XIV. Spinal Cord Injury and Related Neurological Disorders

A. General



Abba J. Kastin, MD; Weihong Pan, MD; William A. Banks, MD
VA Medical Center, New Orleans, LA 70146; Tulane University School of Medicine, New Orleans, LA 70146

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B2004-RA)

PURPOSE--Neurotrophins are involved in cell survival and activity in the central nervous system (CNS). They may promote normal function of the CNS and rescue neurons from degeneration when applied locally. We studied the permeability of the blood-brain barrier (BBB) to neurotrophins to test their therapeutic potential after peripheral administration.

METHODOLOGY--Using radioactive tracer techniques, we studied the penetration of several neurotrophins--nerve growth factor (NGF), bNGF, neurotrophin-3 (NT3), neurotrophin-5 (NT5), and brain-derived neurotrophic factor (BDNF)--from the periphery into the spinal cord of normal mice. Multiple time-regression analysis was used to measure the rate of entry of the neurotrophins into the CNS. Reversed phase high performance liquid chromatography (HPLC), SDS-polyacrylamide gel electrophoresis (SDS-PAGE), and acid precipitation were conducted to verify the intact nature of the recovered cytokine and assess the extent of degradation. The capillary depletion method combined with intracardial perfusion was adopted to demonstrate the compartmental distribution of the neurotrophins, thereby differentiating the complete passage into the CNS parenchyma vs. loose adherence to the capillary walls or residual remaining in the capillary bed vs. endocytosis in the endothelial cells of the capillaries comprising the BBB. Saturability of passage across the BBB was tested by inclusion of unlabeled neurotrophins in the intravenous injection or in the in-situ brain perfusion by a pump.

PROGRESS--The neurotrophins showed relatively high BBB permeability, comparable to some bioactive peptides that have saturable entry to the CNS after intravenous administration. In general, there was a common pattern of regional difference, in that the cervical and lumbar spinal cord had significantly higher permeability than the thoracic spinal cord and the brain. In each CNS region, there were apparent differences among individual neurotrophins. In the brain, the unidirectional influx rate (Ki) for NGF was 8.5×10-4 ml/g-min, followed by bNGF, NT5, NT3, and BDNF in descending order. In contrast, the permeability of the BBB in the three regions of the spinal cord, measured by the Ki, were 2-3 times higher.

  In addition to the fast entry and the self-inhibition by excess unlabeled neurotrophins, suggesting saturability of the transport system, there are two main unexpected findings. First, the entry rate of the 7s NGF (pentomer of about 130 kD) was twice as fast as that of its smaller bioactive subunit bNGF (dimeric protein of about 27 kD), indicating that the two neurotrophins may use different transport systems. Second, BDNF, which had a saturable entry into the brain confirmed by the in-situ brain perfusion studies, demonstrated a paradoxical increase in Ki with multiple-time regression analysis after addition of excess unlabeled BDNF in the intravenous injection, probably suggesting positive cooperativity or interactions with blood components.

  Thus, neurotrophins can cross the BBB from blood to arrive at brain and spinal cord. Passage occurs by fast, saturable transport systems that show regional variations. The individual differences among the neurotrophins suggest involvement of different transport systems because each substance has similar molecular weight and lipophilicity. Since the neurotrophins have certain specific yet overlapping target populations of neurons, these findings may provide a basis for determination of which neurotrophin is the best to administer in certain disease states or lesions in certain regions. In general, neurotrophins have potential therapeutic effects to the CNS diseases after peripheral administration.




Hosea Fu-Shih Huang, PhD; Leonard M. Pogach; John E. Ottenweller
East Orange VA Medical Center, East Orange, NJ 07019; Department of Surgery, Section of Urology, UMD-New Jersey Medical School, Newark, NJ 07103; email: huanghf@umdnj.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B885-RA)

PURPOSE--Previously, we demonstrated a decrease in the number of proliferating spermatogonia in the rat during the acute phase of spinal cord injury (SCI) and disappearance of proliferating spermatogonia in adult rats during the chronic stage of SCI while undifferentiated spermatogonia persisted. These observations suggest that the undifferentiated spermatogonia are unable to undergo normal active proliferation after SCI, resulting in the decrease and eventual disappearance of proliferating spermatogonia in SCI rats. In addition, Sertoli cell function appears to be altered during the chronic stage of SCI. The current study examined the effects of SCI on Sertoli cell functions, as well as the proliferative potential of the undifferentiated spermatogonia in adult rats with Sertoli cell enriched (SCE) testes.

METHODOLOGY--SCE rats were produced by X-irradiation of pregnant rats on the 20th day of gestation. The male rats (75-80 days old) with SCE testes were subjected to surgically induced SCI by transection of the spinal cord at T9. The SCI-SCE rats were killed at various times and their testes used for histology and Northern blot analysis of mRNA transcripts for Sertoli cell proteins.

RESULTS--The SCE testes were characterized by the absence of spermatogenesis in >65 percent of the tubular cross sections in which only Sertoli cells remained. Active spermatogenesis was present in the remaining 30-35 percent of the tubules.

  The effects of SCI on the seminiferous epithelium were demonstrated by the abnormalities in the remaining spermatogenic cells during the first month after SCI. Unexpectedly, testis weights of the SCI-SCE rats were maintained during the course of the experiment, and active spermatogenesis, including qualitatively complete spermatogenesis, persisted in 41 percent of the tubules 90 days after SCI, as compared to 46 percent in control rats. This result is different from that in regular SCI rats in which spermatogenesis is totally regressed 90 days after injury. Northern blot cDNA hybridization revealed that the levels of mRNA for androgen receptor (AR), follicle stimulating hormone receptor (FSH-R), androgen binding protein (ABP) were normal while transferrin (Trf) mRNA had decreased by 40 percent 3 days after SCI. Thereafter, the levels of mRNA for these Sertoli cell proteins increased and remained significantly elevated 90 days after SCI. These results demonstrate that the undifferentiated spermatogonia in the SCE testes were able to proliferate and differentiate continuously after SCI, resulting in the persistence of spermatogenesis during the chronic phase of SCI. The presence of elevated levels of mRNA for AR, FSH-R, ABP and Trf during the chronic stage of SCI suggests an up-regulation of Sertoli cell functions and may reflect the effects of SCI on Sertoli cell functions. These changes in SCE testes may thus contribute to the persistence of spermatogenesis in these testes.

IMPLICATIONS--Maintenance of spermatogenesis in SCI-SCE testes suggests that the behaviors of the undifferentiated spermatogonia after SCI perhaps are dependent upon the paracrine and/or endocrine environment within the seminiferous epithelium. Thus, manipulation of the intratubular environment by endocrine or other therapeutic regimens may modulate the proliferation and differentiation of the undifferentiated spermatogonia and thereby may facilitate the maintenance of spermatogenesis. These results provide scientific rationale for the development of therapeutic regimens to preserve spermatogenic function and sperm function in SCI patients.

FUTURE PLANS--We will investigate the mechanisms responsible for the differences in the effects of SCI on the proliferative behavior of undifferentiated spermatogonia in SCE testes and that in normal testes. In addition, we will examine the efficacy of various endocrine regimens including testosterone and GnRH-antagonist on the maintenance and restoration of spermatogenesis during different phases of SCI.



Hosea Fu-Shih Huang, PhD; Leonard M. Pogach; John E. Ottenweller
East Orange VA Medical Center, East Orange, NJ 07019; Department of Surgery, Section of Urology, UMD-New Jersey Medical School, Newark, NJ 07103; email: huanghf@umdnj.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B885-2RA)

PURPOSE--Our previous results demonstrated that regression of spermatogenesis in surgically induced spinal cord injury (SCI) rats can be prevented by exogenous testosterone (T), but is paradoxically enhanced by follicle stimulating hormone (FSH). Because both FSH and T are essential for normal Sertoli cell functions and spermatogenesis, we undertook additional experiments to delineate the effects of SCI on the responses of Sertoli cells to FSH and T.

METHODOLOGY--SCI was induced in adult Sprague Dawley rats by surgical transection of the spinal cord at T9. Immediately after the surgery, the SCI rats were given daily injection of 0.1 unit of porcine FSH, implantation of 2×5 cm testosterone capsules (TC), or the combination of both for 2 or 4 wks. Control animals were sham-operated and received identical hormonal regimens. The response of Sertoli cells to the hormones was determined by Northern analysis of the steady state level of mRNA for the receptors for androgen (AR) and FSH (FSH-R) as well as specific Sertoli cell proteins, androgen binding protein (ABP) and transferrin (Trf).

RESULTS--In control animals, daily injection of FSH for 2 wks did not affect the expression of mRNA for ABP and Trf. While not affecting ABP mRNA, T when administered alone or in combination with FSH resulted in >40 percent decrease in Trf mRNA (p<0.01). In the testes of SCI rats, Trf mRNA was also significantly suppressed by TC alone (p<0.01), but this effect was prevented by concomitant administration of FSH. On the other hand, FSH and TC when administered alone or in combination resulted in 20-50 percent higher ABP mRNA level in the testes of SCI rats than that in controls (p<0.05). These changes were associated with an up-regulation of FSH-R by FSH and TC. These results suggest that SCI is associated with altered FSH regulation of Sertoli cell functions. In addition, FSH treatment of SCI rats resulted in an increase in testicular and serum testosterone concentrations (p<0.01). These results further suggest that paracrine interaction between Sertoli and Leydig cells might also be affected after SCI, resulting in changes in the steroidogenic function of Leydig cells. These changes perhaps can be attributed to the lack of neural imput to the testes as a resulty of SCI, and may result in abnormal endocrine and/or paracrine environment in the seminiferous epithelium and thereby contribute to the abnormal and eventual regression of spermatogenesis.

IMPLICATIONS--Changes in the responses of Sertoli cell proteins to FSH in SCI rats suggest that the FSH/FSH-R signal transduction system in these rats might have been altered. These observations imply the presence of putative neural-endocrine interaction in the regulation of Sertoli cell function and spermatogenesis. Further identification of the mechanisms involved in this interaction will provide new insights into the neural control of Sertoli cell function and that of proliferation and differentiation of spermatogenic cells, and will facilitate the development of therapeutic regimens to preserve spermatogenesis and reproductive function of SCI men.

FUTURE PLANS--Because the importance of testosterone and FSH in Sertoli cell function and spermatogenesis, it is essential to understand the cause for the changes in Sertoli cell responses to FSH and its interaction with testosterone after SCI. In addition, physiologic significance of these changes on spermatogenesis during the acute and chronic phase of SCI will also be examined. We are currently conducting some of such experiments including the responses of spermatogenic cells to hormone replacement.




