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  • Traumatic Brain Injury Research Advances with $18.8M NIH Award

    UCSF to Administer Major Award, Part of Large International Research Collaboration

    By Jeffrey Norris on October 22, 2013

    The National Institutes of Health is awarding $18.8 million over five years to support worldwide research on concussion and traumatic brain injury.

    The NIH award, part of one of the largest international research collaborations ever coordinated by funding agencies, will be administered through UC San Francisco.

    The award supports a team of U.S. researchers at more than 20 institutions throughout the country who are participating in the International Traumatic Brain Injury (InTBIR) Initiative, a collaborative effort of the European Commission, the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH) and the U.S. Department of Defense (DOD).

    Although the potential long-term harms due to concussions and blows to the head have gained more attention recently – due in part to media coverage of the experiences of athletes and of soldiers returning from the Middle East – traumatic brain injuries, or TBI, that results from automobile crashes or other common accidents impacts many more people.

    Many of those who are affected by TBI are never diagnosed, according to UCSF neurosurgeonGeoffrey Manley, MD, PhD, a principal investigator for the grant who will serve as the U.S. research team’s primary liaison to the NIH, and the chief of neurosurgery at the UCSF-affiliated San Francisco General Hospital, a Level-1 trauma center. SFGH was the first medical center in the nation to achieve certification from the Joint Commission for the treatment of TBI.

    The U.S. Centers for Disease Control and Prevention estimates that 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion.

    “Each year in the United States, at least 1.7 million people seek medical attention for TBI,” Manley said. “It is a contributing factor in a third of all injury-related deaths.”

    In the work funded by the NIH grant – which also is supported by contributions from the private sector and from the nonprofit One Mind for Research – the researchers aim to refine and improve diagnosis and treatment of TBI, which often has insidious health effects, but which frequently is undiagnosed, misdiagnosed, inadequately understood and undertreated, according to Manley.

    New Approach to Lead to Patient-Specific Treatments

    “After three decades of failed clinical trials, a new approach is needed,” Manley said. “We expect that our approach will permit researchers to better characterize and stratify patients, will allow meaningful comparisons of treatments and outcomes, and will improve the next generation of clinical trials. The work will advance our understanding of TBI and lead to more effective, patient-specific treatments.”

    Geoffrey Manley, MD, PhD

    Since 2009, Manley and Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging at UCSF, have helped lay the groundwork for the continuing TBI research by leading the NIH-funded TRACK-TBI project, through which they and their research collaborators have demonstrated the value of gathering common data across research sites, including a standardized approach to imaging, clinical data, bio-specimens, and tracking outcomes.

    Already, TRACK-TBI researchers have made progress toward more useful classification and prognosis of TBI.

    Earlier this year, they reported that cases of concussion, or TBI that are classified as “mild” by standard criteria but that show abnormalities on early magnetic resonance imaging (MRI) scans, are much more likely to have worse outcomes three months after the scan in comparison to cases in which scans reveal no abnormalities. Furthermore, the researchers found that elevated blood levels of a protein released during brain injury was associated with the likelihood of an abnormal CT scan.

    The new NIH award funds a continuation and expansion of TRACK-TBI. Among the goals is the creation of a widely accessible, comprehensive “TBI information commons” to integrate clinical, imaging, proteomic, genomic and outcome biomarkers from subjects across the age and injury spectra. Another goal is to establish the value of biomarkers that will improve classification of TBI and better optimize selection and assignment of patients for clinical trials.

    The researchers also aim to evaluate measures to assess patient outcomes across all phases of recovery and at all levels of TBI severity, to determine which tests, treatments, and services are effective and appropriate – depending on the nature of TBI in particular patients.

    In addition to Manley and Mukherjee, principal investigators for the newly funded project include Claudia Robertson, MD, Baylor College of Medicine; Joseph Giacino, PhD, Harvard University; Ramon Diaz-Arrastia, MD, PhD, Uniformed Services University of the Health Sciences; David Okonkwo, MD, PhD, University of Pittsburgh; and Nancy Temkin, PhD, University of Washington. Each of these leading experts has worked in the TBI field for two decades or more.

    “The principal investigators bring expertise in neurosurgery, neurology, neuroradiology, critical care medicine, rehabilitation medicine, neuropsychology and biostatistics, all of which are essential and do not reside in any single individual,” Manley said.

    Complete list of TRACK-TBI PIs, Core Leaders, Study Site Leader and Co-Investigators: http://www.brainandspinalinjury.org/maint/files/UCSF-BASIC-PDF-qurptv.pdf

    International Funding and Collaboration

    TRACK-TBI clinical enrollment sites throughout the United States will enroll 3,000 patients across the spectrum of mild to severe brain injuries. Clinical, imaging, proteomic, genomic and clinical outcome databases will be linked into a shared platform that will promote a model for collaboration among scientists within InTBIR and elsewhere.

    Geoffrey Manley, MD, PhD, left, works with members of the surgical team at San

    Francisco General Hospital and Trauma Center.

    In addition to the U.S. award, the European Commission, the executive body of the European Union, has awarded €35.2 million to fund the Collaborative European NeuroTrauma Effectiveness-TBI (CENTER-TBI) consortium, also part of the InTBIR. This project will collect data in over 5,000 patients across Europe, where 38 scientific institutes and more than 60 hospitals will participate.

    In Canada, CIHR and its national partners also have made a multimillion dollar investment in TBI research, the details of which will be formally announced in the near future.

    The InTBIR Scientific Advisory Committee met in Vancouver, British Columbia, on Oct. 17-18, and awardees from all three jurisdictions (EU, USA, Canada) now are aligning efforts to share resources and collaborate on strategies for achieving the InTBIR goals.

    UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital.

     

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  • Paraplegics Show Gains in Study of Spinal-Cord Stimulation

    Patients Regain Voluntary Movement in Legs Even Years After Their Initial Injuries

    A new study gives the greatest indication yet that people paralyzed by spinal-cord

    injuries can regain voluntary movement in their legs and feet even years after their

    initial injuries, researchers said.

