Shepherd Center supports basic and applied research efforts that are scientifically sound, safeguard the welfare of research participants, and have the potential to advance the field of rehabilitation medicine.

Shepherd Center partners with business, industry and institutions of higher education to develop solutions that improve treatments and outcomes for people with acquired brain injury.

The following is a summary of current initiatives for acquired brain injury research at Shepherd Center:

Donepezil for Chronic Memory & Behavior Dysfunction following TBI (David Ripley, MD, Ronald T. Seel, PhD, Shepherd Center) [236]

Confrontation Naming Performance in Individuals with Brain Injury (Crawford Research Center; Amy Alderson, PhD, Robert Godsall, PhD, Shepherd Center) [257]

The Impact of Cognitive Impairment on Outcomes following SCI (NIDRR Department of Education; Stephen Macciocchi, PhD, Shepherd Center) [288]

A Multicenter, Double – Blind, Placebo-Controlled, Parallel Group Safety Study of Pulmonary Function in Patients with Reduced Lung Function Treated with BOTOXÒ (Botulinum Toxin Type A) Purified Neurotoxin Complex for Focal Upper Limb Post stroke Spasticity (Allergan; Gerald S. Bilsky, MD, Andrew D. Zadoff, MD, David Apple, MD, Karen Kline, PA, Shepherd Center) [289]

Group Treatment and Aphasia: Assessment of Functional Communication(UGA/ Shepherd Center Grant; Rebecca J. Shisler, PhD, Tracey Bradshaw, MS, CCC-SLP, University of Georgia) [324]

Neuroendocrine Functioning in Patients with Traumatic Brain Injury During Acute Rehabilitation: A Pilot Study (Ron Seel, PhD, Stephen Macciocchi, PhD, Amy Alderson, PhD, Shepherd Center) [345]

Medtronic Early Administration of Intrathecal Baclofen for Management of Dysautonomia Following Traumatic Brain Injury(Medtronic; Gerald Bilsky, MD, Ismari Clesson, RN) [347]

Display Enhanced Testing for Cognitive Impairment: (DETECT) (David W. Wright, MD, Emergency Medicine, Emory, Michelle Laplaca, PhD, Biomedical Engineering, GIT, Felicia Goldstein, PhD, Neurology, Emory, Steve Macchiocchi, PhD, Ron Seel, PhD, Shepherd Center) [349]

Developing Evidence-Based Guidelines: Pharmaceutical Interventions for TBI Patients in Acute Rehabilitation (Ronald T. Seel, Ph.D) [355]

Developing a Computer Adaptive TBI Cognitive Measure (Ronald T. Seel, Ph.D., Craig Velozo, Ph.D) [366]

Comparing Effectiveness of Glycerin and Bisacodyl (Dulcolax) Rectal Suppositories for Bowel Management in the Vegetative and Minimally Conscious Patient (Linda Dufour, Gerald Bilsky, MD) [368]

Biopsychosocial Factors That Predict TBI Post-Acute Rehabilitation Outcomes: A Pilot Study (Ronald Seel, PhD, Gary James, PhD) [376]

Donepezil for Chronic Memory & Behavior Dysfunction following TBI (David Ripley, MD, Ronald T. Seel, PhD, Shepherd Center) [236]

The objective of this project is to assess the impact of Donepezil on memory and behavior following traumatic brain injury, in a randomized, double-blinded, placebo-controlled trial. Subjects will be individuals who have sustained a moderate to severe traumatic brain injury as defined by a lowest Glasgow Coma Scale score of 12 or less, who demonstrated post traumatic amnesia for 24 hours or greater, or who demonstrate radiographic evidence (head CT, brain MRI) of intraparenchymal damage following head trauma. Additionally subjects will demonstrate evidence of chronic memory impairment.

Confrontation Naming Performance in Individuals with Brain Injury (Crawford Research Center; Amy Alderson, PhD, Robert Godsall, PhD, Shepherd Center) [257]

The purpose of the study is to develop and expand normative data documenting the language performance of individuals with acquired brain injury (ABI) and individuals without known neurological disorder. The BNT performances of individuals with ABI will be compared to those of uncompromised individuals with no history of neurological disorder. The collected data will be examined in relation to previously established normative data. Finally, given the expected diversity in premorbid language abilities, the BNT will also be compared to performances on other language measures thought to be more resilient to ABI. By using more resilient language benchmarks, this comparison will provide more generalized guidelines for determining impairment in expressive language.