D.L. Brown-Triolo; Ronald J. Triolo, PhD
Cleveland FES Center, Case Western Reserve University, Cleveland OH 44106; Motion Study Laboratory, Cleveland VA Medical Center, Cleveland, OH 44106; MetroHealth Medical Center, Cleveland, OH; email: rxt24@po.cwru.edu

Sponsor: Department of Veterans Affairs Center of Excellence in FES, Cleveland VA Medical Center, Cleveland OH 44106-1702

PURPOSE--Persons with disabilities are often excluded from the process of developing new technologies aimed at increasing their quality of life. As a first step in incorporating consumer input into the design of functional electric stimulation (FES) systems for lower limb function, a quantitative survey was constructed and applied to identify the personal implications of lack of mobility due to spinal cord injury (SCI). The purpose of this study is to ascertain consumer priorities for mobility function, the acceptable quality of the motions desired, and the tolerable costs required to achieve them. It is designed specifically to determine satisfaction with the outcome of conventional rehabilitation for personal mobility by identifying goals for improvement in lower extremity function. The overall objective is to assess the need for additional rehabilitative services or assistive technologies, specifically lower limb FES systems, as perceived by the eventual recipients of these services or devices. Understanding their perspective will help establish the effectiveness of current rehabilitation practices and direct the development of new rehabilitation interventions.

METHODOLOGY--A quantitative survey was developed with the assistance of rehabilitation professionals and SCI experts, based on preliminary focus group interviews. The survey inquired about prioritized mobility activities of standing, walking, stair climbing, and transferring; determined acceptable quality of the top two priorities; identified willingness to experience risks related to a priority activity to achieve the acceptable level of quality; and compiled demographic information including previous assistive technology use. Random sampling was used with target demographics reflecting national SCI statistics. Phone interviews were conducted after postal contact was made with individuals registered in the SCI database of MetroHealth Medical Center in Cleveland, Ohio. Respondents were grouped into three categories based on injury level for comparison.

PROGRESS--Over 360 individuals with paraplegia from our local registry were contacted, and approximately 100 half-hour telephone surveys have been completed.

PRELIMINARY RESULTS--Initial results indicate that walking and standing functions are highly valued by individuals, regardless of injury level; quality of restored movement does not necessarily need to approach normal; and individuals are willing to invest time and endure surgery to obtain them with little guarantee of success. Standing and walking were consistently ranked as the primary goals of all respondents, while stair climbing and other functions were of significantly lower priority. Results were consistent across injury levels. For most, the acceptable level of quality of their desired mobility maneuvers did not necessarily approach premorbid function. Invasive and time-intensive procedures to attain these functions were often as acceptable as conventional treatments. Persons with SCI were eager to share their mobility-related needs. Contrary to prior opinion based on anecdotal evidence, persons with paraplegia were shown to be willing to accept high costs for limited functional gains in certain mobility activities. By systematically considering the needs of persons with SCI in the development of innovative treatments, clinicians can better insure acceptance and utilization of new technologies.

FUTURE PLANS--We intend to further analyze these data with respect to time postinjury, level of impairment, length of traditional rehabilitation, and other factors, and to extend the survey to stroke survivors with mobility impairments due to hemiparesis. We also plan to expand the study beyond the local cohort to solicit input from consumers of rehabilitation services throughout the VA healthcare system.




Lucas H.V. van der Woude, PhD; Annet J. Dallmeijer, PhD; R.H. Rozendal; A. Peter Hollander, PhD; H. van As; E. Angenot; M.T. Hopman
Institute for Fundamental and Clinical Human Movement Sciences Vrije Universiteit, Faculty of Human Movement Sciences Van der Boechorststraat 9, 1081BT Amsterdam, the Netherlands; Rehabilitation Center Amsterdam, Overtoom 283, Amsterdam, The Netherlands; Department of Physiology, Catholic University Nijmegen, The Netherlands; email: L_H_V_van_der_Woude@FBW.VU.NL

Sponsor: Institute for Fundamental and Clinical Human Movement Sciences, Vrije Universiteit, Faculty of Human Movement Sciences, Van der Boechorststraat 9, 1081 BT, Amsterdam, The Netherlands

PURPOSE--We seek to study the evolution in physical capacity, physical strain, and risk factors for cardio-vascular and musculo-skeletal disease over time in wheelchair-dependent individuals with a spinal cord injury (SCI). Parameters of performance capacity and physical strain in ADL are evaluated with repeated standardized wheelchair exercise tests as well as ADL tests in different groups of subjects with SCI, both those with a long-standing injury (sedentary as well as physically active) and those in the course of rehabilitation. Thus, the effects of wheelchair use and a wheelchair-confined lifestyle on cardio-respiratory (and musculo-skeletal) parameters and risk factors for cardio-vascular disease are evaluated.

METHODOLOGY--Both cross-sectional and longitudinal study experimental designs are used, involving male as well as female subgroups and sedentary as well as physically active individuals who are wheelchair dependent.

  Different subject groups were studied in both cross-sectional as well as longitudinal research designs in the course of the rehabilitation process. Maximum aerobic capacity, anaerobic wheelchair sprint performance, and isometric strength are individually determined in standardized testing procedures at fixed times during and/or after rehabilitation. The physical strain of daily life, and more specifically, the therapy sports activities, are simply evaluated with the Percentage Heart Rate Reserve (%HRR) with a SportTester PE4000. Risk factors for cardio-vascular disease (blood pressure and cholesterol) and musculo-skeletal problems are repeatedly determined with questionnaires, which are also used to study different physical and personal characteristics.

RESULTS--The results on both recently injured, intramurally treated, persons with SCI and those with long-standing SCI indicate an inverse association between physical strain in standardized ADL wheelchair tasks and indicators of maximum performance capacity. Physical strain during rehabilitation does not meet criteria for training as formulated by the American College of Sports Medicine. Intensity, duration, and frequency of physical activity should be increased and tuned more carefully to the individual. Findings on risk indicators for cardio-vascular disease do not show an increased risk among these subjects at study. Physical or sports activities have a significant reducing effect on such risk factors among subjects with longstanding injuries and those involved in rehabilitation, both high and low level lesions.

FUTURE PLANS--Plans for a multi-center study on restoration of mobility and functional work capacity is being initiated. It is anticipated to follow a group of n=150 subjects with recent SCI during and after rehabilitation. A further analysis of the effects of the physical activity components within the rehabilitation process upon performance capacity in subjects with SCI is planned to be conducted in a randomized clinical trial.

  Additionally, the evolution of wheelchair propulsion technique will be studied over time as a mediating component of performance capacity. Thus we hope to grasp the process of learning in this complex motor task. For the latter purpose a 4-year study is being initiated to study the mechanisms of adaptation in co-ordination as well is in the 'hardware' of the musculo-skeletal and cardio-respiratory systems as a consequence of training and learning.




Bryan Kemp, PhD; Robert Waters, MD; Rodney Adkins, PhD; William Bauman, MD; Ann Spungen, EdD; Yaga Szlachic, MD; Douglas Garland, MD; Henry Gong, MD; William Linn, MA; Keith Jamieson, MD; Margaret Murphy, RNNP; Helen Pautsch, RNNP; Joy Yakura, DRPT; James Krause, PhD; Jason Kahan, PhD; Laura Mosqueda, MD; Brad Williams, PharmD; Donald McNeal, PhD; Isis Hernandez, PhD; Lilli Thompson, MSRPT
Los Amigos Research and Education Institute, Rancho Los Amigos Medical Center, Downey, CA 90242; email: info@ranchorep.org

Sponsor: National Institute on Disability and Rehabilitation Research, U.S. Department of Education, Washington, DC 22202

PURPOSE--The establishment of this rehabilitation research and training center (RRTC) in 1993 is associated with the fact that people with spinal cord injury (SCI) are aging in substantial numbers for the first time in history. As they age, many such people are developing new health, functional, support, and psychological problems, some of which seem premature from an aging perspective. Early-onset cardiac disease, diabetes, pulmonary compromise, osteoporosis and fractures, joint pain, fatigue, job loss, caregiver stress, needs for personal assistance, and difficulty coping with these changes are all research topics under consideration. The primary purpose the Center's research is to separate the effects of age, number of years since onset, age at onset, and the historical period of injury and rehabilitation associated with these topics; and, where appropriate and possible, to compare aging parameters in SCI with such parameters in the general population.

METHODOLOGY--Answering questions regarding causes of life course and later life problems for people with SCI requires sophisticated research designs and an adequate database of people for investigations. All projects conducted by the Center utilize modified sequential designs and a large database of subjects representative of the diversity of ethnic groups in America as a common sampling frame. The database contains a minimum data set on nearly 2,300 such persons who range in age from 16 to 83 and who have been injured from 1 to 60 years. Moreover, this sample contains about 50 percent minority members, especially Hispanics and African-Americans. While projects employ the database as a sampling frame, a portion of the research effort is directed at expanding the database itself.

  The research projects address medical, functional, health maintenance, employment, social support, and coping issues (including changes in physiologic, health, and functional status); depression; assessment of social support, lifestyle factors, and cultural beliefs in moderating the natural course of aging with SCI; and use of job accommodation services to maintain employment. Within each, comparisons and contrasts among and across ethnic groups are central themes. There is strong emphasis on prospective versus retrospective collection of data with intervention studies in cardiovascular disease, pulmonary function, and depression.

PROGRESS--Currently prospective data on 845 cases ranging in age from 18 to 83, from 1 to 57 years since onset, ages at onset ranging from 1 to 65 years have been gathered for sequential comparisons.

FUTURE PLANS--Next year, the longitudinal portion of the sequential design will begin with five comprehensive follow-ups.




Michael J. DeVivo, DrPH
University of Alabama at Birmingham, Spain Rehabilitation Center, Birmingham, AL 35233 email: devivom@sun.rehabm.uab.edu

Sponsor: National Institute on Disability and Rehabilitation Research, U.S. Dept. Education, Washington, DC 20202-2646

PURPOSE--There have been several published studies of rehospitalization rates, risk factors for rehospitalization, and associated costs among persons with spinal cord injuries (SCI). However, only limited baseline data on the long-term incidence of a few secondary medical complications, such as renal and bladder stones, have been published, and the relationship between the occurrence of these secondary complications and subsequent rehospitalizations has not been determined.

  Moreover, the National Spinal Cord Injury Statistical Center (NSCISC) data set cannot be used for this purpose because it has no established linkage between reported occurrences of secondary complications and rehospitalizations. The purpose of this study was to provide baseline data documenting the leading causes of unplanned rehospitalizations among person with SCI and the average costs associated with each cause, so that frequent and costly complications can be given higher priority for further study and the effectiveness of techniques to reduce the incidence of complications and hospitalizations can be assessed using rigorous cost-benefit analyses.

  The objectives of this study were to: 1) identify the most frequent causes of unplanned rehospitalizations among persons with spinal cord injuries; 2) determine the average length of stay and cost for each cause of unplanned rehospitalization among these persons; and 3) describe, epidemiologically, the causes and costs of unplanned rehospitalization among persons with SCI.

