Graham Creasey

All Publications

• Bone changes in the lower limbs from participation in an FES rowing exercise program implemented within two years after traumatic spinal cord injury. The journal of spinal cord medicine Lambach, R. L., Stafford, N. E., Kolesar, J. A., Kiratli, B. J., Creasey, G. H., Gibbons, R. S., Andrews, B. J., Beaupre, G. S. 2018: 1–9

  Abstract

  OBJECTIVE: To determine the effect of a functional electrical stimulation (FES) rowing program on bone mineral density (BMD) when implemented within two years after SCI.DESIGN: Prospective.SETTING: Health Care Facility.PARTICIPANTS: Convenience sample; four adults with recent (<2 years) traumatic, motor complete SCI (C7-T12 AIS A-B).INTERVENTION: A 90-session FES rowing exercise program; participants attended 30-minute FES training sessions approximately three times each week for the duration of their participation.OUTCOME MEASURES: BMD in the distal femur and tibia were measured using peripheral Quantitative Computed Tomography (pQCT) at enrollment (T0) and after 30 (T1), 60 (T2), and 90 (T3) sessions. Bone stimulus was calculated for each rower at each time point using the average number of weekly loading cycles, peak foot reaction force, and bone mineral content from the previous time point. A regression analysis was used to determine the relationship between calculated bone stimulus and change in femoral trabecular BMD between time points.RESULTS: Trabecular BMD in the femur and tibia decreased for all participants in T0-1, but the rate of loss slowed or reversed between T1-2, with little-to-no bone loss for most participants during T2-3. The calculated bone stimulus was significantly correlated with change in femoral trabecular BMD (P=0.016; R2=0.458).CONCLUSION: Consistent participation in an FES rowing program provides sufficient forces and loading cycles to reduce or reverse expected bone loss at the distal femur and tibia, at least temporarily, in some individuals within two years after SCI.TRIAL REGISTRATION: NCT02008149.

  View details for DOI 10.1080/10790268.2018.1544879

  View details for PubMedID 30475172

• Genital nerve stimulation increases bladder capacity after SCI: A meta-analysis. journal of spinal cord medicine Bourbeau, D. J., Creasey, G. H., Sidik, S., Brose, S. W., Gustafson, K. J. 2017: 1-9

  Abstract

  Neurogenic detrusor overactivity (NDO) often results in decreased bladder capacity, urinary incontinence, and vesico-ureteral reflux. NDO can trigger autonomic dysreflexia and can impair quality of life. Electrical stimulation of the genital nerves (GNS) acutely inhibits reflex bladder contractions and can increase bladder capacity. Quantifying the effect of GNS on bladder capacity and determining what study factors and subject factors influence bladder capacity improvements will inform the design of clinical GNS interventions.We measured bladder capacity in 33 individuals with NDO, with and without GNS. These data were combined with data from seven previous GNS studies (n=64 subjects). A meta-analysis of the increase in bladder capacity and potential experimental factors was conducted (n=97 subjects total).Bladder capacity increased 131±101 ml with GNS across subjects in all studies. The number of individuals whose bladder capacity was greater than 300 ml increased from 24% to 62% with GNS. Stimulus amplitude was a significant factor predicting bladder capacity gain. The variance of the bladder capacity gain significantly increased with increasing infusion rate. Other factors did not contribute to bladder capacity gain.GNS acutely increases bladder capacity in individuals with NDO. The consistent increase in magnitude of bladder capacities across the eight studies, and the lack of dependence on individual-specific factors, provide confidence that GNS could be an effective tool for many individuals with NDO. Studies of the chronic effect of GNS on bladder control, with clinical measures such as urinary continence, are needed.

  View details for DOI 10.1080/10790268.2017.1281372

  View details for PubMedID 28198657

• Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells. Neurosurgery Mitra, S. S., Feroze, A. H., Gholamin, S., Richard, C., Esparza, R., Zhang, M., Azad, T. D., Alrfaei, B., Kahn, S. A., Hutter, G., Guzman, R., Creasey, G. H., Plant, G. W., Weissman, I. L., Edwards, M. S., Cheshier, S. 2015; 77 (5): 794-802

  Abstract

  The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis.Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells.Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated.PDGFRαCD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree.Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.