The Impact of Cognitive Impairment on Outcomes following SCI (NIDRR Department of Education; Stephen Macciocchi, PhD, Shepherd Center) [288]

Prior research at Shepherd Center (accepted pending revisions) indicates that cognitive impairment affects learning and functional outcome following SCI at discharge from inpatient rehabilitation. The purpose of this research is to determine whether past or present problems in learning and remembering, or different styles of learning and remembering, affect your ability to benefit from spinal cord rehabilitation programs. The ultimate goal of the research is to determine if special programs are needed to fit the needs of persons who have problems learning during rehabilitation. Participants in this research will be asked questions about school and medical history. Review of medical history to document all injuries sustained, and any related hospitalizations. We will also administer a brief set of cognitive tests, and fill out some questionnaires about health, community functioning and life satisfaction. Study goals are to determine whether premorbid (learning disability-cognitive deficits) or comorbid (brain injury) learning and memory problems affect (1) functional skill acquisition, (2) life satisfaction, (3) general health, and (4) community participation at discharge from inpatient rehabilitation, six months to one year post injury. All SCI persons admitted to Shepherd Center ages 18-65 who are able to comply with testing and history taking, will be considered for inclusion. Tests will not require motor skills.

Measuring Long-Term Outcomes Of People Disabled By Brain Injury: Phase 1, Development And Validation Of An Assessment Tool For Members Of A Clubhouse Community (Debra Berens, Georgia State University, Michael Jones, PhD, Shepherd Center, Roger Weed, PhD, Georgia State University, Cindi Johnson, Side by Side Clubhouse [379]

A Multicenter, Double – Blind, Placebo-Controlled, Parallel Group Safety Study of Pulmonary Function in Patients with Reduced Lung Function Treated with BOTOXÒ (Botulinum Toxin Type A) Purified Neurotoxin Complex for Focal Upper Limb Post stroke Spasticity (Allergan; Gerald S. Bilsky, MD, Andrew D. Zadoff, MD, David Apple, MD, Karen Kline, PA, Shepherd Center) [289]

The purpose of this study is to investigate the safety of BOTOXÒ (Botulinum Toxin Type A) Purified Neurotoxin Complex (designated as BOTOXÒ) verses placebo in medically stable post-stroke hemiplegic subjects with stable compromised baseline respiratory status who have spastic muscles in the upper limb that manifest common spasticity induced patterns of upper neuron syndrome. Subjects will be randomized to receive placebo or a total dose of 240 U or 360 U of Botox injected as per clinical discretion of the investigator into spastic muscles of the upper limb.

Group Treatment and Aphasia: Assessment of Functional Communication (UGA/ Shepherd Center Grant; Rebecca J. Shisler, PhD, Tracey Bradshaw, MS, CCC-SLP, University of Georgia) [324]

The overall goal of this project is to explore whether group treatment in combination with individual treatment improves the functional communication skills of individuals with aphasia. Both groups will receive the same number of hours of treatment each week. Measures will be taken related to linguistic ability, pragmatics, social interaction, social support & modeling that takes place, as those are proposed reasons for greater gains. We will address the following specific aims: Specific Aim 1: Whether group treatment, in combination with individual treatment, improves functional communication skills in individuals with aphasia. Specific Aim 2: To find out whether given an equal amount of treatment hours, group treatment, in combination with individual treatment, improve functional communication skills equal to or more than individual treatment alone.