METHODOLOGY--The basic study design was cross-sectional with a 2-yr prospective data collection period (1994-1996). All persons with traumatic SCI who were currently being followed at the University of Alabama at Birmingham Spinal Cord Injury Care System (UAB-SCICS) were eligible for this study, regardless of how long ago their injury occurred.

  Admission sheets for University Hospital were scanned daily to identify rehospitalizations of persons with SCI. Those returning for clinic visits and outpatient annual evaluations were asked whether they had been rehospitalized at another facility since their last contact with us. When appropriate rehospitalization was identified, medical record and billing information was obtained. ICD9CM codes were used to document the primary cause of rehospitalization. Other complications that may have contributed to the need for rehospitalization were documented as secondary causes.

  The percentage of rehospitalizations, average length of stay, and charges due to each type of secondary complication were determined. Mean length of stay and charges (in 1996 dollars) of each cause of rehospitalization were compared by using Student's t test. The distribution of causes of rehospitalization was characterized epidemiologically. The chi-square test was used to compare the percentages of rehospitalizations due to each cause by time postinjury, age group, gender, race, education level, neurologic level of injury, degree of injury completeness, urban/rural hospital location, marital status, and presence of insurance coverage.

FINAL RESULTS--Overall, 203 persons were hospitalized at least once during this time frame. A total of 429 hospitalizations were identified (mean=2.1 per hospitalized person, range=1-14). Urinary tract complications (usually infections) were the most frequent; primary nervous system conditions (usually autonomic dysreflexia: 8.4 percent), digestive system complications (8.2 percent), trauma (6.5 percent), psychoses, drug and alcohol problems (5.0 percent), musculosketetal conditions (4.8 percent), cardiac and circulatory conditions (3.6 percent), diabetes, endocrine and nutritional problems (2.4 percent), and all others (3.0 percent). In 1996 dollars, average charges were highest for skin ($33,621) and musculoskeletal ($32,699) conditions, and were lowest for endocrine and nutritional problems ($6,078). Based on Medicare cost-to-charge ratios for urban and rural hospitals in this state, these cause-specific average charges correspond to average costs of $17,222 for skin, $16,748 for musculoskeletal, and $3,169 for endocrine and nutritional disorders. Significant differences in causes of hospitalizations were observed by age, gender, education level, insurance status, and extent of injury, marital status, urban or rural location of hospital, and length of time postinjury (p<0.05). Persons over age 60 were more likely to be hospitalized for cardiac (23.8 percent) and musculoskeletal (19.0 percent) conditions and less likely to be hospitalized for skin conditions (4.8 percent) than persons below age 30 (3.2, 4.0, and 17.5 percent, respectively). Rural hospitalizations were more likely to be caused by urinary tract (42.4 percent) and respiratory (30.3 percent) complications, but not from skin conditions (0 percent) than urban hospitalizations (27.3, 6.4, and 21.3 percent, respectively) suggesting different treatment or referral practices for urban and rural physicians. This information can help in setting priorities for research and education aimed at preventing unnecessary rehospitalizations, reducing costs, and improving quality of life for persons with SCI.



Samuel L. Stover, MD; L.K. Lloyd, MD
University of Alabama at Birmingham, Spain Rehabilitation Center, Birmingham, AL 35233

Sponsor: National Institute on Disability and Rehabilitation Research, U.S. Dept. of Education, Washington, DC 20202-2646

PURPOSE--Analyzing a spectrum of urologic data acquired from a large number of persons with spinal cord injury (SCI) will help clinicians understand the natural history of the urinary tract and its complications following SCI, thus helping them select those prevention and management methods capable of assuring the most positive prognosis.

  The objectives of this study include: 1) documentation of the natural history and clinical course of urinary tract complications among persons with SCI who utilize various methods of neurogenic bladder management; 2) answer a series of important clinical research questions that can impact future urologic management and improve the medical care and well-being of those persons; and 3) encourage the utilization of the UAB-SCI Urologic Database by other institutions to provide a much larger cohort of persons with SCI for future collaborative studies.

METHODOLOGY--Data are collected prospectively for each patient admitted to the UAB-Spinal Cord Injury Care System (UAB-SCICS) at admission, discharge, and annually thereafter. In addition, data have been collected retrospectively from chart reviews on 596 patients between January 1970 and April 1979. All persons have been followed prospectively since 1979. As a result, the database already includes usable information on 1,388 persons with SCI who had 6,474 completed annual evaluations, include 500 evaluations at postinjury year 1, 259 at postinjury year 10, 137 at postinjury year 15, and 34 at postinjury year 20.

RESULTS--During the previous project period the most extensive analysis accomplished to date was completed on the urology database. A consecutive sample of 1,114 persons, sustaining SCI between 1969 and 1994, were studied. Total and individual effective renal plasma flow (ERPF), which is a measure of renal function, were compared to determine the effect of different bladder management methods on long-term renal function. It was concluded that renal function was adequately preserved in the great majority and did not appear to be influenced to any great extent by the method of management. Extensive studies were also conducted on urologic complications.

  During the past year, another case study was conducted on 29 patients in the database who had died with a diagnosis of some kind of kidney disorders. An effort was made to determine any more specific causes of death, especially secondary renal amyloidosis. Almost all cases of renal involvement were secondary to some other secondary complication and were not the primary cause of death. Only one case of secondary amyloidosis was found in this database, and even the autopsy files in the pathology department were unable to identify the cases. This information supports the investigators clinical opinion that chronic pressure ulcers, which cause secondary amyloidosis and renal failure, and was a frequent cause of renal deaths in the past are now very rare and is one of the key reasons for decreased renal deaths.

  During the current year another study was conducted on 22 patients who have had only a single kidney as a result of pre-injury factors, renal injury requiring surgery at the time of the SCI or renal causes following injury. The long-term outcomes of these persons is still being analyzed.

FUTURE PLANS--Because the database is getting so large, entry of new patients is being decreased and more effort given to long-term follow-up. Therefore, all females with new SCIs are entered, but only every second male with complete or sensory incomplete injuries are now entered.




Michael L. Boninger, MD; Rory A. Cooper, PhD
Human Engineering Research Laboratories, VA Pittsburgh Health Care System, Pittsburgh, PA 15206; email: mlboning+@pitt.edu; e-mail: rcooper+@pitt.edu

Sponsor: National Institutes of Health, Bethesda, MD 20892

PURPOSE--Many studies have shown the prevalence of chronic pain in spinal cord injury (SCI) to be at least 50 percent. Although this pain has many causes, repetitive strain injuries related to manual wheelchair propulsion are likely to play a frequent role. Because the upper limb is so important for activities of daily living, pain in this area can be a serious problem leading to lost independence, increased cost of care, and additional secondary injuries. Despite the high prevalence and cost of upper limb problems in individuals with SCI, there is little literature on the cause and prevention of these injuries. Forces occurring in the upper limbs of manual wheelchair users (MWUs) are dependent on the type and fit of the wheelchair and on the way in which the MWU applies force to the pushrim.

  In this study, we seek to reduce the frequency, severity, and duration of pain episodes and reduce the normal progression of peripheral pathology, such as median nerve dysfunction and rotator cuff inflammation, through improved posture, back support, and provision of a cushioned high-friction pushrim, and to determine how changes in wheelchair set-up affect wheelchair propulsion biomechanics.

METHODOLOGY--The experimental protocol consists of three main components: clinical examination, biomechanical analysis, and follow-up. All subjects are screened for signs of shoulder abnormalities using magnetic resonance imaging (MRI), plain radiographs, and physical examination. Nerve conduction studies are also performed to test for carpal tunnel syndrome (CTS) and/or other median or ulnar nerve damage. A standardized questionnaire is administered to record perceived level of arm pain and injury.

  The biomechanical analysis includes both kinematic and kinetic measurements of the upper body. A motion analysis system captures 3-D real-time motion of the upper limbs during wheelchair propulsion. The 3-D forces and moments applied to the pushrims are simultaneously collected using SMARTWheels attached to the MWU's own chair. Data are collected for 20-s trials while the MWU propels at a self-selected speed at two steady-state speeds of 1.3 and 2.2 m/s under two wheelchair conditions: the original configuration and with specific adaptations.

  The follow-up component involves interviewing all subjects monthly and, at the end of a 2-yr period, repeating the above protocol with the same group.

PROGRESS--During the past year we have made considerable progress toward the specific aims, enrolling over 12 subjects into the study.

PRELIMINARY RESULTS--For the first time, we have been able to link wheelchair biomechanics and CTS, finding that individuals with median nerve damage push differently than those without. We have also found that MWUs have improved ability to generate a propulsive force through the use of the special coated pushrims selected for our randomized control trial.

FUTURE PLANS--We shall continue to aggressively recruit new subjects and repeat the complete protocol for subjects who have been followed for over 2 years. Our next effort will likely involve advertising in the local press. We will continue the monthly follow-up phone call, and we will retest any subject who receives a new wheelchair. In addition we will begin to analyze our data on how back supports and/or high friction pushrims change wheelchair propulsion biomechanics.




Derek B. Smith, MScEE; Dennis F. Lovely, PhD
Institute of Biomedical Engineering, University of New Brunswick, Fredericton, NB CANADA E3B 5A3; email: lovely@unb.ca

Sponsor: University of New Brunswick Research Fund, Fredericton, NB CANADA E3B 5A3

PURPOSE--The purpose of this research is to investigate the effect of the nonwhite biological interference afflicting the measurements of somatosensory evoked potentials (SEPs) and to examine various whitening filter schemes in an attempt to improve matched filter performance.

METHODOLOGY--SEPs contain important physiological information, and have become a widely accepted and employed monitoring technique during back surgery. However, as surface recorded SEPs have very poor signal-to-noise ratios (SNRs), signal processing is required to acquire usable information from the recorded data. Although coherent ensemble averaging is the conventional method of improving the SNR, it consumes a significant amount of time. As a result, alternative techniques, such as matched filters, have been investigated in an attempt to reduce the number of averages needed for detection. A matched filter is the optimum technique for detecting a known signal buried in additive white noise. The effect of the nonwhite biological interference afflicting SEP measurements is investigated in this study, and various whitening filter schemes examined, in an attempt to improve matched filter performance.

PROGRESS--Our emphasis was placed on determining a satisfactory linear adaptive whitening filter routine. Three linear adaptive algorithms: sign adaptive (SA), recursive least-squares (RLS), and least-mean square (LMS), are evaluated, as are a brute force approach and a nonlinear neural-network technique. The LMS algorithm is found to be best suited for the desired implementation.

RESULTS--By applying signal whitening to surface recorded SEPs, substantial improvement was made. This was especially noticeable at high spinal levels, where the contributing noise is contaminated with cardiac and respiratory activity. In the earlier approach, the output of the matched filter showed several peaks from data collected at the T6-T7 level with 400 pre-averages. This precluded using a simple level detection scheme to verify the occurrence of the SEP. In this work, the ambiguity in which peak corresponds to the SEP has been resolved.