  View details for DOI 10.1227/NEU.0000000000000918

  View details for PubMedID 26225855

• Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes. Spinal cord Middleton, J. W., Piccenna, L., Lindsay Gruen, R., Williams, S., Creasey, G., Dunlop, S., Brown, D., Batchelor, P. E., Berlowitz, D. J., Coates, S., Dunn, J. A., Furness, J. B., Galea, M. P., Geraghty, T., Kwon, B. K., Urquhart, S., Yates, D., Bragge, P. 2015; 53 (10): 729-737

  Abstract

  Focus Group.To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand.Australia.A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion.A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities.This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

  View details for DOI 10.1038/sc.2015.87

  View details for PubMedID 26099211

• Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part II: Background to a research strategy. Spinal cord Bragge, P., Piccenna, L., Middleton, J., Williams, S., Creasey, G., Dunlop, S., Brown, D., Gruen, R. 2015; 53 (10): 721-728

  View details for DOI 10.1038/sc.2015.86

  View details for PubMedID 26099209

• Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part I: rapid review of SCI prioritisation literature. Spinal cord Bragge, P., Piccenna, L., Middleton, J. W., Williams, S., Creasey, G., Dunlop, S., Brown, D., Gruen, R. L. 2015; 53 (10): 714-720

  View details for DOI 10.1038/sc.2015.85

  View details for PubMedID 26099213

• Pressure ulcers in people with spinal cord injury in developing nations. Spinal cord Zakrasek, E. C., Creasey, G., Crew, J. D. 2015; 53 (1): 7-13

  Abstract

  Literature review.To explore the prevalence or incidence, risk factors, and costs of pressure ulcers among individuals with spinal cord injury (SCI), specifically in the context of the developing world. To highlight important targets for intervention and research for pressure ulcer management the world over.World Bank 'low-income' and 'middle-income' countries with a gross national income per capita <$12 746.PubMed search.SCI-associated pressure ulcers are very prevalent in developing nations; however, reported prevalence and incidence numbers are highly variable. Risk factors for pressure ulcers are similar in developed and developing countries however many of the risk factors are more prevalent in developing nations.SCI-associated pressure ulcers are common but can be prevented in the developing world. Key targets for interventions include acute care, nurse-to-patient ratios, support surfaces and education.

  View details for DOI 10.1038/sc.2014.179

  View details for PubMedID 25366536

• Traumatic brain injury in US Veterans with traumatic spinal cord injury JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Creasey, G. H., Lateva, Z. C., Rose, S. M., Rose, J. 2015; 52 (6): 669-676

  Abstract

  Patients with both a spinal cord injury (SCI) and traumatic brain injury (TBI) are often very difficult to manage and can strain the resources of clinical units specialized in treating either diagnosis. However, a wide range of estimates exists on the extent of this problem. The aim of this study was to describe the scope of the problem in a well-defined population attending a comprehensive SCI unit. Electronic medical records of all patients with SCI being followed by the SCI unit in a U.S. Veterans' hospital were searched to identify those with concurrent TBI. The data were analyzed for age, sex, cause of injury, level and completeness of SCI, cognitive impairment, relationship with Active Duty military, and date of injury. Of 409 Veterans with a traumatic SCI, 99 (24.2%) were identified as having had a concurrent TBI. The occurrence did not appear to be closely related to military conflict. Reports of TBI were much more common in the last 20 yr than in previous decades. Documentation of TBI in patients with SCI was inconsistent. Improved screening and documentation could identify all patients with this dual diagnosis and facilitate appropriate management.

  View details for DOI 10.1682/JRRD.2014.11.0291

  View details for Web of Science ID 000364501500005

• Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement. Experimental neurology Inoue, T., Lin, A., Ma, X., McKenna, S. L., Creasey, G. H., Manley, G. T., Ferguson, A. R., Bresnahan, J. C., Beattie, M. S. 2013; 248: 136-147

  Abstract

  A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI.