     

    A combination of electrical stimulation and intensive physical therapy helped three

    men with paraplegia wiggle their toes and ankles, flex their legs and stand

    independently for moments at a time, according to a paper published online Tuesday

    in the medical journal Brain.

     

    To the researchers' surprise, the treatment worked in two patients with the most

    complete type of paraplegia, who were previously unable to move or feel their lower

    bodies. The finding suggests that the brain is still capable of sending signals to the

    spinal cord in cases where doctors assume all connection has been lost, the

    researchers said.

     

    The research builds on a 2011 study by the same team in which a stimulation device

    helped a man who had lost movement in his legs—but not all feeling—make

    voluntary movements.  With the new study, four out of four patients in whom the

    treatment has been attempted have regained some voluntary movement, the

    researchers said.

     

    None of the patients was able to make independent walking movements, and

    researchers cautioned the improvements were relatively minor, compared with the

    functionality that patients had before their injuries. The results would have to be

    replicated in larger studies before a stimulation device could be considered for

    approval by the U.S. Food and Drug Administration for patients with spinal-cord

    injuries, a process that is likely to take several years, the researchers said.

     

    Vinod Labhasetwar, a scientist at the Cleveland Clinic who wasn't involved in the

    study, said further research was needed to show that patients continue to benefit

    over longer periods. It is possible that the spinal cord may not respond to sustained

    stimulation, said Dr. Labhasetwar, who also is researching treatments for spinal-cord

    injuries.

     

    Nonetheless, the study is further evidence that people with paralysis may be able to

    realize improvements in motor function and quality of life more than two years after

    their initial injuries, the point at which many doctors say patients' conditions are

    unlikely to improve, said Michael S. Beattie, director of research at the Brain and

    Spinal Injury Center at the University of California, San Francisco, who wasn't involved

    in the study.

     

    "This is now an additional three patients, so it is really strengthening the concept that

    this can work," Dr. Beattie said. "It opens up the possibility that these connections

    that were thought not to be there could actually improve function."

     

    The study was conducted by researchers from the University of California, Los

    Angeles and the University of Louisville in Kentucky, who implanted spinal-cord

    stimulators made by Medtronic Inc. into the backs of three patients who

    had been paralyzed by spinal-cord injuries. Afterward, the patients received about

    eight months of physical rehabilitation and training.

     

    All three were able to voluntarily move their legs and toes within days of beginning

    stimulation. The researchers said they believe that stimulation makes the spinal cord

    more receptive to instructions coming from the brain, even when the signals are

    weak.  The researchers assumed that patients like Dustin Shillcox, who lost both

    motor and sensory capability in his legs after a 2010 car accident, wouldn't benefit

    from stimulation because he was unable to feel any sensation in his lower body,

    suggesting that his brain was unable to communicate with his spinal cord. But within a

    week of his stimulator being turned on, Mr. Shillcox, 29 years old, was able to make

    voluntary movements. Mr. Shillcox said he has since gained greater bone density in

    his legs and better bladder and bowel function.

     

    "It's been a long-held belief by scientists and clinicians alike that if you have no

    ability to move after two years, there's not any possibility that you're going to be

    able to move. What these results show is that is not the case," said Susan Harkema,

    one of the study researchers who is rehabilitation research director at the Kentucky

    Spinal Cord Injury Research Center at the University of Louisville and director of

    research at the Frazier Rehab Institute.

     

    The cost of studying all four patients was approximately $2 million, Ms. Harkema

    estimated. The studies were funded by the U.S. National Institutes of Health, the

    Christopher and Dana Reeve Foundation and other nonprofit foundations.

     

    The researchers plan to conduct a similar study with eight additional patients this

    year.  The new study will seek to gauge quality-of-life improvements, in addition to

    better motor function. Another goal is to develop a new device with more flexibility in

    setting stimulation in different areas of the spinal cord. The device that is currently

    being used has been approved by the FDA for the treatment of chronic pain, and isn't

    optimally designed for rehabilitation, the researchers said.

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  • 07/06/2013: Chief of Neurosurgery at SFGH Describes Spine Injuries of Patients in Flight 214 Plane Crash

    PBS NEWS INTERVIEW WITH DR. GEOFFREY MANLEY, Cheif of Neurosurgery, San Francisco General Hospital.  http://www.youtube.com/watch?v=JchsMc0Ha0s

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  • 05/03/2013: The 2012 Reeve-Irvine Research Medal is awarded to Drs. Michael Beattie and Jacqueline Bresnahan

    Over forty years ago, Joan Irvine Smith, a well known Californian and philanthropist, played a lead roll in the establishment of what is now the University of California at Irvine. Following Christopher Reeve’s tragic injury, and in recognition of his amazing spirit, she worked with UC Irvine to establish a spinal cord injury research center in Christopher’s name. Starting with her lead gift of one million dollars, the Reeve Irvine Research Institute grew to become the world-class research facility that it is today.  

    In 1996, the Reeve-Irvine Research Center and Joan Irvine Smith established an annual award for research in spinal cord injury. The award, originally called the “Christopher Reeve Research Medal”, with Christopher’s blessing became the “Reeve-Irvine Research Medal” in 2003.

    The Reeve-Irvine Research Medal recognizes an individual, or individuals, who have made highly meritorious scientic contributions in the area of spinal cord repair, and whose research has stood the test of time and scrutiny. e medal includes a $50,000 cash award generously provided by Joan Irvine Smith and the Athalie R. Clarke Foundation. eir kindness has made it possible to continue to recognize the work of pioneering investigators whose work has brought us closer to cures for aictions aecting the spinal cord. Between 1996 and 2012 twenty one exceptional researchers have received this prestigious award.

    The 2012 Reeve-Irvine Research Medal is awarded to Drs. Michael Beattie and Jacqueline Bresnahan for critical contributions to promoting repair of the damaged spinal cord and recovery of function.