  With no whitening, the output from the matched filter shows multiple peaks; however, with whitening, only a single peak is resolved with zero latency. Consequently, this is ideal for an amplitude detection scheme.


B. Treatment and Rehabilitation



John S. Kirkpatrick, MD; Ken A. Mann, PhD; Jack E. Lemons, PhD; Steven M. Theiss, MD; Fred J. Molz, IV, MS; Jason I. Partin, BS
Spine Biomechanics Laboratory, Department of Rehabilitation Research and Development, The Birmingham VA Medical Center, Birmingham, Alabama 35233; Division of Orthopaedic Surgery, University of Alabama at Birmingham, Birmingham, AL 35294; email: john.kirkpatrick@ortho.uab.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B365-6RA)

PURPOSE--Appropriate use of internal spine fixation is dependent upon an adequate understanding of the normal motion of the spine and the effects of instrumentation on this motion. This project seeks to improve our understanding of spinal instrumentation effects by addressing three issues: 1) There is limited information on the effect of fusion on the adjacent, nonfused segments. The discs and joints adjacent to a fusion site have been reported to experience an accelerated rate of degeneration. 2) In vivo spinal motion involves time-varying forces and moments, yet most reported in vitro spine studies used static moments or cyclic compressive loads. Thus, previous in vitro results may have been influenced by the time-dependent, viscoelastic properties of the spine. 3) Limited availability of human cadaveric spines restricts in vitro research and an appropriate animal model is desired. This study seeks to explore the validity of the goat spine as a human spine surrogate.

METHODOLOGY--Experimental testing will be completed first on fresh-frozen cadaveric goat, and then human, specimens. Both the cervical and lumbar regions will be studied individually. Testing of the multilevel spines will be completed with a custom platform designed to apply pure moments in flexion, extension, right/left lateral bending, and right/left axial rotation. A pure moment was chosen to allow direct comparison between motion levels (i.e., all levels see the same moment magnitude) and spine types (human and goat). The loading will be controlled by a personal computer that interfaces with pneumatic actuators attached to the specimen by cables. The 3-D motion of vertebral bodies will be recorded and analyzed with a digital motion analysis system. Control algorithms receive position feedback from the specimen during testing and allow three generalized tests: 1) Determination of normal motion of the human and goat spine subjected to pure moments applied at a constant rate; 2) Analysis of "creep" effects through sustained moment application; 3) Application of a constant loading rate until the fused specimen achieves the same maximum displacement as the normal spine. Additional cervical experiments will analyze the effect of cutting spinal ligaments on cervical stability. Internal pressure measurements will be collected on lumbar discs adjacent to the fusion site to further quantify the effect of internal fixation on adjacent segments.

PROGRESS--Acquisition of all goat and human specimens for experimental testing has been completed. The spine platform and control algorithms were designed and tested with nonbiologic and swine spine specimens. Preliminary data indicated that the measurement resolution of the existing motion analysis system was insufficient for obtaining the goals of the grant; therefore, additional funds were obtained for a digital 3-D system with increased resolution. Analysis software was developed to determine the center of rotation between vertebrae, which is a clinical parameter used by surgeons to evaluate spinal stability.

FUTURE PLANS--The high resolution and precision of the new motion analysis system should provide definitive answers on the effects of fusion on the motion of adjacent vertebrae. The motion characteristics of human and goat spines will be compared to determine whether the goat spine can be used as a model for humans. The contribution of specific ligaments to the stability of the cervical spine, and the effect of fusion on lumbar disc pressure, will be quantified.



B. Jenny Kiratli, PhD; Jonathan N. Myers, PhD; Wayne Phillips, PhD; Susan E. Smith, MPT; Heather E Brown, MSPT; Victor F. Froelicher, MD; Inder Perkash, MD
Spinal Cord Injury Service, VA Palo Alto Health Care System; Cardiology Service, VA Palo Alto Health Care System; Exercise Science and Physical Education Department, Arizona State University; email: kiratli@roses.stanford.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B2110-RA)

PURPOSE--The purpose of this study is to evaluate two FES hybrid exercise protocols for reducing CHD risk in individuals with SCI. We will compare the cardiovascular and hemodynamic responses to acute and chronic hybrid exercise in individuals with SCI, measuring a variety of physiological responses including cardiac output, peripheral blood flow, and energy expenditure with particular attention to factors that contribute to CHD risk. The effects of hybrid exercise training on blood lipid profiles and body composition will also be evaluated. This information will allow us to evaluate hybrid exercise protocols for reducing CHD-related mortality and morbidity in persons with SCI and to determine appropriate clinical exercise intervention strategies for reducing cardiac risk in the SCI population.

METHODOLOGY--We will test 30 adult males with SCI who will be divided into three subject groups according to activity level and risk of cardiac disease. During the screening phase of our study, we will perform comparative testing of three exercise protocols. Subjects will undergo maximal and submaximal testing in each exercise protocol. These protocols include arm crank exercise combined with static FES to the leg muscles (static hybrid), arm crank exercise combined with FES applied to leg muscles to produce lower extremity cycling (dynamic hybrid), and arm crank exercise alone. During the training portion of the study each subject will undergo a 12-week training program in one of the three exercise protocols. Subjects will undergo maximal and sub-maximal exercise testing before and after the training program. Cardiovascular and hemodynamic responses will be determined via open circuit spirometry, EKG, and peripheral blood flow measurements. Physiologic variables will include blood lipid levels and body composition. Psychosocial and functional variables will be assessed using established quality of life (QOL) tools and functional independence measures (FIM).

PROGRESS--We are currently recruiting subjects for our study. We have recently completed a modified Monark Arm Ergometer design to enable our subjects to perform arm crank exercise while their legs are electrically stimulated to cycle. We have collected pilot data for each of the three exercise protocols. We have begun the screening phase of our study and will continue data collection throughout 1999.

IMPLICATIONS OF RESEARCH--Our findings will allow us to evaluate the potential for exercise to modify or control CHD risk factors in the SCI population and will be applicable toward informed cost-benefit decisions for implementation of exercise training programs.

FUTURE PLANS--In the future we plan to test these exercise protocols in subjects with history of cardiac disease to evaluate their effectiveness in slowing or reversing the progression of CHD in the SCI population.



B. Jenny Kiratli, PhD; George Sims, Amy Smith, Gail O'Mara, Helen Dorra, Jeanne Rhee-Dechario; Inder Perkash, MD
SCI Center and Surgical Service, VA Palo Alto Health Care System; Epidemiology Program, Stanford University, Stanford, CA 94305; email: kiratli@roses.stanford.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #A2014-RA)

PURPOSE--The purpose of this project is to conduct a retrospective cohort study to evaluate incidence, risk factors, and long-term healing of long bone fractures in people with spinal cord injury (SCI). The research also includes a concurrent prospective study to assess short-term healing. A better understanding of the mechanisms underlying these fractures and the factors which influence optimal healing can help reduce fracture occurrence and lead to improved management of fractures in SCI patients in the future.

METHODOLOGY--An epidemiological approach has been taken; data were gathered on relevant physiologic, demographic, and behavioral characteristics of all persons ever seen in the Palo Alto SCI Center. Those with positive fracture history are interviewed, and data are abstracted from medical records regarding fracture location, morphology, cause, treatment, any complications, and the healing outcome. A systematic review of radiographs is being completed using an established fracture classification system to determine long-term healing outcome. In addition, bone densitometry is performed on persons with SCI with and without fracture history. For the prospective study of acute fractures, follow-up includes biochemical markers of bone turnover from blood and urine samples, bone densitometry, and radiographic evaluation to determine short-term healing responses.

PROGRESS--The basic demographic and medical data have been collected, and those who have had fractures have been identified. Extensive review of medical records is being conducted to obtain information on each of the individual fractures. Patient interviews and radiographic reviews are also ongoing.

PRELIMINARY RESULTS--Some 660 records have been reviewed, and 252 patients with long bone fractures during or after injury have been identified: comprehensive reviews have been completed for 212 fractures. The majority (144 or 68 percent) of post-SCI fractures occur in the lower extremities (LE). Paraplegics are more likely to sustain LE fractures than quadriplegics (67 vs. 33 percent), although they are evenly distributed in the VA SCI population. High level quadriplegics (C5 and above) had an elevated frequency of upper extremity fracture but a very low occurrence of LE fracture (12 percent). History of multiple fractures prior to SCI seems to be associated with increased risk post-injury. The most common cause of LE fracture was falls and occurred more frequently in the femur. Other common causes include (in order): transfers, activities of daily living, and range of motion.

  Although we do not yet have corresponding data from persons with SCI without fractures, our data indicate that those with fractures are quite active. The majority either work (including volunteering) or are retired and spend more than 20 hours out of the house weekly. Fifty percent participate in regular exercise programs or organized sports.

IMPLICATIONS AND FUTURE PLANS--The information about patterns of fracture epidemiology and bone healing in SCI patients can be applied toward fracture prevention through: individualized risk profiles, education programs on fracture prevention, and development of consensus guidelines and clinical pathways for optimal fracture management.



Eric E. Sabelman, PhD; Vincent R. Hentz, MD; Min Hu, MD, PhD; Feng Zhang, MD; Deborah Kenney, MS, OTR; Ewa Komorowska-Timek, MD; Douglas Eng, PhD
Rehabilitation R&D Center, VA Palo Alto Health Care System, Palo Alto, CA 94304; Dept. of Functional Restoration, Stanford University Medical School, Stanford CA 94305; email: sabelman@roses.stanford.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B588-3RA)

PURPOSE--The recovering damaged nerve normally has a high population of Schwann cells that made up the myelin sheaths of axons prior to injury. These cells secrete growth factors and repair the extracellular matrix in preparation for the extension of regenerating axons into the damaged region. This project is based on replacing the Schwann cells in an otherwise acellular artificial nerve graft (ANG) as a substitute for an autograft taken from elsewhere in the patient's body. The latest ANG formulation is to be tested in lieu of an autograft, or to replace sural nerves removed for autografting, in up to 10 patients per year who have had trauma to the hand or arm.

METHODOLOGY--Preparation of the ANG essentially consists of repolymerization of solubilized collagen fibers with added cultured Schwann cells and insertion of this core into a biodegradable conduit. Type I collagen is preferred because it is readily available, relatively inexpensive, and its properties are reasonably well understood. The matrix or conduit walls could include regeneration-promoting agents such as nerve growth factor. The conduit limits penetration of inflammatory cells into the region of axonal regrowth, as well as facilitating microsurgical reanastomosis with the proximal and distal ends of the nerve.