  View details for DOI 10.1016/j.expneurol.2013.06.006

  View details for PubMedID 23770071

• Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection BMC NEUROSCIENCE Wu, Y., Collier, L., Qin, W., Creasey, G., Bauman, W. A., Jarvis, J., Cardozo, C. 2013; 14

  View details for DOI 10.1186/1471-2202-14-81

  View details for Web of Science ID 000322785300001

• Consistency Among Musculoskeletal Models: Caveat Utilitor ANNALS OF BIOMEDICAL ENGINEERING Wagner, D. W., Stepanyan, V., Shippen, J. M., Demers, M. S., Gibbons, R. S., Andrews, B. J., Creasey, G. H., Beaupre, G. S. 2013; 41 (8): 1787-1799

  Abstract

  Musculoskeletal simulation software and model repositories have broadened the user base able to perform musculoskeletal analysis and have facilitated in the sharing of models. As the recognition of musculoskeletal modeling continues to grow as an engineering discipline, the consistency in results derived from different models and software is becoming more critical. The purpose of this study was to compare eight models from three software packages and evaluate differences in quadriceps moment arms, predicted muscle forces, and predicted tibiofemoral contact forces for an idealized knee-extension task spanning -125 to +10° of knee extension. Substantial variation among models was observed for the majority of aspects evaluated. Differences among models were influenced by knee angle, with better agreement of moment arms and tibiofemoral joint contact force occurring at low to moderate knee flexion angles. The results suggest a lack of consistency among models and that output differences are not simply an artifact of naturally occurring inter-individual differences. Although generic musculoskeletal models can easily be scaled to consistent limb lengths and use the same muscle recruitment algorithm, the results suggest those are not sufficient conditions to produce consistent muscle or joint contact forces, even for simplified models with no potential of co-contraction.

  View details for DOI 10.1007/s10439-013-0843-1

  View details for Web of Science ID 000321514300020

  View details for PubMedID 23775441

• The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures JOURNAL OF BIOLOGICAL CHEMISTRY Qin, W., Sun, L., Cao, J., Peng, Y., Collier, L., Wu, Y., Creasey, G., Li, J., Qin, Y., Jarvis, J., Bauman, W. A., Zaidi, M., Cardozo, C. 2013; 288 (19): 13511-13521

  Abstract

  Mechanisms by which muscle regulates bone are poorly understood.Electrically stimulated muscle contraction reversed elevations in bone resorption and increased Wnt signaling in bone-derived cells after spinal cord transection.Muscle contraction reduced resorption of unloaded bone independently of the CNS, through mechanical effects and, potentially, nonmechanical signals (e.g. myokines).The study provides new insights regarding muscle-bone interactions. Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-κB ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization.

  View details for DOI 10.1074/jbc.M113.454892

  View details for Web of Science ID 000318850300035

  View details for PubMedID 23530032

  View details for PubMedCentralID PMC3650388

• Functional electrical stimulation in spinal cord injury respiratory care. Topics in spinal cord injury rehabilitation Jarosz, R., Littlepage, M. M., Creasey, G., McKenna, S. L. 2012; 18 (4): 315-321

  Abstract

  The management of chronic respiratory insufficiency and/or long-term inability to breathe independently has traditionally been via positive-pressure ventilation through a mechanical ventilator. Although life-sustaining, it is associated with limitations of function, lack of independence, decreased quality of life, sleep disturbance, and increased risk for infections. In addition, its mechanical and electronic complexity requires full understanding of the possible malfunctions by patients and caregivers. Ventilator-associated pneumonia, tracheal injury, and equipment malfunction account for common complications of prolonged ventilation, and respiratory infections are the most common cause of death in spinal cord-injured patients. The development of functional electric stimulation (FES) as an alternative to mechanical ventilation has been motivated by a goal to improve the quality of life of affected individuals. In this article, we will review the physiology, types, characteristics, risks and benefits, surgical techniques, and complications of the 2 commercially available FES strategies - phrenic nerve pacing (PNP) and diaphragm motor point pacing (DMPP).