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  • 04/15/2012: Ashlyn Dyer | Presidio 10K Run

    On March 2, 2006 Ashlyn Dyer, an avid marathoner, was the victim of a hit and run accident while running through the Presidio in San Francisco.  Tragically, Ashlyn passed away 10 days later as a result of her Traumatic Brain Injury.

    The strength of Ashlyn’s inspiration and desire to make a difference continues today. In memory of her spirit, the Ashlyn Dyer Foundation for Neurological Research and Support was created. The purpose of the Ashlyn Dyer Foundation is to raise awareness and funding for research, medical support, technological progress and care for the TBI victims.  As a leader in TBI care, San Francisco General Hospital and Trauma Center is the primary recipient of this support.

    Partnered with the Guardsman, the Ashlyn Dyer Foundation hosted its annual Presidio 10K Run on April 15, 2012. In demonstration of our ongoing dedication to TBI care, over a dozen SFGH employees participated in this fun field event to help raise public awareness.

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  • 04/06/2012: Zero Tolerance for Injury Bounty

    April 6, 2012

    By Geoffrey Manley

    The long suspensions handed down by the National Football League to the coaches who orchestrated the New Orleans Saints' injury bounty program may cause some to wonder whether the NFL went too far. Football is a game of hard hits, after all, and is it fair to single out these coaches for such particularly harsh penalties?

    I wonder if the NFL went far enough.

    Like many pro football fans, I felt my stomach turn when I learned of the unsportsmanlike nature of the bounty program. As a neurosurgeon at one of the busiest brain trauma units in the country, I was shocked by the details that have emerged in the past few weeks about the nature of this program.

    Hard hits, whether deliberately intended to injure or not, often result in concussions and brain injuries. I regularly treat athletes of all ages who suffer such injuries, which can end seasons, compromise careers and threaten lives. I also care for U.S. soldiers returning home from war zones with head injuries, as well as civilians involved in car crashes and falls here in San Francisco.

    While medicine has come a long way in the treatment of diseases like cancer, AIDS and diabetes, we are still often operating in the dark when it comes to brain injuries. We have no FDA-approved treatments for concussions. We do not know if some people have risk factors that make concussions worse. We cannot even always diagnose concussions with current technology.

    A growing body of evidence points to severe long-term neurological consequences of concussions and mild traumatic brain injuries. Repetitive head trauma may predispose people for Alzheimer's and other neurodegenerative diseases. But we don't fully understand how.

    It is currently impossible to predict the long-term outcomes of any given injury on the field. We cannot accurately gauge how long it will take any athlete to recover from a traumatic brain injury - not in the same way that we can predict how long broken bones or soft tissue injuries will take to heal. No national registries with long-term follow-up exist for traumatic brain injuries to mirror those for other diseases, like cancer.

    One thing we do know is that the individual and societal costs of these sorts of injuries are extraordinarily high. The combined direct and indirect costs of traumatic brain injuries in the year 2000 (the last year for which we have such figures) were $76.5 billion that year alone. There are some 1.7 million new injuries annually, and an estimated 5.3 million Americans (2 percent of the population) are living with disabilities due to head injuries.

    The NFL, its teams and all its professional football players have been making the right moves with respect to head injuries. One of the items that both players and owners readily embraced in the agreement that ended the NFL lockout at the beginning of last season was the need to protect players from concussions and head injuries.

    New rules aimed at eliminating hard helmet-to-helmet hits and protecting players in defenseless positions have gone into effect. The implementation of a standardized sideline concussion assessment protocol and more stringent return-to-play guidelines is also an important step in the right direction.

    Football fans who were worried about how these new rules would impact the game should have been assured by the season that ensued: We were treated to one of the most exciting and unpredictable playoff races in recent memory, along with one of the best Super Bowls ever.

    Now that the revelations of the New Orleans bounty program have come to light, it is time to start a new national dialogue about concussions and head injuries in all sports. Players and coaches at every level of athletics should take note of the NFL example and follow it.

    Head injuries should never be taken lightly and simply dismissed the way we may have done in the past by saying someone had their "bell rung" when they suffered a hard hit to the head. Head injuries are a serious matter, and it is time that we start thinking about what steps we need to take to protect our athletes from them.

    At the end of the day, however, we need to change the culture of sports. Powerful helmet-to-helmet impacts should be a cause for concern, not celebration. Everyone needs to be aware of the serious risks associated with head injuries, from the parents and coaches of the youngest players to the professional staff on the nation's most elite teams. Every step should be taken to try to avoid potentially harmful collisions in the first place. Players who sustain a concussion should not be allowed back onto the field without medical approval.

    I am not saying we should needlessly soften the game and reduce its entertainment value. As a fan, there is nothing more exciting than watching elite players run, jump, block, throw, catch and - yes - hit. There is absolutely nothing wrong with hard physical play - so long as the head is protected and brain injury is prevented.

    Deliberate attempts to injure others should never be tolerated. Those who advocate for such actions should be suspended forever.

     

    Geoffrey T. Manley, M.D., Ph.D., is the chief of neurosurgery at San Francisco General Hospital and professor and vice chairman of neurosurgery at UCSF. He also co-directs the UCSF Brain and Spinal Injury Center.

    Link to original article on SFGate

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  • 02/15/2012: Improved Emergency Treatment for Prolonged Seizures

    SFGH and UCSF Coordinate San Francisco-wide Participation in Nationwide Study that Finds New Method Safe and Effective

    By Jason Bardi

    When a person is experiencing a prolonged convulsive seizure, quick medical intervention is critical. With every passing minute, the seizure becomes harder to stop, and can place the patient at risk of brain damage and death. This is why paramedics are trained to administer anticonvulsive medications as soon as possible – traditionally giving them intravenously before arriving at the hospital.

    Now a major clinical trial has shown that an even faster method that involves injecting the drugs into the thigh muscle using an autoinjector (similar to a pre-loaded syringe) is just as safe and more effective.

    The trial, carried out in 17 cities and 79 hospitals nationwide, involved 4,314 paramedics who treated some 893 patients ranging in age from young children to the very elderly. It took place from 2009 to 2011.