PROGRESS--After a series of animal implantations, a graft formulation has been achieved having the same functional recovery as an autograft. A patient's Schwann cells will be obtained from remnants of the damaged nerve, or from a short (5-mm) donor nerve biopsy that can later be repaired with an ANG. A pre-clinical phase is underway, in which culture methods for adult human Schwann cells are being optimized. Potentially immunoreactive components are being deleted from the fabrication process, long (60-mm) grafts are being tested for efficacy and durability in a rat model, and clinical sensorimotor measurements for functional recovery are being refined. In the latter activity, former patients having had nerve repair are being recruited for a comparative database. We are also working on immunostaining of regenerated Schwann cell basement membrane and on characterization of collagens from different sources for use in the ANG core, as well as on the measurement of physical properties of collagen core and sheath, toward development of a new method of tensile testing of extremely fragile specimens. We have obtained fresh human nerve specimens for refinement of the in vitro cell purification technique and have approached the Buncke Microsurgical Clinic at R.K. Davies Medical Center in San Francisco to solicit their participation in the referral of clinical patients.

FUTURE PLANS--There is potential for tissue-engineered grafts to bridge traumatic defects in the central nervous system. Our laboratory is collaborating with a private biotechnology company and with researchers at Hines VA Medical Center by fabricating grafts for testing Schwann cell-seeded implants in spinal cord injuries in rats.




V. Rodney Hentz, MD; Felix E. Zajac, PhD; Inder Perkash, MD; Charles Burgar, MD; Kevin McGill, PhD; Machiel Van der Loos, PhD; Francisco J. Valero-Cuevas, PhD; Kai-Nan An, PhD
Surgery Service, Rehabilitation R&D Center, Spinal Cord Injury Center Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304-1200; Departments of Functional Restoration, Mechanical Engineering, and Urology, School of Medicine, Stanford University, Palo Alto, CA 94305-3030; Biomechanics Laboratory, Department of Orthopaedics, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905; email: zajac@roses.stanford.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B898-2RA)

PURPOSE--Our overall objective is to improve the functional grasping of persons with quadriplegia by providing them with the biomechanical ability to grasp objects. Reconstructive surgeries, including tendon transfers, are commonly performed in such cases to restore partial grasping function, but the uncertainty in the functional outcome of new surgical approaches hinders our ability to achieve improvements in their treatment.

METHODOLOGY--A biomechanical model of the hand musculotendinoskeletal system will be developed to provide surgeons with an "in vitro" testbed for improving existing techniques, or trying new techniques, and predicting functional outcomes. A hand model would be, by definition, an encyclopedic knowledge-base relating musculoskeletal anatomy to hand function. Such a model would allow surgeons to determine the precise musculotendinoskeletal parameters to which the functional outcome of a surgical or rehabilitation procedure is most sensitive. Thus, those aspects of the surgical procedure needing close clinical scrutiny could be identified. A model of the index finger and thumb will be the focus because of their importance to grasping (e.g., tip and key pinch) and because of the anatomic similarity between the index finger and the other fingers. The ability of the index finger and the thumb to exert maximum grasping (pinch) forces will be emphasized because they specify the biomechanical limit of grasping performance.

PROGRESS--A computer-implemented musculotendinoskeletal model of the index finger has been developed and modified based on measurements of fingertip forces and EMGs from all seven of its muscles. Further tests of the model have been performed by pulling on cadaver tendons individually and in combination. A model of the thumb is under development. Intramuscular EMGs associated with high thumbtip forces produced in five directions with the thumb in three different postures have been recorded.

RESULTS--In ulnar palsy, where loss of function of the intrinsic muscles of the hand occurs, fingertip force in the palmar direction is reduced to about 25 percent of normal. The claw hand deformity that accompanies ulnar palsy is often prevented by the "Zancolli Lasso," the surgical transfer of the flexor superficialis tendon. However, fingertip force is then reduced even further. Based on the finger model and the cadaver experiments, a modification to the Zancolli Lasso that appears to preserve further loss of fingertip force generation is to increase the moment arm of the flexor profundus at the proximal interphalangeal joint.

FUTURE PLANS--Modeling and cadaver experiments will be used to propose effective modifications to the Zancolli Lasso, or other surgical procedures, to enhance fingertip and thumbtip force production, and thus pinching ability. The thumb data and model will be analyzed to understand the basic components of thumbtip force generation. The complex biomechanical interactions that make pinching possible will be analyzed.




Robert J. Jaeger, PhD; W. Edwin Langbein, PhD
Rehabilitation Research and Development Section, Research Service, Hines VA Hospital, Hines, IL 60141; email: Robert_Jaeger@ed.gov; elangbei@wwa.com

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B2027-RA)

PURPOSE--Currently, pulmonary complications are the major contributor to morbidity and mortality of persons with spinal cord injury (SCI). Our first objective is directed at improving electrically stimulated cough in such individuals. The second is to establish a quantitative measure of the quality of cough in individuals with SCI as a function of the characteristics of their injury, anthropometric measurements, and standard measures of their pulmonary function. The third is to classify patients at risk of pulmonary complications based on cough ability, and suggest those who might benefit from electrically stimulated cough.

METHODOLOGY--Three hypotheses are being tested. The first is that the existing scheme of electrically stimulated cough production, developed in earlier work, can be improved to obtain cough peak flow rates of at least 5.8 liters per second, by triggering the cough based on sensing an event related to glottis closure.

  The second is that efficacy of volitional cough in a given individual with SCI is related primarily to level of injury, sex, and the volume of air exhaled in the first second of a forced exhalation (FEV1). We are measuring peak expiratory air flow rate at the mouth during volitional cough (i.e., cough peak flow rate) in 250-300 individuals over the full range of injury level, while simultaneously documenting traditional pulmonary function tests and anthropometric characteristics. We will then perform multiple linear regression analysis with cough peak flow rate as the dependent variable. The hypothesis will be accepted if level of injury, sex, and FEV1 are the only variables retained in the resulting regression equation.

  And the third is that the individuals studied in the second hypothesis will be classifiable by their cough peak flow rate as to whether or not they have had pulmonary complications in the past two years. Using the cough peak flow rate during volitional cough and information obtained from a review of medical records, we shall add documentation of pulmonary complications in the postacute period. We will divide individuals into two groups (complications and no complications) and verify that cough peak flow rate is normally distributed in each group (as suggested by preliminary data). By employing receiver-operator characteristic curves, we will determine the sensitivity and specificity for prediction of pulmonary complications using cough peak flow rate as a predictor.

PROGRESS--Engineering of the electrical stimulation system for augmentation of cough has now been completed, as have testing and validation. Peak expiratory flow data have now been collected on 6 individuals for electrically stimulated cough with and without the triggering method, 19 remain to be tested. Cough peak flow rates (without stimulation) have been collected from 205 persons with SCI during their annual clinic visit. An additional 50 will be measured. Physician chart reviews are progressing concurrently with data collection.

IMPLICATIONS--In both acute and chronic settings, independence from care givers is a hallmark of effective rehabilitation in nearly every case. The longer-term goals of this research are to make individuals with SCI independent of a care giver with respect to cough, and to lower the incidence of their pulmonary complications.




Todd A. Linsenmeyer, MD; John Ottenweller, PhD; M. Sieba, MD; Robert Anesetti
Kessler Institute for Rehabilitation, West Orange, NJ 07052; University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ 07103; Department of Veterans Affairs, East Orange, NJ 07018; email: bthompson@kmrrec.org

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B887-RA)

PURPOSE--Male infertility due to poor sperm motility is a major problem following spinal cord injury (SCI). While studies have shown that free radicals inhibit sperm motility, and an increased number of free radicals have been documented in the semen of men with SCI, the causes of their poor sperm motility are not certain. The objective of this study was to determine whether antioxidants, Vitamin E/Selenium, would help maintain sperm motility in such persons. Since obtaining ejaculates in men with SCI is difficult, this study was conducted in a well-established SCI infertility animal model.

METHODOLOGY--Sprague Dawley rats underwent T9 transection or T9 sham surgery (controls). SCI subjects and controls were randomized into four groups and given 1 ml of treatment by gavage daily for 10 weeks. Group 1: untreated; Group 2: base solution of corn oil; Group 3: 3-4 IU of Vitamin E in corn oil; Group 4: 3-4 IU of vitamin E and 0.4 µg of selenium in corn oil. After 10 weeks, the epididymis were harvested and analysis done to determine the number of sperm and the motility thereof. Analysis of variance was used to determine statistically significant change in counts and motility between the groups.

PROGRESS--There was no improvement in sperm counts with vitamin E alone or vitamin E/Selenium supplementation. There was no improvement in motility with Vitamin E alone. However, there was a statistical increase in sperm motility (t=1.87 with 27 df; p<0.05).

DISCUSSION--Sperm motility is largely dependent on an intact functioning mitocondrial sheath, which is composed of a high concentration of unsaturated fatty acids. Fatty acids are vulnerable to oxidation by oxygen-free radicals. Vitamin E is one of the major antioxidative molecules in spermatozoa and is found in the cell membrane. It is thought to interrupt the chain reactions with lipid peroxidation and scavenge free radicals generated during the univalent reduction of molecular oxygen and during normal activity of oxidative enzymes. A selenium-associated polypeptide, gluthathione peroxidase, has been described in non-SCI rats to play an important role at inhibiting lipid peroxidation and help maintain sperm motility. This study suggests that a combination of Vitamin E/Selenium plays an important role in maintaining sperm motility following SCI.

FUTURE PLANS--Since sperm motility is the major problem in men following SCI, and animal studies showed improved motility with Vitamin E/Selenium, these findings justify further clinical testing.



Donald R. Bodner, MD; Graham H. Creasey, MD
Cleveland FES Center, VA Medical Center, Cleveland, Ohio 44106; Northeastern Ohio Regional Spinal Cord Injury System, Cleveland Ohio 44109; email: ghc@po.cwru.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420; Department of Veterans Affairs Center of Excellence in FES, Cleveland VA Medical Center, Cleveland, OH
(Project #B804-2RA)

PURPOSE--We seek to evaluate an electrical stimulation technique for improving bladder and bowel function after spinal cord injury (SCI).

METHODOLOGY--Finetech-Brindley stimulators are implanted surgically in human subjects at least 1 yr after clinically complete SCI. A posterior sacral rhizotomy is usually performed during the same surgery. Subjects of either gender are selected on the basis of having significant bladder complications, such as chronic or recurrent infection or reflex incontinence and intolerance of anticholinergic medication. Clinical and laboratory investigation are used to assess bladder emptying, infection, urodynamic parameters, vesico-ureteric reflux, and hydronephrosis. Colorectal studies are used to assess defecation and colo-rectal motility. Each subject is used as his/her own control, comparing measurements before and after the procedure.

PROGRESS--Under a previous project, 20 subjects had stimulators implanted as above in Cleveland and all except two also had posterior sacral rhizotomy. All implants have worked well and produced effective bladder emptying; all are in daily use at home for bladder emptying, except for one only used for bowel emptying and one no longer used owing to the subject's having had a subsequent spinal fracture, causing compression of the cauda equina. The study has now been extended to include patients from the VA Medical Centers in the Bronx and San Diego. A further eleven implants have been performed, all with posterior rhizotomy.

