the years due to breakthroughs in technology and computational methods. Applications of neuroimaging techniques have likewise become farreaching. There is little doubt that in the future, neuroimaging will be a significant technology that will help guide our medical and clinical decision making. Newer methods, both structural imaging

and functional imaging, are continually being developed and refined to quantify damage on images and, hopefully, improve our predictive power. As such, imaging has become increasingly vital to the development of new therapies and may be used to measure patient response to various therapies. Imaging has and will continue to influence therapy and may improve outcomes for individuals with brain injuries, whether mild, moderate or severe. NABIS extends its appreciation to Drs. Willer, Leddy and Silver for providing readers and conference participants with much needed education in neuroimaging and its application to brain injury research and treatment. Finally, I would like to inform all members of NABIS that in support of the International Brain Injury Association’s Tenth World Congress on Brain Injury, the Society will not be holding its regular conferences next year. All NABIS members are encouraged to attend the World Congress that will be held March 19-22, 2014, in San Francisco. NABIS will be back with our regular meetings April 29 – May 2, 2015, at the beautiful Westin Riverwalk Hotel in San Antonio, Texas! Details as they become available will be posted on the NABIS website, www.nabis.org. Ronald Savage, EdD


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guest editors’ message

Jonathan Silver, MD Everyone interested in brain injury, either as a researcher, educator or clinician (and many families and people living with the effects of brain injury) share a profound interest in how the brain works and what happens when it is not working to capacity. The more we learn about brain function the more fascinating and complex it becomes. Imaging has added considerably to the process of evaluating and studying the brain. In the past, imaging was critical to providing much needed information about the structure of the brain and provided some guidance on specific deficits. Today, imaging has become increasingly powerful and reveals exquisite details about the structure and function of the brain, and therefore so much more about dysfunction. This issue of Brain Injury Professional (BIP) is devoted specifically to the topic of advanced neuroimaging. The authors of this issue of BIP will be providing much of this material in a preconference seminar at the North American Brain Injury Society (NABIS) conference in September, 2013. Our primary goal for the seminar and this

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Barry Willer, PhD and John Leddy, MD issue was to provide the reader with basic information about the methods used in imaging and several research and clinical questions that may be addressed through imaging. You can think of this issue of BIP as a brief written course on neuroimaging. The course begins with an introduction from Barry Willer and John Leddy. They published a paper on functional magnetic resonance imaging (fMRI) in the July/August 2013 issue of the Journal of Head Trauma Rehabilitation (JHTR) but took this occasion to elaborate on findings that were only touched upon in the scientific publication. They describe the fact that individuals suffering from mild TBI (mTBI) show hypermetabolic activity to accomplish simple tasks. This, they say, helps to explain the fatigue individuals with mTBI so often experience. In our course this provides a practical example of a direct correlation between imaging and clinical observation. Paul Polak and David Wack are young scientists that have specialized in neuroimaging. For our course they have been charged with the task of describing structur-

al and functional imaging. There are various methods for describing the structures of the brain and whether these structures should work or not. Paul Polak provides us with a wonderful primer on structural imaging that includes the intriguing Diffusion Tensor Imaging (DTI). David Wack does the same with functional imaging, describing both MRI approaches as well as Positron Emission Tomography (PET). The next component of the course examines the usefulness and application of advanced neuroimaging to the clinical setting and the courtroom. Hal Wortzel provides a first-rate historical perspective as he walks us through various examples of the application of advanced imaging in forensic situations. He concludes that there is need for healthy skepticism before we rush to the courtroom with findings from imaging studies. The same skepticism can be applied to clinical applications. Katherine Taber and Robin Hurley provide an important practical approach as to when and why neuroimaging might be used to answer clinical questions. Jonathan Silver provides the exclamation mark at the end of the course. While researchers have contributed significantly to our understanding of brain function through advanced neuroimaging, he urges caution in rushing to premature conclusions based on neuroimaging. He points out that imaging cannot replace careful examination by an experienced clinician. We hope that we see you in person at the NABIS conference and you are able to attend this preconference seminar. As guest editors, we want to thank our colleagues for their generosity and willingness to share their knowledge and wisdom on imaging, in the magazine and at the conference. Barry Willer, PhD John Leddy, MD Jonathan Silver, MD


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Hypermetabolic neural activity in people with post concussion syndrome revealed by functional imaging

by Barry Willer PhD John Leddy MD

Researchers do their best to describe their research in as complete a fashion as possible each time they publish in scientific journals. However, these journals, by their nature, place constraints on telling the ‘whole’ story when it comes to research studies. It is not that they wish to restrict the researcher; it is simply that there are page limitations and certain expectations that force the researcher to focus on the most “significant” results from a statistical point of view, sometimes excluding the most significant results for clinicians or patients. A prime example of this is a recent study we published where our aim was to evaluate metabolic activity in the brains of individuals with post concussion syndrome (PCS). In this study we used functional magnetic resonance imaging (fMRI) to describe the cerebral metabolism associated with a cognitive task performed by subjects with post concussion syndrome (PCS) versus subjects who were similar in age and athleticism but did not have PCS (Leddy et al. 2013). We used fMRI to provide a picture of the metabolic activity in the brain while subjects were completing a simple arithmetic task. We reported that there were differences between those who clearly had PCS and subjects who did not have an injury. Please note that we use a treadmill test to assess and diagnose PCS and in this study only included subjects who demonstrated exacerbation of symptoms during exercise (Leddy et al. 2011). Thus, we have a relatively homogeneous sample of individuals with PCS. Jonathan Silver’s article in this issue of BIP aptly points out the importance of homogeneity in populations under study. So in these individuals with PCS we found reduced metabolic activity in certain areas of the brain: the cerebellum, the thalamus and the posterior cingulate. This was an important finding because these areas of the brain are important junction boxes for neural activity and areas that are often the end points for inflammation. When these individuals with PCS had recovered these differences from the normal (uninjured) controls disappeared. The images of metabolic activity, however, provided more to the story than we were able to include in the publication. The following pictures of the brain activity for one subject illustrate one very important observation. When a person with PCS is asked to complete a task (in this case an arithmetic task) he/she uses much more of his/her brain than uninjured controls. The image on the right represents the subject completing the task. 8

BRAIN INJURY PROFESSIONAL

She is clearly focused on the task and the areas of the prefrontal cortex most associated with working memory for arithmetic are lit up and there is less activity in other parts of the brain. The image below was taken after recovery. The image on the right is the same subject while experiencing PCS. Her brain is lit up in many places not associated with the arithmetic task and less noticeably lit up in the areas of the brain associated with the task. The image on the left is essentially indistinguishable from the image of the healthy controls. Image 1 PCS Subject after recovery

PCS Subject while symptomatic

It is very interesting that this person completed the arithmetic task with the same degree of accuracy when suffering from PCS as when she was recovered. This was the same for all of the subjects. She was slightly slower at completing the task during the PCS period but only by a few milliseconds. However, as illustrated in the figures, when suffering from PCS she used much more brain activity to accomplish the task. We think this provides an explanation for the fatigue that people with PCS report when they carry out normal daily activities. Their brains are simply inefficient and use considerably more brainpower to accomplish what is a relatively simple task for the healthy controls. There are several other researchers that have used similar imaging techniques to study the brain activity in those with persistent concussion effects (Chen et al., 2008; Lovell et al., 2007). Much like us, they reported on the areas of the brain that were


less active but did not report on the hyperactivity we observed. Alain Ptito, one of the researchers doing similar work, was once presenting at the same conference we were so we asked him if he and his group observed the same phenomenon that we did; namely, hypermetabolic activity rather than focused activity. His answer: “absolutely”. However, as it turned out, they did not report the finding for the same reason we did not. We did not find a statistically significant finding. Every subject with PCS had this hypermetabolic activity. However, the pattern of superfluous activity was different for each subject. It was as if the brain was unsure what parts of the brain were necessary for the activity at hand and just fired randomly. Statistical tests look at groups of subjects and compare activity in different regions of the brain (defined as voxels, described below). Despite finding each subject showing hyperactivity the collective picture did not show hyperactivity consistently in the same voxels of the brain. Hyperactivity in one subject’s voxels counter-balanced the hyperactivity in another subject’s voxels and wiped out the effect. Thus a clearly observable finding was not a reportable finding. Functional imaging and other forms of advanced imaging are made possible, in part, because of the improvements in imaging but also because of the advancements made in statistical procedures that allow for evaluation of differences based on very large numbers of observations. Imaging produces microdata on very small areas of the brain called voxels. A voxel is a cube (about 3mm on each side) and houses about a million brain cells. There are approximately 130,000 voxels in a typical scan. The chance of false positives (seeing activity when there is none) is very high since there are so many voxels, but the statistical procedures account for multiple comparisons. Bottom line, our hyperactivity observation that was so obvi-

ous and so important clinically was not statistically significant. The other really important observation from our study is that some of the subjects were completely recovered by the time we conducted the second set of scans and those that were recovered had brain scans that were indistinguishable from the healthy control subjects. Although evaluating whether scans are similar is even more complicated than determining differences (from a statistical point of view) it did appear that recovery in terms of symptoms and physiology is matched by recovery in terms of brain metabolism.

About the Authors

John Leddy MD FACSM FACP is an Associate Professor of Clinical Orthopedics, Internal Medicine, and Rehabilitation Sciences at the University at Buffalo School of Medicine and Biomedical Sciences. He is the Medical Director of the University at Buffalo Concussion Management Clinic, which is the first center in the United States to use a standardized exercise treadmill test to establish recovery from concussion and to use controlled exercise in the rehabilitation of patients with prolonged concussion symptoms. He is published in the fields of orthopedics, physiology, nutrition, concussion and post-concussion syndrome. His primary research interest is the investigation of the basic mechanisms of the disturbance of whole body physiology seen in concussion and how to help to restore the physiology to normal and so help patients to recover and safely return to activity and sport. Barry Willer received his PhD in Psychology from York University (Canada) in 1975. Since this time he has been a Professor of the medical school of the State University of New York at Buffalo. His research interests have focused on psychological and social issues associated with traumatic brain injury. He authored the Community Integration Questionnaire, which is internationally recognized for assessment of participation. Dr. Willer was lead author of the first return to play guidelines after concussion adopted by the International Olympics Association. He currently heads a team of researchers examining emotional regulation following brain injury.

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Structural Magnetic Resonance Imaging in Concussion

By Paul Polak, MASc

Concussion and post-concussion syndrome (PCS) is currently a very active area of research for neurologists, sports medicine doctors, behavioral scientists and medical imaging specialists. PCS can lead to depression, irritability, cognitive decline, chronic headaches, dizziness, and aggressiveness. (McCrory et al. 2009) Moreover, the recent tragic outcomes for some professional athletes (i.e. former NFL linebacker Junior Seau, former NHL defenseman Wade Belak) have been linked to the concussions and sub-concussive blows they experienced in their careers. Typical clinical magnetic resonance imaging (MRI) is often insensitive to the symptoms of concussion and PCS, and thus there is a vital need for research to aid in the prognosis and treatment issues surrounding acute concussions. Some structural MRI techniques show promise in detection of concussion injuries, and these can be used to qualitatively or quantitatively assess the brain’s components – this can be palpable (quantities of white and grey matter tissue), or indirect (evaluation of myelin integrity in white matter). In MRI, we use the resonance of hydrogen atoms in a strong magnetic field and manipulate various pulses to create image contrast between tissue types, for instance between grey and white matter, or between healthy tissue and tumor. In a 2-dimenstional image such as on a flat-screen TV we refer to the smallest possible element as a pixel; however, MRI data is 3-dimensional and thus the smallest element is referred to as a volumetric pixel, or simply voxel. Despite the considerable interest in concussion research in the last few years, the mechanisms have been investigated for some time. A paper by Holbourn (Holbourn 1945) theorized that rotational forces in concussion events cause the various brain tissues to move at different relative speeds. It is believed that the acceleration/deceleration of these tissues can cause 10 BRAIN INJURY PROFESSIONAL

shearing forces on the axons. White matter and grey matter differ in their densities and have varying mechanical properties – white is in general stiffer then grey, but it also has more variability in its composition. (Van Dommelen et al. 2010) In a concussion event the denser tissues can slide over each other, putting strain on the axons which connect these tissues together. This stretching and straining can damage the myelin layer surrounding the axons, causing it to weaken or break. The term used to describe this myelin breakage is diffuse axonal injury (DAI) and it was first investigated in car accident victims by Strich, (Strich 1956) where it was observed that post-mortem brain tissue samples indicated widespread and non-focal degeneration of the white matter and loss of nerve fibers. Diffusion Tensor Imaging (DTI) is an advanced MRI technique that can be used to quantify water diffusion in tissue. The technique works by comparing a standard clinical T2-weighted MRI scan (referred to as the non-diffusion, or b=0 scan) with an identical one that has been prepared by a magnetic diffusion gradient in a particular direction. This diffusion scan indicates preferential movement of water in that direction by a loss of image intensity – the more the diffusion, the less the signal. By using at least 6, but often 15 or more diffusion directions, a very complete picture of diffusion in the brain can be determined. The DTI analysis determines at every voxel the 3 primary diffusion directions and their magnitudes are ranked such that λ1, λ2, and λ3 represent the order from most to least. The primary magnitude λ1 is also referred to as the axial diffusivity (AD), and the average of λ2 and λ3 is denoted as the radial diffusivity (RD). Because myelin restricts diffusion, healthy axons exhibit anisotropic diffusion whereby water is more likely to move along the axon (AD) than perpendicular to it across myelin (RD) (Figure 1). We assess the relative contribution from


Figure 1

Visualization of a DTI scan of a human brain

Depicted are reconstructed fiber tracts through the mid-sagittal plane. White box gives a zoomed view of one tract, with depicted axial diffusivity (AD) measurement along the tract, and radial diffusivity measurement perpendicular. The magnitude of AD would be much greater than RD for this tract and for any in healthy white matter tissue. Image is author’s own work based on work attributed to Thomas Schultz, and used under the Creative Commons AttributionShare Alike 2.5 (CCA-SA-2.5) Generic license.