    San Francisco was the third-highest enrolling city, with 121 patients. The city-wide initiative was coordinated through San Francisco General Hospital and Trauma Center (SFGH), which is part of the city’s Department of Public Health. All eight emergency ambulance destination hospitals in San Francisco participated, as did the paramedics in the San Francisco Fire Department, who administered the medications in the field.

    “This project is a great example of the importance of community-based emergency research and the combined strength of a city’s entire health care system, when we all work together,” said J. Claude Hemphill III, MD, MAS, who led the San Francisco arm of the clinical trial. Hemphill is Chief of Neurology at SFGH and co-director of the UCSF Brain and Spinal Injury Center.

    The results of the trial, sponsored by the National Institutes of Health, are described this week in the New England Journal of Medicine (2/16/12).

    Why Speed Saves Lives

    The particular condition addressed in the study is known as status epilepticus, a seizure that lasts longer than five minutes and does not stop on its own. The episode is a potentially life-threatening emergency that is associated with 55,000 deaths each year. Prolonged status epilepticus can last for hours and sometimes is controlled only with general anesthesia.

    First-line treatment for these seizures has involved administering anticonvulsant medications directly into a vein, but starting an IV line in a patient experiencing convulsive seizures can pose a challenge for paramedics and take precious time.

    Giving an intramuscular shot of anticonvulsant medicine into a patient’s thigh muscle is easier and faster. The motivation for the trial was to determine if it would be as safe and effective as an IV medication. The study compared how well delivery by each method stopped patients’ seizures by the time the ambulance arrived at the emergency department.

    Specifically, the study compared two medicines known to be effective in controlling seizures, midazolam and lorazepam. Both are benzodiazepines, a class of sedating anticonvulsant (antiseizure) drugs. Midazolam was a candidate for injection because it is rapidly absorbed from muscle. But lorazepam must be given by IV.

    What the RAMPART Trial Showed

    The study, formally named the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) study, was the first randomized clinical trial to investigate whether intramuscular (IM) delivery of midazolam was as effective as IV lorazepam. IV medications are the current standard for acute seizure treatment. RAMPART started in June 2009 and completed enrollment in January 2011.

    Paramedics involved in the trial used study boxes with a time-stamped voice recorder that allowed them to indicate the time treatment began and the time the patient’s convulsions stopped, all without having to interrupt patient care to record data. The goal of the study was to stop the patient from having convulsive seizures without having to deliver a second “rescue” dose of medicine.

    In RAMPART, 73 percent of patients in the group receiving IM midazolam were seizure-free upon arrival at the hospital, compared to 63 percent of patients who received IV treatment with lorazepam. Patients treated with midazolam were also less likely to require hospitalization and admission to an intensive care unit than those receiving IV lorazepam. Among those admitted, both groups had similarly low rates of recurrent seizures.

    “It’s much easier to give intramuscular injections than have to start an IV,” said Hemphill. “Given the results of RAMPART, it is time for every emergency medical system in the United States to move toward intramuscular injection of midazolam as a first treatment to stop seizures in the prehospital setting.”

    In the study, paramedics used special autoinjectors that were prefilled with midazolam. The investigators said that while autoinjectors might someday be available for use by epilepsy patients and their family members, more research is required. Because of the strong sedative effect of midazolam, on-site medical supervision is now required for the safety of the patient.

    Another special aspect of the study was that it was conducted under a special federal regulation known as exception from informed consent for emergency research. This exception is designed to protect patients who are involved in research when consent is not possible because of their medical condition. Community consultation is held in advance of the study to raise awareness, ensure transparency, and get input from local residents.

    “This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective,” said Walter Koroshetz, M.D., deputy director of the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH, which funded the study.

    The article, “Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus” by Robert Silbergleit, Valerie Durkalski, Daniel Lowenstein, Robin Conwit, Arthur Pancioli, Yuko Palesch, and William Barsan, for the Neurological Emergencies Treatment Trials (NETT) network is published in the New England Journal of Medicine on Feb. 16, 2012.

    The Neurological Emergencies Treatment Trials (NETT) network of investigators that designed and carried out the trial was established by NINDS to conduct clinical trials on a variety of acute conditions affecting the brain such as seizures, stroke, and traumatic brain injury. NETT investigators are organized into a system of 17 major research hospitals throughout the country, each of which is linked to several community hospitals and other medical centers.

    Additional funding was provided by the NIH Countermeasures Against Chemical Threats (NIH CounterACT) program and the Biomedical Advanced Research and Development Authority (BARDA). The Department of Defense’s Chemical Biological Medical Systems (CBMS) Joint Project Management Office provided the autoinjectors for the trial under a Memorandum of Agreement with NINDS.

    UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

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  • 09/21/2011: 1st in Nation to receive Joint Commission Certification in Traumatic Brain Injury

    Mayor Lee announces SFGH as first hospital in the nation to receive certification in traumatic brain injury in acute care. 

    PRESS RELEASE

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  • 09/08/2011: Dr. Geoff Manley on ABC News

    Dr. Manley discusses the signficance of concussions on ABC's 7live. Click here to watch!

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  • 09/06/2011: Sidelined in Sports Concussions | Interview with Dr. Geoff Manley and Dr. Pratik Mukherjee

    Sidelined: Sports Concussions

    Studying the damage caused by a concussion at its source, inside the brain, is no easy feat. As Dr. Geoffrey Manley, Chief of Neurosurgery at San Francisco General Hospital told me, "What we’re dealing with is one of the most complicated injuries in the most complicated organ in the body. The brain has millions of cells that use many, many neurotransmitters to be able to talk to different regions of the brain, so it’s very complicated."

    It's also an injury that afflicts two million people in the U.S. each year, according to the Centers for Disease Control.

     

    Today, new brain imaging tools are revealing how concussions, which result from a blow to the head that causes the brain to move inside the skull cavity, are more serious than previously thought, producing actual damage to the brain's intricate network of wires that connect key regions of mental activity.