RESULTS--The 20 subjects in the single-center study had injury levels ranging from C5 to T12. Before implantation, 14 individuals used intermittent catherization and 6 used permanent catheterization for bladder emptying. At latest follow-up (mean 27 mo), 1 used intermittent catheterization, 1 used indwelling catheterization, and 18 used the neuroprosthesis for micturition. Post-void residual volume following micturition was reduced and bladder capacity was increased following implantation. After implantation, the rate of symptomatic bladder infections/year was reduced. Changes were also seen in gastrointestinal function postimplantation. The duration of defecation was reduced and a change in bowel FIM scores was noted post implantation.

  No implant infections, erosions or rejection have occurred. In two subjects, the posterior rhizotomy was later found to be incomplete as evidenced by clinical testing. They underwent a subsequent posterior rhizotomy at the conus medullaris and now show clinical and urodynamic evidence of sacral areflexia, and are continent, using the stimulator routinely for micturition. One subject was able to discontinue anticholinergic medication previously used to treat reflex incontinence, but decided to recommence the medication due to sweating. The medication prevents use of the stimulator for micturition, but it is still used to assist defecation.

  A pilot study using life care plan analysis on five subjects suggested that the procedure pays for itself in 5 yrs and may then be expected to save money on health care for the remainder of the individual's life.

FUTURE PLANS--Subjects will be surveyed to determine the effects of this procedure on their quality of life. A larger group of participants will be interviewed by a life care plan analyst to estimate the effects of the procedure on the future costs of their medical care. Their hospital records will also be analyzed to determine their actual usage of prescriptions, devices, out-patient and in-patient services before and after implantation. Bowel function will be investigated in more detail using a barostat and videofluorodefecography.




J. Thomas Mortimer, PhD
Department of Biomedical Engineering, Applied Neural Control Laboratory, Case Western Reserve University Cleveland, Ohio 44106-4912; Cleveland FES Center, Cleveland OH 44106-3052; email: jtm3@po.cwru.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420; VA Center of Excellence in FES, Cleveland VA Medical Center, Cleveland Ohio 44106-1702
(Project #B634-3RA)

PURPOSE--The purpose of this work is to develop a diaphragm pacing system that will support the ventilatory needs of patients with compromised respiratory function. The unique aspect of our approach is the use of intramuscular (IM) electrodes implanted through a laparoscopic procedure rather than nerve cuff electrodes implanted through an open cervical or thoracic surgical procedure.

METHODOLOGY--These studies involve both humans and animals. Animals are used to determine safety and estimate efficacy. Humans are necessary to test our complete system.

PROGRESS--The method we have developed to activate the diaphragm reduces the risk of phrenic nerve damage, requires less time to implant and uses a less invasive implant procedure than conventional methods.

  In preparation for implementation of our pacing system in humans, we have examined the diaphragms of cadavers to identify the location of the phrenic nerve motor points, the thickness of the diaphragm in the region near the motor points and the extent of liver attachment to the abdominal surface of the diaphragm muscle.

  We have further refined our mapping methodology which includes a vacuum attaching device and computer controlled stimulation and data acquisition software to identify the preferred implant site. With this methodology, we can accurately locate the ideal placement site with 95 percent confidence level with four test locations (lasting a total of 15 min).

  We have used this methodology to locate the phrenic nerve motor points in the diaphragms of nine patients as part of our human diaphragm mapping study. These subjects were undergoing routine laparoscopic surgery at University Hospitals of Cleveland. The vacuum attaching device along with the customized software was successfully used to test three to four sites in each patient.

  We continue to train the surgeons in the use of both the mapping methodology and the implant instrument in preparation for implementation in a human.

  We have developed a radio frequency stimulator control unit for the IRS/8 implantable stimulator. This programmable control unit serves as the interface between the computer and the stimulator. We plan to implement a fully implantable diaphragm pacing system in an animal in October 1998.

  We have received approval from the Food and Drug Administration for our Investigational Device Exemption for our percutaneous pacing system and are in the process of recruiting our first patient.

IMPLICATIONS--Cervical spinal cord injuries (above the C5 level) usually result in a loss of respiratory function. At present, treatment of this condition involves primarily mechanical ventilators, and less frequently, phrenic nerve stimulation with cuff electrodes. Both of these techniques have shortcomings.

  The methods and technology we have developed will make diaphragm pacing less risky to the patient and less costly to the healthcare delivery system. The combined effects are expected to enhance the quality of life and independence of the ventilator dependent population.




Rabih Darouiche, MD; Richard A. Hull, PhD
VA Medical Center, Houston, TX 77030; Baylor College of Medicine, Houston, TX 77030; email: Darouiche.Rabih.O.@Houston.VA.Gov; rhull@bcm.tmc.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Project #B2125-RA)

PURPOSE--The urine of persons with structural or functional abnormalities of the urinary tract is likely to contain bacteria. Often urine colonization occurs in the absence of clinical symptoms and is called asymptomatic bacteriuria. Occasionally, symptomatic urinary tract infection occurs, causing a recurrent problem. In some patient groups, treatment of asymptomatic bacteriuria is often not warranted, and the benign bacteria causing asymptomatic colonization may even be beneficial in preventing infection by more antibiotic resistant or virulent organisms. Little is known about bacteria associated with asymptomatic bacteriuria with regard to urinary tract colonization mechanisms. It is the goal of this study to identify bacterial adherence genotypes and phenotypes that promote long-term therapeutic asymptomatic bacterial colonization in the urinary bladder of persons with spinal cord injury.

METHODOLOGY--In this study, experiments are being conducted to investigate the molecular basis by which certain Escherichia coli strains may asymptomatically colonize the urinary bladder. Bacterial adherence, widely held to be central to the urinary tract conlonization process, is the focus of investigation. A prototype strain, E coli 83972, is being studied. This strain has been shown experimentally to establish, and maintain for extended periods, asymptomatic colonization of the human bladder and to suppress symptomatic infection. We are attempting to identify the mechanism used by E coli 83972 to colonize the bladder by introducing mutations in specific adherence genes and then testing the mutant bacteria for capacity to colonize the bladder of human volunteers. Although numerous correlation studies and studies with animal models have suggested roles for various bacterial adhesins in urinary tract colonization, the experiments initiated here will provide the first direct measurement of the contribution of bacterial adherence to human urinary tract colonization.

RESULTS--The genetic potential for expression of P and Type 1 pili was demonstrated and DNA sequences related to Type 1C and G (UCA) pili were also detected. However, E coli 83972 did not express D-mannose resistant, or D-mannose-sensitive hemagglutination after growth under standard conditions in vitro or upon isolation of bacteria from the urine of colonized test subjects. Limited uroepithelial cell adherence was observed in vivo, and weak D-mannose-sensitive hemagglutination was detected after extended growth in urine in vitro.

FUTURE PLANS--Studies using E. coli 83972 adherence gene mutants will be done to examine the contributions of various pili to specific adherence.



James W. Little, MD, PhD; Robert Price, MSME; Stephen Burns, MD
Department of Rehabilitation Medicine, University of Washington, Box 356490, Seattle, WA 98195-6490; email: jwl128@u.washington.edu

Sponsor: Department of Veterans Affairs, VA Rehabilitation Research and Development Service, Washington, DC 20420
(Pilot Project #B2118-PA)

PURPOSE--To understand spasticity pathophysiology and to evaluate spasmolytic treatments, objective and quantitative spasticity measures are needed. Spasticity at the elbow can limit function in persons with injury of the cervical spinal cord and brain as well as other neurological deficits. This research and development activity attempts to develop a prototype instrument for measuring spasticity at the elbow due to biceps and/or triceps hypertonus. The instrument is intended to characterize spasticity in two modes: during voluntary dynamic movement and during passive movement.

METHODOLOGY--The basic components of the system are: 1) a forearm trough which can either be rotated or locked, 2) a motor and speed control system, 3) a linkage to convert continuous motor rotation to oscillating forearm trough movement, 4) displacement, acceleration, and torque transducers and supporting electronics, 5) a 2-channel surface EMG system, 6) a computer and digitizing card and custom software for motor control, data acquisition, and data processing.

  In the dynamic test mode, subjects are asked to flex and extend at their maximal rate over approximately 90° of movement in the horizontal plane. The displacement and acceleration transducers measure the characteristics of this action to detect any deviations from the smooth and rapid motions seen in control subjects. Simultaneous EMG measurements reveal the role of co-contraction and other anomalies in producing abnormal movements. In the passive testing mode, the forearm is oscillated passively about the 45° elbow position over an angular range of 5° at frequencies from 1.5 to 6.0 Hz. This is intended to trigger the stretch response above some threshold frequency which will modify the torque response and be detected by the EMG measurements. Torque and displacement measurements are converted to elastic and viscous stiffness values over the range of frequencies applied. Based on prior research on ankle spasticity using this technique, spasticity enables its own quantification by modifying the stiffness versus frequency characteristics of the joint. In addition, the passive elastic tissue properties may be measured when spasticity is absent, either due to therapeutic interventions or at movement frequencies below threshold for triggering the reflex response. This provides information about the presence and development of contractures.

PROGRESS--Preliminary results in three tetraplegic subjects with triceps spasticity by clinical exam suggest that we can readily distinguish them from control subjects using the dynamic movement technique. The finding of mid-range slowing of dynamic movement was confirmed by triceps EMG activity, consistent with triceps spasticity elicited by voluntary elbow flexion. The passive movement technique is still under development but shows promise. The key issue is triggering the stretch reflex response without applying excessively high movement amplitudes or frequencies. When the reflex response is facilitated (by applying vibration to the triceps), a dramatic increase in the stiffness versus frequency response follows.



Laura A. Cushman, PhD; Marcia J. Scherer, PhD, MPH
University of Rochester Medical Center, Department of Physical Medicine and Rehabilitation, Rochester, NY 14642; The Institute for Matching Person & Technology, Inc., Webster, New York 14580; email: IMPT97@aol.com; laura_cushman@urmc.rochester.edu

Sponsor: American Association of Spinal Cord Injury Psychologists and Social Workers, Jackson Heights, NY 11370-1177.

PURPOSE--The current project sought to further refine assessments of two key factors in psychosocial outcome of SCI: person-technology fit, and meeting the perceived needs and goals of persons with SCI. It was also designed to evaluate an experimental peer-counselor intervention.

METHODOLOGY--The study was a two-group, repeated measures design, involving completion of several instruments, both newly created and in the literature, by persons with new SCI while in acute rehabilitation. This was followed by 1- and 6-mo reassessments.

  The grouping (independent) variable was the presence or absence of need-specific interventions. Group One received the need-specific interventions; Group Two served as a treatment control group and received standard services. A sample of 22 persons with new onset of SCI participated.