  View details for DOI 10.1310/sci1804-315

  View details for PubMedID 23459661

• Functional electrical stimulation for bladder, bowel, and sexual function. Handbook of clinical neurology Creasey, G. H., Craggs, M. D. 2012; 109: 247-257

  Abstract

  The principles of using electrical stimulation of peripheral nerves or nerve roots for restoring useful bladder, bowel, and sexual function after damage or disease of the central nervous system are described. Activation of somatic or parasympathetic efferent nerves can produce contraction of striated or smooth muscle in the bladder, rectum, and sphincters. Activation of afferent nerves can produce reflex activation of somatic muscle and reflex inhibition or activation of smooth muscle in these organs. In clinical practice these techniques have been used to produce effective emptying of the bladder and bowel in patients with spinal cord injury and to improve continence of urine and feces. Stimulation of parasympathetic efferents can produce sustained erection of the penis, and stimulation of the nerves to the seminal vesicles can produce seminal emission. Reflex erection and ejaculation can also be produced by stimulation of afferent nerves. Experimental techniques for controlling emptying and continence by a single device, and prospects for comprehensive control of bladder, bowel, and sexual function by electrical techniques are described. These may include more selective electrodes, inactivation of nerves by specific stimulus parameters, greater use of sensors, and networking of implanted components connected to the central and peripheral nervous system.

  View details for DOI 10.1016/B978-0-444-52137-8.00015-2

  View details for PubMedID 23098717

• Outcome measures in spinal cord injury: recent assessments and recommendations for future directions SPINAL CORD Alexander, M. S., Anderson, K. D., Biering-Sorensen, F., Blight, A. R., Brannon, R., Bryce, T. N., Creasey, G., Catz, A., Curt, A., Donovan, W., Ditunno, J., Ellaway, P., Finnerup, N. B., Graves, D. E., Haynes, B. A., Heinemann, A. W., Jackson, A. B., Johnston, M. V., Kalpakjian, C. Z., Kleitman, N., Krassioukov, A., Krogh, K., Lammertse, D., Magasi, S., Mulcahey, M. J., Schurch, B., Sherwood, A., Steeves, J. D., Stiens, S., Tulsky, D. S., van Hedel, H. J., Whiteneck, G. 2009; 47 (8): 582-591

  Abstract

  Study design:Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. Objectives:Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. Methods:a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. Results:Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. Conclusion:Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial.

  View details for DOI 10.1038/sc.2009.18

  View details for Web of Science ID 000268684500004

  View details for PubMedID 19381157

• International standards to document remaining autonomic function after spinal cord injury SPINAL CORD Alexander, M. S., Biering-Sorensen, F., Bodner, D., Brackett, N. L., Cardenas, D., Charlifue, S., Creasey, G., DIETZ, V., Ditunno, J., Donovan, W., Elliott, S. L., Estores, I., Graves, D. E., Green, B., Gousse, A., Jackson, A. B., Kennelly, M., Karlsson, A., Krassioukov, A., Krogh, K., Linsenmeyer, T., Marino, R., Mathias, C. J., Perkash, I., Sheel, A. W., Shilero, G., Schurch, B., Sonksen, J., Stiens, S., Wecht, J., Wuermser, L. A., Wyndaele, J. 2009; 47 (1): 36-43

  Abstract

  Experts opinions consensus.To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI).The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function.Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function.Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function.This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.

  View details for DOI 10.1038/sc.2008.121

  View details for Web of Science ID 000262297000003

  View details for PubMedID 18957962

• Implantable FES system for upright mobility and bladder and bowel function for individuals with spinal cord injury SPINAL CORD Johnston, T. E., Betz, R. R., Smith, B. T., Benda, B. J., Mulcahey, M. J., Davis, R., Houdayer, T. P., Pontari, M. A., Barriskill, A., CREASEY, G. H. 2005; 43 (12): 713-723