    "The white matter of the brain is essentially the wiring of the brain," said Dr. Pratik Mukherjee, a professor of radiology at the U.C. San Francisco Medical Center. "Brain cells have a transmission unit called the axon, which is a long cable, essentially, that runs for a long distance throughout the brain. And bundles of these axons are called white matter fibers. And they are by analogy the fiber optic cables that produce long-range connection in the brain," he added.

    Diffusion Tensor Imaging, a new, advanced form of Magnetic Resonance Imaging, measures the rate of water movement along the brain's bundle of white matter fibers. Additionally, scientists can also measure changes in the rate of water flow, which would occur in the event of damage to the white matter following, for example, a moderate to severe brain concussion. (Degenerative brain diseases like Alzheimer's Disease can also change the movement of water along white matter fibers). Even more impressively, the direction of this water movement can be tracked, thereby allowing scientists to create 3-D maps which show the connections the fibers make between key brain regions. The different colors in these brain visualizations refer to the different directions the white mater fibers are oriented in the brain, such as up-down and left-right.

    A slide taken from a D.T.I.-rendered visualization of the brain. The arrow points to a region in the frontal lobe that is vulnerable to damage from concussions. Image courtesy Dr. Alexander Leemans.

    Although D.T.I. is not currently in widespread clinical use, it is nonetheless proving to be a promising research tool to better understand the structural damage that concussions can cause.

    "The evidence is that the concussions, especially the ones causing rotational injury to the head, cause microscopic damage to these white matter fibers. And that causes a disconnection of brain regions that should be in communication. And that we believe is the cause of the altered thinking, the altered memory, the altered attention that many concussion patients suffer from," said Dr. Mukherjee.

    This damage is not even visible with Computed Tomography, an x-ray scanning procedure, which has been routinely administered for decades to brain injured patients.

    "A C.T. scan is actually very good for the early phases of trauma," said Dr. Manley. "It tells us whether or not there’s a skull fracture, it tells us whether or not there’s bleeding in the brain. However, we’ve learned over the years that an M.R.I. scan is far more sensitive for looking at abnormalities of soft tissue, and the soft tissue that we’re talking about is the brain. So in fact, an M.R.I. scan gives you a much better picture of the brain than a C.T. scan does," he added.

    Dr. Geoffrey Manley looks at M.R.I brain scans with his colleague, Dr. Alisa Gean, at San Francisco General Hospital.

    Advanced MRI machines that are powered with magnets twice as strong as those employed in conventional MRI machines can now reveal small areas of bleeding, or "micro-bleeds", in the brain after concussions.

    During our filming for this story, Dr. Mukherjee shared with me two sets of scans, one of which was generated with a conventional C.T. scanner, while the other was generated with advanced M.R.I. technology. Both sets of scans were performed on the same concussion-injured patient. Dr. Mukherjee pointed out a black dot on the M.R.I. scans in the left frontal lobe of the patient's brain.

    "This black dot is a micro-bleed, which indicates that there has been damage to the white matter in this location," he said. "This indicates tearing at the level of the brain cells, as well as bleeding in the adjacent blood vessels," he added.

    Damage to the frontal lobe can cause impairments in attention and focus, which Dr. Mukherjee said can be confirmed with timed tests of mental activity given to patients who have suffered concussions.

    Joe Redmond, center, suffered a concussion from a helmet-to-helmet hit while playing on Marin Catholic High School's football team. He lost consciousness after the hit and experienced headaches, confusion and a loss of memory afterwards.

    The new imaging tools are highlighting other regions of the brain that are also vulnerable to damage with concussions. For example, patients who have suffered moderate to severe concussions often complain of memory impairments. Dr. Mukherjee's research is showing that the hippocampus – a structure long known to play a critical role in memory formation and learning – can actually shrink following concussions.

    "It can help explain why some concussion patients have long-term problems with memory, with attention and with other problems with mood and thought," said Dr. Mukherjee.

    But most concussion patients don't suffer any perceptible long-term damage from concussions. In fact, about half the people who suffer concussions recover from their injury in seven to ten days. Nonetheless, they may experience the sluggishness, headaches and mental 'fogginess' that often result from concussions.

    In this group of individuals, the neurological effects of the concussion injury may be due more to neurochemical changes than actual structural damage to the brain's white matter.

    Eric Freitag, a neuropscyhologist based in Walnut Creek, helps roughly 60 to 70 mostly adolescent athletes each year get back on track following their concussion injuries. I asked him to explain to me how a concussion can disrupt the neurochemical activity of brain cells.

    "At the moment of impact of a concussion, all cells in the brain fire. And the brain is asking for more energy, but also in that moment of impact, you have a dramatic decrease in brain blood flow," Freitag said. The energy the brain uses is in the form of glucose which is carried in the blood flowing into the brain.

    "So when the brain is asking for more energy, your body can’t provide it. And it’s this metabolic mismatch that causes the symptoms of a concussion. It causes the confusion, it can cause the loss of consciousness, and also other neurological symptoms that can occur for minutes, hours, days, weeks and sometimes months," he added.

    Both Dr. Mukherjee and Dr. Manley stress that additional work must be done before the widespread adoption of advanced M.R.I imaging techniques in clinical settings like an emergency room. Nonetheless, they hope that the technological advances in brain imaging will help clinicians more nimbly diagnose and more effectively treat this complex and all-too common injury.

    "In the future, a patient will come in, we will have an M.R.I, we will have a blood test where we can go back and we can say, ‘this is the diagnosis that you carry, this is my specific treatment for you.’ But the only way that we’re going to get there is with the same kind of focus, comprehensive and well-funded effort that’s been applied to cancer and heart disease," he said.

    A special thanks to Dr. Alexander Leemans for the kind use of his 3D tractography brain imagery and animations.

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  • 07/16/2011: 2011 Alzheimer’s Association International Conference

    Source:
    Steve Tokar

    415-221-4810 x5202

    July 19, 2011

    Patients diagnosed with traumatic brain injury (TBI) had over twice the risk of developing dementia within seven years after diagnosis compared to those without TBI, in a study of more than 280,000 older veterans conducted by researchers at the San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF).