these two measures by fractional anisotropy or simply FA. FA is a score from 0 to 1, where 0 indicates perfectly isotropic diffusion (like we might expect to find in cerebrospinal fluid) and 1 is perfectly anisotropic. These measures can be used to evaluate myelin integrity, since any damage to this membrane allows water diffusion across the axon, leading to increased radial diffusivity and decreased FA values. Since concussion has been linked to DAI, there has been interest in using DTI in MRI techniques in order to investigate axonal integrity, with varying results, (Mayer et al. 2010; Messé et al. 2012) although one paper found correlations between the number of damaged white matter structures and reduced performance on cognitive tests. (Niogi et al. 2008) These previous works often analyzed concussed patients on a group-wise basis by comparing a cohort of patients with a healthy group of matched controls. A recent technique analyzing subjects on an individual basis has determined that heterogeneous, localized regions of significantly different FA “potholes” are apparent in concussed patients and may linger for weeks or months after the concussion event. (M. L. Lipton et al. 2012) This type of analysis relies on comparing individual concussed subjects with a group of matched controls in order to find brain regions where the DTI FA values are significantly different from the control mean values. The desire to investigate DTI in patients on an individual basis stems from a very practical insight into concussion – since each method of injury for concussion subjects is unique, the damage they present will be unique. Moreover, if concussions result in DAI because of the shearing and stretching of fibers as brain matter moves and slides over other tissue, each patient could present a unique, spatially heterogeneous amount of DAI. Therefore it is quite possible that different concussed patients will thus display different spatially heterogeneous FA potholes, and as such any attempt to compare patients at a group-wise level would only “wash-out” any differences that would be apparent individually. Despite the differences that might be expected for these reasons,

Figure 2

Potholes analysis on a concussed patient

Potholes analysis on a concussed patient, with axial, coronal and sagittal views given from top to bottom. Right side of head indicated with R. Red-yellow areas indicate areas of low FA potholes and blue-light blur indicate regions of high FA values. Splenium of corpus callosum most obviously affected area.

concussed patients often present altered FA in similar regions in the brain such as in the corpus callosum. The reasons for this are related to the structure of fibers in the brain – the corpus BRAIN INJURY PROFESSIONAL

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callosum is the major “highway” through which the two hemispheres of the brain communicate, and thus it has the greatest densities of fibers running through it. Pothole analysis in one of our recent studies (Figure 2) confirms this region’s susceptibility to FA alterations, along with other regions such as the brainstem, anterior and superior corona radiata, internal and external capsules, and the thalamus. Although this methodology indicates significant decreases in FA, which would be in agreement with a theory of myelin damage, it also shows many areas of increased FA values. Recent research has postulated that this phenomenon may be due to axonal swelling post-injury which decreases RD in these voxels, but the actual explanation remains unknown. Longitudinal analysis of these potholes indicates that they do not necessarily resolve over time even as symptoms alleviate, but the brain’s adaptability and plasticity is a confounding component. More research into DTI, PCS and cognitive recovery needs to be conducted in order to draw conclusions. Magnetic resonance spectroscopy (MRS) is a technique used to measure hydrogen metabolites in the brain. These appear not as an image, but rather on a frequency spectrum, with the peaks indicating the concentrations of various molecules, such as Nacetylaspartate (NAA), choline, creatine, lipids, glutamate and glutamine. A recent study by Vognozzi (Vagnozzi et al. 2010) investigated MRS in the anterior corona radiata in 40 concussed athletes, where the authors investigated the ratios of NAA to creatine and choline concentrations. NAA is a particularly interesting metabolite, since it is usually considered to be a biomarker for neuronal integrity, while creatine and choline are useful since their concentrations do not change as a result of concussion. The papers’ findings concluded that despite each athlete reporting themselves symptom free 3-15 days post-injury, the MRS analyses indicated that the average athlete did not return to normal NAA to creatine or NAA to choline ratios until 30 days postinjury. The athletes were compared to an age and sex matched cohort of controls, and did not participate in their sports until the completion of the study. The result of future concussions on NAA levels for already concussed patients remains unknown. One quantitative technique used in neurological research is voxel-based morphometry (VBM) analysis, which is used to determine the volumes of specific tissues in the brain. First, a high-resolution MRI brain scan is obtained, after which the images are segmented into their 3 healthy types – cerebrospinal fluid appears darkest, white matter tissue is the brightest, and grey matter in between. By scanning the same patient over time, a longitudinal analysis can be derived indicating which tissues have changed in volume and by what amount. VBM analysis usually involves the intermediate step of registration, which means aligning the subsequent VBM scans to the initial before performing the volumetric analysis. Gale et al. found in 2005 grey matter atrophy in patients with a history of traumatic brain injury, and this atrophy was correlated with performance in a cognitive attention test. (Gale et al. 2005) Unfortunately, many neurological disorders and processes are correlated with atrophy, including multiple sclerosis, Alzheimer’s syndrome, dementia and even normal aging, making VBM analysis a sensitive, but non-specific, technique when dealing with traumatic brain injury. Susceptibility weighted imaging, or SWI, is an advanced MRI technique whose contrast is driven in part by a tissue’s magnetic properties, such as the paramagnetic properties of 12 BRAIN INJURY PROFESSIONAL

deoxygenated blood in veins compared to arterial blood. It is useful because of its ability to visualize hemorrhage accurately, especially in cases where microbleeds are not evident with more conventional MRI scans. For chronic cases SWI will be sensitive to the iron deposition that can occur around prior hemorrhages. While useful for revealing the extent of traumatic brain injuries, SWI is not necessarily specific enough in terms of diagnosis or prognosis, because the role of bleeding in treating concussion patients is not clear. SWI’s usefulness is often lessened in cases of minor traumatic brain injuries because these injuries may not be accompanied by hemorrhage. SWI is generally more effective at higher MRI magnetic field strengths (3 Tesla), but its role in acute concussion cases is not entirely clear. Structural imaging in concussion research examines the fundamental arrangement of brain tissue in order to detect differences in the concussed patients compared to their baseline normal state. Symptomatic concussion patients often show no structural abnormalities in typical clinical MRI, and thus there is a need for advanced imaging techniques. Concussion events are believed to cause DAI, and while DTI, MRS, SWI and atrophy measurements have all been used in concussion research, DTI is currently receiving the most attention due to its ability to measure axonal and myelin integrity. Research into concussion and PCS is ongoing, and structural MRI is expected to be at the forefront of new methods and analyses into the prognosis of patients. References

Van Dommelen J. a W., Van der Sande T. P. J., et al., Mechanical properties of brain tissue by indentation: interregional variation. Journal of the mechanical behavior of biomedical materials, 3(2): 158–66, 2010. Gale S. D., Baxter L., Roundy N. and Johnson S. C., Traumatic brain injury and grey matter concentration: a preliminary voxel based morphometry study. Journal of neurology, neurosurgery, and psychiatry, 76(7): 984–8, 2005. Holbourn A., The mechanics of brain injuries. British medical bulletin, 1945. Lipton M. L., Kim N., et al., Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: intersubject variation, change over time and bidirectional changes in anisotropy. Brain imaging and behavior, 6(2): 329–42, 2012. Mayer a R., Ling J., Mannell M. V, et al., A prospective diffusion tensor imaging study in mild traumatic brain injury. Neurology, 74(8): 643–50, 2010. McCrory P., Meeuwisse W., et al., Consensus statement on concussion in sport - the Third International Conference on Concussion in Sport held in Zurich, November 2008. Clinical journal of sport medicine, 19(3): 185–200, 2009. Messé A., Caplain S., et al., Structural integrity and postconcussion syndrome in mild traumatic brain injury patients. 283–292, 2012. Niogi S. N., Mukherjee P., et al., Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR. American journal of neuroradiology, 29(5): 967–73, 2008. Strich S. J., Diffuse degeneration of the cerebral white matter in severe dementia following head injury. Journal of neurology, neurosurgery, and psychiatry, 19(3): 163–85, 1956. Vagnozzi R., Signoretti S., et al., Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients. Brain: a journal of neurology, 133(11): 3232–42, 2010.

About the Author

Paul Polak, M.A.Sc is a MRI physicist at the Buffalo Neuroimaging Analysis Center. In that role he designs and develops novel pulse sequences, image reconstruction techniques and analysis software towards investigating neurological disorders. His graduate work in 2008 focused on designing an ultra-fast MRI pulse sequence which utilized pseudo-random trajectories. In 2009 he served at the Sunnybrook Research Center in Toronto, ON with a team investigating minimally-invasive, MR-guided focused ultrasound therapy for prostate cancer, and was instrumental in the first successful human trial. He has also worked for several years as a software consultant with experience across a wide variety of languages and platforms. He has a keen interest in examining advanced imaging techniques in sports-related concussions.


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Functional imaging for concussion assessment and research by David S. Wack, PhD

We use the term functional imaging to separate the purpose of the performed medical imaging from that of structural. With functional imaging, we are concerned with physiological values such as blood flow or metabolism. The physiologic values are often combined with structural images to give someone examining the image structural landmarks to localize and interpret the image. Functional imaging can be carried out with most of the major imaging modalities. Within Magnetic Resonance Imaging (MRI), functional MRI (fMRI) has been used for tens of thousands of studies to assign neural correlates with particular cognitive tasks. For instance, this could be to localize which region of the brain is responsible for listening to a tone, or focusing on an object. This notion is carried much further to include comparisons of how different groups might perform different tasks. It is also extended to imaging where the patient performs no task at all. In this paradigm, several hundred scans (each scan lasting only a couple of seconds) are used for an analysis to determine which regions of the brain are correlated with one another, and gives the researcher or clinician a network view of the brain. An underlying simplistic assumption of functional brain imaging is that the brain doesn’t have reserve storage. That is if there is an increase need in oxygen, then that need is met through an increase in blood flow to that region. A perfusion study can be performed with either MRI or Computed Tomography (CT) and typically generates at least four different physiologic parameters of interests. These parameters are calculated from an analysis of an injected tracer such as Iodine if using CT, or Gadolinium if using MRI. By examining the concentration of tracer at each location of the brain, for many time points, we can form a “Time Activity Curve” (TAC) for each volume element of a scan (voxel). A simple and very sensitive parameter that is calculated for each TAC is the Time To Peak (TTP), which is simply the time that it takes the injected tracer to reach the peak activity at each voxel location. Locations where there is a noticeable delay in perfusion may indicate that there is an underlying problem in that area. Other parameters that can be calculated include Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV), and finally Mean Transit Time (MTT), which is the mean time for an element of the injected 14 BRAIN INJURY PROFESSIONAL

tracer to pass through the tissue region. A difficulty with Gadolinium and Iodine tracers is that in most cases neither crosses the Blood Brain Barrier (BBB), which is to say that the tracers are not taken up into the neural cells. Hence these tracers only occupy a small percentage of any voxel, typically between 2 to 8 percent. In contrast, Xenon which can be used for inhalation with CT imaging does cross the BBB. By only typically occupying a small percentage of volume, the Gadolinium and Iodine tracers have a disadvantage for the effective signal of the tracer. An advantage however is that it is readily apparent as an image hyper-intensity when either tracer does cross the BBB. This is the situation with what are commonly referred to as “Gad enhancing lesions”. Likewise, either tracer still remaining or increasing at a location after a minute or more can indicate a bleed. Positron Emission Tomography (PET) is somewhat similar to perfusion MR or a CT study in that PET always requires an injected tracer. However, PET is fundamentally different because the signal that is measured with PET originates from the tracer. PET can use a variety of radio-isotopes, which typically have halflives ranging from a couple of minutes to a couple of hours. That is, what can be measured from an injected tracer decays exponentially with time. The radio-tracers are created using a cyclotron. Hence, especially for shorter half-life tracers, the cyclotron typically needs to be close to the scanner. Because of the complexity and man power needed in creating the isotope, PET is typically a “during normal business hours” imaging method. In the acute setting a CT scanner may be used to assess brain injury, if the patient meets selection criteria based on factors including loss of consciousness, amnesia, vomiting, and Glasgow Coma Scale. A CT scan can be performed with no worry of metal within the patient’s body such as a pacemaker, or recently placed screws etc., that could prohibit an MRI in some cases. If a tracer is used with CT, such as Iodine, this is readily available “off the shelf ”, as opposed to radioactive tracers used for PET. Furthermore, a CT scan is very fast, and the majority of the time is spent simply getting the patient positioned on the gantry. A high resolution structural image can then be acquired in a few seconds. If Iodine or another tracer is used, the scanning


acquisition typically lasts 1 minute, which is more than enough time for the tracer to pass through the brain in most cases. The TAC of the tracer uptake is used to determine the TTP, CBF, CBV, and MTT parameters. CBV is essentially the fraction of the tissue voxel that is occupied by the blood, and typically has the best noise characteristics of the parameters. Having a measure of the tracer from an artery allows absolute or quantitative values (rather than relative values) of CBV and CBF to be calculated. A bleed can be detected by an accumulation of tracer after a period of time, and can also be seen through subtle change in image intensity on an unenhanced (non-contrast) CT. If a bleed is detected, the patient may not have a concussion, but is rather in a more serious condition. An advantage of using MRI imaging with Gadolinium as a tracer to determine CBF and CBV is that radiation exposure is not a concern. MRI may therefore be ordered in the days following a concussion by the patient’s physician. There are methods that use MRI that are functional without using a tracer. Blood Oxygen Level-Dependent (BOLD) fMRI is able to detect subtle changes in the oxygenation level of the blood. The underlying principle is that in response to performing a given cognitive task (that can be performed in the scanner), more oxygen is required in regions of the brain performing the task. This is accomplished naturally by the brain, resulting in an increase in the blood flow and a decrease in the relative amount of deoxyhemoglobin and the decrease in the magnetic susceptibility of tissue at the imaged location, this in turn results in an increase the MRI signal at the corresponding voxel. Arterial Spin Labeling is another MRI method which essentially tags the blood with a “spin” at one time, and examines the percentage of tagged blood that remains after a small time. Chen et al. found increases in BOLD activation for athletes with concussion vs. controls in the dorsolateral prefontal cortex.1 We demonstrated possible neural differences between recovery methods.2 As care of a patient moves to the post-concussion stage, modalities such as PET and SPECT, which is another nuclear medicine modality, are often considered. Because there are a variety of tracers available for use, PET or SPECT can measure biological function in a variety of ways. The most common tracer used with PET is Fluorodeoxyglucose F18 (FDG). FDG is well known because it is commonly used for the diagnosis and staging of cancer, since tumors have a high metabolic activity. FDG is readily taken into neural cells and because of the underlying kinetics remains for a relatively long period of time before exiting. FDG imaging of the brain can reveal regions that have become relatively hyper or hypo metabolic, and reveal an underlying issue. An advantage of F18 based compounds used as tracers is that the half-life of ~110 minutes allows a business model which allows the transport of the tracer to different nearby cities. Bergsneider et al.3, followed three phases of concussion recovery using FDG: initial hyperglycolysis, followed by decreased activity which resolves about 1 month after injury, followed by a return to normal. However, they found poor correlation between disability ratings and scan activity. Carbon 11 based PET compounds are also commonly used for imaging research, for example Fallypride and Raclopride can be used for the assessment of dopamine uptake. These tracers may be especially useful for assessing attention4, which has been known to be problematic with patients recovering from concussion. Pittsburgh Compound B is yet another common PET tracer, which has been used extensively for detection of

increased amyloid deposition in Alzheimer’s patients. Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that has been closely associated with boxing as so called “punch drunk”. CTE has been found in players from several contact sports including football and hockey, and soldiers exposed to concussive injuries. Sufferers of CTE have brain atrophy and enlargement of ventricles, both of which can be indicative of an underlying issue, not specific to CTE. CTE is associated with tau proteins.5 In recent work using PET imaging with tracer FDDNP, which binds to tau and beta amyloid, Small et al.6 found significant uptake in some of the five former NFL players that they scanned. They argue that the uptake is likely due to tau as opposed to amyloid based on the pattern of uptake. Zhang et al. have performed preclinical in vivo studies with [18F]-T808 which targets tau rather than Amyloid aggregates7.