  Abstract

  Postintervention.To determine the effectiveness of the Praxis multifunctional implantable functional electrical stimulation (FES) system (Neopraxis Pty. Ltd, Lane Cove, NSW, Australia) to provide standing and stepping ability and bladder and bowel management for individuals with motor complete thoracic level spinal cord injuries (SCI).Pediatric orthopedic hospital specializing in SCI.Subjects:Three males, ages 17 and 21 years, with motor-complete thoracic level SCI and intact lower motor neurons to the muscles targeted for stimulation.Each subject was successfully implanted with the Praxis FES system. All three subjects received electrodes for upright mobility and the first two subjects received additional electrodes for stimulated bladder and bowel management. Following training, subjects were evaluated in their ability to use FES for nine mobility activities. Acute and chronic experiments of the effect of stimulation on bowel and bladder function were also performed.All three subjects could independently stand up from the wheelchair and could walk at least 6 m using a swing through gait pattern. Two subjects were able to independently perform swing through gait for 6 min and one subject was able to independently ascend and descend stairs. Suppression of reflex bladder contractions by neuromodulation (subject 1) and stimulated contractions of the rectum (subject 2) were observed in acute experiments. When stimulation was applied over the course of several weeks, a positive effect on bowel function was measured. Stimulated bladder contractions were not achieved.The feasibility of using the Praxis FES system for upright mobility and aiding aspects of bladder and bowel function was demonstrated with three subjects with thoracic level SCI.

  View details for DOI 10.1038/sj.sc.3101797

  View details for Web of Science ID 000233809300003

  View details for PubMedID 16010275

• A urethral afferent mediated excitatory bladder reflex exists in humans NEUROSCIENCE LETTERS Gustafson, K. J., CREASEY, G. H., Grill, W. M. 2004; 360 (1-2): 9-12

  Abstract

  An excitatory reflex between urethral flow receptors and the bladder has been established in animals, but attempts to demonstrate this reflex in humans using urethral fluid flow have been inconclusive. Intraurethral electrical stimulation has recently been shown to generate bladder contractions in animals and was applied to study the presence of an excitatory urethra to bladder reflex in humans. The prostatic urethra was stimulated electrically via a catheter-based electrode in five men with complete spinal cord injury. Bladder contractions were generated in four of five individuals, however, only when the bladder volume was sufficiently large. These results demonstrate the presence of a volume dependent excitatory bladder reflex mediated by urethral afferent nerve fibers and the lumbosacral spinal cord.

  View details for DOI 10.1016/j.neulet.2004.01.001

  View details for Web of Science ID 000221080500003

  View details for PubMedID 15082166

• Clinical applications of electrical stimulation after spinal cord injury. journal of spinal cord medicine Creasey, G. H., Ho, C. H., Triolo, R. J., Gater, D. R., DiMarco, A. F., Bogie, K. M., Keith, M. W. 2004; 27 (4): 365-375

  Abstract

  During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development.

  View details for PubMedID 15484667

• Electrical stimulation for the treatment of bladder dysfunction: Current status and future possibilities NEUROLOGICAL RESEARCH Jezernik, S., Craggs, M., Grill, W. M., Creasey, G., Rijkhoff, N. J. 2002; 24 (5): 413-430

  Abstract

  Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity.

  View details for Web of Science ID 000176706100002

  View details for PubMedID 12117310

• Control of bladder function by electrical activation of spinal neural circuits 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) Grill, W. A., Gustafson, K. J., CREASEY, G. H. IEEE. 2002: 2043–2044

  View details for Web of Science ID 000180194801001

• Selective suppression of sphincter activation during sacral anterior nerve root stimulation NEUROUROLOGY AND URODYNAMICS Bhadra, N., Grunewald, V., Creasey, G., Mortimer, J. T. 2002; 21 (1): 55-64