  Participants completed several psychosocial instruments at baseline (inpatient rehabilitation), 1 and 6 mo later. Multiple dependent variables were collected at each time point. The analysis used t tests or multivariate ANOVAs to compare groups on the dependent measures at each time point.

PROGRESS--To date, baseline data have been gathered for 22 subjects, and 1-mo follow-up data on 17. Collection of 6-month follow-up data is in progress.

PRELIMINARY RESULTS--Results indicated the existence of a number of perceived needs at all time points. Most people experienced fewer needs, and greater life satisfaction, over time. However, some of those with greater psychological distress or more needs at baseline continued in this pattern. The intervention group was in some ways more distressed at baseline, but tended to approach and become similar to the other group over time. However, at 6-mo follow-up, they reported more subjective disability and unmet needs.

FUTURE PLANS--The current goal of the project is to collect all remaining follow-up data on as many subjects as possible. This will allow reanalysis and more complete results regarding changes on the instruments over time, and of outcomes in the groups with and without the peer-counselor intervention. A possible subsequent study will involve further use of the peer-counselor intervention, with each subject serving as her or his own control. Results on several of the instruments used here will guide the content of the peer intervention, and also document change across 6- and 12-mo intervals.



Steven A. Stiens, MD, MS; Robert Price MSME
SCI Unit, VA Puget Sound Health Care System, 1660 S Columbian Way. Seattle, WA 98108-1597; email: stiens@seattle.va.gov

Sponsor: American Paraplegia Society, Jackson Heights, NY 11370-1177

PURPOSE--Recent epidemiologic trends show an increase in functionally significant, motor incomplete (ASIA D) spinal cord injury (SCI). Improved automotive restraints, emergency medical systems, methylprednisolone, and early spinal decompression have likely contributed to this spared motor function. Studies of the chronology of strength recovery after incomplete SCI have demonstrated: maximal recovery rates during the first 3 mo after injury with maximal variation in motor recovery early, and plateauing at 6-12 mo. New therapies are needed to enhance this recovery and improve the number of persons who regain walking after SCI.

  Partial body weight supported ambulation training has been utilized to improve gait performance in subjects with SCI and stroke in a few small prospective series. ASIA C subjects have achieved reciprocal walking movements on the treadmill with partial body weight support in a harness. To date studies have not reported experience with weight supported ambulation (WSA) used as a regular part of the acute rehabilitation of persons with SCI.

METHODOLOGY--SCI subjects must be ASIA B or C and unable to fully support their weight for upright ambulation. Baseline measures will include: ASIA Sensory and Motor Database, Modified Ashworth Spasticity Scale, and Rivermead Motor Assessment Score for the leg and trunk, hand-held myometry measurement of strength, modified Motoricity Index, and Temporal Distance Measurement. Subjects then receive daily 30-min sessions of treadmill-driven WSA for periods of 2 wk alternating with conventional physical therapy for 2 wk in an A-B-A-B design with reassessment of the baseline measures twice weekly.

PROGRESS--A prototype weight support device was designed and modified from a 2-ton capacity hydraulic engine lift. Modifications included a steel yoke fabricated to hold the harness, large diameter low friction casters, a battery-powered, microprocessor-controlled load-sensing device to provide bilateral load monitoring capacity. The goal of these modifications has been to provide support but maintain free limb movement. Modifications of a tandem parachute harness are in progress. Our objective is to achieve up to 90 percent unloading of the lower limbs to allow ambulation exercise upright with the least resistance. One SCI subject has received training with the device and has benefited.

FUTURE PLANS--Continued modifications of the harness to increase freedom of hip movement and trials with other subjects to test the hypothesis that WSA increases the rate of motor recovery and gait reacquisition.

IMPLICATIONS--WSA as a therapy can be implemented through modifications of easily available and inexpensive hydraulic engine lifts. Treatment with WSA may increase the number of gait cycles and the amount of standing time and decrease the number of therapists required to work with given patients during a therapy session.



Ken B. Waites, MD
University of Alabama at Birmingham, Department of Pathology, Birmingham, AL 35233; email: waites@wp.path.uab.edu

Sponsor: National Institute on Disability and Rehabilitation Research, US Department of Education, Washington, DC 20202-2646

PURPOSE--Pulmonary complications, with pneumonia being the most frequent, are a major cause of both morbidity and mortality in persons with spinal cord injury (SCI). Both bacterial and viral immunizations have been recommended to prevent infectious pulmonary complications in patients with neuromuscular disorders producing mechanical dysfunctions of the respiratory system. Although patients with SCI, particularly those with tetraplegia and high paraplegia, have been shown to be at increased risk for the development of such complications, we are unaware of any studies documenting the efficacy of either bacterial or viral immunizations to reduce their incidence this population.

  In this study we seek to document changes in immunologically related laboratory values of patients vaccinated at varying intervals after spinal cord injury and to compare the incidence of pulmonary complications in immunized and unimmunized patients with SCI.

METHODOLOGY--The original study entailed random assignment of SCI patients into one of 6 groups following their entry into the University of Alabama at Birmingham (UAB) Hospital care system. Groups 1 and 2 were to receive the vaccine or placebo at 72 hours (±24 hours) of injury. Groups 3 and 4 were to receive the pneumococcal vaccine or placebo at 17 days(±24 hrs) postinjury. Groups 5 and 6 were to receive the vaccine or placebo at 4-6 mo postinjury. The groups for which a patient was eligible to be randomized as a subject (to receive vaccine) or control (to receive placebo) were determined according to the time at which the patient was admitted to the UAB Hospital or Spain Rehabilitation Center. Following enrollment, 4 blood samples were collected: the first at the time of vaccination or administration of placebo, the second 1 mo later, the third 2 mo later, and the fourth at 1 yr following enrollment. Laboratory tests performed at each blood sampling interval included: anti-pneumococcal antibody titers to four major representative serotypes, quantitative immunoglobulins, complete blood count with differential leukocyte count, liver profile, total serum protein, and albumin. Subjects and controls were monitored during their initial hospitalization and by telephone at post-injury 3-mo intervals for the occurrence of respiratory or other systemic complications of pneumococcal disease. Appropriate microbiological and/or immunological diagnostic procedures were to be implemented whenever possible to determine whether or not such complications were indeed due to infection with Streptococcus pneumoniae.

  Developments in the acute care of persons with SCI made it necessary to alter the study design and eliminate the group immunized immediately postinjury, because of the high dose of methylprednisolone often given within 8 hours of injury. Steroid presence negates the immunogenicity of the pneumococcal vaccine unless at least 2 wk elapse prior to immunization. Groups 1 and 2 were eliminated as no group was vaccinated at 72 hours. All patients were enrolled in Groups 3-6.

  Follow-up laboratory values and their scheduled obtainment were not altered otherwise. Emphasis is placed on the immunogenicity of pneumococcal vaccine, since measurable laboratory data are available. Only the reports from patients themselves are available to document occurrence of pulmonary complications, and rarely were any attempts made to identify Streptococcus pneumoniae as an etiologic agent.

RESULTS--At this writing, 95 persons have been enrolled in the study, none of whom experienced any adverse effects from the vaccination. Seven were lost to follow-up before all data were collected; 48 additional patients refused to participate. Findings demonstrate that most persons with SCI responded immunologically to one or more representative pneumococcal serotypes, that immune response was unrelated to vaccination timing postinjury, that immune response varied among individuals and according to serotype, and that antibody concentrations were maintained in persons for at least 1 yr.

  This study demonstrates that persons with SCI respond immunologically to the pneumococcal vaccine. Although no data are available from persons with SCI, up to 90 percent of nonimpaired persons who mount an adequate immune response following pneumococcal vaccination have a significant reduction in severe pneumococcal infection. All persons with SCI should receive the pneumococcal vaccine soon after injury because of the potential for acquiring these infections.

FUTURE PLANS--Further study will be done in a new study to document duration of immunity greater than 1 yr, the clinical efficacy and need for revaccination in persons with SCI.



Amie B. Jackson, MD
Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL 35233; email: jackson@sun.rehabm.uab.edu

Sponsor: National Institute on Disability and Rehabilitation Research, US Department of Education, Washington, DC 20202-2646

PURPOSE--Aside from the immediate and obvious consequences of spinal cord injury (SCI), many physiological systems ultimately are altered for varying periods: one such is the reproductive axis. In addition to problems with menorrhea, galactorrhea, fertility, and sexual function in women after SCI, their disordered hormone production could potentially result in systemic changes such as accelerated bone loss, accentuated catabolism, and nitrogen imbalance, and possibly hypercholesterolemia and atherosclerosis. To date there is little information concerning these complications. The purpose of this research is to determine the changes in reproductive endocrine function both immediately following SCI and in the first year postinjury. This research will also examine how these changes affect menstruation, ovulation, vaginal and cervical pathology, and sexual function. As it is felt that many complications of SCI, such as autonomic dysreflexia, muscle spasticity, and bladder management problems are influenced by fluctuations in the woman's hormonal cycles, these correlations will be examined as well. Possible factors that could be responsible for postinjury endocrine changes will be explored.

  Objectives of this study are to document hormonal changes that influence ovulation and menstrual cycles, as well as cause complications such as hyperprolactinemia, with or without galactorrhea; to document endocrine imbalances that may occur following SCI as a result of cardiovascular instability, chest trauma, nutritional or metabolic changes, or concomitant head injury; to document the relationship between reproductive hormone levels following SCI and fertility, sexual well-being, and sexual activity; and to determine the relationship between reproductive hormone levels following SCI and complications such as autonomic dysreflexia, increased muscle spasticity, and occurrence of bladder spasms.

METHODOLOGY--The basic design of this project will be that of a prospective cohort study to assess the natural history of reproductive hormonal imbalances that cause changes in the menstrual cycle leading to sexual dysfunction and infertility in women during the first year after SCI. All women agreeing to participate will be interviewed initially by a designated nurse/clinician who will obtain a complete obstetrical and gynecological history. Other information collected during this interview will be first day of the last menstrual period, age, height, weight, etiology of injury, and loss of consciousness, or occurrence of closed head trauma or chest trauma at the time of injury. Also during the initial evaluation, vaginal wall samples will be obtained by gently scraping the upper third of the lateral vaginal wall.

  To evaluate postinjury reproductive endocrine status, blood sampling for hormone assays will be performed once a week for 6 wks. A single electrolyte profile, including serum sodium, chloride, potassium, blood urea nitrogen, albumin, creatinine, and glucose will be obtained on admission to the study to assess the metabolic status of each woman.

  Throughout the initial inpatient stay, careful documentation of the onset, duration, and amount of flow of any menses will be recorded. Upon discharge, each woman will be given a menstrual calendar and instructed on recording this same information.

  Over the 42-mo period of this study, at least 28 women should be enrolled and at least 336 monthly calendars obtained.