Conclusion

The premise behind functional imaging is that it is not enough to map out the underlying anatomy of a patient. Rather, we are acutely interested in the underlying physiology of the imaged tissue. There are multiple physiologic measures that we may be interested in such as blood flow, blood volume, metabolic rates of glucose, uptake values, and binding potentials of various compounds. There are many corresponding tracers which can be injected that enable the quantitation of activity of a tracer over time. However, there are also non-tracer methods such as ASL or BOLD fMRI. In total, each method offers a specialized glimpse of the underlying pathology that would otherwise be missing if only a structural MRI or CT was used. About The Author

Dr. David Wack is a Research Associate Professor in the Department of Nuclear Medicine at SUNY at Buffalo. Dr. Wack’s work specializes on noise reduction, segmentation, and parameter estimation algorithms for medical imaging. He has performed extensive work with MRI, PET, CT, and EEG imaging, and is currently focused on applications for improving imaging for concussion, stroke, and functional auditory imaging. Dr. Wack has published and presented algorithms for pattern recognition, advanced methods of smoothing, and non-parametric de-noising of medical imaging time series. These methods have been utilized to improve physiological parametric images such has blood flow, blood volume, and binding potential. He has co-authored over 30 peer-reviewed research articles.

References 1.

Chen J-K, Johnston KM, Petrides M, Ptito A. Recovery from mild head injury in sports: evidence from serial functional magnetic resonance imaging studies in male athletes. Clinical Journal of Sport Medicine. 2008;18(3):241-247.

2.

Leddy JJ, Cox JL, Baker JG, et al. Exercise Treatment for Postconcussion Syndrome: A Pilot Study of Changes in Functional Magnetic Resonance Imaging Activation, Physiology, and Symptoms. The Journal of head trauma rehabilitation. 2012.

3.

Bergsneider M, Hovda DA, McArthur DL, et al. Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability. The Journal of head trauma rehabilitation. 2001;16(2):135-148.

4.

Badgaiyan RD, Wack D. Evidence of dopaminergic processing of executive inhibition. PloS one. 2011;6(12):e28075.

5.

McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy following repetitive head injury. Journal of neuropathology and experimental neurology. 2009;68(7):709.

6.

Small GW, Kepe V, Siddarth P, et al. PET Scanning of Brain Tau in Retired National Football League Players: Preliminary Findings. The American Journal of Geriatric Psychiatry. 2013;21(2):138-144.

7.

Zhang W, Arteaga J, Cashion DK, et al. A highly selective and specific PET tracer for imaging of tau pathologies. Journal of Alzheimer’s Disease. 2012;31(3):601-612. BRAIN INJURY PROFESSIONAL

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conferences 2013

September 27 – 6th Annual Conference of the Brain Injury Professionals Partnership, Denver, Colorado. For more information, visit www.du.edu/braininjury October 3 – Changing the Game Traumatic Brain Injury Conference, Jacksonville, Florida. For more information, visit toralfamilyfoundation.org 4 – Changing the Game Traumatic Brain Injury Conference, Jacksonville, Florida. For more information, visit toralfamilyfoundation.org . 7 -10 – National Association of State Head Injury Administrators Annual Conference, Dearborn, Michigan. For more information, visit nashia.org

19-22 – 27th Annual Conference on Legal Issues in Brain Injury, San Francisco, CA. For more information, visit www.nabis.org . April 16 -17 – Traumatic Brain Injury Conference, Washington, DC. For more information, visit www.tbiconference.com May 1 -2 – Rehabilitation of the Adult and Child with Traumatic Brain Injury: Practical Solutions to Real World Problems, Williamsburg, VA. For more information, visit www.tbiconferences.org 16-17 – Brain Injury Rehabilitation Conference, San Diego, California. For more information, visit www.scripps.org/events/brain-injuryrehabilitation-conference-may-16-2014

November 12- 16 – ACRM Annual Conference, Orlando, Florida. For more information, visit www.acrm.org/meetings/2013-annual-conference

April 29-2 – NABIS 12th Annual Conference on Brain Injury, San Antonio, Texas. For more information, visit www.nabis.org

2014

march 19-22 – IBIA Tenth World Congress on Brain Injury, San Francisco, CA. For more information, visit www.internationalbrain.org

Restore-Ragland

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29-2 – NABIS 28th Annual Conference on Legal Issues in Brain Injury, San Antonio, Texas. For more information, visit www.nabis.org

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UNIVERSITY OF NORTH FLORIDA JACKSONVILLE, FLORIDA

10.4.13

STATE WIDE TBI CONFERENCE

The Toral Family Foundation (TFF) in partnership with UF Health will host the “TBI: Changing the Game Conference” — an event to educate, inspire and connect medical professionals on the topic of Traumatic Brain Injuries (TBI) and it’s relevancy to all practicing clinicians. KEYNOTE SPEAKER Sanjay Gupta, MD

Cheif Medical Correspondant, CNN

Toral Family Foundation

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A Historical Perspective on Advanced Neuroimaging in Clinics and Courts by Hal S. Wortzel, MD

The aphorism that history repeats itself often holds true. This is readily apparent in the world of science and medicine, where the latest and greatest discoveries and/or technologies may be received with premature enthusiasm before the establishment of a sufficient or credible scientific basis, eventually yielding disappointment when initial promises go unrealized. Illness often breeds desperation, making patients and individuals with various forms of medical and/or neuropsychiatric illness especially susceptible to the promises that occasionally accompany efforts to commercialize new technologies. Litigation, which entails an adversarial environment, and is driven largely by the question of compensation, can lead to early transgressions and/or controversies regarding the interpretation and use of such technologies. Hence, medicolegal experts serve an important role in preserving the scientific integrity of emerging technologies, and neuroimaging is no exception (Wortzel, Kraus et al. 2011). Although it often seems that the controversies surrounding neuroimaging in courts of law is a new phenomenon the problem is actually a historically well-established one. History offers up some rather illustrative and dramatic examples of neuroimaging and neurodiagnostic techniques being deployed in a manner that have not withstood the test of time. While many Americans know the Jack Ruby shot John F. Kennedy’s assassin, far fewer know that he claimed to have done so during a seizure, and that controversy surrounding the interpretation of a “rhythmic temporal theta burst” pattern on electroencephalography (EEG) was at issue in a trial occurring nearly half a century ago (Gutmann, 2007). A defense expert, based upon the EEG evidence, and despite a host of clinical and historical factors suggesting otherwise, offered testimony that Ruby was unable to distinguish right from wrong 18 BRAIN INJURY PROFESSIONAL

at the time of his offense. The guilty verdict handed down by the jury was later overturned on appeal, and Jack Ruby died of cancer while awaiting a new trial. Importantly, the psychomotor variant of epilepsy alleged at Ruby’s trial is now referred to as rhythmic temporal theta bursts of drowsiness and “as a type of epilepsy, has become a historical footnote” (Gutmann, 2007). While violent criminal acts are seldomly the result of seizures, there remain genuine instances of ictal and peri-ictal behaviors resulting in otherwise criminal behaviors, and such defendants should have legitimate affirmative defense opportunities available to them. Unfortunately, abuses of the epilepsy defense and scientifically inappropriate introduction of EEG evidence have arguably yielded an environment of skepticism that makes even the most legitimate of claims difficult to successfully litigate (Wortzel, Strom, Anderson, Maa, & Spitz, 2012). There are potential consequences to “crying wolf,” and it is thus appropriate to reflect upon the potential long-term ramifications of contemporary medicolegal uses of neuroimaging, and what the implications might be for future criminal defendants and/or plaintiffs with real illness/injury. Another striking example from history is the case of John Hinckley, who was found to be legally insane when he attempted to assassinate President Ronald Reagan. The case and its outcome were quite controversial, and disconcertion surrounding this verdict is frequently cited as inducing widespread change in legal definitions around the nation, in particular the abandonment of volitional prongs to legal criteria for insanity. How much did neuroimaging evidence influence the jury offering this verdict, a verdict which arguably had far-reaching societal consequences, resetting the bar for legal insanity at a higher level? While we do not know the answer to that question, we do know this: claims/


testimony that Hinckley’s CAT scan of the brain evidenced his diagnosis of schizophrenia have not withstood the test of time, and thirty years later we remain without a diagnostic imaging study for that neuropsychiatric disorder. The next generation of neuroimaging/neurodiagnostic controversy has arguably surrounded the clinical and medicolegal commercialization of quantitative electroencephalography (qEEG)(Arciniegas, 2011; Coburn, Lauterbach, Boutros et al. 2006) and single photon emitted computed tomography(SPECT) (Adinoff & Devous, 2010; Wortzel, Filley et al. 2008). Both of these technologies feature considerable merits, and each has been used effectively in numerous areas of research to advance our understanding of the human brain and various forms of neuropsychiatric illness. Both have also been heavily commercialized, and purported to have diagnostic ability/accuracy that critics are quick to refute. The Committee on Research of the American Neuropsychiatric Association identified that: “A pivotal question remains unanswered concerning the actual clinical utility of qEEG and related electrophysiological methods: are the techniques sufficiently sensitive and specific to answer practical clinical questions about individual patients suffering from recognized psychiatric disorders?”(Coburn, et al., 2006) The committee also recognized real substance regarding fears that unsophisticated practitioners might use the technology to substitute for (instead of augment) clinical diagnosis. They note a history involving widespread commercialization, including vendors aggressively marketing qEEG as virtually a standalone diagnostic test. Despite the number of published investigations espousing the merits of qEEG, the committee identified “several broad problems” regarding methodology that reflected “the difficulty of translating the methodological freedom of research into the uniform standardization necessary for clinical application.” Readers are referred to the committee’s report for additional details regarding methodological concerns/limitations; there are many (Coburn, et al., 2006). Notably, Arciniegas (Arciniegas, 2011) offers a detailed review of the literature directly addressing the issue of EEG and qEEG as applied to persons with mild traumatic brain injury (mTBI); “qEEG discriminant functions are of debatable value in the clinical or forensic diagnostic evaluation of persons with mTBI. Having said this, it is important for clinicians and forensic practitioners to remain mindful that this is a matter of controversy. Clinicians involved in the care and medicolegal evaluation of individuals with mild TBI are advised to consider all arguments regarding this technology before deciding on the advisability and value of using qEEG” (Arciniegas, 2011). A remarkably similar history of commercialization and controversy surrounds SPECT imaging as applied to neuropsychiatric disorders (Adinoff & Devous, 2010; Wortzel, et al., 2008). That controversy is well illustrated in an exchange of letters(Adinoff & Devous, 2010; Amen, 2010) that featured in the American Journal of Psychiatry. Adinoff and Devous offer a compelling argument that early misapplications of neuroimaging, if left unchallenged, may poison the waters such that when the technology becomes appropriate for meaningful clinical application its history of misapplication erects untenable barriers to acceptance in clinical and medicolegal venues. This prediction rings familiar, being not unlike the previously described unfortunate history surrounding EEG and epilepsy in criminal courts. My own early experience with SPECT, dating back to

fellowship days in neuropsychiatry, featured a couple troubling clinical encounters involving SEPCT being misused to substantiate otherwise untenable diagnostic formulations, and in association with active litigation. Such experiences prompted a review and analysis of the subject of SPECT as applied to mild TBI by the Neurobehavioral Disorders Program at the University of Colorado (Wortzel, et al., 2008) and subsequent exposures continue to reveal that this technology is not infrequently deployed to “prove” brain injury in isolation of or in contrast to clinical presentations and history, often times in association with interpretive reports that fail to live up to existing ethical reporting requirements (Society of Nuclear Medicine, 2002; Society of Nuclear Medicine Brain Imaging Council, 1996). This is not to say that SPECT is without its merits or potential clinical utilities (there are typically legitimate arguments to be had on both sides of most controversies), but it is reflective of an irrefutable historical trend: neuroimaging technologies carry the potential for misapplication, commercial and/or medicolegal. Technology’s advances has brought about even more modern neuroimaging techniques, some yielding truly spectacular images of the brain that are unlike anything previously available. Should the cutting-edge nature of these techniques or the stunning quality of associated images cause us to forget our history lessons? Newness and youth are fleeting conditions, and EEG once enjoyed that same status much as function MRI (fMRI), Positron Emission Tomography (PET), or Diffusion Tensor Imaging (DTI) do today. With this new generation of neuroimaging comes the next wave of controversy. As with generations past, there are worthwhile arguments proffered by both camps. But history and persisting limitations (see points of caution offered by Dr. Jonathan Silver in his article in this current issue) warrant (if not mandate) healthy skepticism regarding the ability of these latest modalities to differentiate between various neuropsychiatric conditions, or even to discern “abnormal” from what is an extraordinary broad range of inter-individual differences when it comes to brain structure and metabolism (Mayberg, 1996; Reeves, Mills, Billick, & Brodie, 2003; Silver, 2012; Wortzel, et al., 2008; Wortzel, et al., 2011). It remains prudent to recognize that these new neuroimaging techniques carry the potential for misapplication in medicolegal settings, with perhaps previously unrealized influential power predicated upon eye-catching technology and images. In light of the existing controversies surrounding the use of various forms of advanced neuroimaging, especially in medicolegal settings typically involving single subject applications, guidelines that simultaneously facilitate legitimate uses while minimizing the risk and/or impact of misuses are needed. A tremendous void has recently been filled by a multidisciplinary consensus conference regarding the ethical use of neuroimaging in medical testimony held on December 7 and 8, 2012 at Emory University. The report (Meltzer, Sze, Rommelfanger et al. 2013 in press) describes the process involving an interactive forum and a highly select group of experts including: neuroradiologists, neurologists, forensic psychiatrists, neuropsychologists, neuroscientists, legal scholars, imaging statisticians, judges, practicing attorneys, and neuroethicists. While the entire report should be required reading for all those who encounter neuroimaging in medicolegal contexts, a few particularly salient aspects warrant mention herein. The BRAIN INJURY PROFESSIONAL