    “This finding is important because TBI is so common,” said senior investigator Kristine Yaffe, MD, chief of geriatric psychiatry at SFVAMC and professor of psychiatry, neurology and epidemiology at UCSF. She noted that about 1.7 million Americans are diagnosed with TBI each year. In addition, she said, TBI is often referred to as the “signature wound” of the wars in Iraq and Afghanistan, where it accounts for 22 percent of casualties overall and affects up to 59 percent of troops exposed to blasts.

    The study authors analyzed the medical records of 281,540 veterans age 55 or older who received care through the VA from 1997 to 2000 and did not have a prior history of dementia. They found that 15 percent of veterans who received a diagnosis of TBI developed dementia by 2007, compared with 7 percent of those not diagnosed with TBI. Even after controlling for factors such as age, medical history and cardiovascular health, the authors found that a TBI diagnosis still doubled the risk of dementia.

    The findings were presented at the 2011 Alzheimer’s Association International Conference on Alzheimer’s Disease in Paris, France.

    Lead author Deborah Barnes, PhD, a mental health researcher at SFVAMC, said that the study is one of the first to examine the association between dementia and different types of TBI diagnosis, including intra-cranial injuries, concussion, post-concussion syndrome and skull fracture. “It didn’t matter what type of diagnosis it was – they were all associated with an elevated risk of dementia,” said Barnes, also an associate professor of psychiatry at UCSF.

    The authors speculated that among potential causes for the increased risk, the most plausible is that TBI is associated with diffuse axonal injury, or swelling of the axons that form connections between neurons in the brain. This swelling, explained Yaffe, is accompanied by the accumulation of proteins, including beta-amyloid, which is a hallmark of Alzheimer’s disease. “The loss of axons and neurons could result in earlier manifestation of Alzheimer’s symptoms,” said Yaffe.

    Barnes said that for veterans, the findings have different implications depending on the age of the veteran. “Older veterans who have had some kind of head injury should be monitored over time, so that if signs of dementia develop, treatment can begin as soon as possible,” she said. “For younger veterans, early treatment and rehabilitation following TBI may help prevent the development of dementia over the long term.”

    Co-authors are Kristine R. Krueger, PhD, of the South Texas Veterans Health Care System; Amy L. Byers, PhD, MPH, of SFVAMC and UCSF; and Ramon Diaz-Arrastia, MD, MPH, of the University of Texas Southwestern Medical Center.

    The research was supported by funds from the Department of Defense that were administered by the Northern California Institute for Research and Education.

    NCIRE - The Veterans Health Research Institute - is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

    SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

    UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

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  • 07/10/2011: Bryan Stow's Family Has Hope Amid Uncertainty

    Relatives of Injured Fan Cling to Hope of Recovery

    By Demian Bulwa


    CHRONICLE STAFF WRITER


    Bryan Stow’s eyes track his children as they circle his bed at San Francisco General Hospital, and he seems to watch his two sisters when they rub lotion into his feet and ask him, “How does that feel?”

    He turns his head toward a Giants game on TV, and at times blinks on command. When his girlfriend kisses him, he doesn’t kiss her back. But she says, perhaps hopefully, “He kind of pushes his lips out, like he’s attempting to pucker.”

    They are signs of life, and seeds of hope. But more than three months after an a ttack outside Dodger Stadium shocked the public and left Stow with a wounded brain, the cold reality is this: No one knows where these small steps will lead.

    Not Stow’s family members, who make a daily trip from Santa Cruz County to his bedside. And
    not his doctor, who calls traumatic brain injuries — which kill 50,000 Americans a year and disable 80,000 more — an unconquered frontier.

    “We haven’t gotten to first base with traumatic brain injuries,” said Dr. Geoff Manley, the hospital’s chief neurosurgeon. “We’ve gotten much better at getting people to survive, but we have a lot of work to do to help people recover.”

    Stow is anything but alone among Manley’s
    patients, who have suffered falls and car wrecks, bullet wounds and bludgeonings. As with many of them, Manley doesn't know where Stow will "plateau," whether he will walk, speak or go home.

    Stow would not have survived his assault a decade ago, Manley said. But looking deeper into the brain and making better predictions about how patients like Stow will fare in the long term, he said, remains "one of the holy grails."

    Waiting game

    For now, an excruciating waiting game surrounds Stow, a 42-year-old paramedic from Santa Cruz who, according to Los Angeles police, was taunted and then punched and kicked by two men in Dodgers attire after an Opening Day game against the Giants on March 31.

    Stow's loved ones, meanwhile, are locked in a surreal routine, scrutinizing his every move. He isn't comatose, but Manley won't attach a word to his condition beyond that.

    Some days are rewarding and others dispiriting, because Stow's progress, while slow, is not steady. In the hospital parlance, he "waxes and wanes." So do the emotions of his family.

    "I'm just so tired," his mother, church secretary Ann Stow, said on a recent afternoon after emerging from her son's room. Crying, she said, "When you see a response that's there one day, and then not there the next day, it's hard."

    No-cry zone

    It's not clear if Stow sees that his family is with him, but if he does, he doesn't see the tears.

    "If we start to cry, we leave the room," said his sister Erin Collins. "We just don't want him to see us upset. Maybe that will scare him."

    Stow's family talks to him for hours each day, saying, "You can do it," and, "We're not leaving." Or they say, "Bryan, you've got to wake up and read all this stuff they're saying about you. You're a rock star!"

    They get him up to speed on his kids, 12-year-old Tyler and Tabitha, 9, and his beloved Giants. They play the 1980s metal tunes he grew up with, and read him the messages of support that flood in. Collins and Bryan's other sister, Bonnie Stow, give him manicures and pedicures.

    "He's a major metrosexual," explained Bonnie Stow, laughing.

    Yes, there is also laughter at the hospital, because that has always been Stow's way, as quick with a joke as he was to fix his gelled-up hair if it fell out of place. He would expect loved ones to make light of his situation, they said, and so the blue helmet that Stow wears when he's moved to a chair is his "big boy helmet."