  Abstract

  The purpose of this work was to electrically activate small-diameter motor fibers in the sacral anterior roots innervating the urinary bladder, without activating the large-diameter fibers to the sphincter. Quasitrapezoidal current pulses were applied through tripolar spiral nerve electrodes on selected anterior sacral roots during acute experiments on eight dogs, maintained under pentobarbital anesthesia. Pressures were recorded from the bladder and sphincter with catheter-mounted gauges. Stimulation with biphasic quasitrapezoidal pulses showed decrease in sphincter recruitment with increasing pulse amplitudes. The minimum current amplitude that resulted in maximum sphincter suppression was used to stimulate the roots with trains of 20 Hz pulses, with 60 mL of saline filling the bladder. Pressures were also recorded when 100 micros rectangular pulse trains at 20 Hz, both continuous and intermittent, were applied. Trains of stimuli were applied before and after dorsal root rhizotomy. Suppression of sphincter activation was defined to be a percentage, [(Maximum pressure -Minimum pressure)/Maximum pressure x100. The results from 22 roots in eight animals show that with single pulses, the average percentage suppression of sphincter activation was 76.3% (+/-14.0). The minimum current for maximum sphincter suppression was 1.29 mA (+/-0.62). The average bladder pressure evoked was 50 cm of water during pulse train stimulation, with no significant difference due to pulse type. With pulse trains, the sphincter pressures were significantly higher when the bladder was filled. Evacuation of fluid occurred in three animals with average flow rates of 1.0 mL/s.

  View details for Web of Science ID 000173106000009

  View details for PubMedID 11835425

• An implantable neuroprosthesis for restoring bladder and bowel control to patients with spinal cord injuries: A multicenter trial ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Creasey, G. H., Grill, J. H., Korsten, M., Sang, H., Betz, R., Anderson, R., Walter, J. 2001; 82 (11): 1512-1519

  Abstract

  To evaluate the safety and efficacy of an implanted neuroprosthesis for management of the neurogenic bladder and bowel in individuals with spinal cord injury (SCI).Prospective study comparing bladder and bowel control before and at 3, 6, and 12 months after implantation of the neuroprosthesis.Six US hospitals specializing in treatment of SCI.Twenty-three neurologically stable patients with complete suprasacral SCIs.Implantation of an externally controlled neuroprosthesis for stimulating the sacral nerves and posterior sacral rhizotomy.Ability to urinate more than 200mL on demand and a resulting postvoid residual volume of less than 50mL.At 1-year follow-up, 18 of 21 patients could urinate more than 200mL with the neuroprosthesis, and 15 of 21 had postvoid volumes less than 50mL (median, 15mL). Urinary tract infection, catheter use, reflex incontinence, anticholinergic drug use, and autonomic dysreflexia were substantially reduced. At 1-year follow-up, 15 of 17 patients reduced the time spent with bowel management.Neural stimulation and posterior rhizotomy is a safe and effective method of bladder and bowel management after suprasacral SCI.

  View details for DOI 10.1053/apmr.2001.25911

  View details for Web of Science ID 000171959600002

  View details for PubMedID 11689969

• Economic consequences of an implanted neuroprosthesis for bladder and bowel management ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION CREASEY, G. H., Dahlberg, J. E. 2001; 82 (11): 1520-1525

  Abstract

  To determine whether an implanted neuroprosthesis for bladder and bowel management is less costly than conventional techniques.Retrospective cost-identification analysis with comparison before and after implantation of the neuroprosthesis.Life-care planning interviews in patients' homes.Twelve patients with complete suprasacral spinal cord injuries and neurogenic bladder and bowel.Implantation of a neuroprosthesis for electric stimulation of the sacral nerves and posterior sacral rhizotomy.Annual costs of bladder and bowel care with and without the neuroprosthesis, projected over 10 years.Bladder and bowel care costs were reduced by over 80%, from a median of 8152 dollars a year for conventional care to a median of 948 dollars a year. With the neuroprosthesis, median annual costs for bladder supplies were reduced from 3368 dollars to 58 dollars; for medications, from 1866 dollars to 108 dollars; for medical care, from 656 dollars to 96 dollars; and for bowel care supplies, from 205 dollars to 87 dollars. After 5 years, the cumulative costs of treatment with the neuroprosthesis, including the cost of the device and its implantation and maintenance, equaled those of conventional care. Thereafter, savings from the implanted neuroprosthesis are projected to increase progressively throughout the patient's life.A neuroprosthesis implant with posterior rhizotomy greatly reduces the cost of managing the neurogenic bladder and bowel.