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report explicitly notes that advanced imaging techniques (fMRI, DTI, PET, and SPECT) are used “only in a few clinical settings” wherein sensitivity and specificity have been established. “Further, the applicability of normative imaging databases (typically comprising young, healthy subjects) in courtroom testimony is questionable. We also note that the use of normative imaging databases for comparisons to individual subjects for the purpose of expert witness testimony may constitute an inappropriate use of materials collected from research subjects” (Meltzer, et al., 2013). This latter point warrants some additional comment. Normative databases are built from data collected from individual participants. Conference attendees expressed concern surrounding the likelihood that the consent process surrounding such participation includes notice that the normative database will be used for purposes other than research, including potentially medicolegal applications. Furthermore, participants are likely unaware that the normative database, including their own individual data, may be sought from opposing parties in legal contests to assess the fidelity of analyses and interpretations offered. Participation for many reflects a beneficent effort to contribute to the advancement of science with the understanding that their own data will not be shared. The decision to participate, and/or what constitutes appropriate compensation, is potentially radically altered if/when normative databases become part of a lucrative clinical and/or medicolegal neuroimaging practice, and otherwise guarded individual data is disclosed in medicolegal proceedings. Absent a consent process that addresses these issues, the application of normative databases obtained for research purposes to medicolegal endeavors raises serious ethical concerns. The report/conference explores a few select cases “that were exemplary of use and abuse of neuroradiological data in the courtroom,” and brain trauma was among them. In particular, the controversy and potential pitfalls of DTI in this context are highlighted: This technique promises to offer unique insights into the natural history of brain injury and potentially inform therapeutic approaches. Yet the manner in which DTI data are acquired produces findings that not only lack specificity, but also continue to be highly variable across institutions and among researchers. The American Society for Functional Neuroradiology (ASFNR) has developed general guidelines for the acquisition and postprocessing of DTI data. But the rapidity of evolution of this technique has contributed to the challenge of achieving true standardization. At present, the ASFNR guidelines include a suggested disclaimer in clinical reports of DTI and notes that “it is critical that physicians basing clinical decisions on DTI be familiar with the limitations and potential pitfalls inherent to the technique”. Furthermore, the neuroradiology community has not arrived at a consensus view of the value of DTI in (particularly mild) head trauma. Non-specific patterns or findings obtained with DTI prohibit the confirmation or diagnosis of mild TBI with reliability. If DTI or other non-specific imaging findings are introduced into legal evidence, the expert should offer alternative explanations for the findings, including technical factors and normal variation (Meltzer, et al., 2013). The identification of the particular subject of DTI in TBI litigation for exposition in this report reflects the degree of controversy and concern surrounding this practice, and communal 22 BRAIN INJURY PROFESSIONAL

concern that transgressions are occurring. Notably, the report’s statement regarding the lack of consensus regarding DTI’s utility in cases of mild TBI suggests that general acceptance has yet to be achieved, a statement that is not without precedent or importance for considering the evidentiary appropriateness of DTI for mild TBI litigation (Wortzel et al., 2011). In an effort to facilitate appropriate medicolegal applications of neuroimaging while mitigating the potential for abuse, the report offers proposed standards that “may both serve to guide subspecialty societies like the American Society of Neuroradiology and inform the legal community.” The proposed standards include (Meltzer, et al., 2013): 1. Experts should present all relevant facts available in their testimony, ensure truthfulness and balance, and consider opposing points of view 2. Experts should specify known deviations from standard practice 3. Experts should have substantive knowledge and experience in the area in which they are testifying 4. Experts should use standard terminology and describe standardization methods and the cohort characteristic from which claims are determined, where applicable 5. Nonvalidated findings that are used to inform clinical pathology should be approached with great caution 6. Recognized appropriateness guidelines should be used to assess whether the imaging technique used is appropriate for the particular question 7. Experts should avoid drawing conclusions about specific behaviors based on the imaging data alone 8. Experts should be willing to submit their testimony for peer review 9. Experts should be prepared to provide a description of the nature of the neuroimages (e.g., representational/statistical maps when derived from computational postprocessing of several images) and how they were acquired 10. Raw images and raw data should be made available for replication if requested 11. Experts should be able to explain the reasoning behind their conclusions 12. False positive rates should be known and considered if the expert’s testimony includes quantitative imaging 13. Experts should be prepared to discuss limitations of the technology and provide both confirming research as well as disconfirming studies The importance of these standards is difficult to overstate. While somewhat similar guidelines have been published previously (largely for functional imaging techniques) (Society of Nuclear Medicine, 2002; Society of Nuclear Medicine Brain Imaging Council, 1996), the extent to which such standards have been embraced by those offering such testimony, or enforced by evidentiary gatekeepers, has been rather disappointing. Fortunately, the imminent publication of these new guidelines (representing consensus from truly multi-disciplinary proceedings) represents a renewed opportunity for medical and legal professions to meaningfully adopt and impose such guiding principles. These standards serve to protect the integrity of both medical science and legal proceedings, and thus ought to be embraced by all who aspire towards virtuous medicolegal practice.


About The Author

Dr. Wortzel graduated from Amherst College majoring in Biology in 1996 and then went on to medical school at NYU, graduating AOA in 2001. He completed his training in general psychiatry at the University of Colorado in 2005, serving as Chief Resident for the University’s Outpatient and Consultation-Liaison services. Following residency, Dr. Wortzel completed the University of Colorado’s Fellowship in Forensic Psychiatry. He then went on to complete a two year combined fellowship integrating the University’s Behavioral Neurology & Neuropsychiatry Fellowship with the VA’s MIRECC Fellowship in Advanced Psychiatry, emphasizing research in suicidology. He now brings his combined training and skills as a forensic neuropsychiatrist to the Denver VA’s VISN 19 MIRECC, where he serves as director of Neuropsychiatric Consultation Services and the MIRECC Psychiatric Fellowship, and as the University of Colorado’s Department of Psychiatry, where he serves as the Michael K. Cooper Professor of Neurocognitive Disease, Director of the Neuropsychiatry Service, and as faculty for the Division of Forensic Psychiatry. Current areas of clinical and academic focus include aggression and suicide in the context of PTSD and TBI, incarcerated veterans, and the application of emerging neuroscientific tools to the legal arena.

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References

Adinoff, B., & Devous , M. (2010). Scientifically unfounded claims in diagnosing and treating patients. Am J Psychiatry, 167(5), 598. Amen, D. (2010). Brain SPECT imaging in clinical practice. Am J Psychiatry, 167(9), 1125; author reply 1125-1126. Arciniegas, D. B. (2011). Clinical electrophysiologic assessments and mild traumatic brain injury: state-of-the-science and implications for clinical practice. Int J Psychophysiol, 82(1), 41-52. Coburn, K. L., Lauterbach, E. C., Boutros, N. N., Black, K. J., Arciniegas, D. B., & Coffey, C. E. (2006). The value of quantitative electroencephalography in clinical psychiatry: a report by the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci, 18(4), 460-500. Gutmann, L. (2007). Jack Ruby. Neurology, 68(9), 707-708. Mayberg, H. S. (1996). Medical-Legal Inferences From Functional Neuroimaging Evidence. Semin Clin Neuropsychiatry, 1(3), 195-201 Meltzer, C. C., Sze, G., Rommelfanger, K. S., Kinlaw, K., Banja, J., Wolpe, P. R., (2013). Guidelines for the Ethical Use of Neuroimages in Medical Testimony: Report of a Multi- disciplinary Consensus Conference. Americal Journal of Neuroradiology (in press). Reeves, D., Mills, M. J., Billick, S. B., & Brodie, J. D. (2003). Limitations of brain imaging in forensic psychiatry. J Am Acad Psychiatry Law, 31(1), 89-96. Silver, J. M. (2012). Diffusion tensor imaging and mild traumatic brain injury in soldiers: abnormal findings, uncertain implications. Am J Psychiatry, 169(12), 1230-1232. Society of Nuclear Medicine: Society of Nuclear Medicine Procedure Guideline for Brain Perfusion Single Photon Emission Computed Tomagraphy (SPECT) Using Tc-99m Radiopharmaceuticals. Society of Nuclear Medicine Procedures Guidelines Manual June 1999. Reston VA: SNM, 2002, pp 113–18. Society of Nuclear Medicine Brain Imaging Council: Ethical clincial practice of functional brain imaging (1996). J Nucl Med 37, 1256 –9. Wortzel, H. S., Filley, C. M., Anderson, C. A., Oster, T., Arciniegas, D. B. (2008). Forensic applications of cerebral single photon emission computed tomography in mild traumatic brain injury. J Am Acad Psychiatry Law, 36(3), 310-322. Wortzel, H. S., Kraus, M. F., Filley, C. M., Anderson, C. A., & Arciniegas, D. B. (2011). Diffusion tensor imaging in mild traumatic brain injury litigation. J Am Acad Psychiatry Law, 39(4), 511-523. Wortzel, H. S., Strom, L. A., Anderson, A. C., Maa, E. H., & Spitz, M. (2012). Disrobing associated with epileptic seizures and forensic implications. J Forensic Sci, 57(2), 550- 552.

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Imaging for TBI: Current and Future Prospects by Katherine H. Taber, PhD and Robin A. Hurley, MD

Structural and functional imaging are the two very different approaches to brain imaging currently available. Structural brain imaging provides information about physical aspects of the brain. Structural imaging techniques are not affected by neuronal activity. Computed tomography (CT) and magnetic resonance imaging (MRI) are the standard clinical methods. Many other structural brain imaging techniques are under development for clinical use. Diffusion-based approaches, such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI), presently show the most promise for imaging of TBI (Bigler & Maxwell, 2012; Shenton et al., 2012; Taber & Hurley, 2013). Functional brain imaging provides information related to neuronal activity. Most functional brain imaging techniques utilize indirect measures of neuronal activity, such as blood flow, metabolism, or oxygen extraction. Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate (rCMR) are the most commonly used measures. Although there is a relatively close coupling between neuronal activity, rCBF and rCMR, the activity-induced increase in blood flow is usually more than what is required to meet the increased need for oxygen and glucose. If acquired under resting conditions, both rCMR and rCBF provide a way to assess the baseline functional state of brain areas. If acquired during performance of a mental or physical task, they provide a way to assess specific neuronal pathways or structures with performance-related alterations in neuronal activity. This allows brain activity under specific cognitive or affective conditions to be measured. Pharmacologic challenges are also utilized. Functional brain imaging techniques currently used in clinical practice include single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance spectroscopy (MRS). Functional imaging techniques under development for clinical use include functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Research utilizing these techniques has provided insights into multiple aspects of cognitive and emotional functioning, including learning, memory, emotional regulation, control of attention, and modulation of behavior. The vast majority of studies are based on comparing groups of individuals with a specific disorder to groups of normal healthy individuals. Such studies have identified functional impairments that commonly occur in par24 BRAIN INJURY PROFESSIONAL

ticular psychiatric conditions, such as major depressive disorder, schizophrenia, obsessive-compulsive disorder, and attention deficit hyperactivity disorder. However, results often vary considerably across studies. Factors that are known to strongly influence results are the differences across individuals in both preexisting state and disorder-related symptoms. Thus, clinical applications of functional brain imaging have been limited by the challenges of translating insights based on group comparisons to understanding the individual patient. Unlike structural brain imaging, functional brain imaging is highly state-dependent and therefore always changing. Many factors can influence scan results of a particular individual on a particular day. Functional brain imaging is particularly useful for identification of areas that are structurally normal but functionally abnormal, the “hidden” lesions. Evaluation of the resting state also has shown potential for prediction of treatment response in some conditions.

Clinical Indications for Brain Imaging From the historic perspective, structural brain imaging has been obtained after positive physical exam findings in order to “ruleFigure 1

. Magnetic Resonance Imaging Appearance of Diffuse Axonal Injury (DAI)

Clinical history: An adult male (mid-20’s) suffered multiple bone and facial fractures resulting in prolonged unconsciousness. Residual symptoms at 2 years post injury include personality change, low frustration tolerance, impaired set shifting, poor concentration, impaired attention, stuttering, and symptoms of depression and post traumatic stress disorder. Neuroimaging: Left. At 2 years after the event, multiple areas of DAI are clearly visible on T2 weighted MRI. An area in the posterior white matter containing several DAIs is circled. Right. The area containing a single DAI has been enlarged (x1000) to show the individual blocks that form the image. For a DAI to be visualized by neuroimaging, it must change the signal intensity of multiple adjacent blocks, which typically are at least 1 mm per side. Thus, a DAI must have a considerable volume to be visible on clinical imaging.