PROGRESS--To date, enlistment continues to be slow. Several factors are responsible for this and include a decrease overall of women census in SCI (a trend seen at most SCI Model Systems). Furthermore many women who have been admitted to the SCI unit have been excluded due to pre-injury oral birth control usage, an occurance not anticipated. Finally, loss of research personnel temporarily interrupted active recruitment. Seven subjects have been initiated, three have completed the study, two dropped out, and two are in progress.

PRELIMINARY RESULTS--Data have not been analyzed.

FUTURE PLANS--Continue aggressive recruitment of patients with newly hired nurse researcher.



J.S. Richards, PhD; Richard Shewchuk, PhD
University of Alabama at Birmingham, Spain Rehabilitation Center, Birmingham, AL 35233-7330; email: richards@sun.rehabm.uab.edu

Sponsor: National Institute on Disability and Rehabilitation Research, U.S. Dept. of Education, Washington, DC 20202-2646

PURPOSE--Much of the research in spinal cord injury (SCI) has been focused on its acute medical aspects, with relatively little emphasis being placed on follow-up concerns, particularly quality of life issues. Recent work has suggested that there is a strong relationship between both physical health and emotional well being of the person with SCI and the existence of an effective social support system. There is very little information, however, on the impact of care demands on the caregiver who also most typically is the major source of social support. The purpose of this project is to investigate on a longitudinal basis, the relationship between the physical and emotional care needs both of the person with SCI and of the caregiver at several intervals postinjury.

  To carry out this project, we shall: 1) examine the relationship between factors of well-being in persons with SCI and their caregivers, measured at preselected times postinjury; 2) determine the association between physical and psychosocial characteristics of the person with SCI and feelings-of-burden variables in caregiver(s) at preselected times postinjury; 3) determine the interrelationships between feelings of well-being of the person with SCI and his caregiver(s) in different cohorts over time; and 4) determine the interrelationships between physical and psychosocial characteristics of the person with SCI and the feeling of burden in the caregiver over time.

METHODOLOGY--This is a longitudinal study consisting of four waves of data. A sample size of 100 SCI/caregiver pairs has been targeted. Individuals who identify themselves as most likely to be the primary caregiver are approached regarding participation in the study. The caregivers are administered 4 structured interviews: one in-person during the rehabilitation phase prior to discharge, and three by mail at 1, 6, and 12 mo postdischarge. The predischarge interview serves as a baseline of caregiver mental and physical health, as well as an indicator of "anticipated" burden of care.

RESULTS--Data collection has ended; analysis and publication have begun. The caregiving sample is 88 percent female; 66 percent have a high school education or better; and 47 percent were employed outside the home at the time of injury. With regard to relationship to the person with SCI, 32 percent are spouses, 29 percent are mothers, and 12 percent are brothers. Of the persons with SCI, 78 percent are male and 57 percent have a high school education or greater. Fifty-two percent of the persons with SCI have a cervical injury, while the remaining 48 percent have paraplegia. Preliminary analysis of data reveals the caregivers are experiencing increasing negative affect secondary to caregiving over the first year postdischarge. Decreasing instrumental support is also apparent over the same period.




Steven A. Stiens, MD, MS; Tammy Pidde, RN, CRRN; Brenda Veland, RBP; Marguerite David, BA, MSW; Kathy Chadband
SCI Unit, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108; Department of Rehabilitation, University of Washington, Seattle, WA 98195; email: stiens@seattle.va.gov

Sponsor: Paralyzed Veterans of America, Education and Training Foundation, Consortium for Spinal Cord Injury Medicine, Washington, DC 20006

PURPOSE--Neurogenic bowel dysfunction due to SCI can significantly detract from quality of life. Colonic motility, sphincter control, and total body mobility interact to produce a situation that complicates life with unpredictable fecal elimination, constipation, cramping, bloating, and excessive gas, just to name a few of the common symptoms. The current clinical approach to managing these symptoms and achieving functional bowel continence of the person with SCI is to design a custom bowel program. A bowel program is defined as the comprehensive plan for management of bowel dysfunction and includes the components of diet, fluids, medications, exercise, and scheduled bowel care. Bowel care is the process for assisted defecation and may include stimulant medication, client positioning, digital stimulation, manual evacuation, and assistive maneuvers. To achieve the best outcome, an understanding and correct performance of bowel care is critical. After a review of a number of educational databases revealed no recent or complete teaching tool for this purpose, we sought to produce a video that would present the problems of neurogenic bowel and solutions through assistance to enhance the ability of a person with SCI to train caregivers about his or her individual care routines.

METHODOLOGY--A video script has been written to present information on anatomy, physiology, and pathophysiology, as well as problems and solutions associated with assisted management of bowel care for persons with of the upper motor neuron bowel. Content starts with a synopsis of the message, then continues with an in-depth discussion and dramatization of the consequences of neurogenic bowel dysfunction. Then the step-by-step bowel care procedure is taught, using a format that captures interaction between a clinic nurse, a physician, a client, and an attendant. Aversive aspects of the subject are then addressed and dispelled in the taboo section of the video through informal discussions in a virtual chat room among attendants and persons with SCI. Finally, an attendant, a nurse, and a person with SCI use the side-lying position to demonstrate the actual process of bowel care. Commentary by nurses, other attendants, and persons with SCI are interspersed between the actual demonstration of the steps to the procedure. These cutaways will provide tips, reinforce theory, and avert the pitfalls during the process of bowel care.

PROGRESS--To date, the script has been written, finalized, and cast. A review was conducted that included comments from professionals (rehabilitation nursing, social work, psychology, and physical medicine and rehabilitation) as well as consumers and attendants. Taping is in progress and editing has begun. Concurrently, members of the production team have collaborated on a variety of other educational projects related to the neurogenic bowel. These include the Clinical Guidelines for Management of Neurogenic Bowel and the consumer guide for management of neurogenic bowel in cooperation with the Consortium for Spinal Cord Medicine. Contributions have also been made to the bowel management sections to two CD-ROM educational programs, the Association of Spinal Cord Injury Nurses clinical guidelines for management of neurogenic bowel, and the National SCI Outpatient Support Clinic training.

FUTURE PLANS--We plan to continue sharing parts of our production with other educational tool developers. When our video is completed we plan to evaluate the effect it has on knowledge about and performance of bowel care. Distribution is targeted for SCI units around the country.

IMPLICATIONS--Until recently there were very few educational tools for use in education about the neurogenic bowel after SCI. Now a varied and expanding set of options is available.




Steven A. Stiens, MD, MS; J Glenn House, MD; Lance L. Goetz, MD, Benson Ong-Hai, MD, Linghwa Chang, RN
SCI Unit, VA Puget Sound Health Care System, Seattle, WA 98108-1597; University of Washington Department of Rehabilitation; email: stiens@seattle.va.gov

Sponsor: None

PURPOSE--Neurogenic bowel dysfunction resulting from spinal cord injury (SCI) can produce constipation, incontinence, and inability to willfully defecate. Many persons with SCI rank bowel and bladder dysfunction among their major life-limiting problems. The upper motor neuron (UMN) bowel results from a lesion of the spinal cord above the conus medullaris. This condition typically presents with fecal distention of the colon, overactive segmental peristalsis, underactive propulsive peristalsis, and a hyperactive holding reflex with spastic anal constriction. These impairments of sphincter control, along with gross immobility from paralysis, interact to compound their functional significance.

  Rehabilitative interventions to regain personal control of fecal elimination emphasize the importance a carefully designed bowel program with regularly scheduled bowel care. A bowel program is a comprehensive individualized treatment plan focused on prevention of incontinence, effective efficient colonic evacuation, and prevention of complications of neurogenic bowel dysfunction. Bowel care, a subcomponent of the bowel program, is the individually developed and prescribed procedure carried out by the patient or attendant to periodically evacuate stool from the colon. The goals of bowel care are to facilitate normal defecation of the maximal stool volume in the least amount of time with avoidance of stool incontinence thereafter. The bowel care procedure typically consists of introduction of a colonic stimulant medication into the rectum and mechanical facilitation of reflex defecation with intermittent digital rectal stimulation. Unfortunately, some bowel care sessions can require up to 3 hr for completion, and still yield insufficient stool results. More than 20 percent of persons with SCI report difficulty with evacuation of their bowels.

  There are many medications on the market utilized as chemical stimulants to enhance reflex defecation. Bisacodyl is a common active ingredient. The effectiveness of hydrogenated vegetable oil-based bisacodyl (HVB) suppositories, polyethylene glycol-based bisacodyl (PGB) suppositories, and polyethylene glycolbased, glycerine, docusate sodium mini enemas (TVC) was compared in subjects with UMN SCI. Thereafter, general strategies for bowel programs and techniques of bowel care were published for consumers and practitioners.

METHODOLOGY--The HVB suppositories contained 10 mg bisacodyl in a hydrogenated vegetable-oil base. The PGB suppositories contained 10 mg bisacodyl dissolved in a mixed polyethylene glycol polymer base of two molecular weights: E1450 and E400. TVC consists of a solution of polyethylene glycol, glycerine, and docusate sodium. Separate open label and randomized, prospective, double-blind studies comparing bowel care initiated by these agents were completed.

  The outcome parameters were as follows. The total bowel care period was divided into intervals by discrete timed events: First Flatus (end of the interval from insertion of the suppository until the first flatus is passed), Begin Stool Flow (beginning of the defecation interval), End Stool Flow (marks the end of the defecation interval), Time Off Toilet (marks the end of the interval from the last stool flow to transfer off toilet or completion of clean-up if in bed), Total Time (includes the time from insertion of the suppository to the last stool flow). Both duration and frequency of digital stimulations and manual evacuations were recorded. Stool results were recorded as: 0, 1 minimal, 2 small, 3 moderate, 4 large, 5 very large. All episodes of incontinence were recorded and defined as: any passage of substance through the anus (include stool, mucus, liquid, and so forth) at any time outside the designated bowel care session.

PROGRESS--Both studies revealed a significant decrease in total bowel care time using the PGB suppository with comparable stool volumes and numbers of bowel incontinence episodes. TVC mini enemas and PGB suppository initiated bowel care sessions were similar in all time intervals, stool production, incontinence, and the number of digital stimulations required.

  The mean bowel program interval that was most reduced when comparing the suppositories was the Time to Flatus (PGB 15 min, HVB 36 min) suggesting that the rate of dissolution of the base is directly related to the bioavailability of the bisacodyl and the subsequent peristaltic response of the colon.

FUTURE PLANS--We are currently developing automated quantitative instrumentation to record the progress of bowel care, with the intent to test other pharmacologic triggers and enhancers of defecation and the effectiveness of various techniques of bowel care.

IMPLICATIONS--The findings to date suggest that the delivery of bisacodyl to the colonic mucosae in a polyethylene glycol base initiates defecation sooner and can reduce the average duration of bowel care by up to one half as compared with HVB.



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Last revised Thu 04/29/1999