  View details for Web of Science ID 000171959600003

  View details for PubMedID 11689970

• Functional Electrical Stimulation for control of internal organ function - Commentary NEUROMODULATION Creasey, G. 2001; 4 (4): 162-163

  View details for Web of Science ID 000171985400011

• Urethral pressure profiles in the female canine implanted with sacral anterior nerve root electrodes WORLD JOURNAL OF UROLOGY Bhadra, N., Grunewald, V., Creasey, G., Mortimer, J. T. 2001; 19 (4): 272-277

  Abstract

  The purpose of this work was to study the pressure distribution along the urethra in female canines with and without electrical stimulation of the sacral anterior roots innervating the bladder and urethra. Urethral pressure profiles were recorded in two orientations, dorsal and ventral, with microtransducer catheters. Two pulse types were applied at 1 Hz, 500 micros quasitrapezoidal pulses to selectively activate the small axons and 100 micros rectangular pulses. Four parameters were measured from each profile; maximum urethral pressure (MUP), bladder pressure (Pv), functional urethral length (FUL), and the position of the maximum peak from the bladder neck (PMP). Two derived measures, the estimated maximum urethral closing pressure (UCP) and the position of the maximum as a percentage of the FUL (PM%) were calculated. There were highly significant differences (P<0.01) in the value and position of the estimated UCP in the two orientations of the transducers. The highest pressures were recorded in the ventral orientation near the terminal portions of the urethra. Principal sphincter activity during electrical stimulation of the ventral sacral roots was also confined to this part. Selective small fiber activation did not result in any significant increase in this peak pressure from passive values.

  View details for Web of Science ID 000170606900011

  View details for PubMedID 11550789

• Functional neuromuscular stimulation in spinal cord injury. Physical medicine and rehabilitation clinics of North America Chae, J., Kilgore, K., Triolo, R., Creasey, G. 2000; 11 (1): 209-?

  Abstract

  With recent advances in clinical medicine and biomedical engineering, functional neuromuscular stimulation (FNS) can now be added to the psychiatric armamentarium to decrease the debilitating effects of traumatic spinal cord injury. In this article, the components of FNS systems and their evolution in design are presented. The clinical implications of FNS are discussed with respect to upper and lower extremities and bladder applications, and perspectives on future developments and directions are reviewed.

  View details for PubMedID 10680166

• Electrical stimulation to restore respiration Engineering Foundation Conference on Neural Prostheses - Motor Systems IV Creasey, G., Elefteriades, J., DiMarco, A., Talonen, P., Bijak, M., Girsch, W., KANTOR, C. JOURNAL REHAB RES & DEV. 1996: 123–32

  Abstract

  Electrical stimulation has been used for over 25 years to restore breathing to patients with high quadriplegia causing respiratory paralysis and patients with central alveolar hypoventilation. Three groups have developed electrical pacing systems for long-term support of respiration in humans. These systems consist of electrodes implanted on the phrenic nerves, connected by leads to a stimulator implanted under the skin, and powered and controlled from a battery-powered transmitter outside the body. The systems differ principally in the electrode design and stimulation waveform. Approximately 1,000 people worldwide have received one of the three phrenic pacing devices, most with strongly positive results: reduced risk of tracheal problems and chronic infection, the ability to speak and smell more normally, reduced risk of accidental interruption of respiration, greater independence, and reduced costs and time for ventilatory care. For patients with partial lesions of the phrenic nerves, intercostal muscle stimulation may supplement respiration.

  View details for Web of Science ID A1996UK19900004

  View details for PubMedID 8724168

• Tendon transfers and functional electrical stimulation for restoration of hand function in spinal cord injury JOURNAL OF HAND SURGERY-AMERICAN VOLUME Keith, M. W., Kilgore, K. L., Peckham, P. H., Wuolle, K. S., Creasey, G., LeMay, M. 1996; 21A (1): 89-99

  View details for Web of Science ID A1996TR34500015

• Tendon transfers and functional electrical stimulation for restoration of hand function in spinal cord injury. journal of hand surgery Keith, M. W., Kilgore, K. L., Peckham, P. H., Wuolle, K. S., Creasey, G., LeMay, M. 1996; 21 (1): 89-99