    $56 billion

    If the family is anguished, Manley is frustrated. At a recent news conference, while updating Stow's condition, the 50-year-old Kentucky native, who is stocky and intense, looked into the cameras and urged people to call their legislators to demand more funding for research into brain damage.

    "This is really a political issue," he said.

    According to government figures, 1.7 million Americans suffer traumatic brain injuries each year, costing $56 billion in treatment and lost productivity. Today, 5 million people need help with daily activities because of such injuries, which impair everything from speech to memory to personality.

    The shooting of Arizona Democratic Rep. Gabrielle Giffords, increased focus on football concussions, and combat casualties in U.S. wars in Iraq and Afghanistan have brought attention to brain injuries.

    Still, the National Institutes of Health funds just $85 million in research per year. The Defense Department, faced with escalating troop injuries, has filled some of the void, spending nearly $900 million since 2007 to study brain injuries and post-traumatic stress disorder, a spokeswoman said.

    Specific treatment needed

    In a series of interviews, Manley complained of the "primitive" tools of his trade, like the pressure monitors that are drilled into patients' heads. Extensive research into cancer and AIDS have prompted quantum leaps in treatment of those diseases, Manley said, but brain injuries await their moment.

    In essence, he said, there aren't specific treatments or drugs for injured brains, nor diagnostic tools to help tailor such therapies. "Right now we kind of use a one-size-fits-all approach," he said.

    One hurdle is the complexity of the brain. In the laboratories of San Francisco General Hospital, researchers study how the brain learns and heals, but translating their findings to patients remains difficult. Another problem is the way humans think about traumatic injuries.

    "You and I probably believe we have a chance of getting prostate cancer," Manley said. "Our wives and mothers worry about breast cancer. But for some reason, people never believe they're going to be walking down the street and be hit by a car."

    The ravages of brain injuries were apparent during Manley's rounds in the brain trauma unit one recent morning.

    The 'dark side'

    A slender teen with a mop of hair moved his arms and legs back and forth but couldn't close his eyes when prompted by chief neurosurgery resident Michael Oh. A collage of pinned-up photos showed him smiling, laughing, wearing a tie for a school dance, before the car crash.

    "He's really coming around now," Manley said of the boy, who had been given heavy opiates. "That doesn't mean he's going to be the kid in those pictures. But he could be."

    A toddler who had fallen down stairs slept, his mother curled beside him. A young athlete - his muscled body a stark contrast to his breathing and feeding tubes - showed progress, but with a catch.

    "He's been trying to get up," reported his nurse, Kevin Langley. "He was a five-person hold-down at one point."

    As he moved from one patient's room to another, Manley said, "We sort of make sure nothing bad happens, and wait and watch, and hope they wake up."

    In the past, he said, doctors were quicker to give up and take patients off life support. Now, aggressive doctors are saving more lives, and some of those people are returning to work.

    Such an approach, though, comes with a "dark side," Manley said.

    "If we treat (a patient), get him through the live-die phase, and he doesn't recover, that's a bad outcome," he said. "It would probably be easier on some families if a patient dies after three days rather than three months."

    Langley added, "It's self-destroying to watch people linger in a state they'll never recover from."

    Near death

    Stow has come a long way since he was rushed from the Dodger Stadium parking lot to Los Angeles County-USC Medical Center.

    He had a fracture in the middle of his head, back to front, perhaps from falling and striking the parking lot concrete, said his original doctor, assistant clinical professor of neurosurgery Gabriel Zada.

    Worse, Stow had severe contusions to both of the frontal lobes of his brain, a known cause of coma. The underlying sinus - which drains blood from the brain - was also injured.

    Zada drilled a hole in Stow's skull for the monitor that measures pressure and drains fluid. The procedure worked at first, but Stow's injured brain continued to swell on the second day, and Zada had to remove half of his skull to give it room.

    "The skull cavity is a closed system," Zada said. "If the pressure goes up in the brain, nothing else can get in there, like oxygen and blood and nutrients."

    Induced coma

    Doctors had another challenge: controlling seizures that can do more damage to the brain. Experts were brought in to give Stow more than a half dozen antiseizure drugs, and he was put into a coma for several weeks.

    "The idea," Zada said, "is to put the brain almost into a hibernation mode, to completely shut down its electrical activity and let it heal, and then jump-start it."

    Once the fight to control the seizures had been won, Stow was flown to San Francisco General, where he has been slowly weaned from his antiseizure medications - a delicate process that continues. Although the drugs were pivotal, Manley said, they also depressed Stow's consciousness.

    "The thing that's really clouding the picture of the future now," said Manley, "is that we don't know whether his exam is being altered by the medications, or whether this is just where he is."

    Dreaded questions

    Stow's family believes the public thinks he's doing better than he is, especially after his condition was upgraded late last month, from critical to serious. Still, they remain optimistic, partly because of how far Stow has come - and partly because there's not much of an alternative.

    "I can't picture anything less than him being Bryan," said Collins, his sister. "On those negative days, I get to thinking about lifelong care, and that gets me down, because I just can't picture that."

    When Tyler and Tabitha visit, they touch and hug and kiss their dad. But they also ask what their mother, Jacque Kain of Scotts Valley, calls the "dreaded questions," including: "Is he going to remember us?"

    "We've talked about what happens when he does wake up," said Kain, who remained good friends with Stow after the couple's divorce. "I tell them, 'Daddy spent all these years teaching you, and now you may need to teach your dad.' "

    For Ann Stow, the only way to cope is to remain in the moment. Asked what her expectations are for her son's future, she said, "Ask me tomorrow."

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  • 04/17/2011: Ashlyn Dyer | Presidio 10K Run 2011

    ASHLYN DYER FOUNDATION FOR NEUROLOGICAL RESEARCH

    The donation of Ashlyn Dyer's organs gave the gift of life to many. In this same spirit, The Ashlyn Dyer Foundation for Neurological Research and Support has been created to honor her memory by making a positive impact for other affected with Traumatic Brain Injury.