Figure 2

Added Value Example - SPECT Imaging

Clinical history: An adult male (mid-40’s) suffered a blow to the head from a piece of equipment. He later described being dazed and confused immediately after the event, but he was able to drive himself home. He experienced a progressive decline in functioning. New onset symptoms included problems with short term memory recall, stutter, depression, and suicidal ideas. These symptoms were unresponsive to all medication trials. Neuroimaging: Clinical MRI was unremarkable other than mild enlargement of the lateral sulcus in the temporal lobe. SPECT identified areas of increased perfusion in the medial portion of the temporal lobe (circled), suggesting the presence of a seizure focus that was located too deep in the brain to be identified with surface electroencephalography. Clinical Management: Aggressive seizure treatment cleared all of the new onset symptoms including the stutter.

in” or document neurological lesions. Development of the circuit-based view for brain functions such as emotions, memory and behavior led to a more detailed examination of patients with small cortical and subcortical lesions (Mega & Cummings, 1994). Symptom presentation became more understandable in the context of small lesions localized within specific circuits. This new understanding of the neuroanatomic bases for brain functions has been particularly applicable to psychiatric presentation after traumatic brain injury (TBI), multiple sclerosis, ruptured aneurysms, and cerebral vascular accidents. For the astute clinician, this knowledge can at times lead to prognostic information for patients and treatment plan changes (Erhart, Young, Marder, & Mintez, 2005; Diwadkar & Keshavan, 2002; Gupta, Elheis, & Pansari, 2004; Symms, Jäger, Schmierer, & Yousry, 2004). For example, a study of psychiatric patients without dementia found that treatment was changed in 15% of patients after imaging exams (Erhart et al., 2005). Clinical indicators for brain imaging include exposure to a poison or toxin, dementia or cognitive decline of unknown etiology, delirium, brain injuries of any type with ongoing symptoms, new onset psychiatric symptoms after age 50, acute mental status changes with abnormal neurological exam or autonomic responses, new-onset atypical psychosis, and presence of symptoms that do not match with the “clinical norm” for the history. In general, patients whose clinical symptoms do not fit the classic historical picture for the working diagnosis should be considered for some form of neuroimaging.

Cernak & Noble-Haeusslein, 2010; McAllister & Stein, 2010). Traumatic brain injury (TBI) is a common occurrence in the United States in both the civilian and military populations. An estimated 1.7 million people receive urgent medical care for TBI each year, and the true occurrence may be as high as 3.8 million annually (Laker, 2011). Many of the estimated 2.4 million military personnel who have deployed to recent combat operations have sustained at least one mild TBI (Rigg & Mooney, 2011; Epidemiology Program, 2012). Most individuals who experience a mild TBI attain a complete recovery. Some will have residual cognitive and/or emotional symptoms sufficient to affect adjustment to civilian life and family relationships. Multiple other conditions may be present. Post traumatic stress disorder (PTSD), substance misuse, depression, and chronic pain are commonly reported after return from service. Recent studies suggest possible long-term adverse health effects, including the development of chronic traumatic encephalopathy (Chen, Kang, & Lin, 2011; McMillian, Teasdale, Weir, & Stewart, 2011; Omalu et al., 2011; Goldstein et al., 2012; McKee et al., 2012). Both diffuse and focal injuries can occur in TBI (Taber, Warden, & Hurley, 2006; Andriessen, Jacobs, & Vos, 2010; McAllister & Stein, 2010). The most common type of injury, particularly in mild TBI, is to the fibers (axons) that form the connections (white matter) within the brain. This is called diffuse axonal injury (DAI). The name is highly appropriate as this type of injury usually affects only a small percentage of the fibers in an area and frequently occurs in multiple locations within an individual brain (Bigler & Maxwell, 2012; Shenton et al., 2012; Taber & Hurley, 2013). Areas of DAI are commonly too small for identification on any of the standard clinical imaging techniques (Bigler & Maxwell, 2012; Shenton et al., 2012; Taber & Hurley, 2013). If large enough for visualization (Figure 1), they will be much more likely Figure 3

Added Value Example - SPECT Imaging

Clinical history: An adult male (early 30”s) was exposed to explosions multiple times (>30). Several events resulted in alterations in consciousness (e.g., dazed, confused) and one event resulted in loss of consciousness ( ~ 1 hour). In the year since that event he has experienced multiple new onset symptoms included problems with memory, headaches, dizziness, word retrieval difficulties, photosensitivity, irritability, confusion, mood lability, increased anxiety, nightmares, hypervigilance and insomnia. Neuroimaging: Upper Row. At 1 year after the most recent event, multiple areas of DAI are clearly visible on clinical MRI. Note that areas are better visualized on FLAIR than T2 weighted (T2W) MRI, and not well visualized on T1 weighted (T1W) MRI. Lower Row. Several areas were present in the white matter of one hemisphere in which the fractional anisotropy (FA) was clearly lower than the same area of white matter in the other hemisphere. One of these (circled) was used as a seed for tractography. Using a lesion as the starting point for tract reconstruction may provide insight into the areas that have been disconnected by the lesion. (case and images courtesy of Dr. Shane McNamee, Hunter Holmes McGuire VAMC, Richmond VA)

Traumatic Brain Injury (TBI) Many types of forces can injure the brain, including rapid acceleration or deceleration, rotation, blunt trauma, and impact trauma. Additional forces present following an explosion (blast) include a pressure wave (shockwave), an electromagnetic field, loud sound, chemical fumes, and heat (Moore et al., 2008; Wolf, Bebarta, Bonnett, Pons, & Cantrill, 2009; Elder, Mitsis, Ahlers, & Cristian, 2010; Hicks, Fertig, Desrocher, Koroshetz, & Pancrazio, 2010; BRAIN INJURY PROFESSIONAL

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to be seen by MRI than CT. Gradient echo MRI is very sensitive to the small areas of hemorrhage that sometimes occur in DAI. Although clinical MRI is more sensitive than CT in detecting DAI, even MRI is often negative, particularly in the chronic stage. Functional imaging (cerebral blood flow, cerebral metabolic rate) may be considerably more sensitive to the presence of TBI than structural imaging (Figure 2). However, these techniques come with their own challenges as they lack specificity. Although still considered only research techniques at this time, newer methods of MRI, such as DTI and DKI, are showing promise for identifying small areas of white matter injury (Bigler & Maxwell, 2012; Shenton et al., 2012; Hori et al., 2012). This is important, because such injuries may have devastating functional consequences. Multiple DTI studies have reported abnormalities in specific metrics at various times after mild TBI, as recently reviewed in detail (Shenton et al., 2012). DTI provides metrics of the speed and direction of water diffusion within each block (voxel) that makes up the image. Fractional anisotropy (FA), a measure (scale of 0 to 1) of the average directionality of water diffusion, is the most promising metric for identifying DAI. This is because water diffuses much faster parallel to fibers than perpendicular to fibers. White matter is rich in fibers and so has a high FA. FA is expected to be reduced in areas where fibers are disrupted. The most common finding in mild TBI is multiple small areas of reduced FA in white matter (Figure 3) (Shenton et al., 2012). However, application of DTI to the study of mild TBI is still at an early stage of development. For DTI, or any other new brain imaging technique, to become clinically meaningful it must meet certain standards. Most importantly, it must be able to reliably provide reproducible evaluations of an individual patient. This is very different from its use in research studies, where groups of patients can be compared to groups of healthy individuals. A much better understanding of how much these measures vary within and across individuals is needed in order to determine clinically meaningful change. There are potentially multiple changes in the brain that, if reliably quantified, might be of value in diagnosis and clinical management of mild TBI. These include the actual areas of injury as well as areas undergoing changes as a result of metabolic, degenerative, adaptive, and/or compensatory processes. References

Andriessen, T. M. J. C., Jacobs, B., & Vos, P. E. (2010). Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury. J Cell Mol Med, 14, 2381-2392. Bigler, E. D. & Maxwell, W. L. (2012). Neuropathology of mild traumatic brain injury: relationship to neuroimaging findings. Brain Imaging Behav, 6, 108-136. Cernak, I. & Noble-Haeusslein, L. (2010). Traumatic brain injury: an overview of pathobiology with emphasis on military populations. J Cereb Blood Flow Metab, 30, 255-266. Chen, Y. H., Kang, J. H., & Lin, H. (2011). Patients with traumatic brain injury: Populations study suggests increased risk of stroke. Stroke, 42, 2733-2739. Diwadkar, V. A. & Keshavan, M. S. (2002). Newer techniques in magnetic resonance imaging and their potential for neuropsychiatric research. J Psychosom Res, 53, 677-685. Elder, G. A., Mitsis, E. M., Ahlers, S. T., & Cristian, A. (2010). Blast-induced mild traumatic brain injury. Psychiatr Clin North Am, 33, 757-781. Epidemiology Program. (2012). Analysis of VA health care utilization among Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn Veterans, from 1st qtr FY 2002 through 3rd qtr FY 2012. http://www.publichealth.va.gov/epidemiology/reports/oefoifond/health-care-utilization/index.asp Erhart, S. M., Young, A. S., Marder, S. R., & Mintez, J. (2005). Clinical utility of magnetic resonance imaging radiographs for suspected organic syndromes in adult psychiatry. J Clin Psychiatry, 66, 968-973. Goldstein, L. E., Fisher, A. M., Tagge, C. A., Zhang, X.-L., Velisek, L., Sullivan, J. A. et al. (2012). Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med, 4, 134ra60. Gupta, A., Elheis, M., & Pansari, K. (2004). Imaging in psychiatric illness. Int J Clin Pract, 58,

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850-858. Hicks, R. R., Fertig, S. J., Desrocher, R. E., Koroshetz, W. J., & Pancrazio, J. J. (2010). Neurological effects of blast injury. J Trauma, 68, 1257-1263. Hori, M., Fukunaga, I., Masutani, Y., Taoka, T., Kamagata, K., Suzuki, Y. et al. (2012). Visualizing non-gaussian diffusion: clinical application of q-space imaging and diffusional kurtosis imaging of the brain and spine. Magn Reson Med Sci, 11, 221-233. Laker, S. R. (2011). Epidemiology of concussion and mild traumatic brain injury. PMR, 3, S354S358. McAllister, T. W. & Stein, M. B. (2010). Effects of psychological and biomechanical trauma on brain and behavior. Ann NY Acad Sci, 1208, 46-57. McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E. et al. (2012). The spectrum of disease in chronic traumatic encephalopathy. Brain, epub ahead of print. McMillian, T. M., Teasdale, G. M., Weir, C. J., & Stewart, E. (2011). Death after head injury: the 13 year outcome of a case control study. J Neurol Neurosurg Psychiatry, 82, 931-935. Mega, M. S. & Cummings, J. L. (1994). Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci, 6, 358-370. Moore, D. F., Radovitzky, R. A., Shupenko, L., Klinoff, A., Jaffee, M. S., & Rosen, J. M. (2008). Blast physics and central nervous system injury. Future Neurology, 3, 243-250. Omalu, B., Hammers, J. L., Bailes, J., Hamilton, R. L., Kamboh, M. I., Webster, G. et al. (2011). Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurg Focus, 31, E3. Rigg, J. L. & Mooney, S. R. (2011). Concussion and the military: issues specific to service members. PM R, 3, S380-S386. Shenton, M. E., Hamoda, H. M., Schneiderman, J. S., Bouix, S., Pasternak, O., Rathi, Y. et al. (2012). A review of magnetic resonance imaging and diffusion tensor imaging findings in mild traumatic brain injury. Brain Imaging Behav, 6, 137-192. Symms, M., Jäger, H. R., Schmierer, K., & Yousry, T. A. (2004). A review of structural magnetic resonance neuroimaging. J Neurol Neurosurg Psychiatry, 75, 1235-1244. Taber, K. H. & Hurley, R. A. (2013). Update on mild traumatic brain injury: neuropathology and structural imaging. J Neuropsychiatry Clin Neurosci, 25, iv, 1-5. Taber, K. H., Warden, D. L., & Hurley, R. A. (2006). Blast-related traumatic brain injury: what is known? J Neuropsychiatry Clin Neurosci, 18, 141-145. Wolf, S. J., Bebarta, V. S., Bonnett, C. J., Pons, P. T., & Cantrill, S. V. (2009). Blast injuries. Lancet, 374, 405-415.

About the Authors

Dr. Hurley received her Doctorate of Medicine from Medical University of South Carolina in 1990 and completed her psychiatry residency with subspecialty focus on neuropsychiatry and neuroimaging research at Baylor College of Medicine, Houston, Texas in 1994. Dr. Hurley remained at Baylor College of Medicine and the Houston VAMC as faculty in Psychiatry and Radiology until 2003. At that time, she transferred to the Salisbury, NC VAMC, and joined the Wake Forest School of Medicine, where she is a Professor of Psychiatry and Radiology. Dr. Hurley is a Diplomate of both the American Board of Psychiatry and the United Council for Neurologic Subspecialties Certification in Behavioral Neurology & Neuropsychiatry. Dr. Taber received an MS in Neuroscience from the University of Florida in 1977 and a PhD in Neurophysiology from the University of Texas Houston in 1982. She joined Baylor College of Medicine (Houston TX) in 1982 as a Research Associate in the Departments of Neurology and Radiology, where she conducted electrophysiological studies in rat hippocampal slices, magnetic resonance spectroscopy studies of intact brain in developing rat pups, and participated in the founding of Baylor’s magnetic resonance imaging and spectroscopy research center. From 1985 to 2003 she was faculty in the Departments of Radiology and Psychiatry. During this time Dr. Taber received the Fulbright & Jaworski Faculty Excellence Award for both her teaching (2001) and for her enduring educational materials (2002). In 2003, Dr. Taber pursued her long standing interest in medical informatics by joining the School of Health Information Sciences at the University of TexasHouston as a Research Fellow. In 2004 she collaborated with VA personnel in North Carolina on a successful proposal for a VA-funded Mental Illness Research, Education and Clinical Center (MIRECC). Dr. Taber has served as the Assistant Director of Education for the VISN 6 MIRECC since 2005, and as a Research Professor in the Division of Biomedical Sciences at the Edward Via College of Osteopathic Medicine in Blacksburg, Virginia since 2007. She is also a Research Health Scientist at the Salisbury VA, where her major focus is facilitating development of new researchers. Dr. Taber is the author of more than 180 peer reviewed journal articles and more than 30 book chapters. She is co-editor of the “Graphic Anatomy” series for the Journal of Computer Assisted Tomography and the “Windows to the Brain” series for the Journal of Neuropsychiatry and Clinical Neurosciences. She was elected a Fellow of the American Neuropsychiatric Association in 2005 and to ANPA’s Advisory Council in 2010. Her research interests include traumatic brain injury, neuroimaging, medical informatics and education.


brain bytes The Defense Department added new NFL Settlement The NFL agreed to a $765 million settlement deal with more than 4500 former players who sued the league, accusing it of hiding the dangers of brain injury while profiting from the sport’s violence, according to court papers. The NFL agreed to fund medical exams, concussion-related compensation and a program of medical research as well as to cover some legal expenses. “This is a historic agreement, one that will make sure that former NFL players who need and deserve compensation will receive it, and that will promote safety for players at all levels of football,” Judge Phillips said. “Rather than litigate literally thousands of complex individual claims over many years, the parties have reached an agreement that, if approved, will provide relief and support where it is needed at a time when it is most needed.”

study what happens to service members and veterans who suffer mild traumatic brain injuries or concussions. The principal investigator on the grant is David X. Cifu, M.D., chair of the VCU School of Medicine’s Department of Physical Medicine and Rehabilitation and executive director of VCU’s Center of Researcher Sciences and Engineering (CERSE). Groups of veterans who have been injured in prior wars, such as Korea or Vietnam, in more recent wars in Iraq and Afghanistan and in car accidents, sports and falls in the United States will be studied. The researchers will try to determine who is more likely to have problems after these injuries, how the injured can be better treated and cared for, and what the injured and their families can expect over their lifetime.