  Abstract

  Spinal cord injury at the C5 and C6 level results in loss of hand function. Electrical stimulation of paralyzed muscles is one approach that has demonstrated significant capacity for restoring grasp and release function. One potential limitation of this approach is that key muscles for stimulation may have lower motor neuron damage, rendering the muscles unexcitable. We have used surgical modification of the biomechanics of the hand to overcome this limitation. Tendon transfer of paralyzed but lower motor neuron intact muscles can compensate for potential function lost owing to muscles with lower motor neuron damage. Such procedures have been performed to provide finger extension, thumb extension, finger flexion, and wrist extension. Additional surgical procedures have been performed to enhance the function provided with electrical stimulation. These are side-to-side synchronization of the finger flexor and extensor tendons, the flexor digitorium superficialis Zancolli-lasso procedure, and thumb interphalangeal joint arthrodesis. These procedures have been performed in 11 patients with C5 and C6 level spinal injuries and functional electrical stimulation neuroprostheses. In these patients, 41 different functional electrical stimulation-related procedures were performed and 38 gave the desired result after surgery. One procedure resulted in no increase or decrease in function or muscle output, and two procedures resulted in a decrease in muscle force or joint range of motion. The issues that must be considered in performing functional electrical stimulation-related tendon transfers are discussed.

  View details for PubMedID 8775202

• SACRAL ROOT STIMULATION FOR SELECTIVE ACTIVATION OF THE CANINE BLADDER USING QUASITRAPEZOIDAL ELECTRICAL PULSES 12th Symposium for Experimental Urology Wipfler, G., Grunewald, V., Bhadra, N., CREASEY, G. H., Mortimer, J. T. GEORG THIEME VERLAG. 1995: 13–15

  View details for Web of Science ID A1995RX09300006

• Review of sacral electrical stimulation in the management of the neurogenic bladder. NeuroRehabilitation CREASEY, G. H., Bodner, D. R. 1994; 4 (4): 266-274

  Abstract

  In patients with spinal cord injury above the conus medullaris, electrical stimulation of the sacral anterior nerve roots can produce micturition with low residual volumes of urine and reduced urinary tract infection. Vowing pressures appear to be maintained at safe levels by the use of an intermittent pattern of stimulation. The procedure is usually combined with division of the sacral posterior roots, which increases bladder capacity and continence; this also increases bladder compliance, which may be protective for the upper urinary tracts.The procedure has now been applied in about 900 patients with spinal cord injury, some of whom have been followed up for over 15 years. The nerves do not appear to be damaged by long-term stimulation and technical faults with the equipment are now uncommon.

  View details for DOI 10.3233/NRE-1994-4411

  View details for PubMedID 24525414

• MULTIPLE CASES OF BURKITTS-LYMPHOMA AND OTHER NEOPLASMS IN FAMILIES IN THE NORTH MARA DISTRICT OF TANZANIA INTERNATIONAL JOURNAL OF CANCER Brubaker, G., Levin, A. G., Steel, C. M., Creasey, G., Cameron, H. M., LINSELL, C. A., Smith, P. G. 1980; 26 (2): 165-170

  Abstract

  In an area of Tanzania in which Burkitt's lymphoma (BL) is endemic, five families are described in which multiple cases of BL were found or BL occurred with other neoplasms. The patients include two brothers and one half-brother with BL, two brothers with BL, a woman with nasopharyngeal carcinoma (NPC) whose daughter had BL, a boy with BL whose sister developed chronic myelogenous leukaemia (CML), and a man with CML whose son developed BL. The two full-sib pairs with BL is significantly more than would be expected to have arisen by chance and the association of BL with NPC and CML among close relatives is remarkable in view of the rarity of the last two neoplasms in the study area. It is suggested that genetic factors may be important. It is suggested that genetic factors may be important in determining susceptibility to the three malignancies in this population, but the possibility that the clustering of cases within families may be due to local environmental factors cannot be excluded.

  View details for Web of Science ID A1980KE34100006

  View details for PubMedID 6937447