Neuroendocrine Functioning in Patients with Traumatic Brain Injury During Acute Rehabilitation: A Pilot Study (Ron Seel, PhD, Stephen Macciocchi, PhD, Amy Alderson, PhD, Shepherd Center) [345]

This pilot research study proposes to improve our understanding of how traumatic brain injury affects patients' neuroendocrine levels and behavior. Participants (n=30) would be measured for levels of selected steroid hormones found in their blood (e.g. testosterone, progesterone, cortisol, DHEA) and problems with memory, depression, and apathy. Participants' neuroendocrine levels will be compared with symptoms to see if these symptoms might be related to their neuroendocrine profile. The expected duration of participation is the length of acute rehabilitation treatment, about 4 -6 weeks. Participants will be asked to provide a blood sample at three timeframes during acute rehabilitation stay: (a) when the patient has become oriented, (b) sometime during the middle of stay, and (c) within a few days of discharge. Immediately following taking blood samples, a psychologist will assess whether patients had symptoms associated with depression, apathy, and memory. This will require patients to answer some questions and take a learning and memory test. Participation for each of the three timeframes is expected to take no longer than 30 minutes.

Medtronic Early Administration of Intrathecal Baclofen for Management of Dysautonomia Following Traumatic Brain Injury (Medtronic; Gerald Bilsky, MD, Ismari Clesson, RN) [347]

This study is a double-blinded, randomized trial comparing continuous intrathecal baclofen (ITB) to a placebo control (saline) in reducing dysautonomia in patients after ABI. All patients enrolled in the study will complete baseline assessment of all dependent variables and receive trial injections of ITB. The trial administration will be conducted using the appropriate dosing regimen of bolus injections. Adverse and therapeutic effects will be monitored during this trial administration. Participants who demonstrate a favorable (and no adverse) response to ITB will be implanted with a Medtronic SynchromedTM (or Synchromed II) infusion pump. Patients will be randomized to either an immediate- or delayed-treatment group. Those in the immediate treatment group will begin receiving continuous delivery of ITB (with a starting dosage of 125mg); those in the delayed-treatment group will begin receiving normal saline. Over the next three days, the treating physician will titrate the dosage at up to 20% increments in an effort to achieve therapeutic benefit. On Day 4 post-implant, no changes will be made to the participant's medication and primary dependent variables will be assessed to compare symptom abatement (tone, vital sign fluctuations, episodes of storming) for patients in each group. On Day 5 post-implant, patients who fail to show any therapeutic benefit from medication will be unblinded. Those receiving saline (control) will begin ITB therapy at a starting dosage of 125mg. For patients who are already receiving ITB therapy, titration will resume until a therapeutic dosage is achieved. All participants will be followed for one year to assess long-term safety. Dependent variables will be documented daily beginning at patient enrollment and continuing for two weeks post-implant. Additional rounds of assessment of each dependent variable will be completed at 3-, 6-, 9-, and 12-months post-implant. All patients will be followed for two years after injury date or until NDA approval or study termination. Dosage requirements, system function and side effects will be assessed at each follow-up.

Display Enhanced Testing for Cognitive Impairment: (DETECT) (David W. Wright, MD, Emergency Medicine, Emory, Michelle Laplaca, PhD, Biomedical Engineering, GIT, Felicia Goldstein, PhD, Neurology, Emory, Steve Macchiocchi, PhD, Ron Seel, PhD, Shepherd Center) [349]

The purpose of this study is to compare software used in a virtual reality display device with standard neuropsychological evaluation for detecting mild cognitive impairment (problems with memory, concentration, reaction time, etc.) and concussions. The long-term goal is to develop a concise and effective tool for measuring cognitive impairment. 100 persons with mild to moderate TBI will be enrolled into the study. Approximately 45 minutes of each subject's time will be used to perform the study tests. First, an evaluation will be conducted by one of the study team members involving questions regarding memory, concentration, and orientation. This evaluation requires participants to answer questions and fill out questionnaires. Testing will take approximately 30 minutes. The same tests will then be administered via laptop software with a virtual reality device to assess memory, concentration, and orientation. The computer software test version will take a 15 minutes or less. Participants' test performance will be compared between administration modalities and with norm-referenced scores.

Developing Evidence-Based Guidelines: Pharmaceutical Interventions for TBI Patients in Acute Rehabilitation (Ronald T. Seel, Ph.D) [355]

The purpose of this research is to develop empirically-based pharmaceutical treatment guidelines based on relevant patient and process factors that achieve desirable outcomes. Phase I Objectives include: 1) utilize Clinical Practice Improvement (CPI) techniques; 2) select discrete samples of TBI patients to be studied; 3) evaluate treatment efficacy based on diverse aspects of patient outcomes; 4) identify efficacious pharmaceutical treatments; and 5) analyze the timing, dosage, and duration of drug administration.