The Concussed Brain at Work: fMRI Study Documents Brain Activation During Concussion Recovery SyNAPSe: A Randomized Double-Blind, PlaceboControlled Study to Investigate the Efficacy and Safety of Progesterone in Patients with Severe Traumatic Brain Injury BHR is conducting SyNAPSe® (Study of the Neuroprotective Activity of Progesterone in Severe Traumatic Brain Injuries), a global, Phase 3, multi-center pivotal trial in severe TBI. The study is evaluating the effectiveness of its proprietary BHR-100 progesterone product as a neuroprotective agent for the acute treatment of severe traumatic brain injury (TBI) patients. Approximately 1,200 patients with severe (Glasgow Coma Scale scores of 3-8), closed-head TBI will be enrolled in the study at more than 150 medical centers in 21 countries. Sites are located in the United States, Argentina, Europe, Israel, and Asia.

VCU awarded $62 million to study traumatic brain injuries in military personnel Virginia Commonwealth University has been awarded a $62 million federal grant to oversee a national research consortium of universities, hospitals and clinics that will

For the first time, researchers have documented irregular brain activity within the first 24 hours of a concussive injury, as well as an increased level of brain activity weeks later -- suggesting that the brain may compensate for the injury during the recovery time. The findings are published in the September issue of the Journal of the International Neuropsychological Society. The concussed athletes showed the expected postconcussive symptoms, including decreased reaction time and lowered cognitive abilities. Imaging via fMRI (functional magnetic resonance imaging) showed decreased activity in select regions of the right hemisphere of the brain, which suggests the poor cognitive performance of concussion patients is related to that underactivation of attentional brain circuits. Seven weeks post-injury, the concussed athletes showed improvement of cognitive abilities and normal reaction time. However, imaging at that time showed the post-concussed athletes had more activation in the brain’s attentional circuits than did the control athletes. BRAIN INJURY PROFESSIONAL

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Imaging for Brain Trauma: Questions to Be Answered By Jonathan M. Silver, MD

The rapid and exciting advances in brain imaging techniques provide increasingly sensitive methods to examine brain structure and function. Compared to computed tomography (CT), high powered 3 Tesla magnetic resonance imaging (MRI) provides anatomic detail that could only be visualized post-mortem. Diffusion tensor imaging (DTI) examines white matter tracts in exquisite detail. The development of functional techniques, such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI), enable us to see that even normal appearing brain does not always function normally, and different regions may activate depending on the stimulus provided. Magnetic resonance spectroscopy (MRS) analyzes chemical systems, volumetric analysis detects minute changes in brain volume, and resting connectivity network analysis examines communication among different networks. The promise of newer techniques, such as shown in clarity where individual nerves and synapses can be seen in preparations of brain tissue (although not in the living animal) and the Blue Brain project (2013) the human brain project (2013) show that even the current “high-power” techniques reveal a fraction of what occurs in the brain. While there is uniform excitement about the developments in the detection of detailed neuroanatomical and physiologic changes in patients who have sustained traumatic brain injury (TBI), there is controversy about the clinical application of this technology. It is interesting to observe that discussions on 28 BRAIN INJURY PROFESSIONAL

the role of imaging in the assessment of patients with TBI can reach the emotional level of politics, global warming, or evolution. Psychiatrists are accustomed to treating patients with disorders for which there are no “objective tests” to confirm the biologic basis of their symptoms. We know that imaging in other neurologic disorders do not always demonstrate pathology: for example, individuals with developmental disability, Parkinson disease, epilepsy, migraine headaches, early Alzheimer disease, may have normal imaging on MRI or functional imaging. However, in none of these instances do we believe that the disorders do not involve the brain. Similarly, when a disease involves imaging abnormalities (such as white abnormalities in migraine or multiple sclerosis), the extent of the abnormality may not correlate with symptoms or disability. We also know that careful imaging may help us in the clinical arean, such as to determine if dementia is of the Alzheimer type vs. frontotemporal dementia. However, treatment usually is based on a careful history, symptoms, and examination. Unlike many other diseases, TBI occurs in unique and more complicated situations, which involve an entirely new arena: different types of insurers (worker’s compensation, no-fault, disability) with their own process of evaluation, and the legal arena. In addition, when “independent” evaluations are requested, we must realize that payment can influence opinion, and set up a “conflict of interest” that differs from the doctor-patient relationship. Instead of relying on history and symptoms, there is


the desire for an objective “gold-standard” confirmation that injury “really” occurred. This differs from the way tests are used in medicine- and hence, the polarization of opinions. Therefore, it is important, as a foundation, to not only understand what is involved in how these tests are performed, but compare them to those we use frequently in medicine. For patients with severe TBI, who have significant contusions or bleeding, the routine imaging modalities demonstrate sufficient pathology to guide treatment (especially if we need to determine there is a subdural hematoma that requires neurosurgical intervention). But in the injuries for which there is brief or no loss of consciousness or transient amnesia, what is the role for advanced imaging? Do we know if obtaining these studies helps or complicates recovery? Sensitivity and specificity

Many medical tests have been used for years, and we have information about the sensitivity (presence of the abnormality in those who have the disease), and specificity (how likely are you to have the disease if the test is abnormal). We need to know how many in the general population will have the abnormality and not have the disease, the natural history of the test (how it changes with time in relationship to the disease), and if they correlate with symptoms? The electrocardiogram (ECG) is a routine test to detect myocardial injury. The ECG may not detect many autopsyproven MI’s. ECG evidence of MI’s can disappear and return to normal.(McQueen MJ 1983) Of non-fatal MI’s, half may be “silent” (no clinical symptoms) and only discovered on subsequent ECG(Macfarlane 2007). Similar data is available for large screening tests such as mammography or PSA,(Meigs, Barry et al. 1996) where the “false positive” rate can be high enough to question the utility of these as “screening tests.” It is necessary to know the rate of abnormality of the test in the general population to determine this. (For those interested, this involves a very important concept known as Bayes Theorem). In the 1980’s in psychiatry, there was excitement about the use of neuroendocrine tests to diagnose depression (dexamethasone suppression test and thyrotropin hormone stimulation test). (Carroll, Feinberg et al. 1981; Extein, Pottash et al. 1982) However, enthusiasm waned when it was found that the false positive rate in the general population made the test nonspecific for diagnosis. Possibly most comparable to imaging for brain injury is the literature on back pain. Studies have demonstrated that for patients with low back pain, there is no relationship between findings on MRI and recovery. In fact, more than twice as many of those having MRI’s had lumbar spine operations than those who received routine lumbar radiographs evaluations, yet outcomes were similar. (Jarvik, Hollingworth et al. 2003)A finding as “definite” as a lumbar disc bulge or protrusion (but not extrusion) is found in over half of individuals without back pain. (Jensen, Brant-Zawadzki et al. 1994)An MRI obtained one year after surgery or conservative treatment for sciatica and lumbar disc herniation in 283 patients did not distinguish between favorable and unfavorable outcome.(el Barzouhi, Vleggeert-Lankamp et al. 2013) Disk herniation was visible in 39% with favorable outcome, and 33% with unfavorable outcome (21% surgical group, 60% conservative treatment). A favorable

outcome was obtained in 85% with and 83% without disk herniation. Even in a disorder with much simpler pathology than TBI, imaging has its problems. Is more powerful imaging better?

A study that compared diffusion-weighted MRI in acute stroke in 135 patients compared 1.5 vs. 3.0 Tesla magnets. The accuracy, sensitivity, and specificity was superior for 1.5T. Thus, stronger may not be better. (Rosso C 2010) Uniformity of analysis

Another issue with the newer technologies is whether there is a uniformly accepted methodology of analysis. There are several possible ways to analyze an imaging study: Whole brain vs. region of interest; Statistical group analysis; individual scans or types of lesions (Jorge RE 2013; Kim N 2013), visual vs. computer (volumetric analysis) (Zhou, Kierans et al. 2013). When there is a lesion, do we know the natural history of the abnormality, whether it is static or dynamic.(Lipton ML 2012) We want to avoid calling a lesion permanent if it changes with time. This has especially been true for the “functional” (SPECT, PET) imaging that can change based on mood, pain, anxiety, and the conditions of the room. Co-occurring disorders

Does the co-occurrence of other disorders influence abnormalities? Many individuals have had a prior concussion (which is fairly common)- so we are unable to determine when the abnormality may have occurred. Abnormalities may be seen with a variety of neuropsychiatric conditions, such as anxiety, depression, pain, and migraine headaches. Implications for abnormal imaging

What are the implications for an abnormal imaging study? At this time, there is no treatment based on an abnormal image. We know that expectation of prognosis influences prognosis for a number of diseases, including concussion.(Hou, Moss-Morris et al. 2011; Snell, Siegert et al. 2011) Would an abnormal brain imaging study make the person feel more or less optimistic about recovery? Does this depend on the chronicity of the symptoms. For example, would a patient react differently if an abnormal study was obtained 3 months vs. 3 years after continuing symptoms? In reality, we do not know, and no one has ever asked this question. How does an abnormal result correlate with prognosis? How many asymptomatic patients have been studied with a specific modality to see how the result correlates with symptoms (similar to the herniated disc studies)? Many patients with migraines and multiple sclerosis are functioning well despite the presence of significant white matter pathology. While an abnormal imaging study may significantly help a lawyer to demonstrate that a brain injury occurred, clinicians must be aware of the promises as well as potential limitations and adverse consequences of these tests. Neuroimaging of brain injury is a rapidly developing and important modality in our understanding of the changes that occur during all severities of TBI. We must not let our enthusiasm override the critical questions that need to be asked (and answered) so that we are able to use these techniques to help our patients. BRAIN INJURY PROFESSIONAL

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References “Breast Cancer Topics.” 2013, from http://www.cancer.gov/cancertopics/pdq/screening/breast/ healthprofessional/page8. “Blue Brain Project.” Retrieved 2013, from http://bluebrain.epfl.ch/. Carroll, B. J., M. Feinberg, et al. (1981). “A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.” Arch Gen Psychiatry 38(1): 15-22. el Barzouhi, A., C. L. Vleggeert-Lankamp, et al. (2013). “Magnetic resonance imaging in followup assessment of sciatica.” N Engl J Med 368(11): 999-1007. Extein, I., A. L. Pottash, et al. (1982). “Thyroid-stimulating hormone response to thyrotropinreleasing hormone in unipolar depression before and after clinical improvement.” Psychiatry Res 6(2): 161-169. Hou, R., R. Moss-Morris, et al. (2011). “When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.” J Neurol Neurosurg Psychiatry. “Human Brain Project.” retreived 2013 from http://www.humanbrainproject.eu Jarvik, J. G., W. Hollingworth, et al. (2003). “Rapid magnetic resonance imaging vs radiographs for patients with low back pain: a randomized controlled trial.” JAMA 289(21): 2810-2818. Jensen, M. C., M. N. Brant-Zawadzki, et al. (1994). “Magnetic resonance imaging of the lumbar spine in people without back pain.” N Engl J Med 331(2): 69-73. Jorge RE, A. L., White T, Tordesillas-Gutierrez D, Pierson R, Crespo-Facorro B, Magnotta VA (2013). “White matter abnormalities in veterans with mild traumatic brain injury.” Am J Psychiatry 169(12): 1284-1291. Kim N, B. C., Kim M, Lipton ML (2013). “Whole brain approaches for identification of microstructural abnormalities in individual patients: comparison of techniques applied to mild traumatic brain injury.” PLoS One. 8(3): e59382. Lipton ML, K. N., Park YK, Hulkower MB, Gardin TM, Shifteh K, Kim M, Zimmerman ME, Lipton RB, Branch CA (2012). “Robust detection of traumatic axonal injury in individual mild traumatic brain injury patients: intersubject variation, change over time and bidirectional changes in anisotropy.“ Brain Imaging Behav 6(2): 329-342. Macfarlane, P., Norrie J, On behalf of WOSCOPS Executive Committee (2007). “The value of the electrocardiogram in risk assessment in primary prevention: Experience from the West of Scotland Coronary Prevention Study.” Journal of Electrocardiology 40(1): 101-109. McQueen MJ, H. D., El-Maraghi NR. (1983). “Assessment of the accuracy of serial electrocardiograms in the diagnosis of myocardial infarction.” Am Heart J 105(2): 258-261. Meigs, J. B., M. J. Barry, et al. (1996). “Interpreting results of prostate-specific antigen testing for early detection of prostate cancer.” J Gen Intern Med 11(9): 505-512.