    Injury to the brain or spinal cord affects nearly 2 million people in the United States each year, causing permanent functional disabilities including paraplegia, quadriplegia, and cognitive disorders. Every 15 seconds someone receives a head injury, and every five minutes one of these people will die. Survivors of severe brain injury typically face five to ten years of intensive services. The cumulative mean cost of this care is currently 4 million dollars per patient.

    Bringing new treatments from the laboratory setting to patients requires an integrated effort among basic researchers, clinical researchers, and clinicians. With this in mind, the UCSF Brain and Spinal Injury Center (BASIC) was formed in 2002 to promote collaborative basic, translational, and clinical studies on injuries to the brain and spinal cord.

    The Ashlyn Dyer Foundation for Neurological research aims to fund research and raise public awareness. Its ultimate goal is to improve care and reduce the burden of this disease often referred to as The Silent Epidemic.

    April 17,2011 will be the fourth year for the Presidio Run in San Francisco that is sponsored by the Guardsmen philanthropic group in San Francisco. It is a 10K and 10 mile run through the Presidio and over the Golden Gate Bridge and has been well attended. You can register on line at the Presidio 10 Race 2011 website. We cannot thank the Guardsmen enough for their support and helping us with awareness for brain and spinal cord injury.

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  • 03/31/2011: Update on Traumatic Brain Injury and Stroke

    Traumatic Brain Injury and stroke continue to impact morbidity and mortality in the United States. Our mission is to improve recovery through early diagnosis and intervention.

    The program spanned diagnosis to discussions of current and developing strategies to manage TBI and Stroke. 

    Handout formats of the presentations are linked below: 

    Unraveling the Mysteries of Traumatic Brain Injury: Why we do what we do! Twyila Lay, NP

    Neurological Exam Made Easy! Mathieu Laroche, MD

    DVT Prophylaxis in Neurotrauma, Michael Huang, MD

    Rancho Los Amigos Cognitive Scale, Lisa Pascual, MD

    Management of Hemi-Neglect, Phoebe Belsky, MS, CCC-SLP & Daniel Drummer, DPT, PT

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  • 03/01/2011: For Brain Injuries, A Treatment Gap

    The first two doctors who examined Scott Hamilton 's fractured skull told his wife that he wouldn't make it through the night. A third believed he could save Hamilton's life.

    How does funding affect your rehabilitation?

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  • 02/18/2011: The Today Show | Mysteries of the Brain

    Dr. Nancy Schneiderman's special reports on how the brain works, concussion and traumatic brain injury. 'Surviving Traumatic Brain Injury' features the care provided at San Francisco General Hospital and two survivors of TBI cared for by Dr. Geoff Manley and his team at SFGH. Click on the links below to watch the report.

    Brain Blast: Best of TODAY'S 'Mysteries of the Brain' Series

    How Serious are Concussions?

    Surviving Traumatic Brain Injury

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  • 01/22/2011: What will Gifford's Recovery Involve?

    Dr. Geoff Manley comments on what Congresswoman's recovery from a gunshot wound to the head involve on the Today Show. 

    What will Gifford's Recovery Involve? 

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  • 12/15/2010: Jacqueline C. Bresnahan Named SAC Chair

    Jacqueline C. Bresnahan, PhD has been named chair of the Reeve Foundation Science Advisory Council. Click here to read more. 

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  • 10/25/2010: 9th Annual Neurotrauma Symposium

    Every fall, the Brain and Spinal Injury Center holds a multi-disciplinary symposium on the current topics in traumatic brain injury and spinal cord injury. This is an all day affair that is currently held on the UCSF Mission Bay campus. Typically, eight to ten specialists throughout the Bay Area present their latest research findings or treatment protocols. This is a day of education and collaboration amongst the neurotrauma specialists.

    This year, the complete power point presentations will be listed here and are available for printing prior to the symposium. Click below to access:

    Epidemiology: Pre-hospital Care, Brain and Spinal Injury, Geoffrey Manley, MD, PhD

    Imaging Brain and Spinal Injury, Alisa Gean, MD, PhD

    Fatigue after TBI: Understanding the role of depression, sleep, pain and hormones, Jeffrey Englander, MD

    Coagulopathy in Traumatic Brain Injury, Mathieu Laroche, MD

    Decisional Capacity in the Traumatically Injured, Christina Weyer Jamora, PhD

    Post-Traumatic Hydrocephalus, Julia Galletly, ACNP

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  • 10/18/2010: Dr. Geoff Manley Featured on Discovery Channel's "Mythbusters"

    The Discovery Channel contacted Dr. Geoff Manley to appear on an upcoming segment exploring the myth that humans only use 10% of their brain. Grant Imahara, the mythbuster, visited the Brain & Spinal Injury Center in June 2010 to discuss the details behind this myth. Click here to watch.

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  • 05/19/2010: Dr. Geoff Manley Receives NIH Grant for Traumatic Brain Injury Research

    The chief of neurosurgery at San Francisco General Hospital and professor of neurosurgery at UCSF treats hundreds of brain- and spinal-trauma patients every year. UCSF and Manley recently received a $4.1 million grant to conduct a pilot study that would redefine the way traumatic brain injuries are classified. Read more at the San Francisco Examiner.

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  • 04/16/2010: New Guidelines Aim to Improve Studies of Traumatic Brain Injury

    The U.S. Centers for Disease Control and Prevention estimates that 1.7 million Americans suffer a traumatic brain injury (TBI) each year in car accidents, falls, or other mishaps. Unfortunately, the doctors who treat them have limited options. Click here to read more.

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  • 08/28/2009: Alzheimer's Drug Could Delay Dementia | Dr. Susanna Rosi on ABC News

    Dr. Susanna Rosi investigates a drug that might work to treat Alzheimer's disease if it's used in time. Click here to watch.

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  • 06/20/2008: Spinal Cord Repair | A Conversation with Jacqueline Bresnahan and Michael Beattie

    Spinal cord repair: Daydream or New Day? Drs. Bresnahan and Beattie discuss current research to limit paralysis after spinal cord injury with Science Cafe's Jeff Miller.

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