Developing a Computer Adaptive TBI Cognitive Measure (Ronald T. Seel, Ph.D., Craig Velozo, Ph.D) [366]

Measures of cognitive functional status are critical tools for clinical assessment and research on the effectiveness of rehabilitation interventions in TBI. Global functional measures such as the Functional Independence Measure are widely used in rehabilitation settings, but only provide a cursory evaluation of cognition. Traditional neuropsychological measures, while standardized and psychometrically sound, are lengthy and often criticized for having weak ecological validity. The purpose of this project is to build an ecologically valid item bank and computer adaptive testing (CAT) prototype for an applied cognitive measure for TBI. Modern test theory provides a basis for developing a measure that is both efficient to administer and precise for assessing cognition along the continuum of TBI recovery. Item Response Theory methodologies, specifically Rasch analysis, can be used to calibrate items thereby providing a means to match item difficulty to cognitive ability levels across stages of TBI recovery. Patient and caregiver participation in this study consists of providing information based on an initial item bank of how well the patient is able to do daily activities related to cognition since their TBI. Patients and caregivers may also be asked to provide feedback on the readability and quality of the item bank questions. Participation may either be in a group setting (focus group) or on a one-on-one basis. Patients will also be asked to take some neuropsychological tests. Likewise, interested staff may participate in rating patients' daily activities related to cognition using the initial item bank. Staff may also be asked to provide feedback on the readability and quality of the item bank questions, likely in a group setting (focus group).

Comparing Effectiveness of Glycerin and Bisacodyl (Dulcolax) Rectal Suppositories for Bowel Management in the Vegetative and Minimally Conscious Patient (Linda Dufour, Gerald Bilsky, MD) [368]

This study is important because there is little information available in the scientific literature to support evidence- based practice in this clinical population. Most clinical practice guidelines suggest the use of some form of suppository, but do not provide treatment recommendations for the type, frequency or what constitutes success. Contrary to the SCI and Stroke literature, there is little to guide brain injury practitioners in specific bowel management strategies. The main aim of this research is to establish the type of suppository as a clinical practice guideline for bowel management in the Rancho I-III patient. All PREP patients are currently placed on a bowel program on ABI; however, it has not been determined which program is more effective in terms of bowel results, cost of treatment and side effects. Glycerin is a milder suppository, with fewer side effects and less potential for physical dependency. It is also a less expensive treatment option that makes it more affordable for family caregivers. In doing so, it is anticipated that the practitioner will be better able to maintain bowel health as well as decrease the burden of care for the family. When patients have a predictable bowel pattern it reduces the amount of time needed for personal cleaning, protects the skin as well as decreases the embarrassment factor of bowel accidents. Family members have also reported more time to engage their loved one in community re-entry and leisure activities when bowel movements are better controlled.

Biopsychosocial Factors That Predict TBI Post-Acute Rehabilitation Outcomes: A Pilot Study (Ronald Seel, PhD, Gary James, PhD) [376]

Persons with moderate to severe TBI now enter post-acute rehabilitation programs earlier in their recovery course. After being discharged home from inpatient rehabilitation, many persons with TBI have difficulty understanding the scope of their impairments and question their need for continued rehabilitative services. A critical challenge for post-acute rehabilitation providers is how to facilitate clients' participation and progress in therapies. Unfortunately, there are no clinical assessment protocols or predictive models to help providers understand the factors that promote or impede post-acute rehabilitation progress, outcomes, and charges. We propose to develop models of biopsychosocial factors that predict post-acute rehabilitation LOS, charges, and functional outcomes. Testing empirically based models is a necessary first step toward improving our understanding of individuals with TBI. Specifically, validated models that identify significant protective and risk factors can serve as assessment protocols that would improve treatment planning and increase the overall efficiency and efficacy of post-acute rehabilitation services. The primary goal of this pilot study is to determine whether the MBMD can be reliably completed by clients in day program treatment. A secondary goal will be to conduct preliminary data analysis to examine whether clients' or family members' ratings of clients' coping style in a medical setting is more related to clients' outcomes.