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Rosso C, D. A., Lacroix D, Mutlu G, Pires C, Lehéricy S, Samson Y, Dormont D : (2010). “Diffusion-weighted MRI in acute stroke within the first 6 hours: 1.5 or 3.0 Tesla? Neurology. 2010 Jun 15;74(24):1946-53. doi: 10.1212/WNL.0b013e3181e396d1. Epub 2010 May 12. ).” Neurology 74(24): 1946-1953. Snell, D. L., R. J. Siegert, et al. (2011). “Associations between illness perceptions, coping styles and outcome after mild traumatic brain injury: preliminary results from a cohort study.” Brain Inj 25(11): 1126-1138. Zhou, Y., A. Kierans, et al. (2013). “Mild traumatic brain injury: longitudinal regional brain volume changes.” Radiology 267(3): 880-890.

about the author

Jonathan M. Silver, M.D. is Clinical Professor of Psychiatry at New York University School of Medicine. Dr. Silver is a Fellow and past- President of the American Neuropsychiatric Association. He is a Diplomate in Behavioral Neurology & Neuropsychiatry by the United Council for Neurologic Subspecialties (UCNS), and is Chair of their committee that developed the first certification examination. He is Associate Editor of the Journal of Neuropsychiatry and Clinical Neurosciences and Journal Watch Psychiatry, and Psychiatry Section Editor for UpToDate. He has held past positions as Director of Neuropsychiatry at Columbia-Presbyterian Medical Center, and Assistant Chair of Clinical Services and Research and Director of Ambulatory Services in the Department of Psychiatry at Lenox Hill Hospital in New York City. He has authored over 45 papers and 55 chapters, focusing on the neuropsychiatric problems subsequent to traumatic brain injury and the pharmacologic treatment of those problems. He has lectured widely throughout the United States and Canada on these topics, and has made over 160 presentations at scientific meetings. He is senior editor of the books “Neuropsychiatry of Traumatic Brain Injury,” and “Textbook of Traumatic Brain Injury”, which has just published the second edition. He has been listed in “Best Doctors in America” since 1992 for the area of neuropsychiatry. He received the award for “Innovative Clinical Treatment” from the North American Brain Injury Society.


brain bytes Traumatic Brain Injury Treatment for Service members Service members who have suffered severe traumatic brain injuries and psychological ills can benefit from an intensive four-week program at the National Intrepid Center of Excellence. Dr. James Kelly, Director of the National Intrepid Center of Excellence, states that “When service members with severe TBI fail to respond to conventional medical treatment, they often are referred to NICoE’s program, which finds the best methods to treat their conditions on an individual basis. The patients must also have a co-existing psychological health issue, such as post-traumatic stress disorder, depression or anxiety.” The only center of its kind, the Defense Department’s NICoE “…offers a wealth of medical and alternative approaches for such service members, with medical

professionals such as neurologists, therapists and counselors working in an interdisciplinary team approach”, Dr. Kelly explained. “Whatever patients need, they get,” the Director said, adding that “NICoE does not operate in an assembly-line format, but rather as a compact, intensive care outpatient program that treats different patients with individualized forms of care that fit their particular needs.” Reported by Terri Moon Cronk, American Forces Press Service Project Brain announced by President Obama President Obama announced that his budget for 2014 will include $100 million for the project called BRAIN: Brain Research through Advancing Innovative Neurotechnologies (BRAIN). Already the

initiative is being compared to the Human Genome Project, which finished decoding the genetic pattern that makes all humans unique in 2003. While the brain mapping project has also been compared to President John F. Kennedy’s 1961 challenge to land a human on the moon, brain researcher Professor Eric Kandel says this will be harder. “Going to the moon – I don’t mean to in any way minimize it – was in part an engineering project. This brain research is going into the unknown. This is like Columbus discovering America, if you will,” Dr. Kandel, who won the Nobel Prize in 2000 for his research on the brain. Neuroscientists hope Project BRAIN will allow them to map the connections between individual neurons and large circuits of neurons to unlock the secrets behind Alzheimer’s, Autism, strokes, traumatic brain injuries (TBIs), and some psychiatric disorders.

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legal spotlight Hope2 It has often been said that Hope is not a plan, but maybe it shoul\d be. As one of the pastors at our local church I often encounter people who have lost hope are just about ready to give up and surrender to their circumstances. In those moments I have a choice. I can pat them on the back and say “I’ll pray for you” and be on my way or I can impart something eminently more useful. I can give them Hope. Regrettably, Hope is not something that we were taught in our legal or medical school education as a means by which we could in many cases care for our clients and patients. But maybe it should have been. As a TBI lawyer having represented clients from the homeless to CEO’s I have discovered a fundamental human need: people need Hope. I recall a few years ago meeting with Jim, the CEO of a healthcare company many of whose patients were in the acute phase of TBI. Jim came to see me because his 19 year old son had just been in a terrible car accident leaving him in a coma. When I first saw Jim who was usually a very well dressed, confident looking executive, he looked uncharacteristically tired, disheveled, and worried. Although Jim was a person of influence and understood well the complexities of a TBI, he was on that day as he described it, “in a fog”. After listening to him and explaining how our law firm could help, I sensed he needed something more than a legal analysis and an explanation of our in-house care management services. I could see in his eyes that what he really needed was Hope. I didn’t have the courage or confidence to tell him that his son was going to be ok. But I did listen and encouraged him to believe that through the long road to recovery, his son would get better. I am relieved to report that he did. Today, Jim’s son is in graduate school and doing well. Since then, every time I see Jim I can perceive his gratitude for our conversation that day. I believe my impact on Jim’s life had less to do with the settlement we obtained and more to do with taking the time to compassionately connect with him. Lesson learned. It is similarly impactful to be the recipient of Hope. Two months ago my older brother, Jorge suffered a stroke. That he survived is nothing short of miraculous. He was left with right sided hemiparesis. Jorge has received excellent and compassionate medical and rehabilitative care. But the best care he received, in my opinion, came recently. He was seen by a prominent South Florida neurologist whose normal waiting room time is several hours. He waited. It was worth the wait. During the 30 minutes, my brother went from anxiety and discouragement about his condition and future prospects, to being motivated and encouraged. So what happened? My brother wouldn’t share with me precisely what the neurologist

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told him but I got the gist of what happened. This neurologist went beyond his training and intuitively sensed that my brother needed more than a physical exam, diagnosis and a prescription for OT, PT and Speech. He accurately perceived that he needed Hope and he gave it to him. I have not seen my brother this motivated to do anything, ever. He is committed to regaining his life. Whatever inspiration that neurologist gave Jorge; it’s working, because he is well on his way to an excellent recovery. These two experiences I have shared with you underscore an important lesson for all of us as we represent and care for families living with TBI. The lesson is this: there is great power in an encouraging word given at the appropriate time. But all too often we can be dismissive of hope since it is not quantifiable or we assume that it will only lead to patient/client disappointment and unfulfilled expectations. As medical and legal professionals we are uniquely positioned to positively influence our patient/clients perspective on their brain injury. Our opportunity to help transform lives can help move the families we serve from being brain injury survivors to brain injury triumphants.

About the Author

Frank Toral is the Senior Partner of Toral Garcia Battista, a Florida-based law firm focusing on brain and spinal cord injury cases. Frank is a passionate advocate for brain and spinal cord injury survivors and their families and has served in various leadership and advisory roles with multiple organizations including Brain Injury Association of Florida, Brain Injury Association of America, Sarah Jane Brain Foundation and the University of Florida Presidents Council. Frank received his Bachelor of Science in Political Science from the University of Florida and his Juris Doctorate from Shepard Broad Law School at Nova Southeastern University. Frank is a frequent speaker and contributor on Brain injury topics and issues and has also authored the handbook Brain Injury: Where do we go from here?. Frank founded the Toral Family Foundation whose mission is to collaborate with the healthcare community to improve the lives of all persons with a brain or spinal cord injury through research, education and access to resources.


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bip expert interview Interview with Jamshid Ghajar, MD, PhD

Jamshid Ghajar completed the MD/PhD program at Cornell University Medical College, with a PhD dissertation in neurochemistry and brain metabolism during coma. After completing his residency training in neurosurgery at the New York Presbyterian Hospital, he joined the Cornell faculty and founded the Brain Trauma Foundation (BTF), where he currently serves as President. Dr. Ghajar is Chief of Neurosurgery at Jamaica Hospital-Cornell Trauma Center, Clinical Professor of Neurological Surgery at Weill Cornell Medical College and President of BTF. He resides in New York City with his wife and three daughters.

What is the Brain Trauma Foundation’s mission? BTF’s mission is to translate neuroscience into effective solutions. BTF’s evidence-based severe TBI Guidelines have led to a 50% reduction in head injury deaths in the U.S. and are the standard of traumatic brain injury care worldwide. BTF currently has a contract with the U.S. Department of Defense (DOD) to develop an eye tracking device that can assess cognitive performance and concussion within 30 seconds. This device is being field tested in 10,000 soldiers and athletes. BTF is also funded by the DOD on evidence based concussion guidelines, in collaboration with the CDC. What is “Eye-tracking” and what does it measure? At BTF, when we say “Eye-Tracking” we are most frequently referring to two specific types of eye-movement: Saccadic (quick, repositioning of the eyes) and SPEM (Smooth Pursuit EyeMovement; ontinuous stabilization of a visual image of a moving target). Humans use a combination of saccadic and smooth pursuit eye movements to select visual information for processing, or in lay terms, to “pay attention.” Numerous previous studies have demonstrated that SPEM is highly dependent on attention and attentional and oculomotor processes are tightly integrated at the neuronal level. Functional magnetic resonance imaging (fMRI) research has demonstrated that SPEM control relies on a neural network comprising the motion perception area V5, the posterior parietal 34 BRAIN INJURY PROFESSIONAL

cortex (PPC), the frontal eye field (FEF), the supplementary eye field (SEF), the dorsolateral prefrontal cortex (DLPFC), and the cerebellum. These areas are also activated in other attention dependent tasks. SPEM is a particularly sensitive measure of attention as it requires an individual to predict and maintain target velocity and trajectory, employing spatial working memory and visual feedback to continuously adjust eye gaze position for accuracy when following a target. Using a target moving in a predictable circular path, predictive timing can be accurately measured. BTF working closely with its neuro-technology partner SyncThink (www.syncthink.com) developed a specific test of SPEM, called EYESYNC. This test measures eye tracking performance within 30 seconds, has high test retest reliability and little effort or learning effect, which are inherent problems in neurocognitive testing. What are the current applications for the EYE-SYNC test? Currently, the military is interested in using EYE-SYNC to assess a soldier’s readiness for duty, such as understanding potential impairment from fatigue or concussion. Athletic organizations also recognize the importance of first accurately describing and then appropriately triaging a concussed athlete. EYE-SYNC is one metric that can help characterize changes in attention functioning that may have an impact on an athlete’s return to play, or a soldier’s return to duty.

What is the goal of your current Concussion work? We are using an evidence-based method (that is, a systematic, transparent process using only data from high quality published literature) to derive clinically useful instruments for immediate identification, diagnosis, and prognosis of concussion. Screening and diagnostic criteria already exist. Why are you creating another version? From our review of the existing methods for diagnosing concussion, we found that all - either entirely or at least in part - rely on expert opinion or group consensus. The evidence-based method relies solely on solid data. As such we believe the instruments that method will render will be more reliable and valid. Our hope is that, after sufficient validation, the instruments will become standard across settings, and will minimize the vast amount of variation we see in both diagnosis and treatment of concussion. You have used the evidence-based method to develop guidelines for severe brain trauma. What do you think has been accomplished by this work? We recently conducted an analysis that is in press, culminating data from a 10-year project to implement the Guidelines in New York State trauma centers. The results show there was a 50% reduction in mortality associated with adherence to the Guidelines. The magnitude of that improvement far exceeds what is generally seen in research about clinical interventions for any disease, and far exceeds any expectations from TBI clinical or basic science research.


literature review Textbook of Traumatic Brain Injury, 2nd Edition. By Jonathan M. Silver, MD Thomas W. McAllister, MD Stuart C. Yudofsky, MD American Psychiatric Publishing, Inc. Washington, D.C., 2011. While some might say the review of a 2011 Textbook on Traumatic Brain Injury is a bit delayed, that’s accurate, yet the contribution of this text to the field of brain injury should not go un-recognized in the Brain Injury Professional albeit late. Many years ago, as a young behavioral psychologist, a client taught me a powerful lesson in differential diagnosis. Severe orientation and memory impairments mimicked psychosis when this gentleman presented with what appeared to be visual hallucinatons of gremlins prompted by a horror movie the evening before, an inability to accurately connect the dots from real events, and an overwhelming sense of fear. Not long after, another client who mistook his rehabilitation facility for a submarine, attempted to order drinks from a floor plant, had a history of 4 point restraint with a 24 hr. guard, experienced middle of the night “awakenings” and lucid moments. His major depression and subsequent course of pharmacotherapy and behavioral therapy might have taken a different route had we mistaken his cognitive difficulties for psychosis. We all have our stories of successes or near misses in which we could have gone down a misguided treatment path and in some cases we may not have known we missed a crucial piece of the neuropsychiatric equation. Dr’s Silver, McAllister, and Yudofsky have been literally writing the book on neuropsychiatry and brain injury for the past two decades. They teach us to look beyond the more obvious explanations to help determine the underlying neuropsychiatric issues that may often be misdiagnosed, misunderstood, or underrepresented. This oversight can result in inadequate or ineffective treatment or delayed treatment which may result in more challenging or resilient future unwanted behaviors or symptomotology. Changes in personality and behavioral issues are often cited as having the most enduring impact 1, 5, and 15 years fol-

lowing brain injury. This 2nd edition text includes 39 chapters in 5 sections, Epidemiology and Pathophysiology, Neuropsychiatric Disorders, Neuropsychiatric Symptomatologies, Special Populations and Issues, and Treatment. It includes contemporary issues in sports injuries, brain injury in the context of war, PTSD, substance issues, and pediatric brain injury and abuse. It reflects evidence based or best available evidence approaches and offers a chapter on emerging complementary treatment approaches. The authors outline a comprehensive neurorehabilitation approach that includes neuroradiological, neuropsychological, and neuropsychiatric assessment including possible genetic testing and combined psychopharmacological, cognitive therapy, psychotherapy, and positive behavioral approaches to treatment. The book is intended as a reference for practitioners by ensuring each chapter can stand alone with a format that includes Key Clinical Points and Recommended Readings and References following each chapter. The authors also chose a powerful foreword by Bob and Lee Woodruff who know firsthand the life-altering impact of a brain injury and who like many families, derive hope from new research and treatments. I do however, think in future editions the title “Textbook of Neuropsychiatry in Traumatic Brain Injury” might better reflect the contents while continuing to outline a broad perspective on contributing issues and in assessing and treating neuropsychiatric issues in persons with brain injury throughout their developmental life-span.

About the reviewer

Dr. Debra Braunling-McMorrow is the President and CEO of Learning Services. She serves on the board of the North American Brain Injury Society. Dr. McMorrow is a past chair of the American Academy for the Certification of Brain Injury Specialists (AACBIS) and has served on the Brain Injury Association of America’s board of executive directors. Additionally, Dr. McMorrow has served on several national committees, editorial boards, and peer review panels. Dr. McMorrow has published in numerous journals and books and has presented extensively in the field of brain injury rehabilitation. She has been working for persons with brain injuries for almost 30 years.

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non-profit news NORTH AMERICAN BRAIN INJURY SOCIETY Close to 400 brain injury professionals gathered at the InterContinental Hotel in New Orleans to attend the North American Brain Injury Society’s 11th Annual Conference on Brain Injury and the concurrent event, the 26th Annual Conference on Legal Issues in Brain Injury. The meeting opened with a special pre-conference workshop on state of the art neuroimaging chaired by John Silver, MD, Barry Willer, PhD and John Leddy, MD. The plenary session during the first day of the meeting featured talks by Jonathan Silver, Keith Cicerone, Gary Ulicny, Matthew Dodson, Barry Willer, Jeffrey Kreutzer, Tom Gennarelli and Asghar Rezaei. The following two days featured 35 invited speakers and 38 oral presentations from peer reviewed submissions. NABIS was honored to present achievement awards to Geoff Lauer (Public Policy), Jeffrey Kreutzer (Innovative Treatment) and Keith Cicerone (Research). It is not too early to mark your calendars for the 2015 NABIS meeting! In support of the International Brain Injury Association’s Tenth World Congress on Brain Injury, NABIS will not be holding its regular conferences next year, and all NABIS members are encouraged to attend the World Congress to be held March 18-21, 2014, in San Francisco. NABIS will be back with our regular meetings April 29 – May 2, 2015, at the beautiful Westin Riverwalk Hotel in San Antonio, Texas! Details as they become available will be posted on the NABIS website, www.nabis.org.

Brain Injury association of america The Brain Injury Association of America (BIAA) has announced that Donald G. Stein, Ph.D. has been named as the recipient of the 2013 William Fields Caveness Award, and that Brent E. Masel, M.D. will receive the Sheldon Berrol M.D. Clinical Service Award. Awards will be presented at ACRM’s fall meeting in Orlando, FL in November. BIAA is actively lobbying for reauthorization of the TBI Act (H.R. 1098) to continue and expand protection and advocacy grant programs as well as the critical work of the Centers for Disease Control and Prevention. Please contact your congressional representative and ask him/her to co-sponsor the bill. Sens. Mark Kirk (R-IL) and Tim Johnson (D-SD) introduced S. 1027 on May 22, 2013 to improve, coordinate, and enhance rehabilitation

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research at the National Institutes of Health (NIH). The bipartisan legislation would implement some of the recommendations raised in the Final Report of the Blue Ribbon Panel on Medical Rehabilitation Research at NIH. BIAA will present the 2014 Brain Injury Business Practice College at the Green Valley Ranch Resort and Spa in Las Vegas, NV, Jan. 21-23, 2014. Sessions offered can enable business executives and managers to improve their business methods and metrics. For more information, visit: www.biausa.org/businesspracticecollege.

DEFENSE CENTERS OF EXCELLENCE This quarter’s update from DCoE highlights the new website T2WRL, pronounced “twirl.” T2WRL is a resource locator for Defense Department and Veterans Affairs traumatic brain injury (TBI) case managers and care coordinators supporting the discharge planning and ongoing care for service members, veterans and their families coping with TBI and associated psychological health concerns. TBI has been described as the signature wound of the Afghanistan and Iraq conflicts. Modern body armor has greatly enhanced a warrior’s chance of survival after sustaining a TBI; however, with increased awareness and screening measures, mild TBI (also known as concussion) has become a clinical challenge for those charged with caring for chronic symptomatic mild TBI patients. Ms. Katherine Helmick, Deputy Director for the Defense Veterans Brain Injury Center (DVBIC), stated, “This new resource gives case managers and care coordinators centralized access to military, Veterans Affairs and community TBI resources and information including 200 websites and 1,200 facilities with updates being added regularly. T2WRL is a tremendous asset for those caring for our military members and veterans suffering from TBI.” Additional features of the T2WRL website include: •

• •

Over 40 search topics are listed and include advocacy, behavioral health, community reintegration, emergency services, occupational therapy, sleep disorder treatment, social services and vocational training and work therapy Searches can be filtered by treatment areas, organization or service type Results are displayed by geographic proximity using inter-


active maps Users may suggest new resources and updates to existing resources

To create a profile to access the locator, visit ttwrl.dcoe.mil. For information about DCoE, please visit dcoe.health.mil or email the DCoE Outreach Center at resources@dcoeoutreach.org or phone 866-966-1020 (staffed 24/7).

INTERNATIONAL BRAIN INJURY ASSOCIATION The official Call for Abstracts for the Tenth World Congress on Brain Injury submission deadline is October 11, 2013. Members of NABIS and all multidisciplinary brain injury professionals are encouraged to submit their original research to what is expected to be one of the most important brain injury events ever held in the United States. The event is scheduled for March 19-23, 2014, in San Francisco, California. The Congress scientific committee will determine the most appropriate format for the presentation, either oral platform or poster. In addition to the oral and poster sessions, the Congress will feature a host of world renowned invited speakers, panels and workshops providing attendees with state-of-the-art research on brain injury research, assessment and treatment. Members of NABIS should note that they are entitled to register for the Congress at the discounted IBIA member rate. For more information, visit www.internationalbrain.org.

NATIONAL ASSOCIATION OF STATE HEAD INJURY ADMINISTRATORS The National Association of State Head Injury Administrators 24nd Annual State of the States (SOS) in Head Injury Meeting “From Model T’s to Modern Times: Emerging Trends in Brain Injury” will be held October 7-10, 2013, in Detroit, Michigan at the Dearborn Inn. The SOS Meeting is the only annual national gathering which provides professional development opportunities among state government program administrators specifically in the field of traumatic brain injury. The Meeting will feature keynote speakers presenting on issues impacting brain injury and state services, national trends, and federal policy. The pre-conference, “Brain Injury, Violence and At-Risk Populations” will focus on shedding light on the connections of pediatric, adult and older adult violence and brain injury

and learning how states can foster connections within these areas of focus. Save the Date: 2014 SOS Conference October 27 - 30, 2014 in Philadelphia, PA! NASHIA, its partners, and the Congressional TBI Taskforce continue their efforts on the re-authorization of the TBI Act which includes: •

• •

The Health Resources and Services Administration (HRSA) to provide funds to states to develop TBI programs that improve access to service delivery for individuals with TBI. Funding to Protection and Advocacy services in each state to ensure legal services are available for individuals with TBI. Funding to Centers for Disease Control and Prevention (CDC) for surveillance, outreach, and prevention efforts specific to TBI, including the creation and dissemination of treatment guidelines.

Remember to contact your legislators to support this vital piece of legislation! Information on SOS, state TBI programs, NASHIA technical assistance, and other resources may be found at www.nashia.org.

UNITED STATES BRAIN INJURY ALLIANCE One year ago, a handful of leading brain injury groups joined forces to create the United States Brain Injury Alliance (USBIA). Today, the success of the initiative can be measured by the joining of 20 state groups as USBIA members. More importantly, though, it is a testament to the groups’ collective commitment to working towards enhancing the quality of life for people affected by brain injury. To see the list of member states, visit www.usbia.org. While we reflect on the attainment of USBIA and the growing strength of the brain injury awareness movement, we remain committed to our mission. On July 29, 2013, USBIA Board Chair Barbara Geiger-Parker attended a meeting with U.S. Department of Health and Human Services Secretary Kathleen Sebilius and several of her advisors. Organized by the Sarah Jane Brain Foundation, Barbara was part of a delegation of 10 people from around the nation, including former Congressman Patrick Kennedy, representing those affected directly by brain injury, professionals and advocates to discuss issues of importance regarding pediatric brain injury.

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legislative roundup “It’s the same old story but it’s told a different way. The more things change the more they stay the same - the same sunrise, it’s just another day.” — Bon Jovi When Congress returns in September, members will be faced with spending bills to continue federal programs beginning October 1st, the new fiscal year, while at the same time needing to address the debt ceiling in order to pay bills already authorized in prior spending bills. In the middle of this debate is the implementation of “ObamaCare”, the Affordable Care Act (ACA), which authorized federal and state health insurance exchanges to be open on October 1st to help people to compare and purchase health insurance. The House of Representatives, however, continues to pass legislation repealing the healthcare reform law, having passed repeal legislation 40 times. As in the past four years, Congress is likely to extend federal spending beyond September 30th through a short-term continuing resolution (CR). Both the House and the Senate Appropriations Committees are far apart with regard to spending for domestic discretionary programs, including the continuation of the across-theboard cuts enacted in the spring due to sequestration. The House appropriation bills would limit total FY 2014 funding to the sequester level plus additional cuts to domestic programs in order to restore defense spending. In July, the Senate Appropriations Committee approved the Labor-HHS-Education FY 2014 spending bill, which funds prevention, research, education, and disability and health care programs. The recommendations include funding increases for CDC’s Injury Center to reduce gun violence through research and to expand the National Violent Death Reporting System beyond the current 18 states which participate in the reporting system. The Senate Committee also proposed using $3 million through the Prevention and Public Health Fund (PPHF) to expand older adult falls prevention activities in coordination with the U.S. Department of Health and Human Services’ (HHS) Administration for Community Living (ACL), which was provided an increase of $7 million through PPHF for complimentary activities. The Committee also included report language to encourage CDC to collaborate with academic centers and sports-affiliated organizations to test and improve sports safety equipment to reduce traumatic brain injury (TBI)/ concussions. The Senate Committee on Health, Education, Labor, and Pensions (HELP) has marked up S.1356, the Workforce Investment Act of 2013, which reauthorizes the job training programs authorized under the Workforce Investment Act of 1998 and programs authorized by the Rehabilitation Act of 1973, as amended. The legislation makes a number of substantial changes with regard to the administration of the vocational rehabilitation (VR) programs. The bill renames the Rehabilitation Services Administration (RSA) to the “Disability Employment Services and Supports Administration” and transfers RSA from the U.S Department of Education (DOE) to the U. S. Department of Labor (DOL); moves the Independent Living Program from DOE to the HHS’ ACL; moves the National Institute on Disability and Rehabilitation Research (NIDRR) to the ACL; and changes the name of NIDRR to the “National Institute on Disability, Independent Living and Rehabilitation.” 38 BRAIN INJURY PROFESSIONAL

During the summer, the Commission on Long-Term Care, created by the American Taxpayer Relief Act of 2012, convened meetings in keeping with its charge to develop a plan for a comprehensive, coordinated, and high-quality system that ensures the availability of long-term services and supports for individuals who are elderly, or with substantial cognitive or functional limitations, or who require assistance to perform activities of daily living, as well as individuals desiring to plan for future long-term care needs. You can follow the Commission’s work on its website: www.ltccommission.senate.gov. While Congress addresses federal spending and other issues, the Administration continues to push forward on the implementation of health care reform. To assist individuals seeking information on health insurance through the health exchanges, HHS has awarded Navigator grant applicants in Federally-facilitated and State Partnership Marketplaces. HHS has launched a new website for consumers, HealthCare.gov, and a 24-hours-a-day consumer call center ready to answer questions in 150 languages. More than 1,200 community health centers across the country are preparing to help enroll Americans who are uninsured. At the same time, the Administration is also proposing changes which would reduce spending for post-acute care under the Medicare program. These proposed changes include bundled payments, beginning in 2018, for post-acute care providers, including longterm care hospitals, inpatient rehabilitation facilities, skilled nursing facilities, and home health providers. Members of Congress are also reviewing the President’s budget proposals and the impact on individuals with disabilities and health care providers. Meanwhile, in accordance with the TBI Act 2008 amendments, CDC has released its report to Congress, Traumatic Brain Injury in the United States: Understanding the Public Health Problem among Current and Former Military Personnel. The report presents the major findings and recommendations of the members of the CDC, NIH, Department of Defense (DoD), and Department of Veterans Affairs (VA) Leadership Panel, who were charged with determining how best to improve the collection and dissemination of information on the incidence and the prevalence of TBI among persons who sustained these injuries while in the military. It is available on the CDC website: www.cdc.gov/traumaticbraininjury/ pubs/congress_military.html. About the Editor

Susan L. Vaughn, S.L. Vaughn & Assoc., is the Director of Public Policy for the National Association of State Head Injury Administrators and consults with the Brain Injury Association of America on state policy issues. She retired from the State of Missouri in 2002, after working nearly 30 years in the field of disabilities and public policy. She served as the first director of the Missouri Head Injury Advisory Council, a position she held for17 years. She founded NASHIA in 1990, and served as its first president.


“Our goal is to provide the highest quality, individualized transitional and long term care for persons with acquired brain injury.” Nathan D. Zasler, MD Founder, CEO & Medical Director Tree of Life Services, Inc.

Chief Editor Nathan D. Zasler, MD

www.Tree-of-Life.com 1-888-886-5462 • Fax 804-346-1956 Administrative Offices 3721 Westerre Parkway, Suite B • Richmond, Virginia 23233


Legal Representation Care Management Brain Injury Attorneys “In every serious injury case we have the opportunity to help make a difference in the recovery and the quality of life of our clients and their families that goes far beyond the legal scope.” -Frank Toral, Esq., Senior Partner

Improving Lives through Caring, Commitment and Community Toral Garcia Battista Attorneys at Law firmly believe that the responsibility of a law practice is not simply a successful settlement but rather providing an individual who has suffered a lifealtering injury, the resources needed to lead a greater quality of life. Focusing on Traumatic Brain Injuries and Spinal Cord Injuries, the TGB firm structure supports care management in the medical and social elements of the clients’ situation through the employment of a team that includes a Registered Nurse and Licensed Clinical Social Worker. The legal and care management team works collaboratively to address the comprehensive needs of the client and facilitate navigating the complex system of care.

The Toral Family Foundation, a 501(c)3 nonprofit organization based in Ft. Lauderdale Florida, is committed to collaborating with the healthcare community to improve the lives of all persons with a brain or spinal cord injury through research, education and access to resources. www.toralfamilyfoundation.org

1-877-TORAL-LAW 4780 Davie Rd., Suite 101 Ft. Lauderdale, FL 33314 www.torallaw.com 40 Tampa

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Advanced Neuroimaging  

This issue of BIP focuses on the latest advances in neuroimaging and provides an overview of how these new technologies can be applied to br...

Advanced Neuroimaging  

This issue of BIP focuses on the latest advances in neuroimaging and provides an overview of how these new technologies can be applied to br...